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Article ; Online: Double-Chambered Right Ventricle in Adulthood: A Case Series.

Malone, Richard Joseph / Henderson, Everett Randall / Wilson, Zachary Ryan / McMullan, Matthew R / Skelton, Thomas N / Campbell, William F / McMullan, Michael R

CASE (Philadelphia, Pa.)

2024 Volume 8, Issue 3Part A, Page(s) 202–209

Language	English
Publishing date	2024-03-08
Publishing country	United States
Document type	Case Reports
ISSN	2468-6441
ISSN (online)	2468-6441
DOI	10.1016/j.case.2023.12.012
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Article ; Online: Male mice placed on a ketogenic diet from postnatal day (P) 21 through adulthood have reduced growth, are hypoactive, show increased freezing in a conditioned fear paradigm, and have spatial learning deficits.

Miles, Keila N / Skelton, Matthew R

Brain research

2020 Volume 1734, Page(s) 146697

Abstract: The ketogenic diet (KD) is a non-pharmacological treatment for specific types of epilepsy. In addition, it has been shown to be effective in mitigating other neurologic disorders. The KD is also effective in reducing body mass, leading to an increase in ... ...

Abstract	The ketogenic diet (KD) is a non-pharmacological treatment for specific types of epilepsy. In addition, it has been shown to be effective in mitigating other neurologic disorders. The KD is also effective in reducing body mass, leading to an increase in use by the general population for weight loss. As the popularity of the clinical and general use of the KD has increased, it is important to develop adequate mouse models to better understand the effects of the KD in both normal and diseased states. Many times, the best outcome for disorders treatable with the KD would be achieved by commencing treatment in early life. Few studies have evaluated the cognitive effect of starting the KD in early life. To better understand these effects, male C57BL6/J mice were placed on a KD from postnatal day (P) 21 through young adulthood (~P90). KD-fed mice had increased blood ketone levels, reduced blood glucose, and reduced weight gain versus mice fed a control diet (CD). The weight loss in the KD-fed mice was not accompanied by a change in body fat percentage, suggesting that there was a loss of lean mass. Behavioral testing began on P60 while the mice were still on the diet. KD-fed mice were hypoactive with CD-fed mice. In the Morris water maze, KD-fed mice showed decreased path efficiency, suggesting a spatial learning deficits. No differences were observed in spatial memory or in novel object recognition memory. In a contextual and conditioned fear paradigm, the KD-fed mice had an increase in freezing behavior. These data suggest that early-life exposure to a KD leads to impaired body composition and long-term cognitive changes.
MeSH term(s)	Age Factors ; Animals ; Animals, Newborn ; Body Composition/physiology ; Body Weight/physiology ; Conditioning, Psychological/physiology ; Diet, Ketogenic/adverse effects ; Diet, Ketogenic/trends ; Fear/physiology ; Fear/psychology ; Immobilization/physiology ; Immobilization/psychology ; Locomotion/physiology ; Male ; Memory Disorders/physiopathology ; Memory Disorders/psychology ; Mice ; Mice, Inbred C57BL ; Spatial Learning/physiology
Language	English
Publishing date	2020-01-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2020.146697
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Article ; Online: Blueberry Supplementation in Midlife for Dementia Risk Reduction.

Krikorian, Robert / Skelton, Matthew R / Summer, Suzanne S / Shidler, Marcelle D / Sullivan, Patrick G

Nutrients

2022 Volume 14, Issue 8

Abstract: Late-life dementia typically develops over a period of many years beginning in midlife. Prevalence of metabolic disturbance also accelerates in middle age and is a prominent risk factor for dementia. Preliminary studies indicate that blueberry ... ...

Abstract	Late-life dementia typically develops over a period of many years beginning in midlife. Prevalence of metabolic disturbance also accelerates in middle age and is a prominent risk factor for dementia. Preliminary studies indicate that blueberry supplementation can improve cognitive performance and influence metabolism and brain function and therefore may have a role in early intervention to prevent neurodegeneration. In a randomized controlled trial, we investigated the effects of daily blueberry supplementation in a middle-aged sample of insulin-resistant participants with elevated risk for future dementia. We enrolled overweight men and women, aged 50 to 65 years, with subjective cognitive decline (SCD) and performed pre- and post-intervention assessments of cognition and metabolism and exploratory measures of peripheral mitochondrial function. We observed improved performances for the blueberry group on measures of lexical access,
MeSH term(s)	Blueberry Plants ; Cognition ; Cognitive Dysfunction/epidemiology ; Cognitive Dysfunction/prevention & control ; Dementia/epidemiology ; Dementia/prevention & control ; Dietary Supplements ; Female ; Humans ; Male ; Middle Aged ; Risk Reduction Behavior
Language	English
Publishing date	2022-04-13
Publishing country	Switzerland
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14081619
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Article ; Online: A Gad2 specific Slc6a8 deletion recapitulates the contextual and cued freezing deficits seen in Slc6a8

