Dopamine-producing Cells Research Articles

A comprehensive review of natural compounds and their structure-activity relationship in Parkinson's disease: exploring potential mechanisms.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine-producing cells in the Substantia nigra region of the brain. Complementary and alternative medicine approaches have been utilized as adjuncts to conventional therapies for managing the symptoms and progression of PD. Naturalcompounds have gained attention for their potential neuroprotective effects and ability to target various pathways involved in the pathogenesis of PD. This comprehensive review aims to provide an in-depth analysis of the molecular targets and mechanisms of natural compounds in various experimental models of PD. This review will also explore the structure-activity relationship (SAR) of these compounds and assess the clinical studies investigating the impact of these natural compounds on individuals with PD. The insights shared in this review have the potential to pave the way for the development of innovative therapeutic strategies and interventions for PD.

Management of Kampavata (Parkinson’s Disease) through Panchakarma: A Successful Case Study

Introduction Parkinson’s disease (PD) affects the central nervous system and is primarily characterized by the degeneration of dopamine-producing cells in the substantia nigra. Early signs include tremor, rigidity, bradykinesia, and postural instability, with later cognitive, sensory, sleep, and emotional issues. Ayurveda correlates these symptoms with Kampavata, primarily linked to Vata (bio-entities) imbalance. The prime aim of this paper is to study Panchakarma’s efficacy in managing Kampavata (PD). Case Presentation This is a case presentation of a 55-year-old male patient who has experienced tremors in the left upper and lower limbs, numbness in the left lower limb, loss of balance for 10 years, abnormal facial expression (masked face), difficulty in speech, and sleep disturbance for 5 years. The patient was treated with Panchakarma therapy for 30 days. Results Following treatment, the patient exhibited significant improvement in symptoms, assessed using the PD composite scale, with the total score decreasing from 68 to 19, along with evaluated by specific examination, bradykinesia test, reflexes, functional activities, and clinical features also notably improved. Discussion Panchakarma therapy, rooted in Ayurvedic principles, shows promise in managing Kampavata, associated with PD. Conservative management focuses on Vata balance, which offers substantial comfort and enhances patient quality of life. Conclusion Panchakarma therapy presents a potential avenue for treating Kampavata, addressing symptoms associated with PD, and improving patient satisfaction and well-being. Further research is warranted to validate these findings and explore the broader applicability of Ayurvedic approaches in neurodegenerative conditions.

A Holistic Approach to Parkinson's Disease: Integrating Advances in Pathophysiology, Diagnosis, and Therapy

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder affecting millions worldwide, with an increasing burden projected in the coming years. It involves complex neurological decline primarily affecting the Substantia nigra and Locus coeruleus, leading to motor and non-motor symptoms. Objective: This study aims to provide a comprehensive overview of Parkinson's disease, including its epidemiology, pathophysiology, diagnosis, and available therapies, encompassing both traditional pharmaceutical treatments and emerging technological advancements. Methods: A thorough review of literature was conducted, synthesizing information from various studies and clinical trials to elucidate the current understanding of Parkinson's disease and its management strategies. Results: Parkinson's disease is characterized by the gradual loss of dopamine-producing cells and the presence of Lewy bodies in the brain. Diagnosis relies on clinical evaluation, and treatment typically involves pharmaceutical interventions such as levodopa, COMT inhibitors, dopamine agonists, and deep brain stimulation. Additionally, advancements in technology offer promising avenues for objective symptom assessment and personalized treatment approaches. Conclusion: The management of Parkinson's disease requires a multidisciplinary approach, integrating traditional pharmacological treatments with emerging technologies and complementary therapies like dance therapy, tai chi, and speech therapy. By combining these diverse modalities, healthcare professionals can provide more effective and personalized care, ultimately enhancing the quality of life for individuals living with Parkinson's disease. Keywords: Parkinson's disease, medical therapy, device-aided therapy, alternative interventions, personalized treatment, neurodegenerative disorder

