Resequencing the complete SNCA locus in Indian patients with Parkinson's disease.

The genetic loci implicated in familial Parkinson's disease (PD) have limited generalizability to the Indian PD population. We tested mutations and the frequency of known mutations in the SNCA gene in a PD cohort from India. We selected 298 PD cases and 301 age-matched controls for targeted resequencing (before QC), along with 363 PD genomes of Indian ancestry and 1029 publicly available whole genomes from India as healthy controls (IndiGenomes), to determine the frequency of monogenic SNCA mutations. The raw sequence reads were analyzed using an in-house analysis pipeline, allowing the detection of small variants and structural variants using Manta. The in-depth analysis of the SNCA locus did not identify missense or structural variants, including previously identified SNCA mutations, in the Indian population. The familial forms of SNCA gene variants do not play a major role in the Indian PD population and this warrants further research in the under-represented population.

Understanding the Solid-Electrolyte-Interface (SEI) Formation in Glyme Electrolyte Using Time-Of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS).

Lithium-ion batteries are commonly used for energy storage due to their long lifespan and high energy density, but the use of unsafe electrolytes poses significant health and safety concerns. An alternative source is necessary to maintain electrochemical efficacy. This research demonstrates new safe glyme-based electrolytes for silica/carbon (SiOx/C) nanocomposite derived from Australian rice husk (RH). The quality of SiOx/C was preserved by using deep eutectic solvent-based pre-treatment and single-step carbonization, which was confirmed through the X-ray analysis of the crystalline phase of silica. The electrochemical assessment of SiOx/C anode using various glyme-based electrolytes for LIBs was carried out. Among them, the resultant half cells based on diglyme electrolyte is superior to others with the first discharge capacity at 1274 mAh/g and a reversible discharge capacity of 759.7 mAh/g. Ex-situ SEM and Time-of-Flight Secondary Ion Mass Spectrometry (ToF- SIMS) analysis of the electrode indicated that diglyme not only improves the capacity but also sustains the electrode architecture for longer cycle life with more LiF-based components and also showed the absence of HF components. Importantly, the addition of fluoroethylene carbonate (FEC) additive enhanced the cycling stability. These results provide a new perspective on developing advanced SiOx/C anode using glyme electrolytes for Li-ion batteries.

Exosomal microRNAs in Parkinson's disease: insights into biomarker potential and disease pathology.

Parkinson's disease (PD) is a prevalent neurodegenerative condition primarily affecting the elderly population. Despite its high incidence in aged individuals, there are no reliable blood-based biomarkers for clinical diagnosis of PD and early screening of susceptible individuals. Recent studies have revealed the significance of exosomes in mediating cell-to-cell communications by transferring bioactive molecules, such as proteins, nucleic acids (including miRNAs), lipids, and metabolites, between cells. Due to their ability to carry diverse molecular cargo and their involvement in various physiological and pathological processes, exosomes have gained significant attention as potential disease biomarkers. Notably, exosomes have the ability to cross the blood-brain barrier, and as a result, they can be found in circulating body fluids, including cerebrospinal fluid (CSF), serum, and plasma. Therefore, the identification of PD-specific exosomes in blood samples could be a promising avenue with biomarker potential for advancing clinical diagnosis and planning therapeutic strategies. This review highlights the current understanding of exosomal miRNAs in PD pathology, emphasising their potential for clinical utility as biomarkers even though several challenges may have to be overcome to precisely utilize exosomal miRNAs as biomarkers specific to PD.

A data mining approach to analyze the role of biomacromolecules-based nanocomposites in sustainable packaging.

