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Article: The emerging postural instability phenotype in idiopathic Parkinson disease.

Skidmore, Frank M / Monroe, William S / Hurt, Christopher P / Nicholas, Anthony P / Gerstenecker, Adam / Anthony, Thomas / Jololian, Leon / Cutter, Gary / Bashir, Adil / Denny, Thomas / Standaert, David / Disbrow, Elizabeth A

NPJ Parkinson's disease

2022 Volume 8, Issue 1, Page(s) 28

Abstract: Identification of individuals at high risk for rapid progression of motor and cognitive signs in Parkinson disease (PD) is clinically significant. Postural instability and gait dysfunction (PIGD) are associated with greater motor and cognitive ... ...

Abstract	Identification of individuals at high risk for rapid progression of motor and cognitive signs in Parkinson disease (PD) is clinically significant. Postural instability and gait dysfunction (PIGD) are associated with greater motor and cognitive deterioration. We examined the relationship between baseline clinical factors and the development of postural instability using 5-year longitudinal de-novo idiopathic data (n = 301) from the Parkinson's Progressive Markers Initiative (PPMI). Logistic regression analysis revealed baseline features associated with future postural instability, and we designated this cohort the emerging postural instability (ePI) phenotype. We evaluated the resulting ePI phenotype rating scale validity in two held-out populations which showed a significantly higher risk of postural instability. Emerging PI phenotype was identified before onset of postural instability in 289 of 301 paired comparisons, with a median progression time of 972 days. Baseline cognitive performance was similar but declined more rapidly in ePI phenotype. We provide an ePI phenotype rating scale (ePIRS) for evaluation of individual risk at baseline for progression to postural instability.
Language	English
Publishing date	2022-03-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819218-7
ISSN	2373-8057
ISSN	2373-8057
DOI	10.1038/s41531-022-00287-x
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Article ; Online: Religiosity may alter the cold pressor stress response.

Mulligan, Thomas / Skidmore, Frank M

Explore (New York, N.Y.)

2009 Volume 5, Issue 6, Page(s) 345–346

MeSH term(s)	Blood Pressure ; Christianity ; Cold Temperature ; Humans ; Hydrocortisone/blood ; Pain ; Prospective Studies ; Pulse ; Spirituality ; Stress, Physiological
Chemical Substances	Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2009-11
Publishing country	United States
Document type	Controlled Clinical Trial ; Letter
ZDB-ID	2183945-1
ISSN	1878-7541 ; 1550-8307
ISSN (online)	1878-7541
ISSN	1550-8307
DOI	10.1016/j.explore.2009.08.002
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Article ; Online: Allocentric But Not Egocentric Pseudoneglect of Peripersonal Space.

Kesayan, Tigran / Williamson, John B / Falchook, Adam D / Skidmore, Frank M / Heilman, Kenneth M

Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology

2016 Volume 29, Issue 1, Page(s) 18–23

Abstract: Background and objective: Healthy adults often deviate leftward on line bisection tasks (allocentric pseudoneglect) but rightward on body part bisection tasks (egocentric pseudoneglect). People visually estimate distance in peripersonal space by ... ...

Abstract	Background and objective: Healthy adults often deviate leftward on line bisection tasks (allocentric pseudoneglect) but rightward on body part bisection tasks (egocentric pseudoneglect). People visually estimate distance in peripersonal space by comparing the distance to the length of a body part such as an arm's length (an egocentric reference) or using standard units of distance such as inches (an allocentric reference). Our objective was to learn whether people have pseudoneglect when estimating distances in peripersonal space using egocentric versus allocentric reference frames. Methods: Twelve healthy participants standing either next to or 5 feet away from a wall were asked to move away from or toward the wall such that their shoulder would be what they judged to be an arm's length or a distance of 1, 2, or 3 feet from the wall. Results: The participants estimated their arm's length more accurately than the standard units of distance (possibly related to learning and practice). Participants were more precise when estimating the length of their left than their right arm. When estimating standard units of distance, participants underestimated the distances on their left side more than on their right. Conclusions: Our results support the postulate that left pseudoneglect is an allocentric phenomenon related to a hemispheric asymmetry in computing allocentric distances. The participants underestimated 2 and 3 feet, but overestimated 1 foot. This dichotomy may relate to using focused versus distributed attention. The brain mechanisms leading to these asymmetries remain to be determined.
MeSH term(s)	Aged ; Attention ; Cognition/physiology ; Distance Perception/physiology ; Female ; Humans ; Learning ; Male ; Middle Aged ; Perceptual Disorders/physiopathology ; Self Concept ; Space Perception/physiology
Language	English
Publishing date	2016-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2108112-8
ISSN	1543-3641 ; 1543-3633
ISSN (online)	1543-3641
ISSN	1543-3633
DOI	10.1097/WNN.0000000000000085
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Article ; Online: Parkinson's disease-related network topographies characterized with resting state functional MRI.

