673,227 results match your criteria therapeutic potential


Incidence and Direct Medical Cost of Acute Stress Disorder and Post-traumatic Stress Disorder in Korea: Based on National Health Insurance Service Claims Data from 2011 to 2017.

J Korean Med Sci 2021 May 10;36(18):e125. Epub 2021 May 10.

Department of Psychiatry, Kangwon National University Hospital, Kangwon University School of Medicine, Chuncheon, Korea.

Background: We aimed to investigate the annual incidence of trauma and stress-related mental disorder including acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) using the National Health Insurance Service Database. In addition, we estimated direct medical cost of ASD and PTSD in Korea.

Methods: To examine the incidence, we selected patients who had at least one medical claim containing a 10th revision of the International Statistical Classification of Diseases and Related Health Problems code for ASD (F43. Read More

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A pilot study investigating a novel particle-based growth factor delivery system for preimplantation embryo culture.

Hum Reprod 2021 May 11. Epub 2021 May 11.

School of BioSciences, The University of Melbourne, Parkville, VIC, Australia.

Study Question: Can vascular endothelial growth factor (VEGF)-loaded silica supraparticles (V-SPs) be used as a novel mode of delivering VEGF to the developing preimplantation embryo in vitro?

Summary Answer: Supplementation of embryo culture media with V-SPs promoted embryonic development in a manner equivalent to media supplemented with free VEGF.

What Is Known Already: VEGF is a maternally derived growth factor that promotes preimplantation embryonic development in vitro. However, its use in clinical media has limitations due to its low stability in solution. Read More

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Aryl hydrocarbon receptor interacting protein (AIP) significantly influences prognosis of pancreatic carcinoma.

Ann Diagn Pathol 2021 Mar 31;53:151742. Epub 2021 Mar 31.

Medical College, Universidad Rey Juan Carlos, Móstoles, Madrid, Spain.

Introduction: Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. Aryl hydrocarbon receptor interacting protein (AIP) in one of AHR ligands. The aim of this study is to analyze the prognostic influence of AIP in pancreatic carcinoma. Read More

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Genetics and therapy for pediatric eye diseases.

EBioMedicine 2021 May 7;67:103360. Epub 2021 May 7.

Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892 USA. Electronic address:

Ocular morphogenesis in vertebrates is a highly organized process, orchestrated largely by intrinsic genetic programs that exhibit stringent spatiotemporal control. Alternations in these genetic instructions can lead to hereditary or nonhereditary congenital disorders, a major cause of childhood visual impairment, and contribute to common late-onset blinding diseases. Currently, limited treatment options exist for clinical phenotypes involving eye development. Read More

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Synthesis, molecular docking, and in silico ADMET studies of 4-benzyl-1-(2,4,6-trimethyl-benzyl)-piperidine: Potential Inhibitor of SARS-CoV2.

Bioorg Chem 2021 May 5;112:104967. Epub 2021 May 5.

Department of Chemistry, Texas A&M University, College Station, TX 77842, USA. Electronic address:

Nowadays, over 200 countries face a wellbeing emergency because of epidemiological disease COVID-19 caused by the SARS-CoV-2 virus. It will cause a very high effect on the world's economy and the worldwide health sector. The present work is an investigation of the newly synthesized 4-benzyl-1-(2,4,6-trimethyl-benzyl)-piperidine (M1BZP) molecule's inhibitory potential against important protein targets of SARS-CoV-2 using computational approaches. Read More

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XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IkB.

Transl Oncol 2021 May 8;14(8):101114. Epub 2021 May 8.

Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue Ullmann 813 Bronx, NY 10461, United States; Department of Pediatrics, Albert Einstein College of Medicine, United States.

Across many cancer types in adults, upregulation of the nuclear-to-cytoplasmic transport protein Exportin-1 (XPO1) correlates with poor outcome and responsiveness to selinexor, an FDA-approved XPO1 inhibitor. Similar data are emerging in childhood cancers, for which selinexor is being evaluated in early phase clinical studies. Using proteomic profiling of primary tumor material from patients with high-risk neuroblastoma, as well as gene expression profiling from independent cohorts, we have demonstrated that XPO1 overexpression correlates with poor patient prognosis. Read More

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Kisspeptin modulates gamma-aminobutyric acid levels in the human brain.