Recent decades have witnessed a surge in research interest in bio-nanocomposite-based packaging materials, but still, a lack of systematic analysis exists in this domain. Bio-based packaging materials pose a sustainable alternative to petroleum-based packaging materials. The current work employs bibliometric analysis to deliver a comprehensive outline on the role of bio nanocomposites in packaging. India, Iran, and China were revealed to be the top three nations actively engaged in this domain in total publications. Islamic Azad University in Iran and Universiti Putra Malaysia in Malaysia are among the world's best institutions in active research and publications in this field. The extensive collaboration between nations and institutions highlights the significance of a holistic approach towards bio-nanocomposite. The National Natural Science Foundation of China is the leading funding body in this field of research. Among authors, Jong whan Rhim secured the topmost citations (2234) in this domain (13 publications). Among journals, Carbohydrate Polymers secured the maximum citation count (4629) from 36 articles; the initial one was published in 2011. Bio nanocomposite is the most frequently used keyword. Researchers and policymakers focussing on sustainable packaging solutions will gain crucial insights on the current research status on packaging solutions using bio-nanocomposites from the conclusions.

Kenaf-based activated carbon: A sustainable solution for high-performance aqueous symmetric supercapacitors.

This study presents an innovative method for synthesizing activated carbon with an exceptionally high surface area (3359 m2 g-1) using kenaf fiber-based biochar through chemical activation. The achieved specific surface area surpasses activated carbon derived from other reported fiber-based precursors. The resulting activated carbon was investigated as electrodes for supercapacitors, revealing a remarkable maximum capacitance of 312 F g-1 at a current density of 0.5 A g-1. An aqueous symmetric supercapacitor employing these high-surface-area electrodes exhibited an outstanding energy density of 18.9 Wh kg-1 at a power density of 250 W kg-1. Notably, the supercapacitor retained exceptional capacitance, maintaining 93% of its initial capacitance even after 5000 charge-discharge cycles.

Quantitative susceptibility mapping from basal ganglia and related structures: correlation with disease severity in progressive supranuclear palsy.

OBJECTIVE: We examined whether mean magnetic susceptibility values from deep gray matter structures in patients with progressive supranuclear palsy (PSP) differed from those in patients with Parkinson's disease (PD) and healthy volunteers, and correlated with the PSP rating scale. METHODS: Head of caudate nucleus, putamen, globus pallidus, substantia nigra and red nucleus were the regions of interest. Mean susceptibility values from these regions in PSP patients were estimated using quantitative susceptibility mapping. Correlations with clinical severity of disease as measured by the PSP rating scale were examined. The mean susceptibility values were also compared with those from healthy volunteers and age- and disease duration-matched patients with PD. RESULTS: Data from 26 healthy volunteers, 26 patients with PD and 27 patients with PSP, were analysed. Patients with PSP had higher mean susceptibility values from all regions of interest when compared to both the other groups. The PSP rating scale scores correlated strongly with mean susceptibility values from the red nucleus and moderately with those from the putamen and substantia nigra. The scores did not correlate with mean susceptibility values from the caudate nucleus or globus pallidus. In patients with PD, the motor deficits correlated moderately with mean susceptibility values from substantia nigra. CONCLUSIONS: In patients with PSP, mean susceptibility values indicating the severity of mineralization of basal ganglia and related structures correlate with disease severity, the correlation of red nucleus being the strongest. Further studies are warranted to explore whether mean susceptibility values could serve as biomarkers for PSP.

Unravelling the Parkinson's puzzle, from medications and surgery to stem cells and genes: a comprehensive review of current and future management strategies.

Parkinson's disease (PD) is a neurodegenerative disorder, prevalent in the elderly population. Neuropathological hallmarks of PD include loss of dopaminergic cells in the nigro-striatal pathway and deposition of alpha-synuclein protein in the neurons and synaptic terminals, which lead to a complex presentation of motor and non-motor symptoms. This review focuses on various aspects of PD, from clinical diagnosis to currently accepted treatment options, such as pharmacological management through dopamine replacement and surgical techniques such as deep brain stimulation (DBS). The review discusses in detail the potential of emerging stem cell-based therapies and gene therapies to be adopted as a cure, in contrast to the present symptomatic treatment in PD. The potential sources of stem cells for autologous and allogeneic stem cell therapy have been discussed, along with the progress evaluation of pre-clinical and clinical trials. Even though recent techniques hold great potential to improve the lives of PD patients, we present the importance of addressing the safety, efficacy, ethical, cost, and regulatory concerns before scaling them to clinical use.