Sugimoto, Chiho / Perna, Marla K / Regan, Samantha L / Tepe, Erin A / Liou, Rosalyn / Fritz, Adam L / Williams, Michael T / Vorhees, Charles V / Skelton, Matthew R

Brain research

2023 Volume 1825, Page(s) 148690

Abstract: The creatine (Cr)-phosphocreatine shuttle is essential for ATP homeostasis. In humans, the absence of brain Cr causes significant intellectual disability, epilepsy, and language delay. Mutations of the creatine transporter (SLC6A8) are the most common ... ...

Abstract	The creatine (Cr)-phosphocreatine shuttle is essential for ATP homeostasis. In humans, the absence of brain Cr causes significant intellectual disability, epilepsy, and language delay. Mutations of the creatine transporter (SLC6A8) are the most common cause of Cr deficiency. In rodents, Slc6a8 deletion causes deficits in spatial learning, novel object recognition (NOR), as well as in contextual and cued freezing. The mechanisms that underlie these cognitive deficits are not known. Due to the heterogeneous nature of the brain, it is important to determine which systems are affected by a loss of Cr. In this study, we generated mice lacking Slc6a8 in GABAergic neurons by crossing Slc6a8
MeSH term(s)	Humans ; Animals ; Mice ; Brain ; Cognition Disorders ; Cognitive Dysfunction/genetics ; Creatine ; Phosphocreatine ; Mice, Knockout
Chemical Substances	Creatine (MU72812GK0) ; Phosphocreatine (020IUV4N33)
Language	English
Publishing date	2023-11-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2023.148690
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Article ; Online: Primary Bone Marrow Epithelioid Hemangioendothelioma Treated With Gemcitabine and Docetaxel.

Sabile, Jean M G / Stump, Michael S / Fitzpatrick, Fielding C / Skelton, Matthew R

JCO oncology practice

2020 Volume 17, Issue 2, Page(s) 118–120

MeSH term(s)	Bone Marrow ; Bone Neoplasms ; Deoxycytidine/analogs & derivatives ; Docetaxel/therapeutic use ; Hemangioendothelioma, Epithelioid/drug therapy ; Humans
Chemical Substances	Deoxycytidine (0W860991D6) ; Docetaxel (15H5577CQD) ; gemcitabine (B76N6SBZ8R)
Language	English
Publishing date	2020-09-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/OP.20.00360
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Zs.A 7198: Show issues

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Article ; Online: Intranasal carnosine attenuates transcriptomic alterations and improves mitochondrial function in the Thy1-aSyn mouse model of Parkinson's disease.

Bermúdez, Mei-Ling / Skelton, Matthew R / Genter, Mary Beth

Molecular genetics and metabolism

2018 Volume 125, Issue 3, Page(s) 305–313

Abstract: Mitochondrial dysfunction plays a central role in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). This study was designed to determine whether the dipeptide carnosine, which has been shown to protect against oxidative ... ...

