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Ornithine aminotransferase was purified from rat kidney by sonication of the isolated kidney mitochondria followed by ammonium sulfate fractionation of the solubilized protein. The ammonium sulfate precipitate was washed with distilled water and the insoluble material was extracted with 0.01 M-phosphate buffer containing 0.016 mMpyridoxal phosphate. This treatment preferentially solubilized the ornithine aminotransferase. The final preparation was purified 550-fold with a specific activity of 23.7 u/mg protein and a yield of 56%. One protein band was demonstrated by polyacrylamide gel disc electrophoresis. The molecular weight of the purified enzyme was estimated to be 165,000 by gel filtration on Sephadex G-200 column. The purified kidney enzyme was specific for L-ornithine as an amino group donor and a-oxoglutarate as an amino group acceptor. The Km for L-ornithine and aoxoglutarate was 5.9 mmol/1 and 1.0 mmol/1 respectively. The pH optimum was between 7.6 and 7.8. Kidney ornithine aminotransferase was induced by estrogen treatment. The increase in activity was due to an increase in enzyme amount as indicated by the augmentation in the specific activity of the mitochondrial preparation and in the yield of the purified enzyme. Liver ornithine aminotransferase was not affected by estrogen. The enzyme from liver could not be distinguished from the kidney enzyme by chemical or physical methods. Therefore, the variable response to estrogen seems to be organ-specific.

Background: Repetitive mild traumatic brain injury (RmTBI) is increasingly common in adolescents. Anabolic–androgenic steroid (AAS) consumption among younger professional athletes is a significant risk factor for impaired neurodevelopment. Given the increased rates and overlapping symptomology of RmTBI and AAS use, we sought to investigate the behavioural and neuropathological outcomes associated with the AAS Metandienone (Met) and RmTBI on rats. Methods: Rats received either Met or placebo and were then administered RmTBIs or sham injuries, followed by a behavioural test battery. Post-mortem MRI was conducted to examine markers of brain integrity and qRT-PCR assessed mRNA expression of markers for neurodevelopment, neuroinflammation, stress responses, and repair processes. Results: Although AAS and RmTBI did not produce cumulative deficits, AAS use was associated with detrimental outcomes including changes to depression, aggression, and memory; prefrontal cortex (PFC) atrophy and amygdala (AMYG) enlargement; damaged white matter integrity in the corpus callosum; and altered mRNA expression in the PFC and AMYG. RmTBI affected general activity and contributed to PFC atrophy. Conclusions: Findings corroborate previous results indicating that RmTBI negatively impacts neurodevelopment but also demonstrates that AAS results in significant neuropathological insult to the developing brain.

While the physical and behavioral symptomologies associated with a single mild traumatic brain injury (mTBI) are typically transient, repetitive mTBIs (RmTBI) have been associated with persisting neurological deficits. Therefore, this study examined the progressive changes in behavior and the neuropathological outcomes associated with chronic RmTBI through adolescence and adulthood in male and female Sprague Dawley rats. Rats experienced 2 mTBIs/week for 15 weeks and were periodically tested for changes in motor behavior, cognitive function, emotional disturbances, and aggression. Brain tissue was examined for neuropathological changes in ventricle size and presentation of Iba1 and GFAP. We did not see progressively worse behavioral impairments with the accumulation of injuries or time, but did find evidence for neurological and functional change (motor disturbance, reduced exploration, reduced aggression, alteration in depressive-like behavior, deficits in short-term working memory). Neuropathological assessment of RmTBI animals identified an increase in ventricle size, prolonged changes in GFAP, and sex differences in Iba1, in the corpus callosum, thalamus, and medial prefrontal cortex. Telomere length reduced exponentially as the injury load increased. Overall, chronic RmTBI did not result in accumulating behavioral impairment, and there is a need to further investigate progressive behavioral changes associated with repeated injuries in adolescence and young adulthood.

Employee deviance and time theft is an expensive and pervasive workplace problem. Research indicates that a primary reason employees engage in deviant behaviour is the perception of injustice often associated with psychological contract breach (i.e., broken promises). This study used a rodent model to mimic said experience of broken promises and then examined the subsequent neurophysiological changes that lead to the display of deviant behaviours. Specifically, we generated a psychological contract using a 3 choice serial reaction task, then broke the promise, and finally examined deviant behaviours and neurological correlates. After the broken promise, rats had elevated levels of corticosterone and testosterone, engaged in riskier behaviour, and were more aggressive. The most prominent changes in gene expression were associated with serotonin and stress, and were found in the nucleus accumbens. This study highlights the value of pre-clinical models in the investigation of the theoretical tenants of industrial and organizational psychology.