Psychoneuroendocrinology 2021 Apr 26;129:105244. Epub 2021 Apr 26.

Division of Diabetes, Endocrinology & Metabolism, Imperial College London, UK; Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK. Electronic address:

Gamma-aminobutyric acid (GABA) is a key inhibitory neurotransmitter that has been implicated in the aetiology of common mood and behavioural disorders. By employing proton magnetic resonance spectroscopy in man, we demonstrate that administration of the reproductive neuropeptide, kisspeptin, robustly decreases GABA levels in the limbic system of the human brain; specifically the anterior cingulate cortex (ACC). This finding defines a novel kisspeptin-activated GABA pathway in man, and provides important mechanistic insights into the mood and behaviour-altering effects of kisspeptin seen in rodents and humans. Read More

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Outcomes of patients with solid tumour malignancies treated with first-line immuno-oncology agents who do not meet eligibility criteria for clinical trials.

Eur J Cancer 2021 May 8;151:115-125. Epub 2021 May 8.

Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada. Electronic address:

Background: Immuno-oncology (IO)-based therapies have been approved based on randomised clinical trials, yet a significant proportion of real-world patients are not represented in these trials. We sought to compare the outcomes of trial-ineligible vs. -eligible patients with advanced solid tumours treated with first-line (1L) IO therapy. Read More

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Respiratory axon regeneration in the chronically injured spinal cord.

Neurobiol Dis 2021 May 8:105389. Epub 2021 May 8.

Department of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address:

Promoting the combination of robust regeneration of damaged axons and synaptic reconnection of these growing axon populations with appropriate neuronal targets represents a major therapeutic goal following spinal cord injury (SCI). A key impediment to achieving this important aim includes an intrinsic inability of neurons to extend axons in adult CNS, particularly in the context of the chronically-injured spinal cord. We tested whether an inhibitory peptide directed against phosphatase and tensin homolog (PTEN: a central inhibitor of neuron-intrinsic axon growth potential) could restore inspiratory diaphragm function by reconnecting critical respiratory neural circuitry in a rat model of chronic cervical level 2 (C2) hemisection SCI. Read More

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Analysis of therapeutic potential of monocytic myeloid-derived suppressor cells in cardiac allotransplantation.

Transpl Immunol 2021 May 8:101405. Epub 2021 May 8.

Department of Biofunctional Microbiota, Juntendo University Graduate School of Medicine, Tokyo, Japan; Division of Cell Biology, Biomedical Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address:

Background: Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are attractive immune cells to induce immune tolerance. To explore a strategy for improving the efficacy of MDSC therapies, we examined the impact of adoptive transfer of several types of MDSCs on graft rejection in a murine heart transplantation model.

Methods: We analyzed the effects of induced syngeneic and allogeneic bone marrow-derived MDSCs (BM-MDSCs) on graft survival and suppressive capacity. Read More

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Targeting RNA Editing of Antizyme Inhibitor 1: a Potential Oligonucleotide-Based Antisense Therapy for Cancer.

Mol Ther 2021 May 8. Epub 2021 May 8.

Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Singapore 117599; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, Singapore 117594. Electronic address:

Dysregulated adenosine-to-inosine (A-to-I) RNA editing is implicated in various cancers. However, no available RNA editing inhibitors have so far been developed to inhibit cancer-associated RNA editing events. Here we decipher the RNA secondary structure of antizyme inhibitor 1 (AZIN1), one of the best-studied A-to-I editing targets in cancer, by locating its editing site complementary sequence (ECS) at the 3'end of exon 12. Read More

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Plastrum testudinis extract suppresses osteoclast differentiation via the NF-κB signaling pathway and ameliorates senile osteoporosis.

J Ethnopharmacol 2021 May 8:114195. Epub 2021 May 8.