Abstract	Mitochondrial dysfunction plays a central role in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). This study was designed to determine whether the dipeptide carnosine, which has been shown to protect against oxidative stress and mitochondrial dysfunction, would provide a beneficial effect on mitochondrial function in the Thy1-aSyn mouse model of PD. Thy1-aSyn mice, which overexpress wild-type human alpha-synuclein (aSyn), exhibit progressive non-motor and motor deficits as early as 2 months of age. Two-month old Thy1-aSyn mice and wild-type littermates were randomly assigned to treatment groups with intranasal (IN) and drinking water carnosine, with controls receiving 10 μl of sterile waster intranasally or carnosine-free drinking water, respectively. After two months of treatment, mice were euthanized, and the midbrain was dissected for the evaluation of the gene expression and mitochondrial function. Transcriptional deficiencies associated with the aSyn overexpression in Thy1-aSyn mice were related to ribosomal and mitochondrial function. These deficiencies were attenuated by IN carnosine administration, which increased the expression of mitochondrial genes and enhanced mitochondrial function. These results suggest a potential neuroprotective role for IN-carnosine in PD patients.
MeSH term(s)	Administration, Intranasal ; Animals ; Carnosine/administration & dosage ; Corpus Striatum/drug effects ; Corpus Striatum/pathology ; Disease Models, Animal ; Humans ; Mice ; Mice, Transgenic ; Mitochondria/drug effects ; Mitochondria/genetics ; Parkinson Disease/drug therapy ; Parkinson Disease/genetics ; Parkinson Disease/pathology ; Thy-1 Antigens/genetics ; Transcriptome/drug effects ; alpha-Synuclein/genetics
Chemical Substances	SNCA protein, human ; Thy-1 Antigens ; alpha-Synuclein ; Carnosine (8HO6PVN24W)
Language	English
Publishing date	2018-08-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1418518-0
ISSN	1096-7206 ; 1096-7192
ISSN (online)	1096-7206
ISSN	1096-7192
DOI	10.1016/j.ymgme.2018.08.002
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Article ; Online: Creatine transporter knockout mice (Slc6a8) show increases in serotonin-related proteins and are resilient to learned helplessness.

Abdulla, Zuhair I / Pennington, Jordan L / Gutierrez, Arnold / Skelton, Matthew R

Behavioural brain research

2019 Volume 377, Page(s) 112254

Abstract: Approximately 20% of adults in the U.S. will experience an affective disorder during their life. While it is well established that serotonin (5-HT) is a crucial factor in mood, impaired cellular bioenergetics are also implicated. Creatine (Cr), through ... ...

Abstract	Approximately 20% of adults in the U.S. will experience an affective disorder during their life. While it is well established that serotonin (5-HT) is a crucial factor in mood, impaired cellular bioenergetics are also implicated. Creatine (Cr), through the Cr/Phospho-Cr (PCr) shuttle, maintains high ATP concentrations in the neuron. This system may be implicated in the etiology of affective disorders, as reduced Cr, PCr, and ATP are often seen in the brains of affected patients. To address this issue, Cr transporter (Crt) deficient male mice (Slc6a8
MeSH term(s)	Animals ; Anxiety/metabolism ; Anxiety/physiopathology ; Behavior, Animal/physiology ; Corpus Striatum/metabolism ; Creatine/metabolism ; Depression/metabolism ; Depression/physiopathology ; Disease Models, Animal ; Energy Metabolism/physiology ; Female ; Helplessness, Learned ; Hippocampus/metabolism ; Male ; Membrane Transport Proteins/deficiency ; Membrane Transport Proteins/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Resilience, Psychological ; Serotonin/metabolism
Chemical Substances	Membrane Transport Proteins ; creatine transporter ; Serotonin (333DO1RDJY) ; Creatine (MU72812GK0)
Language	English
Publishing date	2019-09-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	449927-x
ISSN	1872-7549 ; 0166-4328
ISSN (online)	1872-7549
ISSN	0166-4328
DOI	10.1016/j.bbr.2019.112254
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Article: Dodecyl creatine ester improves cognitive function and identifies key protein drivers including KIF1A and PLCB1 in a mouse model of creatine transporter deficiency.

Mabondzo, Aloïse / Harati, Rania / Broca-Brisson, Léa / Guyot, Anne-Cécile / Costa, Narciso / Cacciante, Francesco / Putignano, Elena / Baroncelli, Laura / Skelton, Matthew R / Saab, Cathy / Martini, Emmanuelle / Benech, Henri / Joudinaud, Thomas / Gaillard, Jean-Charles / Armengaud, Jean / Hamoudi, Rifat

Frontiers in molecular neuroscience

2023 Volume 16, Page(s) 1118707

Abstract: Creatine transporter deficiency (CTD), a leading cause of intellectual disability is a result of the mutation in the gene encoding the creatine transporter SLC6A8, which prevents creatine uptake into the brain, causing mental retardation, expressive ... ...

Abstract	Creatine transporter deficiency (CTD), a leading cause of intellectual disability is a result of the mutation in the gene encoding the creatine transporter SLC6A8, which prevents creatine uptake into the brain, causing mental retardation, expressive speech and language delay, autistic-like behavior and epilepsy. Preclinical
Language	English
Publishing date	2023-03-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452967-9
ISSN	1662-5099
ISSN	1662-5099
DOI	10.3389/fnmol.2023.1118707
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Article ; Online: UK reporting radiographers' perceptions of AI in radiographic image interpretation - Current perspectives and future developments.