A Review on Implantable Neuroelectrodes.

The efficacy of every neuromodulation modality depends upon the characteristics of the electrodes used to stimulate the chosen target. The geometrical, chemical, mechanical and physical configuration of electrodes used in neurostimulation affects several performance attributes like stimulation efficiency, selectivity, tissue response, etc. The efficiency of stimulation in relation to electrode impedance is influenced by the electrode material and/or its geometry. The nature of the electrode material determines the charge transfer across the electrode-tissue interface, which also relates to neuronal tissue damage. Electrode morphology or configuration pattern can facilitate the modulation of extracellular electric field (field shaping). This enables selective activation of neurons and minimizes side effects. Biocompatibility and biostability of the electrode materials or electrode coating have a role in glial formation and tissue damage. Mechanical and electrochemical stability (corrosion resistance) determines the long-term efficacy of any neuromodulation technique. Here, a review of electrodes typically used for implantable neuromodulation is discussed. Factors affecting the performance of electrodes like stimulation efficiency, selectivity and tissue responses to the electrode-tissue interface are discussed. Technological advancements to improve electrode characteristics are also included.

Deep Brain Stimulation for Parkinson's Disease-the Developing World's Perspective.

Background: Deep brain stimulation (DBS) is the most widely used device-assisted therapy in patients with moderately advanced stages of Parkinson's disease (PD) experiencing motor complications. Only a minority of eligible patients get the opportunity to undergo DBS in the developing world. Objectives: To examine the proportion and characteristics of patients with motor complications of PD who are willing for DBS and who undergo surgery. Methods: Patients with motor complications of PD eligible for DBS over a five-year study period (2016-2020) were included. The demographic, clinical and socio-economic characteristics and information on their status in 2021 were collected and analyzed. Results: Among 1017 patients, 223 had motor symptoms qualifying for DBS and follow-up information available. Only 78 (35%) opted for surgery. The willing patients had higher socioeconomic status, were older and had longer duration of PD and motor complications, more freezing of gait, cognitive symptoms, and neuropsychiatric disturbances. 37 of them were found unfit during pre-operative work-up; only 41 (18%) with motor complications were finally taken up for DBS. Age, duration or severity of motor symptoms did not differ between patients who were finally selected for surgery and those who were not. Conclusions: Less than one-fifth of our patients with motor complications of PD finally underwent DBS. The patients appeared to wait till the late stages of PD, before making a decision on availing surgical treatment. The delay resulted in nearly half of them being found unfit in pre-operative work-up. Our findings may enable clinicians to counsel eligible patients more efficiently.

Cerebellar and basal ganglia structural connections in humans: Effect of aging and relation with memory and learning.