Effect of Boxing Exercises on the Functional Ability and Quality of Life of Individuals with Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) is a neurological disorder caused by the loss of dopamine-producing cells in the substantia nigra and characterized by motor and non-motor symptoms. Boxing is a type of complementary therapy to improve symptoms in PD. The purpose of the present study was to examine the effect of boxing training on the functionality and quality of life of patients with PD. The literature search was performed on PubMed, Scopus, PEDro, Cochrane Library, and Google Scholar search engines. The PEDro scale was used to assess the methodological quality of the studies. This systematic review included three studies that examined disease severity, mobility, physical activity, balance, and quality of life. According to the PEDro scale criteria, the three articles included were of high methodological quality. Statistically significant improvements after the implementation of boxing training was shown for balance and quality of life in contrast to the other variables. Boxing training intervention programs had a positive effect on balance and quality of life in patients with PD; however, the results are conflicting regarding certain functionality variables. Therefore, it is necessary to conduct further research to examine the effectiveness of boxing training on the functionality and quality of life of patients with Parkinson's disease.

Comparative Analysis Using Machine Learning Algorithms to Detect Parkinson’s Disease using Voice Dataset

Abstract: Parkinson's disease is a degenerative disorder that affects the control of movement, and its symptoms include tremors, stiffness, and difficulties in balance and coordination. This disease results from a decrease in dopamine-producing cells in the brain, and although there is currently no cure for Parkinson's, medication and therapeutic interventions can help alleviate the symptoms. Parkinson's disease usually begins to show its effects in middle to late adulthood. A new measure of dysphonia, Pitch Period Entropy (PPE) assesses the variability or randomness of pitch periods in speech signals, providing insights into the diversity of vocal characteristics. Higher entropy values suggest greater pitch variability in a speaker's voice. PPE is included in the dataset. The methodologies used in this project are Random Forest, Support vector classifier, Extreme gradient boosting (XGB). This comparative study includes performance metrics: Accuracy, precision, Recall, f1 score, and support. The aim is to predict Parkinson's disease and compare performance metrics using various methods.

The Relationship Between COMT and MAO-B Gene Polymorphisms with Levodopa in Parkinson’s Disease Patients; A Review

Parkinson's disease is a degenerative nervous system disorder caused by the death of dopamine-producing cells in the substantia nigra. Dopaminergic treatment could alleviate motor symptoms for a period. One of the effective dopaminergic medications for symptomatic relief was Levodopa and dopamine agonists. Clinically, Levodopa was always combined with Dopa Decarboxylase (DDC) inhibitors, which redirected Levodopa metabolism towards the COMT pathway, increasing its bioavailability in the central nervous system. The purpose of this article was to investigate the relationship between COMT and MAO-B gene polymorphisms and Levodopa in Parkinson's disease patients, starting by gathering literature on the association between COMT and MAO-B polymorphisms and Levodopa in Parkinson's disease patients using various databases. Reviewed literature revealed that the most frequent polymorphism in the COMT gene was rs4680. Some polymorphisms significantly impacted the treatment of Parkinson's disease patients. However, despite efforts to identify genetic factors influencing the risk of side effects or treatment ineffectiveness, the role of pharmacogenetics in Parkinson's disease has not been fully explored and lacks consistent clinical recommendations. Further research was needed to tailor treatment to individual polymorphisms so that pharmacogenomic approaches could be applied more consistently

