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Background: Choline supplementation (+Ch) improves cognitive function in impaired animals and humans. Chemotherapy-related cognitive deficits (CRCDs) occur in cancer patients, and these deficits persist following treatment, adversely impacting quality of life. To date, there are no approved treatments for this condition., Aim: Because +Ch improves impaired memory, it was of interest to determine whether +Ch can attenuate spatial memory deficits induced by the chemotherapeutic agents doxorubicin (DOX) and cyclophosphamide (CYP)., Methods: Female BALB/C mice, 64 days of age, were trained in the Morris water maze and baseline performance determined on day 15. Following baseline assessment, mice were placed on +Ch diet (2.0% Ch) or remained on standard diet (0.12% Ch). Mice received intravenous injections of DOX (2.5 mg/kg) and CYP (25 mg/kg), or equivalent volumes of saline (0.9% NaCl), on days 16, 23, 30, and 37, and spatial memory was assessed weekly from day 22 to 71., Results: DOX and CYP produced a prolonged impairment in spatial memory as indicated by an increased latency to the correct zone ( p  < 0.05), and a decrease in time in the correct zone ( p  < 0.05), % of total swim distance in the correct zone ( p  < 0.05) and % entries to the correct zone ( p  < 0.05). These effects were attenuated by +Ch., Conclusion: Although it remains to be determined whether this effect extends to other cognitive domains and whether +Ch is prophylactic or therapeutic, these findings suggest that +Ch may be an effective intervention for CRCDs.

Over the past decades, two persisting priorities in science, technology, engineering, and mathematics (STEM) training have been: 1) increasing the knowledge of and access to careers beyond academic scientist; and 2) increasing the diversity of the STEM workforce. Previous studies show that a uniquely constructed career coaching group provides strong support and progress for both priorities. This report extends this design into a more sustainable model that is positioned within the professional context of rising young scientists. This new model is based in the American Society for Pharmacology and Experimental Therapeutics (ASPET)-the ASPET Mentoring Network. Groups of PhD students and postdocs were assigned to an ASPET professional (academic or other career) member (the coach) with an initial meeting held the day before the society's annual meeting. The coaching groups interacted during the meeting and then virtually for a year. Extensive survey and interview evaluation data gathered from the first three cohorts (12 coaching groups) in 2016- 2018 provided strong evidence of the perceived and real benefits of the network. This new version of career coaching groups is both feasible and linked to career success due to its close association with a scientific society, peers, and coaches who share scientific identities and aspirations.

Introduction: Friedreich's Ataxia (FA) is a devastating, progressive, neurodegenerative disease. Objective measures that detect changes in neurological function in FA patients are needed to facilitate therapeutic clinical trials. The purpose of this pilot study was to analyze longitudinal changes in gait and balance in subjects with FA using the GAITRite Walkway System ® and Biodex Balance System™, respectively, and to test the ability of these measures to detect change over time compared to the Friedreich's Ataxia Rating Scale (FARS)., Methods: This was a 24-month longitudinal study comparing ambulatory FA subjects with age- and gender-matched, healthy controls. Eight FA subjects and 8 controls were tested at regular intervals using the GAITRite and Biodex Balance systems and the FARS., Results: In the FA group, comfortable and fast gait velocity declined 8.0% and 13.9% after 12 months and 24.1% and 30.3% after 24 months, respectively. Postural stability indices increased in FA subjects an average of 41% from baseline to 24 months, representing a decline in balance. Subjects with FA also demonstrated a 17.7% increase in FARS neurological exam scores over 24 months. There were no changes in gait or balance variables in controls. In the FA group, multiple gait and balance measures correlated significantly with FARS neurological exam scores., Conclusions: The GAITRite and Biodex Balance systems provided objective and clinically relevant measures of functional decline in subjects with FA that correlated significantly with performance measures in the FARS. Gait velocity may be an important objective measure to identify disease progression in adults with FA., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Self-reports of chemotherapy-related cognitive deficits (CRCDs) are more prevalent among women than men, suggesting that women may be more vulnerable to the cognitive-impairing effects of chemotherapy. However, there have been no direct comparisons of females and males using objective measures of cognitive function either during or following exposure to the same chemotherapeutic regimen. The present study used an animal model, and a prospective longitudinal design, to assess sex differences in the manifestation and persistence of spatial memory deficits resulting from exposure to doxorubicin (DOX) and cyclophosphamide (CYP), commonly used anticancer drugs. The spatial memory of female and male BALB/C mice was assessed using the Morris water maze prior to, during and following 4 weekly intravenous injections of DOX (2.5mg/kg) and CYP (25mg/kg) or vehicle. Females receiving DOX+CYP experienced significant deficits in spatial memory during and following injections when compared to baseline or females receiving vehicle. These deficits persisted for at least 34 days following the final injection. In contrast, males receiving DOX+CYP injections did not exhibit alterations in spatial memory relative to baseline or males receiving vehicle. These findings indicate that females may be more vulnerable than males to the cognitive-impairing effects of DOX+CYP and demonstrate that deficits in females persist for at least several weeks following drug exposure. Preclinical studies of CRCDs should parallel clinical work by including females and examine sex specific factors as potential mechanisms., (Copyright © 2016. Published by Elsevier B.V.)