The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address:

Ethnopharmacological Relevance: Plastrum testudinis (PT) is a kind of single traditional Chinese medicine that can tonify kidney and strengthen bone. Plastrum testudinis extract (PTE) has been approved to promote the osteogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro. However, the mechanism by which PTE reduces osteoclast differentiation has not yet been reported. Read More

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Shenqi Yizhi Granule attenuates Aβ induced cognitive dysfunction via inhibiting JAK2/STAT3 activated astrocyte reactivity.

Exp Gerontol 2021 May 8:111400. Epub 2021 May 8.

Institute of Meterial Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China. Electronic address:

Shenqi Yizhi Granule (SYG), a modern preparation herbs based on the theory of traditional Chinese medicine, has been proved to be effective against Alzheimer's disease in clinical trials, APP/PS1 mice and 5XFAD transgenic mice. But the underlying mechanism remains ambiguous. Increasing evidence supports the crucial role of astrocyte reactivity in the pathogenesis of Alzheimer's disease (AD). Read More

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Isolation, structural characterization and neuroprotective activity of exopolysaccharide from Paecilomyces cicada TJJ1213.

Int J Biol Macromol 2021 May 8. Epub 2021 May 8.

College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, PR China. Electronic address:

Two exopolysaccharide fractions (EPS1 and EPS2) were obtained from Paecilomyces cicadae TJJ 1213, and their structures were elucidated. The EPS1 and EPS2 were mainly composed of mannose and galactose with molar ratios of 3.2: 1. Read More

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Intermittent hypoxia and respiratory recovery in pre-clinical rodent models of incomplete cervical spinal cord injury.

Exp Neurol 2021 May 8:113751. Epub 2021 May 8.

Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Impaired respiratory function is a common and devastating consequence of cervical spinal cord injury. Accordingly, the development of safe and effective treatments to restore breathing function is critical. Acute intermittent hypoxia has emerged as a promising therapeutic strategy to treat respiratory insufficiency in individuals with spinal cord injury. Read More

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African Americans With p16+ and p16- Oropharyngeal Squamous Cell Carcinomas Have Distinctly Poor Treatment Outcomes Independent of Medical Care Access.

JCO Oncol Pract 2021 May;17(5):e695-e702

Department of Otolaryngology-Head and Neck Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH.

Purpose: Human papilloma virus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), diagnosed with p16 immunohistochemistry, is associated with favorable prognosis; however, this connection was established using European American (EA)-skewed populations. The impact of p16/human papillomavirus status on outcomes in African American (AA) OPSCC patients remains to be settled. In this study, we determine the association between cancer disparity and p16 status in an OPSCC cohort controlling for time to treatment initiation (TTI), a surrogate for medical care access. Read More

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Prevalence of Targetable Mutations in Black Patients With Lung Cancer: A Systematic Review and Meta-Analysis.

JCO Oncol Pract 2021 May;17(5):e629-e636

Division of Hematology and Medical Oncology, Department of Medicine, Miller School of Medicine, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL.

Purpose: Inferior outcomes of Black patients with lung cancer compared with other racial groups are often linked to socioeconomic factors. It is crucial to determine whether a varying prevalence of targetable mutations limits treatments and contributes to disparities.

Materials And Methods: We conducted a meta-analysis on the prevalence of lung cancer , , , and mutations in Black patients compared with White, Hispanic, and Asian patients. Read More

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Glutathione-Depleting Nanomedicines for Synergistic Cancer Therapy.

ACS Nano 2021 May 11. Epub 2021 May 11.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing 210096, P.R. China.

Cancer cells frequently exhibit resistance to various molecular and nanoscale drugs, which inevitably affects the drugs' therapeutic outcomes. Overexpression of glutathione (GSH) has been observed in many cancer cells, and solid evidence has corroborated the resulting tumor resistance to a variety of anticancer therapies, suggesting that this biochemical characteristic of cancer cells can be developed as a potential target for cancer treatments. The single treatment of GSH-depleting agents can potentiate the responses of the cancer cells to different cell death stimuli; therefore, as an adjunctive strategy, GSH depletion is usually combined with mainstream cancer therapies for enhancing the therapeutic outcomes. Read More

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Kinetic degradation and biocompatibility evaluation of polycaprolactone-based biologics delivery matrices for regenerative engineering of the rotator cuff.