Potential Novel Treatments for Parkinson’s Disease

This review aims to evaluate novel developments in treatments for Parkinson’s disease that focus on slowing, stopping, and/or reversing the neurodegeneration associated with the disease. Parkinson’s disease (PD) is a neurodegenerative disease that affects dopaminergic neurons in the substantia nigra, located in the basal ganglia of the brain. This region also contains high levels of alpha synuclein, a protein found abundantly in the brain due to its important role in neurotransmitter release. α-synuclein has been found to be misfolded and overexpressed in people with PD, which leads to fibril formation and aggregation, which directly interfere with basic cellular processes and results in neurodegeneration. In PD patients, dopaminergic neurons are most affected; therefore, an artificial supply of dopamine must be provided to them via dopamine precursors that can cross the blood-brain barrier. However, these medications fail to slow, stop, or reverse the progression of PD and merely pose as treatments for physical symptoms, such as tremors. Researchers are now focusing on 2 major avenues for new PD treatments: treatments that target α-synuclein aggregates/Lewy body assemblies and treatments that focus on replacement of lost dopaminergic neurons in the brain. The use of antibodies (immunotherapy) to target and clear αsynuclein aggregates or the upregulation of genes that encode autophagic mechanisms to destroy dysfunctional proteins were shown to reduce α-synuclein aggregation and behavioral deficits in mice. Results from clinical trials have shown a 96.5% reduction in the concentration of extracellular α-synuclein aggregates, and doses were well tolerated with no serious side effects. In order to rebuild the neurons that were lost to PD neurodegeneration, a renewable source of dopamine-producing cells that can integrate into the host brain and survive for years is required. More specifically, the reprogramming of astrocytes can be used to develop functional dopaminergic neurons. To reprogram the astrocytes and fibroblasts, the RNA binding protein PTB was suppressed; PTB suppresses numerous neuronal genes required for neuronal maturation, thus, downregulation of PTB generates functional, mature neurons. When in vivo astrocyte reprogramming was performed in a mouse model of PD, researchers found new, successful dopaminergic neurons in the substantia nigra and increased dopamine levels. Although both avenues for treatment require further clinical trials and testing in human subjects, they both hold significant promise in the future.

Simulating combined monoaminergic depletions in a PD animal model through a bio-constrained differential equations system.

Historically, Parkinson's Disease (PD) research has focused on the dysfunction of dopamine-producing cells in the substantia nigra pars compacta, which is linked to motor regulation in the basal ganglia. Therapies have mainly aimed at restoring dopamine (DA) levels, showing effectiveness but variable outcomes and side effects. Recent evidence indicates that PD complexity implicates disruptions in DA, noradrenaline (NA), and serotonin (5-HT) systems, which may underlie the variations in therapy effects. We present a system-level bio-constrained computational model that comprehensively investigates the dynamic interactions between these neurotransmitter systems. The model was designed to replicate experimental data demonstrating the impact of NA and 5-HT depletion in a PD animal model, providing insights into the causal relationships between basal ganglia regions and neuromodulator release areas. The model successfully replicates experimental data and generates predictions regarding changes in unexplored brain regions, suggesting avenues for further investigation. It highlights the potential efficacy of alternative treatments targeting the locus coeruleus and dorsal raphe nucleus, though these preliminary findings require further validation. Sensitivity analysis identifies critical model parameters, offering insights into key factors influencing brain area activity. A stability analysis underscores the robustness of our mathematical formulation, bolstering the model validity. Our holistic approach emphasizes that PD is a multifactorial disorder and opens promising avenues for early diagnostic tools that harness the intricate interactions among monoaminergic systems. Investigating NA and 5-HT systems alongside the DA system may yield more effective, subtype-specific therapies. The exploration of multisystem dysregulation in PD is poised to revolutionize our understanding and management of this complex neurodegenerative disorder.

NCOG-33. GLIOBLASTOMA AND PARKINSONISM, IS DEPLETED DOPAMINE A PROTECTIVE SURVIVAL FACTOR? A CASE SERIES OF 3 GBM PATIENTS

Abstract Glioblastoma multiforme (GBM) is the most common malignant brain tumor, and carries a grave prognosis with a median survival of 15 months. The pathophysiologic hallmark of Parkinson’s disease is neuronal loss of dopamine producing cells in the substantia nigra. Dopamine has been shown to modify cell-cycle status in neural progenitor cells. Dopamine agonism is adequate to increase progenitor proliferation in the subventricular zone (SVZ). Dopamine receptor antagonists have antiproliferative effects. A few clinical trials use selective dopamine receptor D2 (DRD2) inhibitors. Parkinsonism can have organic etiologies like stroke or neoplasm, while idiopathic Parkinsonism is known as Parkinson’s disease. While uncommon to have dual diagnoses, we identified three patients with both GBM and Parkinsonism, all were IDH wildtype, 2 patients were MGMT methylated, mean age was 67 years. Our 3 patients have a combined median PFS of 23.4 months, mean PFS of 25.4 months, which compares favorably to historical control median PFS of 6.9 months. Our 3 patients with dual diagnosis have a median OS of 47.3 months, and mean OS of 43.7 months, which compares favorably to historical median OS of 14.6 months. One might expect a patient with a neurodegenerative disease like Parkinson’s disease and a highly malignant tumor like GBM to have an extremely poor prognosis, yet our patient cohort reveals the opposite. The improved overall survival in GBM patients with Parkinsonism supports further clinical research into selective dopamine receptor inhibitors.