Vo, An / Sako, Wataru / Fujita, Koji / Peng, Shichun / Mattis, Paul J / Skidmore, Frank M / Ma, Yilong / Uluğ, Aziz M / Eidelberg, David

Human brain mapping

2017 Volume 38, Issue 2, Page(s) 617–630

Abstract: Spatial covariance mapping can be used to identify and measure the activity of disease-related functional brain networks. While this approach has been widely used in the analysis of cerebral blood flow and metabolic PET scans, it is not clear whether it ... ...

Abstract	Spatial covariance mapping can be used to identify and measure the activity of disease-related functional brain networks. While this approach has been widely used in the analysis of cerebral blood flow and metabolic PET scans, it is not clear whether it can be reliably applied to resting state functional MRI (rs-fMRI) data. In this study, we present a novel method based on independent component analysis (ICA) to characterize specific network topographies associated with Parkinson's disease (PD). Using rs-fMRI data from PD and healthy subjects, we used ICA with bootstrap resampling to identify a PD-related pattern that reliably discriminated the two groups. This topography, termed rs-MRI PD-related pattern (fPDRP), was similar to previously characterized disease-related patterns identified using metabolic PET imaging. Following pattern identification, we validated the fPDRP by computing its expression in rs-fMRI testing data on a prospective case basis. Indeed, significant increases in fPDRP expression were found in separate sets of PD and control subjects. In addition to providing a similar degree of group separation as PET, fPDRP values correlated with motor disability and declined toward normal with levodopa administration. Finally, we used this approach in conjunction with neuropsychological performance measures to identify a separate PD cognition-related pattern in the patients. This pattern, termed rs-fMRI PD cognition-related pattern (fPDCP), was topographically similar to its PET-derived counterpart. Subject scores for the fPDCP correlated with executive function in both training and testing data. These findings suggest that ICA can be used in conjunction with bootstrap resampling to identify and validate stable disease-related network topographies in rs-fMRI. Hum Brain Mapp 38:617-630, 2017. © 2016 Wiley Periodicals, Inc.
Language	English
Publishing date	2017-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1197207-5
ISSN	1097-0193 ; 1065-9471
ISSN (online)	1097-0193
ISSN	1065-9471
DOI	10.1002/hbm.23260
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Zs.A 4028: Show issues

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Article ; Online: High-Intensity Exercise Acutely Increases Substantia Nigra and Prefrontal Brain Activity in Parkinson's Disease.

Kelly, Neil A / Wood, Kimberly H / Allendorfer, Jane B / Ford, Matthew P / Bickel, C Scott / Marstrander, Jon / Amara, Amy W / Anthony, Thomas / Bamman, Marcas M / Skidmore, Frank M

Medical science monitor : international medical journal of experimental and clinical research

2017 Volume 23, Page(s) 6064–6071

Abstract: BACKGROUND Pathologic alterations in resting-state brain activity patterns exist among individuals with Parkinson's disease (PD). Since physical exercise alters resting-state brain activity in non-PD populations and improves PD symptoms, we assessed the ... ...

Abstract	BACKGROUND Pathologic alterations in resting-state brain activity patterns exist among individuals with Parkinson's disease (PD). Since physical exercise alters resting-state brain activity in non-PD populations and improves PD symptoms, we assessed the acute effect of exercise on resting-state brain activity in exercise-trained individuals with PD. MATERIAL AND METHODS Resting-state functional magnetic resonance imaging (fMRI) was collected twice for 17 PD participants at the conclusion of an exercise intervention. The acute effect of exercise was examined for PD participants using the amplitude of low frequency fluctuation (ALFF) before and after a single bout of exercise. Correlations of clinical variables (i.e., PDQ-39 quality of life and MDS-UPDRS) with ALFF values were examined for the exercise-trained PD participants. RESULTS An effect of acute exercise was observed as an increased ALFF signal within the right ventromedial prefrontal cortex (PFC), left ventrolateral PFC, and bilaterally within the substantia nigra (SN). Quality of life was positively correlated with ALFF values within the vmPFC and vlPFC. CONCLUSIONS Given the role of the SN and PFC in motor and non-motor symptoms in PD, the acute increases in brain activity within these regions, if repeated frequently over time (i.e., exercise training), may serve as a potential mechanism underlying exercise-induced PD-specific clinical benefits.
MeSH term(s)	Aged ; Brain/pathology ; Brain Mapping ; Exercise/physiology ; Female ; High-Intensity Interval Training/methods ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Membrane Potentials/physiology ; Middle Aged ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/physiopathology ; Parkinson Disease/therapy ; Prefrontal Cortex/physiopathology ; Substantia Nigra/diagnostic imaging ; Substantia Nigra/physiopathology
Language	English
Publishing date	2017-12-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	1439041-3
ISSN	1643-3750 ; 1234-1010
ISSN (online)	1643-3750
ISSN	1234-1010
DOI	10.12659/msm.906179
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Zs.A 4924: Show issues

