Kelly D. Foote

Bio: Kelly D. Foote is an academic researcher from University of Florida. The author has contributed to research in topics: Deep brain stimulation & Essential tremor. The author has an hindex of 57, co-authored 287 publications receiving 14411 citations. Previous affiliations of Kelly D. Foote include Australian National University & Royal Hampshire County Hospital.

Genome-wide association study reveals genetic risk underlying Parkinson's disease

Abstract: We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding a-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 x 10(-16)) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 x 10(-16)). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS1, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 x 10(-8)) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 x 10(-5)). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.

Deep Brain Stimulation for Parkinson Disease: An Expert Consensus and Review of Key Issues

Abstract: Objective: To provide recommendations to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD). Data Sources and Study Selection: An international consortium of experts organized, reviewed the literature, and attended the workshop. Topics were introduced at the workshop, followed by group discussion. Data Extraction and Synthesis: A draft of a consensus statement was presented and further edited after plenary debate. The final statements were agreed on by all members. Conclusions: (1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients. Arch Neurol. 2011; 68(2):165-171. Published online October 11, 2010. doi:10.1001/archneurol.2010.260

Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience.

Abstract: Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a ‘learning curve’ both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior–posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.

Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson’s disease

Abstract: Background: Long term effects of subthalamic nucleus (STN) stimulation on cognition, mood, and behaviour are unknown. Objective: This study evaluated the cognitive, mood, and behavioural effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson's disease (PD) followed up for three years. Methods: A consecutive series of 77 PD patients was assessed before, one, and three years after surgery. Mean (SD) age at surgery was 55 (8). Seven patients died or were lost for follow up. Neuropsychological assessment included a global cognitive scale, memory, and frontal tests. Depression was evaluated using the Beck depression inventory. Assessment of thought disorders and apathy was based on the unified Parkinson's disease rating scale. Reports of the behavioural changes are mainly based on interviews done by the same neuropsychologist at each follow up. Results: Only two cognitive variables worsened (category fluency, total score of fluency). Age was a predictor of decline in executive functions. Depression improved whereas apathy and thought disorders worsened. Major behavioural changes were two transient aggressive impulsive episodes, one suicide, four suicide attempts, one permanent apathy, one transient severe depression, four psychoses (one permanent), and five hypomania (one permanent). Conclusions: Comparing baseline, one year, and three year postoperative assessments, STN stimulation did not lead to global cognitive deterioration. Apathy scores mildly increased. Depression scores mildly improved. Behavioural changes were comparatively rare and mostly transient. Single case reports show the major synergistic effects of both medication and stimulation on mood and behaviour, illustrating the importance of a correct postoperative management.

Cognition and mood in Parkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: The COMPARE Trial†

Abstract: Objective There is a paucity of level-one evidence comparing STN and GPi DBS. Our aim in this prospective blinded randomized trial was to compare the cognitive and mood effects of unilateral subthalamic nucleus (STN) vs. unilateral globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with Parkinson disease (PD).

Database resources of the National Center for Biotechnology Information

Abstract: In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's website. NCBI resources include Entrez, PubMed, PubMed Central, LocusLink, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, SARS Coronavirus Resource, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD) and the Conserved Domain Architecture Retrieval Tool (CDART). Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih.gov.

Sources of Method Bias in Social Science Research and Recommendations on How to Control It

Abstract: Despite the concern that has been expressed about potential method biases, and the pervasiveness of research settings with the potential to produce them, there is disagreement about whether they really are a problem for researchers in the behavioral sciences. Therefore, the purpose of this review is to explore the current state of knowledge about method biases. First, we explore the meaning of the terms “method” and “method bias” and then we examine whether method biases influence all measures equally. Next, we review the evidence of the effects that method biases have on individual measures and on the covariation between different constructs. Following this, we evaluate the procedural and statistical remedies that have been used to control method biases and provide recommendations for minimizing method bias.

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1

Abstract: Parkinson's disease is the most common neurodegenerative movement disorder. Mutations in PINK1 and PARKIN are the most frequent causes of recessive Parkinson's disease. However, their molecular contribution to pathogenesis remains unclear. Here, we reveal important mechanistic steps of a PINK1/Parkin-directed pathway linking mitochondrial damage, ubiquitylation and autophagy in non-neuronal and neuronal cells. PINK1 kinase activity and its mitochondrial localization sequence are prerequisites to induce translocation of the E3 ligase Parkin to depolarized mitochondria. Subsequently, Parkin mediates the formation of two distinct poly-ubiquitin chains, linked through Lys 63 and Lys 27. In addition, the autophagic adaptor p62/SQSTM1 is recruited to mitochondrial clusters and is essential for the clearance of mitochondria. Strikingly, we identified VDAC1 (voltage-dependent anion channel 1) as a target for Parkin-mediated Lys 27 poly-ubiquitylation and mitophagy. Moreover, pathogenic Parkin mutations interfere with distinct steps of mitochondrial translocation, ubiquitylation and/or final clearance through mitophagy. Thus, our data provide functional links between PINK1, Parkin and the selective autophagy of mitochondria, which is implicated in the pathogenesis of Parkinson's disease.