Early Detection of Parkinson's disease using a Machine Learning-Based Framework for Differentiating the Disease's with Various Stages

The term "Parkinson's disease" (PD) is mostly brought on by a disturbance of a brain's dopamine-producing cells, a chemical which permits communication between brain cells. Brain cells that produce dopamine control movement, flexibility, and fluency. After 60% to 80% of these cells are gone, dopamine production is inhibited, and Parkinson's disease symptoms start to emerge. Researchers are concentrating their efforts on finding any early non-movement symptoms to stop the disease's development because it is thought that the disease starts many years before any evident movement-related indicators occur. Early correct diagnosis of the condition is crucial to halt the continuous advancement of Parkinson's disease and give people access to medications that can slow the disease. To do this, ongoing research into the premotor stage of Parkinson's disease is necessary.

Microglia-secreted TNF-α affects differentiation efficiency and viability of pluripotent stem cell-derived human dopaminergic precursors.

Disease is a neurodegenerative disorder characterised by the progressive loss of dopaminergic cells of the substantia nigra pars compacta. Even though successful transplantation of dopamine-producing cells into the striatum exhibits favourable effects in animal models and clinical trials; transplanted cell survival is low. Since every transplant elicits an inflammatory response which can affect cell survival and differentiation, we aimed to study in vivo and in vitro the impact of the pro-inflammatory environment on human dopaminergic precursors. We first observed that transplanted human dopaminergic precursors into the striatum of immunosuppressed rats elicited an early and sustained activation of astroglial and microglial cells after 15 days' post-transplant. This long-lasting response was associated with Tumour necrosis factor alpha expression in microglial cells. In vitro, conditioned media from activated BV2 microglial cells increased cell death, decreased Tyrosine hydroxylase-positive cells and induced morphological alterations on human neural stem cells-derived dopaminergic precursors at two differentiation stages: 19 days and 28 days. Those effects were ameliorated by inhibition of Tumour necrosis factor alpha, a cytokine which was previously detected in vivo and in conditioned media from activated BV-2 cells. Our results suggest that a pro-inflammatory environment is sustained after transplantation under immunosuppression, providing a window of opportunity to modify this response to increase transplant survival and differentiation. In addition, our data show that the microglia-derived pro-inflammatory microenvironment has a negative impact on survival and differentiation of dopaminergic precursors. Finally, Tumour necrosis factor alpha plays a key role in these effects, suggesting that this cytokine could be an interesting target to increase the efficacy of human dopaminergic precursors transplantation in Parkinson's Disease.

In silico Pharmacological Evaluation of Tetrahydro-β-carboline Derivatives as Putative Inhibitors of Alpha-Synuclein and Dopa Decarboxylase for Parkinson’s Disease