J Biomed Mater Res A 2021 May 11. Epub 2021 May 11.

Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, Connecticut, USA.

Whereas synthetic biodegradable polymers have been successfully applied for the delivery of biologics in other tissues, the anatomical complexity, poor blood supply, and reduced clearance of degradation byproducts in the rotator cuff create unique design challenges for implantable biomaterials. Here, we investigated lower molecular weight poly-lactic acid co-epsilon-caprolactone (PLA-CL) formulations with varying molecular weight and film casting concentrations as potential matrices for the therapeutic delivery of biologics in the rotator cuff. Matrices were fabricated with target footprint dimensions to facilitate controlled and protected release of model biologic (Bovine Serum Albumin), and anatomically-unhindered implantation under the acromion in a rodent model of acute rotator cuff repair. Read More

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Infection of humanized mice with a novel phlebovirus presented pathogenic features of sever fever with thrombocytopenia syndrome.

PLoS Pathog 2021 May 11;17(5):e1009587. Epub 2021 May 11.

School of Life Sciences, Ningxia University, Yinchuan, P.R. China.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne emerging phlebovirus with high mortality rates of 6.0 to 30%. SFTSV infection is characterized by high fever, thrombocytopenia, leukopenia, hemorrhage and multiple organ failures. Read More

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NMDA receptor inhibition increases, synchronizes, and stabilizes the collective pancreatic beta cell activity: Insights through multilayer network analysis.

PLoS Comput Biol 2021 May 11;17(5):e1009002. Epub 2021 May 11.

Faculty of Medicine, University of Maribor, Maribor, Slovenia.

NMDA receptors promote repolarization in pancreatic beta cells and thereby reduce glucose-stimulated insulin secretion. Therefore, NMDA receptors are a potential therapeutic target for diabetes. While the mechanism of NMDA receptor inhibition in beta cells is rather well understood at the molecular level, its possible effects on the collective cellular activity have not been addressed to date, even though proper insulin secretion patterns result from well-synchronized beta cell behavior. Read More

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Midterm Results of Primary Exeter Cemented Stem in a Select Patient Population.

J Bone Joint Surg Am 2021 May 11. Epub 2021 May 11.

Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota.

Background: Most North American surgeons predominantly use uncemented stems in primary total hip arthroplasties (THAs) and reserve cemented stems for selected older patients and those with poor bone quality. However, data on this "selective use" strategy for cemented stems in the population at risk for periprosthetic fracture and implant loosening are limited. The purpose of this study was to describe implant survivorship, complications, and radiographic results of a specific collarless, polished, tapered cemented stem (Exeter; Stryker) used selectively in a predominantly elderly population undergoing primary THA. Read More

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Prevalence and Outcomes of Unexpected Positive Intraoperative Cultures in Presumed Aseptic Revision Hip Arthroplasty.

J Bone Joint Surg Am 2021 May 11. Epub 2021 May 11.

Division of Orthopaedic Surgery, Department of Surgery, Schulich School of Medicine & Dentistry, Western University and London Health Science Centre, London, Ontario, Canada.

Background: The prevalence and outcomes of unexpected positive cultures (UPCs) of specimens taken during presumed aseptic revision total hip arthroplasty (THA) are unclear. The purpose of this study was to determine the prevalence of UPC and infection-free implant survival in this patient population. Secondary aims included identifying factors associated with subsequent infection-related failure in patients with UPC. Read More

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A role for IL-33-activated ILC2s in eosinophilic vasculitis.

JCI Insight 2021 May 11. Epub 2021 May 11.