Alterations in gait and balance are manifest in numerous neurological disorders such as the ataxias and Parkinson's disease, and may occur as a consequence of stroke, traumatic brain injury and chemical insults to the brain. Although the underlying etiology of these disorders differs, disturbances in gait and balance appear to reflect deficits in cholinergic pathways within the brain. During the past 40 years, both clinical case studies and preclinical data have provided evidence that nicotinic cholinergic activation is beneficial for alleviating gait and balance deficits in many disorders. Further, studies indicate that activation of neuronal nicotinic receptors leads to neuroprotective and neurotrophic actions. And yet, despite these findings, there hsas been no concerted effort to develop neuronal nicotinic agonists for the treatment of abnormal gait and balance. The goal of this review is to shed light on the therapeutic benefit of the cholinergic nicotinic system for the treatment of ataxia, and discuss the challenges and limitations associated with developing drugs to treat disorders involving deficits in gait and balance.

The frequency of neuropsychiatric disorders is greater than that of cancer, cardiovascular disease, and diabetes combined, and is growing at a faster rate than any other ailments in the United States or Europe. Despite a considerable need for the development of treatments for central nervous system disorders, pharmaceutical companies continue to reduce investment in this area of research. Of particular concern is the treatment of diseases and disorders that affect cognitive function, which are often given a lower priority for research investment than life threatening conditions or those with overt physical symptoms. Several reasons exist for this reduced investment, including a poor understanding of the mechanisms underlying impaired cognitive function, costly and long periods of development for these medications, disproportionately lower success rates, and a stigma associated with the medical treatment of mental illness. This paper will discuss these issues, review some of the successes resulting from research investment and discuss opportunities that should encourage increased research investment in cognitive disorders and their treatment.

Friedreich's ataxia (FA) is an autosomal recessive, neurodegenerative disease characterized by progressive muscle weakness and sensory loss, balance deficits, and gait ataxia. Gait and balance impairments become worse as the disease progresses, but limited research has quantitatively assessed these deficits in adults with FA. The purpose of this study was to analyze gait and balance in this population and investigate the relationship between these variables. Eight subjects with genetically confirmed FA (29.4±9.0 years) and eight healthy, matched control subjects (29.6±9.1 years) participated in this study. Spatiotemporal gait parameters were examined using the GAITRite Walkway System while balance was examined utilizing the Biodex Balance System SD and the Berg Balance Scale (BBS). The FA group exhibited approximately 50% slower gait velocity and 32% shorter step and stride lengths compared to the control group for both comfortable and fast walking (p<0.001). Further, stride length variability in the FA group was 3.4 and 2.7 times that of controls for comfortable and fast walking, respectively (p<0.01). Subjects with FA took 72% longer to complete the limits of stability (LOS) test and attained an overall directional control score that was 50% that of controls (p<0.05). Lastly, age at FA symptom onset correlated with stride length variability during fast walking (p<0.05), and BBS and LOS test scores correlated with stride length variability during both comfortable and fast walking (p<0.05). Results demonstrate that adults with FA have significantly impaired gait and balance and several measures of these impairments are correlated., (Copyright © 2015 Elsevier B.V. All rights reserved.)