Parkinson’s disease (PD) is a neurological problem that results mostly in disability globally due to therapeutic challenges. Alpha-synuclein (ASN) and Dopa decarboxylase (DDC) are strongly implicated in the pathogenesis of PD including the aggregation of Lewy bodies and degeneration of dopamine-producing cells. These make them plausible drug targets commonly explored by researchers in the quest for potent inhibitors. However, up to this moment, no inhibitor of ASN has been approved for clinical application while only a handful is available for DDC, as such, searching for effective inhibitors of the dual targets remains essential. In this study, the in-house databases of tetrahydro-β-carboline and carbazole derivatives were virtually screened for putative ligands with multitarget inhibitory mechanisms against the ASN and DDC using molecular docking protocols. Relevant drugs such as phenylbutyrate, anle138b, levodopa, carbidopa and benserazide were used as references. The physicochemical, pharmacokinetics, pharmacodynamics and toxicological profiles of the selected ligands and references were also evaluated in silico using pkCSM. From the virtual screening, ligands 172, 082 and 013 interacted more strongly with ASN receptors with SP glide gscores of –9.154, –9.124 and –8.971 kcal/mol respectively as compared to phenylbutyrate and anle138b with SP glide gscores of –7.181 and –5.875 kcal/mol. They also showed higher binding affinities to DDC receptor by higher SP glide gscores of –6.758, –5.212 and –6.271 kcal/mol than levodopa, carbidopa and benserazide with values of –4.217, –4.502 and –4.18 kcal/mol respectively. Among the 3 ligands, ligand 172 satisfies Lipinski’s Rules of 5 (RO5) and demonstrates ADMET parameters that favor a central nervous system (CNS) drug which was identified as potent inhibitors of ASN and DDC responsible for PD. The potential ligands with stronger inhibitory interactions and good ADMET profile are amenable for further experimental validation in the quest for potent inhibitors of ASN and DDC as anti-PD agents. HIGHLIGHTS Parkinson’s disease (PD) is a complex neurological disorder No effective medication has been approved for PD treatment Alpha-synuclein and dopa decarboxylase are relevant therapeutic targets Putative inhibitors are identified from tetrahydro-β-carboline (THBC) derivatives THBC derivatives deserve further studies as promising candidates for PD GRAPHICAL ABSTRACT

Circadian influence on neurons of the substantia nigra

Circadian rhythms, such as body temperature, hormone secretion, sleep/wake, and activity/rest, are generated by the oscillation of the clock genes in the cells of the suprachiasmatic nucleus, thus considered the main circadian oscillator. Dopamine, whose synthesis occurs in centers such as the substantia nigra pars compacta (SNc) can influence autonomic oscillation. Dopamine can modulate the expression of clock genes; meanwhile, the presence of clock genes in this area could indicate a cyclic mechanism in dopamine-producing cells. Although the involvement of SNc in motor and non-motor functions is well known, the role of the circadian system in this region is not clear. In this study, we investigated the presence of Per1, Per2, and Cry1 in dopaminergic neurons of the SNc. Per1, Per2, and Cry1 imunorreactivity were analyzed at specific times of the light-dark phase by immunohistochemistry technique in a diurnal primate. The mapping performed by immunohistochemistry showed expressive Per1-IR with predominance during daytime. The Per2-IR and Cry1-IR were similar between the light and dark times analyzed. These results reinforce the presence of proteins that regulate circadian rhythms in the SNc, an important dopaminergic source.

CLASSIFICATION OF PARKINSON'S DISEASE IN BRAIN MRI IMAGES USING DEEP RESIDUAL CONVOLUTIONAL NEURAL NETWORK

In our aging culture, neurodegenerative disorders like Parkinson's disease (PD) are among the most serious health issues. It is a neurological condition that has social and economic effects on individuals. It happens because the brain's dopamine-producing cells are unable to produce enough of the chemical to support the body's motor functions. The main symptoms of this illness are eyesight, excretion activity, speech, and mobility issues, followed by depression, anxiety, sleep issues, and panic attacks. The main aim of this research is to develop a workable clinical decision-making framework that aids the physician in diagnosing patients with PD influence. In this research, we proposed a technique to classify Parkinson’s disease by MRI brain images. Initially, normalize the input data using the min-max normalization method and then remove noise from input images using a median filter. Then utilizing the Binary Dragonfly Algorithm to select the features. Furthermore, to segment the diseased part from MRI brain images using the technique Dense-UNet. Then, classify the disease as if it’s Parkinson’s disease or health control using the Deep Residual Convolutional Neural Network (DRCNN) technique along with Enhanced Whale Optimization Algorithm (EWOA) to get better classification accuracy. Here, we use the public Parkinson’s Progression Marker Initiative (PPMI) dataset for Parkinson’s MRI images. The accuracy, sensitivity, specificity, and precision metrics will be utilized with manually gathered data to assess the efficacy of the proposed methodology.