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Article ; Online: Influence of left versus right hemibody onset Parkinson's disease on cardiovascular control.

Foster, Paul S / Drago, Valeria / Harrison, David W / Skidmore, Frank / Crucian, Gregory P / Heilman, Kenneth M

Laterality

2011 Volume 16, Issue 2, Page(s) 164–173

Abstract: Whereas the left hemisphere is involved in regulating the parasympathetic nervous system, the right hemisphere regulates the sympathetic. Given the asymmetrical onset of motor symptoms and neuropathology in PD, differences in cardiovascular functions ... ...

Abstract	Whereas the left hemisphere is involved in regulating the parasympathetic nervous system, the right hemisphere regulates the sympathetic. Given the asymmetrical onset of motor symptoms and neuropathology in PD, differences in cardiovascular functions might be expected between PD patients with left hemibody onset (LHO) versus right hemibody onset (RHO). A total of 66 PD patients served as participants, including 31 LHO patients and 35 RHO PD patients. All participants had their resting heart rate (HR) and blood pressure (BP) recorded. Although the LHO group had lower systolic BP, it had higher resting HR than did the RHO group. The reason for this dissociation is not known but might be related to asymmetrical vagus nerve control of the heart (SA node). Future researchers might want to use additional indices of cardiovascular functioning that are more precise measures of parasympathetic and sympathetic functioning, as well as learn the influence of dopaminergic medications.
MeSH term(s)	Aged ; Autonomic Nervous System Diseases/etiology ; Autonomic Nervous System Diseases/physiopathology ; Cardiovascular Physiological Phenomena ; Female ; Functional Laterality/physiology ; Humans ; Male ; Middle Aged ; Parasympathetic Nervous System/physiopathology ; Parkinson Disease/complications ; Parkinson Disease/physiopathology ; Sympathetic Nervous System/physiopathology
Language	English
Publishing date	2011-03
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	2028955-8
ISSN	1464-0678 ; 1357-650X
ISSN (online)	1464-0678
ISSN	1357-650X
DOI	10.1080/13576500903483507
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Article ; Online: Hypometric allocentric and egocentric distance estimates in Parkinson disease.

Kabasakalian, Anahid / Kesayan, Tigran / Williamson, John B / Skidmore, Frank M / Falchook, Adam D / Harciarek, Michal / Heilman, Kenneth M

Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology

2013 Volume 26, Issue 3, Page(s) 133–139

Abstract: Objective and background: Persons with Parkinson disease (PD) show hypometric movements and make hypometric estimates of imagined actions. These deficits may be related to misestimates of the length of body parts. Our objective was to learn whether ... ...

Abstract	Objective and background: Persons with Parkinson disease (PD) show hypometric movements and make hypometric estimates of imagined actions. These deficits may be related to misestimates of the length of body parts. Our objective was to learn whether patients with PD are impaired in their estimations of their arm's length and standard units of distance. Methods: We tested 20 patients with PD, all on therapeutic doses of dopaminergic medications, and 13 healthy controls. In half of the trials, the participants stood so that either their right or left shoulder was adjacent to a wall; in the other half, their right or left shoulder was 5 feet from the wall. In the egocentric testing condition, they were asked to move their body toward or away from the wall to what they considered was an arm's length from the wall. In the allocentric testing condition, they were to move toward or away from the wall so that their proximal shoulder was a standard unit distance of 1, 2, or 3 feet from the wall. Results: The patients with PD made much greater hypometric (too close to the wall) errors. Since at 5 feet from the wall they had to move farther to underestimate distances, their errors cannot be explained by hypometric movements. The results did not differ significantly by egocentric or allocentric estimation, side of shoulder proximity, or side of PD onset. Conclusions: Our findings support the idea that the egocentric and allocentric hypometria associated with PD is a perceptual rather than motor disorder.
MeSH term(s)	Activities of Daily Living ; Aged ; Analysis of Variance ; Female ; Functional Laterality ; Humans ; Imagination ; Learning ; Male ; Middle Aged ; Parkinson Disease/complications ; Parkinson Disease/drug therapy ; Parkinson Disease/physiopathology ; Perceptual Disorders/diagnosis ; Perceptual Disorders/etiology ; Perceptual Disorders/physiopathology ; Space Perception
Language	English
Publishing date	2013-09
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2108112-8
ISSN	1543-3641 ; 1543-3633
ISSN (online)	1543-3641
ISSN	1543-3633
DOI	10.1097/WNN.0000000000000007
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Article ; Online: Ventral tegmental area/midbrain functional connectivity and response to antipsychotic medication in schizophrenia.