Sport-related concussion is an increasingly common injury among adolescents, with repetitive mild traumatic brain injuries (RmTBI) being a significant risk factor for long-term neurobiological and psychological consequences. It is not uncommon for younger professional athletes to consume anabolic-androgenic steroids (AAS) in an attempt to enhance their performance, subjecting their hormonally sensitive brains to potential impairment during neurodevelopment. Furthermore, RmTBI produces acute neuroendocrine dysfunction, specifically in the anterior pituitary, disrupting the hypothalamic-pituitary adrenal axis, lowering cortisol secretion that is needed to appropriately respond to injury. Some AAS users exhibit worse symptoms post-RmTBI if they quit their steroid regime. We sought to examine the pathophysiological outcomes associated with the abrupt cessation of the commonly abused AAS, Metandienone (Met) on RmTBI outcomes in rats. Prior to injury, adolescent male rats received either Met or placebo, and exercise. Rats were then administered RmTBIs or sham injuries, followed by steroid and exercise cessation (SEC) or continued treatment. A behavioral battery was conducted to measure outcomes consistent with clinical representations of post-concussion syndrome and chronic AAS exposure, followed by analysis of serum hormone levels, and qRT-PCR for mRNA expression and telomere length. RmTBI increased loss of consciousness and anxiety-like behavior, while also impairing balance and short-term working memory. SEC induced hyperactivity while Met treatment alone increased depressive-like behavior. There were cumulative effects whereby RmTBI and SEC exacerbated anxiety and short-term memory outcomes. mRNA expression in the prefrontal cortex, amygdala, hippocampus, and pituitary were modified in response to Met and SEC. Analysis of telomere length revealed the negative impact of SEC while Met and SEC produced changes in serum levels of testosterone and corticosterone. We identified robust changes in mRNA to serotonergic circuitry, neuroinflammation, and an enhanced stress response. Interestingly, Met treatment promoted glucocorticoid secretion after injury, suggesting that maintained AAS may be more beneficial than abstaining after mTBI.

Background: Most health services research uses claims or administrative data for rhythm diagnosis. Including coded data from electrocardiogram (ECG) repositories may enhance diagnostic yield, but validation is needed. Objective: We performed a diagnostic study comparing the Marquette Universal System for Electrocardiography (MUSE, GE Healthcare) coded ECG interpretation of atrial fibrillation and atrial flutter (AF/AFL) and conduction diseases with that of expert over-readers. Methods: We used the institutional MUSE repository to develop ECG cohorts for AF/AFL (n = 369) and conduction diseases (n = 800). We randomly selected 50 cardiologist-interpreted ECGs coded for each diagnosis, plus competing diagnoses and normal controls. Two reviewers unaware of MUSE interpretation independently interpreted all ECGs, with discrepancies resolved by consensus (Reference). We tested agreement between MUSE and Reference using Cohen’s kappa statistic, and assessed diagnostic accuracy with sensitivity and specificity. Results: For both AF/AFL and conduction diseases, agreement between MUSE and Reference was acceptable (See Table 1). Sensitivity of MUSE for AF/AFL was between 60.6 - 75.7% depending on diagnostic criteria. Sensitivity for conduction diseases ranged from 68.1% for non-specific interventricular conduction block to > 88% for 2nd or 3rd degree atrioventricular block. Specificity was ≥ 93% for all diagnoses. Conclusion: Routine ECG interpretation using MUSE coding is highly specific and moderately sensitive. These findings validate use of MUSE data to enhance AF/AFL and conduction diseases case identification algorithms based on claims or administrative data.

Background Administrative data have limited sensitivity for case finding of atrial fibrillation/atrial flutter (AF/AFL). Linkage with clinical repositories of interpreted ECGs may enhance diagnostic yield of AF/AFL. Methods and Results We retrieved 369 ECGs from the institutional Marquette Universal System for Electrocardiography (MUSE) repository as validation samples, with rhythm coded as AF (n=49), AFL (n=50), or other competing rhythm diagnoses (n=270). With blinded, duplicate review of ECGs as the reference comparison, we compared multiple MUSE coding definitions for identifying AF/AFL. We tested the agreement between MUSE diagnosis and reference comparison, and calculated the sensitivity and specificity. Using a data set linking clinical registries, administrative data, and the MUSE repository (n=11 662), we assessed the incremental diagnostic yield of AF/AFL by incorporating ECG data to administrative data‐based algorithms. The agreement between MUSE diagnosis and reference comparison depended on the coding definitions applied, with the Cohen κ ranging from 0.57 to 0.75. Sensitivity ranged from 60.6% to 79.1%, and specificity ranged from 93.2% to 98.0%. A coding definition with AF/AFL appearing in the first 3 ECG statements had the highest sensitivity (79.1%), with little loss of specificity (94.5%). Compared with the algorithms with only administrative data, incorporating ECG data increased the diagnostic yield of preexisting AF/AFL by 14.5% and incident AF/AFL by 7.5% to 16.1%. Conclusions Routine ECG interpretation using MUSE coding is highly specific and moderately sensitive for AF/AFL detection. Inclusion of MUSE ECG data in AF/AFL case identification algorithms can identify cases missed using administrative data‐based algorithms alone.