Rainey, C / O'Regan, T / Matthew, J / Skelton, E / Woznitza, N / Chu, K-Y / Goodman, S / McConnell, J / Hughes, C / Bond, R / Malamateniou, C / McFadden, S

Radiography (London, England : 1995)

2022 Volume 28, Issue 4, Page(s) 881–888

Abstract: Introduction: Radiographer reporting is accepted practice in the UK. With a national shortage of radiographers and radiologists, artificial intelligence (AI) support in reporting may help minimise the backlog of unreported images. Modern AI is not well ... ...

Abstract	Introduction: Radiographer reporting is accepted practice in the UK. With a national shortage of radiographers and radiologists, artificial intelligence (AI) support in reporting may help minimise the backlog of unreported images. Modern AI is not well understood by human end-users. This may have ethical implications and impact human trust in these systems, due to over- and under-reliance. This study investigates the perceptions of reporting radiographers about AI, gathers information to explain how they may interact with AI in future and identifies features perceived as necessary for appropriate trust in these systems. Methods: A Qualtrics® survey was designed and piloted by a team of UK AI expert radiographers. This paper reports the third part of the survey, open to reporting radiographers only. Results: 86 responses were received. Respondents were confident in how an AI reached its decision (n = 53, 62%). Less than a third of respondents would be confident communicating the AI decision to stakeholders. Affirmation from AI would improve confidence (n = 49, 57%) and disagreement would make respondents seek a second opinion (n = 60, 70%). There is a moderate trust level in AI for image interpretation. System performance data and AI visual explanations would increase trust. Conclusions: Responses indicate that AI will have a strong impact on reporting radiographers' decision making in the future. Respondents are confident in how an AI makes decisions but less confident explaining this to others. Trust levels could be improved with explainable AI solutions. Implications for practice: This survey clarifies UK reporting radiographers' perceptions of AI, used for image interpretation, highlighting key issues with AI integration.
MeSH term(s)	Artificial Intelligence ; Clinical Competence ; Humans ; Radiologists ; Radiology/education ; United Kingdom
Language	English
Publishing date	2022-07-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1289102-2
ISSN	1532-2831 ; 1078-8174
ISSN (online)	1532-2831
ISSN	1078-8174
DOI	10.1016/j.radi.2022.06.006
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Zs.A 4438: Show issues

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Article ; Online: Deciphering neuronal deficit and protein profile changes in human brain organoids from patients with creatine transporter deficiency.

Broca-Brisson, Léa / Harati, Rania / Disdier, Clémence / Mozner, Orsolya / Gaston-Breton, Romane / Maïza, Auriane / Costa, Narciso / Guyot, Anne-Cécile / Sarkadi, Balazs / Apati, Agota / Skelton, Matthew R / Madrange, Lucie / Yates, Frank / Armengaud, Jean / Hamoudi, Rifat / Mabondzo, Aloïse

eLife

2023 Volume 12

Abstract: Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake in the brain results in intellectual disability, behavioral disorders, language delay, and seizures. In this work, we ... ...

Abstract	Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake in the brain results in intellectual disability, behavioral disorders, language delay, and seizures. In this work, we generated human brain organoids from induced pluripotent stem cells of healthy subjects and CTD patients. Brain organoids from CTD donors had reduced creatine uptake compared with those from healthy donors. The expression of neural progenitor cell markers SOX2 and PAX6 was reduced in CTD-derived organoids, while GSK3β, a key regulator of neurogenesis, was up-regulated. Shotgun proteomics combined with integrative bioinformatic and statistical analysis identified changes in the abundance of proteins associated with intellectual disability, epilepsy, and autism. Re-establishment of the expression of a functional SLC6A8 in CTD-derived organoids restored creatine uptake and normalized the expression of SOX2, GSK3β, and other key proteins associated with clinical features of CTD patients. Our brain organoid model opens new avenues for further characterizing the CTD pathophysiology and supports the concept that reinstating creatine levels in patients with CTD could result in therapeutic efficacy.
MeSH term(s)	Humans ; Intellectual Disability/genetics ; Creatine/genetics ; Creatine/metabolism ; Glycogen Synthase Kinase 3 beta/metabolism ; Mental Retardation, X-Linked/genetics ; Mental Retardation, X-Linked/metabolism ; Brain/metabolism ; Organoids/metabolism
Chemical Substances	Creatine (MU72812GK0) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1)
Language	English
Publishing date	2023-10-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.88459
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