Introduction: The cerebellum and basal ganglia were initially considered anatomically distinct regions, each connected via thalamic relays which project to the same cerebral cortical targets, such as the motor cortex. In the last two decades, transneuronal viral transport studies in non-human primates showed bidirectional connections between the cerebellum and basal ganglia at the subcortical level, without involving the cerebral cortical motor areas. These findings have significant implications for our understanding of neurodevelopmental and neurodegenerative diseases. While these subcortical connections were established in smaller studies on humans, their evolution with natural aging is less understood. Methods: In this study, we validated and expanded the previous findings of the structural connectivity within the cerebellum-basal ganglia subcortical network, in a larger dataset of 64 subjects, across different age ranges. Tractography and fixel-based analysis were performed on the 3 T diffusion-weighted dataset using Mrtrix3 software, considering fiber density and cross-section as indicators of axonal integrity. Tractography of the well-established cerebello-thalamo-cortical tract was conducted as a control. We tested the relationship between the structural white matter integrity of these connections with aging and with the performance in different domains of Addenbrooke's Cognitive Examination. Results: Tractography analysis isolated connections from the dentate nucleus to the contralateral putamen via the thalamus, and reciprocal tracts from the subthalamic nucleus to the contralateral cerebellar cortex via the pontine nuclei. Control tracts of cerebello-thalamo-cortical tracts were also isolated, including associative cerebello-prefrontal tracts. A negative linear relationship was found between the fiber density of both the ascending and descending cerebellum-basal ganglia tracts and age. Considering the cognitive assessments, the fiber density values of cerebello-thalamo-putaminal tracts correlated with the registration/learning domain scores. In addition, the fiber density values of cerebello-frontal and subthalamo-cerebellar (Crus II) tracts correlated with the cognitive assessment scores from the memory domain. Conclusion: We validated the structural connectivity within the cerebellum-basal ganglia reciprocal network, in a larger dataset of human subjects, across wider age range. The structural features of the subcortical cerebello-basal ganglia tracts in human subjects display age-related neurodegeneration. Individual morphological variability of cerebellar tracts to the striatum and prefrontal cortex was associated with different cognitive functions, suggesting a functional contribution of cerebellar tracts to cognitive decline with aging. This study offers new perspectives to consider the functional role of these pathways in motor learning and the pathophysiology of movement disorders involving the cerebellum and striatum.

Three-Dimensional Graphene-TiO2-SnO2 Ternary Nanocomposites for High-Performance Asymmetric Supercapacitors.

Ternary nanocomposites synergistically combine the material characteristics of three materials, altering the desired charge storage properties such as electrical conductivity, redox states, and surface area. Therefore, to improve the energy synergistic of SnO2, TiO2, and three-dimensional graphene, herein, we report a facile hydrothermal technique to synthesize a ternary nanocomposite of three-dimensional graphene-tin oxide-titanium dioxide (3DG-SnO2-TiO2). The synthesized ternary nanocomposite was characterized using material characterization techniques such as XRD, Raman spectroscopy, FTIR spectroscopy, FESEM, and EDXS. The surface area and porosity of the material were studied using Brunauer-Emmett-Teller (BET) studies. XRD studies showed the crystalline nature of the characteristic peaks of the individual materials, and FESEM studies revealed the deposition of SnO2-TiO2 on 3DG. The BET results show that incorporating 3DG into the SnO2-TiO2 binary nanocomposite increased its surface area compared to the binary composite. A three-electrode system compared the electrochemical performances of both the binary and ternary composites as a battery-type supercapacitor electrode in different molar KOH (1, 3, and 6 M) electrolytes. It was determined that the ternary nanocomposite electrode in 6 M KOH delivered a maximum specific capacitance of 232.7 C g-1 at 1 A g-1. An asymmetric supercapacitor (ASC) was fabricated based on 3DG-SnO2-TiO2 as a positive electrode and commercial activated carbon as a negative electrode (3DG-SnO2-TiO2//AC). The ASC delivered a maximum energy density of 28.6 Wh kg-1 at a power density of 367.7 W kg-1. Furthermore, the device delivered a superior cycling stability of ∼97% after 5000 cycles, showing its prospects as a commercial ASC electrode.

Pearls & Oy-sters: SCA21 Due to TMEM240 Variation Presenting as Myoclonus Dystonia Syndrome.