New Hope in Parkinson’s Disease Management

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, projected to affect at least 12 million people worldwide by 2040. The Hoehn and Yahr Scale stages 4 or 5 are referred to as advanced Parkinson’s disease (PD), which is characterized by significant motor deficits, a high risk of falling, extremely limited independence in terms of mobility, and cognitive and psychotic disorders. Motor fluctuations and dyskinesias frequently affect persons living with advanced PD, in which dyskinesia develops within 5.81 years from diagnosis, and motor fluctuations within 10 years. Continuous monitoring is necessary when motor fluctuations first appear to decide when to start an advanced treatment. Consequently, there is a vast need for improved treatments to address these motor symptoms. Deep brain stimulation, apomorphine subcutaneous infusion, levodopa-carbidopa intestinal gel infusion, and magnetic resonance-guided high-intensity focused ultrasound (FUS) are four device-aided therapies that provide new hope for treating PD in its advanced stages. The selection of device-assisted therapies is now mostly driven by the motor profile of the patient, with non-motor symptoms having a minimal impact on the decision-making process for the delivery and maintenance of successful therapy. In preliminary human trials, passive and active antiprotein á—synuclein vaccinations are being investigated. Monoclonal antibodies (mAbs) like prasinezumab that target the aggregates of á— synuclein can reduce the levels of free á—synuclein in serum by 97% by passive vaccination. The use of á—synuclein fragments or equivalent epitopes in active vaccination to stimulate an immune response is also being investigated. Although cell-based regeneration therapies utilizing fetal brain cells are successful in a small number of cases, this treatment is not practical due to the lack of fetal tissue. A sustainable source of dopamine-producing cells, such as stem cells, dopaminergic progenitors obtained from induced pluripotent stem cells (iPSCs), or cells derived from embryonic stem cells (ESCs), is currently being researched. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 182-183

Therapeutic Routes for Movement Disorders in Patients with Parkinson’s Disease: A Narrative Review Study

Introduction: Parkinson's disease (PD) is a progressive and chronic disorder that has one of the fastest worldwide growths among the neurological diseases. The main problem of the patients with PD is the loss of dopamine producing cells in their nervous system, which causes symptoms such as tremors, slowness of movements, walking disorder and postural instability. Parkinson's disease, by affecting the neuromuscular system as well as the proprioceptive feedback integration and processing, can lead to postural instability and falling of the patients. Treatments included pharmaceutical therapy, electrotherapy, and new methods of brain stimulation and exercise therapy. The pharmaceutical therapy is the most important part of treatment, but it comes with side effects for the patients. Electrotherapy and exercise therapy have been widely used to treat the patients' movement disorders. This narrative review study aimed to mention various routes of pharmaceutical therapy and electrotherapy methods, and then focused on exercise therapy to reduce movement disorders in the patients with PD.
 Conclusion: Stretching and resistance exercises, performing yoga and tai chi movements, as well as using the virtual reality system caused reduced displacement of the center of pressure while standing, increased speed of walking, improved quality of life and reduced frequency of falls.

Effect of Melatonin on Alpha Synuclein and Autophagy in Dopaminergic Neuronal Differentiation of Adipose Mesenchymal Stem Cells.

The current work investigated the effect of melatonin on differentiation of adipose mesenchymal stem cells (AD-MSCs) into dopamine producing cells and its effect on autophagy process and alpha-Synuclein (α-Syn) secretion. AD-MSCs were characterized by flow cytometry and divided into 4 groups; i) control group (AD-MSCs without any treatment), ii) M+MSCs group (MSCs treated with 1 µM melatonin for 12 days), iii) DN group (MSCs cultured in neurobasal A medium and essential neuronal growth factors for 12 days) and iv) DN+M group (MSCs cultured in neurobasal A medium and 1µM melatonin for 12 days. By the end of experiments, the dopamine and α-Syn levels using ELISA, the expression of MAP-2, m-TOR and α-Syn genes at the level of mRNA and detection of autophagosomes formation using transmission electron microscope were performed. We found that the isolated cells were MSCs due to their positivity expression for CD105 and CD90 and negativity expression for CD34 and CD45. The concentration of dopamine was significantly higher and α-Syn concentration was significantly lower in DN+M group when compared to other groups (P< 0.005). Also, this group showed the highly expression for MAP-2 gene and less expression for m-TOR and α-Syn genes (P< 0.005). Moreover, there was significantly increase in autophagosomes formation in this group than another group (P< 0.005). It is concluded that the melatonin promotes the differentiation of rat AD-MSCs into dopaminergic cells via induction of autophagy process and reduction of α-Syn secretion.