Department of Internal Medicine, Cochin Hospital, Paris, France.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease with poorly understood mechanisms. Here we report that patients with EGPA have elevated levels of TSLP, IL-25, and sST2, well characterized cytokine "alarmins" that activate or modulate type 2 innate lymphoid cells (ILC2s). Patients with active EGPA have a concurrent reduction in circulating ILC2s, suggesting a role for ILC2s in the pathogenesis of this disease. Read More

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Rap1 in the VMH regulates glucose homeostasis.

JCI Insight 2021 May 11. Epub 2021 May 11.

Department of Pediatrics, Baylor College of Medicine, Houston, United States of America.

The hypothalamus is a critical regulator of glucose metabolism and is capable of correcting diabetes conditions independently of an effect on energy balance. The small GTPase Rap1 in the forebrain is implicated in high-fat diet (HFD)-induced obesity and glucose imbalance. Here, we report that increasing Rap1 activity selectively in the medial hypothalamus elevated blood glucose without increasing the body weight of HFD-fed mice. Read More

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Novel hyaluronic acid oligosaccharide-loaded and CD44v6-targeting oxaliplatin nanoparticles for the treatment of colorectal cancer.

Drug Deliv 2021 Dec;28(1):920-929

Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, PR China.

Oxaliplatin resistance is one of the main causes of failed colorectal cancer treatment, followed by recurrence and metastasis. In this study, we found that colorectal cancer cells secrete a high level of hyaluronic acid (HA), which interacts with its receptor CD44v6 to mediate colorectal cancer resistance to chemotherapy. HA oligosaccharide (oHA) is a degradation product of HA. Read More

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December 2021

Bayesian Framework to Augment Tumor Board Decision Making.

JCO Clin Cancer Inform 2021 May;5:508-517

Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer & Research Institute, Tampa, FL.

Purpose: Ideally, specific treatment for a cancer patient is decided by a multidisciplinary tumor board, integrating prior clinical experience, published data, and patient-specific factors to develop a consensus on an optimal therapeutic strategy. However, many oncologists lack access to a tumor board, and many patients have incomplete data descriptions so that tumor boards must act on imprecise criteria. We propose these limitations to be addressed through a flexible but rigorous mathematical tool that can define the probability of success of given therapies and be made readily available to the oncology community. Read More

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Design and Synthesis of Highly Selective Brain Penetrant p38α Mitogen-Activated Protein Kinase Inhibitors.

J Med Chem 2021 May 11. Epub 2021 May 11.

Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.

Stress-induced p38α mitogen-activated protein (MAP) kinase activation modulates cytokine overproduction and is associated with neuroinflammation and neurodegeneration. As a potential therapeutic approach, novel Skepinone-based p38α MAP kinase inhibitors were optimized to cross the blood-brain barrier via either amino acid transporters or hydrophobic diffusion. To enhance absorption from the oral route, we used methyl ester prodrugs of the active carboxy analogs. Read More

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Nanozyme Impregnated Mesenchymal Stem Cells for Hepatic Ischemia-Reperfusion Injury Alleviation.

ACS Appl Mater Interfaces 2021 May 11. Epub 2021 May 11.

School of Materials Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.

Mesenchymal stem cell (MSC) based therapy holds great potential for treating numerous diseases owing to their capability to heal injured tissue/organs through paracrine factors secretion and immunomodulation. Despite the high hopes, the low viability of transplanted cells in the injured tissues due to the elevated oxidative stress levels remains the largest obstacle in MSC-based cell therapy. To achieve desired therapeutic efficiency, the survival of the transplanted MSCs in the high oxidative stress environment needs to be ensured. Read More

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Supraspinal Effects of Dorsal Root Ganglion Stimulation in Chronic Pain Patients.

Neuromodulation 2021 May 11. Epub 2021 May 11.

Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.

Objectives: Dorsal root ganglion stimulation (DRGS) has become a popular neuromodulatory treatment for neuropathic pain. We used magnetoencephalography (MEG) to investigate potential biomarkers of pain and pain relief, based on the differences in power spectral density (PSD) during varying degrees of pain and how these oscillations change during DRGS-mediated pain relief.

Materials And Methods: Thirteen chronic pain patients with implanted dorsal root ganglion stimulators were included in the MEG analysis. Read More

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