Spinocerebellar ataxia 21 due to TMEM240 disease-associated variation characteristically presents insidiously with a delay in language, motor, and social skill acquisition. The condition typically progresses to severe cognitive impairment. We report a patient with SCA21 who presented with myoclonus dystonia (M-D) syndrome and whose dystonia showed a modest response to levodopa. Affected family members (mother and sibling of the proband) also had a similar phenotype. Neuropsychology evaluation of the proband and afflicted family members revealed moderate impairments in attention, executive function, short-term and episodic memory, and marked impairments in planning, abstract reasoning, language, and visuospatial functions. Normal EEG, α-fetoprotein levels, and somatosensory evoked potentials helped to delineate SCA21 from other differential diagnoses. Motor impairment, pyramidal signs, and sensory impairment are usually absent in SCA21. This case highlights the importance of genetic testing in patients with M-D syndrome and supports a trial of levodopa for patients with dystonia from SCA21 due to TMEM240 variation.

Depotentiation of associative plasticity is intact in Parkinson's disease with mild dyskinesia.

OBJECTIVE: Depotentiation of homosynaptic plasticity of the primary motor cortex (M1) is impaired in patients with Parkinson's disease (PD) who have developed dyskinesias. In this exploratory study, we tested whether this holds true for heterosynaptic plasticity induced by paired associative stimulation (PAS). METHODS: Dyskinetic (n=11) and Non-dyskinetic (n=11), levodopa-treated PD patients were tested in M1 with PAS25ms alone, PAS25ms preceded by continuous theta-burst stimulation of the cerebellum (cTBSCB-PAS) as a method to evoke a larger plastic response in M1, and each of these two interventions followed by a depotentiation protocol (cTBS150pulses) to M1. RESULTS: PAS25ms and cTBSCB-PAS25ms induced long-term potentiation (LTP)-like responses in both groups of PD patients, with cTBSCB significantly boosting the plastic response. Both these LTP-like responses could be depotentiated by cTBS150, in both groups of patients. CONCLUSIONS: Cerebellar stimulation enhances heterosynaptic plasticity in PD irrespective of dyskinesias. Depotentiation mechanisms of heterosynaptic plasticity are preserved in PD patients, including those with dyskinesias. The lack of depotentiation of LTP-like plasticity as a hallmark of dyskinesia in PD patients is not absolute. The ability to depotentiate LTP-like plasticity may potentially depend on the type of plasticity induced (homosynaptic or heterosynaptic), the circuits involved in these responses and the adequacy of dopaminergic stimulation.

Oromandibular Dystonia - A Systematic Review.

Oromandibular dystonia (OMD) is a clinical problem which is commonly encountered in the practice of movement disorders. OMD results from a variety of genetic and acquired etiologies and can occur as an isolated manifestation, or as part of an isolated generalized or a combined dystonia syndrome. There are only very few systematic reviews on this condition which often causes significant disability. We review here the etiology, clinical features, diagnostic approach and management of OMD.

Cognitive outcome following bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease-a comparative observational study in Indian patients.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms and motor complications of Parkinson's disease (PD). The intervention is expected to result in some cognitive changes, the nature of which is not uniform across the studies which have reported them. PD itself is associated with progressive cognitive decline and hence longitudinal follow-up studies with medically managed control group of patients are needed to explore the cognitive deficits attributable to DBS. METHODS: We conducted a prospective comparative observational study to assess the effects of bilateral STN DBS on cognition. Cognitive functions were assessed at baseline and after a minimum of two years after surgery, and compared with baseline and follow-up assessments in patients on medical management alone. RESULTS: Thirty-four patients with PD who underwent bilateral STN DBS and thirty-four medically managed patients participated in the study. At a mean follow-up of around 33 months, we found a significant decline in verbal fluency scores in the DBS group compared to those on medical management alone (1.15 ± 1.23 vs 0.59 ± 0.93, p = 0.034) and a trend for decline was noted in digit span test. There was no difference in the performance in tests addressing other cognitive domains, or tests of global cognitive function. No patient developed dementia. Motor functions and activities of daily living (ADL) were significantly better in the surgical group. CONCLUSION: STN DBS results in minor deficits in executive functions, particularly verbal fluency. These may be inconsequential, considering the marked improvement in motor functions and ADL.