Refining PD classification through ensemble bionic machine learning architecture with adaptive threshold based image denoising

Parkinson's disease (PD) manifests as a loss of dopamine-producing cells present in the substantia nigra region of the brain’s central nervous system (CNS). The proposed model influences magnetic resonance imaging (MRI) for detection. The research paper consist of four stages: pre-processing, feature extraction, feature selection and classification. The proposed model influences MR images for detection during the pre-processing stage, composed with an adaptive median filter along with threshold computation. The primarily getting a binary image is that it reduces the complexity of the data and makes the recognition and classification processes easier. To reduce the training period, reducing over fitting and enhancing the accuracy, first and second order features are extracted. In third stage, adapted fused slime salp mould (AFSSM) soft computing approach is used in feature selection. The AFSSM give a fixed threshold for the selection process and find optimum values very rapidly. The ensemble machine learning model (SVM, Random Forest and XGBoost) is introduced along with Ebola optimisation through voting method. The proposed achieves the mean square error, peak signal-to-noise ratio and image enhancement factor values of 4.15, 39.1 and 0.92 respectively when compared with the existing filtering models like mean, Kalman, gaussian and weiner filter. Along with this, the performance measures like accuracy, sensitivity, precision, F1-score and specificity are examined and attains an outcome of 98.4%, 98.4%, 98%, 98.8% and 98.2%, respectively.

Clinical Trials of Stem Cell Therapy in Japan: The Decade of Progress under the National Program

Stem cell therapy is a current world-wide topic in medical science. Various therapies have been approved based on their effectiveness and put into practical use. In Japan, research and development-related stem cell therapy, generally referred to as regenerative medicine, has been led by the government. The national scheme started in 2002, and support for the transition to clinical trials has been accelerating since 2011. Of the initial 18 projects that were accepted in the budget for preclinical research, 15 projects have begun clinical trials so far. These include the transplantation of retinal, cardiac, and dopamine-producing cells differentiated from human induced pluripotent stem (iPS) cells and hepatocyte-like cells differentiated from human embryonic stem (ES) cells. The distinctive feature of the stem cell research in Japan is the use of iPS cells. A national framework was also been set-up to attain the final goal: health insurance coverage. Now, insurance covers cell transplantation therapies for the repair and recovery of damaged skin, articular cartilage, and stroke as well as therapies introduced from abroad, such as allogeneic mesenchymal stem cells for graft-versus-host disease and chimeric antigen receptor-T (CAR-T) cell therapy. To prepare this review, original information was sought from Japanese authentic websites, which are reliable but a little hard to access due to the fact of multiple less-organized databases and the language barrier. Then, each fact was corroborated by citing its English version or publication in international journals as much as possible. This review provides a summary of progress over the past decade under the national program and a state-of-the-art factual view of research activities, government policy, and regulation in Japan for the realization of stem cell therapy.

Testing of Motor Coordination in Degenerative Neurological Diseases.

Parkinson’s disease (PD) is a progressive movement disorder caused by the death of dopamine-producing cells in the midbrain. PD is the most prevalent movement disorder of the central nervous system and affects more than 6.3 million people in the world. The changes in the motor functions of patients are not easy to be clearly and on-time observed by the clinicians and to make the most well-informed decisions for the treatment. The aim of this paper is the monitoring PD by designing, developing, and evaluating a prototype mobile App using a pressure pen, which collects quantitative and objective information about PD patients, thus allowing clinicians to understand better and make assumptions about the severity and the stage of Parkinson’s disease. This study presents a dynamic spiral test that can only be performed with tablet and pen pressure. Furthermore, the handwriting samples by PD patients and healthy controls individuals are collected by a computerized system, and the measurements of Spiral Deviation, Total Time, and Pen Pressure are processed. The results showed an accurate evaluation of the stage of Parkinson’s disease. Thus, the clinician may use the proposed PD telemonitoring system as a screening test, storing the history of all the patient’s measurements.