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Locomotor analysis identifies early compensatory changes during disease progression and subgroup classification in a mouse model of amyotrophic lateral sclerosis

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Neural Regeneration Research 2017年第10期12卷 1664-1679页

作者： Melissa M.Haulcomb Rena M.Meadows Whitney M.miller kathryn p.mc mil.an Me Kenzie J.Hilsmeyer Xuefu Wang Wesley T.Beaulieu Stephanie L.Dickinson Todd J.Brown Virginia M.Sanders kathryn J.Jones Department of Anatomy and Cell Biology Indiana University School of MedicineIndianapolisINUSA Research and Development Service Roudebush Veterans Administration Medical CenterIndianapolisINUSA program in Medical Neurosciences Indiana University School of MedicineIndianapolisINUSA Department of Statistics Indiana UniversityBloomingtonINUSA Department of Epidemiology and Biostatistics Indiana UniversityBloomingtonINUSA Department of Cancer Biology and Genetics The Ohio State University Wexner Medical CenterColumbusOHUSA

Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in *** identification and enhanced understanding of symptomatic patterns could aid in diagnosis and provide an avenue for monitoring disease *** of the m SOD1 G93 A mouse model provides control of the confounding environmental factors and genetic heterogeneity seen in amyotrophic lateral sclerosis patients,while investigating underlying disease-induced *** the present study,we performed a longitudinal behavioral assessment paradigm and identified an early hindlimb symptom,resembling the common gait abnormality foot drop,along with an accompanying forelimb compensatory mechanism in the m SOD1 G93 A *** these initial changes,m SOD1 mice displayed a temporary hindlimb compensatory mechanism resembling an exaggerated steppage *** the disease progressed,these compensatory mechanisms were not sufficient to sustain fundamental locomotor parameters and more severe deficits *** next applied these initial findings to investigate the inherent variability in B6 SJL m SOD1 G93 A *** identified four behavioral variables that,when combined in a cluster analysis,identified two subpopulations with different disease progression rates：a fast progression group and a slow progression *** behavioral assessment paradigm,with its analytical approaches,provides a method for monitoring disease progression and detecting m SOD1 subgroups with different disease *** affords researchers an opportunity to search for genetic modifiers or other factors that likely enhance or slow disease *** factors are possible therapeutic targets with the potential to slow disease progression and provide insight into the underlying pathology and disease mechanisms.

关键词： nerve regeneration amyotrophic lateral sclerosis motoneuron degenerative disease locomotor disease progression disease variability SOD1 mouse neural regeneration

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Adiposity and spinal cord injury

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World Journal of Orthopedics 2015年第8期6卷 567-576页

作者： Ashraf S Gorgey kathryn M Wells Timothy L Austin Spinal Cord Injury and Disorder Service Hunter Holmes Mc Guire VA Medical Center Department of physical Medicine and Rehabilitation Virginia Commonwealth University College of Health and Human performance Virginia Commonwealth University

The drastic changes in body composition following spinal cord injury(SCI) have been shown to play a significant role in cardiovascular and metabolic health. The pattern of storage and distribution of different types of adipose tissue may impact metabolic health variables similar to carbohydrate, lipid and bone metabolism. The use of magnetic resonance imaging provides insights on the interplay among different regional adipose tissue compartments and their role in developing chronic diseases. Regional adipose tissue can be either distributed centrally or peripherally into subcutaneous and ectopic sites. The primary ectopic adipose tissue sites are visceral, intramuscular and bone marrow. Dysfunction in the central nervous system following SCI impacts the pattern of distribution of adiposity especially between tetraplegia and paraplegia. The current editorial is focused primarily on introducing different types of adipose tissue and establishing scientific basis to develop appropriate dietary, rehabilitation or pharmaceutical interventions to manage the negative consequences of increasing adiposity after SCI. We have also summarized the clinical implications and future recommendations relevant to study adiposity after SCI.

关键词： Adiposity Magnetic resonance imaging Dual-energy X-ray absorptiometry Ectopic adiposity Visceral and subcutaneous adiposity Intramuscular fat Spinal cord injury

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Antecedents and sex/gender differences in youth suicidal behavior

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World Journal of psychiatry 2014年第4期4卷 120-132页

作者： Anne E Rhodes Michael H Boyle Jeffrey A Bridge Mark Sinyor paul S Links Lil Tonmyr Robin Skinner Jennifer M Bethell Corine Carlisle Sarah Goodday Travis Salway Hottes Amanda Newton kathryn Bennett purnima Sundar Amy H Cheung peter Szatmari Institute for Clinical Evaluative Sciences Toronto M4N 3M5 Ontario Canada Department of psychiatry University of Toronto Toronto M5T 1R8 Ontario Canada Suicide Studies Unit St. Michael’s Hospital Toronto M5B 1W8 Ontario Canada Dalla Lana School of public Health University of Toronto Toronto M5T 3M7 Ontario Canada Department of psychiatry and Behavioural Neurosciences Mc Master University Hamilton L8N 3K7 Ontario Canada The Offord Centre for Child Studies Hamilton L8S 4K1 Ontario Canada The Research Institute at Nationwide Children’s Hospital Columbus OH 43205 United States The Ohio State University College of Medicine Columbus OH 43210 United States Sunnybrook Health Sciences Centre Toronto M4N 3M5 Ontario Canada Department of psychiatry University of Western Ontario London N6A 5W9 Ontario Canada The Injury and Child Maltreatment Section Public Health Agency of Canada Ottawa K1A 0K9 Ontario Canada The Centre for Addiction and Mental Health Toronto M6J 1H4 Ontario Canada Department of pediatrics University of Alberta Edmonton Alberta T6G 1C9 Canada The Department of Clinical Epidemiology and Biostatistics Mc Master University Hamilton L8S 4K1 Ontario Canada The Ontario Centre of Excellence for Child and Youth Mental Health Ottawa K1G 0Z1 Ontario Canada The Hospital for Sick Children Toronto M5G 1X8 Ontario Canada

Suicide is the second leading cause of death in youth globally; however, there is uncertainty about how best to intervene. Suicide rates are typically higher in males than females, while the converse is true for suicide attempts. We review this "gender paradox" in youth, and in particular, the age-dependency of these sex/gender differences and the developmental mechanisms that may explain them. Epidemiologic, genetic,neurodevelopmental and psychopathological research have identified suicidal behaviour risks arising from genetic vulnerabilities and sex/gender differences in early adverse environments, neurodevelopment, mental disorder and their complex interconnections. Further, evolving sex-/gender-defined social expectations and norms have been thought to influence suicide risk. In particular, how youth perceive and cope with threats and losses(including conforming to others' or one's own expectations of sex/gender identity) and adapt to pain(through substance use and helpseeking behaviours). Taken together, considering brain plasticity over the lifespan, these proposed antecedents to youth suicide highlight the importance of interventions that alter early environment(s)(e.g., childhood maltreatment) and/or one's ability to adapt to them. Further, such interventions may have more enduring protective effects, for the individual and for future generations, if implemented in youth.

关键词： Suicide Attempted suicide Sex Gender Child Adolescent Review

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