Hadley, Jennifer A / Nenert, Rodolphe / Kraguljac, Nina V / Bolding, Mark S / White, David M / Skidmore, Frank M / Visscher, Kristina M / Lahti, Adrienne C

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2013 Volume 39, Issue 4, Page(s) 1020–1030

Abstract: Medication management in schizophrenia is a lengthy process, as the lack of clinical response can only be confirmed after at least 4 weeks of antipsychotic treatment at a therapeutic dose. Thus, there is a clear need for the discovery of biomarkers that ... ...

Abstract	Medication management in schizophrenia is a lengthy process, as the lack of clinical response can only be confirmed after at least 4 weeks of antipsychotic treatment at a therapeutic dose. Thus, there is a clear need for the discovery of biomarkers that have the potential to accelerate the management of treatment. Using resting-state functional MRI, we examined the functional connectivity of the ventral tegmental area (VTA), the origin of the mesocorticolimbic dopamine projections, in 21 healthy controls and 21 unmedicated patients with schizophrenia at baseline (pre-treatment) and after 1 week of treatment with the antipsychotic drug risperidone (1-week post-treatment). Group-level functional connectivity maps were obtained and group differences in connectivity were assessed on the groups' participant-level functional connectivity maps. We also examined the relationship between pre-treatment/1-week post-treatment functional connectivity and treatment response. Compared with controls, patients exhibited significantly reduced pre-treatment VTA/midbrain connectivity to multiple cortical and subcortical regions, including the dorsal anterior cingulate cortex (dACC) and thalamus. After 1 week of treatment, VTA/midbrain connectivity to bilateral regions of the thalamus was re-established. Pre-treatment VTA/midbrain connectivity strength to dACC was positively correlated with good response to a 6-week course of risperidone, whereas pre-treatment VTA/midbrain connectivity strength to the default mode network was negatively correlated. Our findings suggest that VTA/midbrain resting-state connectivity may be a useful biomarker for the prediction of treatment response.
MeSH term(s)	Adult ; Analysis of Variance ; Antipsychotic Agents/therapeutic use ; Brain Mapping ; Female ; Follow-Up Studies ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neural Pathways/blood supply ; Neural Pathways/drug effects ; Oxygen/blood ; Psychiatric Status Rating Scales ; Risperidone/therapeutic use ; Schizophrenia/drug therapy ; Schizophrenia/pathology ; Severity of Illness Index ; Ventral Tegmental Area/blood supply ; Ventral Tegmental Area/drug effects ; Young Adult
Chemical Substances	Antipsychotic Agents ; Risperidone (L6UH7ZF8HC) ; Oxygen (S88TT14065)
Language	English
Publishing date	2013-10-29
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/npp.2013.305
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Zs.A 2379: Show issues

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Article ; Online: Interventions to address potentially inappropriate prescriptions and over-the-counter medication use among adults 65 years and older in primary care settings: protocol for a systematic review.

Beck, Andrew / Persaud, Navindra / Tessier, Laure A / Grad, Roland / Kidd, Michael R / Klarenbach, Scott / Korownyk, Christina / Moore, Ainsley / Thombs, Brett D / Mangin, Dee / McCracken, Rita K / McDonald, Emily G / Sirois, Caroline / Kanji, Salmaan / Molnar, Frank / Nicholls, Stuart G / Thavorn, Kednapa / Bennett, Alexandria / Shaver, Nicole /

Skidmore, Becky / Mitchelmore, Bradley R / Avey, Marc / Rolland-Harris, Elizabeth / Little, Julian / Moher, David

Systematic reviews

2022 Volume 11, Issue 1, Page(s) 225

Abstract: Purpose: To inform recommendations by the Canadian Task Force on Preventive Health Care on potentially inappropriate prescribing and over-the-counter (OTC) medication use among adults aged 65 years and older in primary care settings. This protocol ... ...

Abstract	Purpose: To inform recommendations by the Canadian Task Force on Preventive Health Care on potentially inappropriate prescribing and over-the-counter (OTC) medication use among adults aged 65 years and older in primary care settings. This protocol outlines the planned scope and methods for a systematic review of the benefits and harms and acceptability of interventions to reduce potentially inappropriate prescriptions and OTC medication use. Methods: De novo systematic reviews will be conducted to synthesize the available evidence on (a) the benefits and harms of interventions to reduce potentially inappropriate prescriptions and OTC medications compared to no intervention, usual care, or non- or minimally active intervention among adults aged 65 years and older and (b) the acceptability of these interventions or attributes among patients. Outcomes of interest for the benefits and harms review are all-cause mortality, hospitalization, non-serious adverse drug reactions, quality of life, emergency department visits, injurious falls, medical visits, and the number of medications (and number of pills). Outcomes for the acceptability review are the preference for and relative importance of different interventions or their attributes. For the benefits and harms review, we will search MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials. For the acceptability review, we will search MEDLINE, Embase, PsycInfo, Cochrane Central Register of Controlled Trials, and the NHS Economic Evaluation Database for experimental and observational studies with a comparator. Websites of relevant organizations, other grey literature sources, and reference lists of included studies and reviews will be searched. Title and abstract screening will be completed by two independent reviewers using the liberal accelerated approach. Full-text review, data extraction, risk of bias assessments, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers, with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE approach will be used to assess the certainty of the evidence for outcomes. Discussion: The results of this systematic review will be used by the Canadian Task Force on Preventive Health Care to inform their recommendation on potentially inappropriate prescribing and OTC medication use among adults aged 65 years and older. Systematic review registration: PROSPERO (KQ1: CRD42022302313; KQ2: CRD42022302324); Open Science Framework ( https://osf.io/urj4b/ ).
MeSH term(s)	Humans ; Adult ; Inappropriate Prescribing/prevention & control ; Quality of Life ; Canada ; Bias ; Primary Health Care ; Systematic Reviews as Topic
Language	English
Publishing date	2022-10-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2662257-9
ISSN	2046-4053 ; 2046-4053
ISSN (online)	2046-4053
ISSN	2046-4053
DOI	10.1186/s13643-022-02044-w
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Article ; Online: Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment.

Chiorazzi, Michael / Martinek, Jan / Krasnick, Bradley / Zheng, Yunjiang / Robbins, Keenan J / Qu, Rihao / Kaufmann, Gabriel / Skidmore, Zachary / Juric, Melani / Henze, Laura A / Brösecke, Frederic / Adonyi, Adam / Zhao, Jun / Shan, Liang / Sefik, Esen / Mudd, Jacqueline / Bi, Ye / Goedegebuure, S Peter / Griffith, Malachi /

Griffith, Obi / Oyedeji, Abimbola / Fertuzinhos, Sofia / Garcia-Milian, Rolando / Boffa, Daniel / Detterbeck, Frank / Dhanasopon, Andrew / Blasberg, Justin / Judson, Benjamin / Gettinger, Scott / Politi, Katerina / Kluger, Yuval / Palucka, Karolina / Fields, Ryan C / Flavell, Richard A

Journal for immunotherapy of cancer

2023 Volume 11, Issue 7

Abstract: Background: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as ... ...

Abstract	Background: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors. Method: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient's hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual's TME. We used this system to prospectively study tumor-immune interactions in patients with solid tumor. Results: Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent vascular endothelial growth factor A (VEGFA) signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth. Conclusions: Humanization of the interleukin 6 locus in MISTRG6 mice enhances HSPC engraftment, making it feasible to model tumor-immune interactions in an autologous manner from a bedside bone marrow aspirate. The TME from these autologous tumors display hallmarks of the human TME including innate and adaptive immune activation and provide a platform for preclinical drug testing.
MeSH term(s)	Humans ; Animals ; Mice ; Vascular Endothelial Growth Factor A ; Tumor Microenvironment ; Neoplasms ; Medical Oncology ; Disease Models, Animal
Chemical Substances	Vascular Endothelial Growth Factor A
Language	English
Publishing date	2023-07-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2023-006921
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