ABSTRACT
Attention-deficit/hyperactivity disorder, the most prevalent developmental disorder in childhood, is a biologically heterogenous condition characterized by impaired attention and impulse control as well as motoric hyperactivity and anomalous motor skill development. Neuropsychological testing often demonstrates impairments in motivation and reward-related decision making in attention-deficit/hyperactivity disorder, believed to indicate dysfunction of the dopamine reward pathway. Development of reliable, non-invasive, easily obtained and quantitative biomarkers correlating with the presence and severity of clinical symptoms and impaired domains of function could aid in identifying meaningful attention-deficit/hyperactivity disorder subgroups and targeting appropriate treatments. To this end, 55 (37 male) 8-12-year-old children with attention-deficit/hyperactivity disorder and 50 (32 male) age-matched, typically-developing controls were enrolled in a transcranial magnetic stimulation protocol-used previously to quantify cortical disinhibition in both attention-deficit/hyperactivity disorder and Parkinson's Disease-with a child-friendly reward motivation task. The primary outcomes were reward task-induced changes in short interval cortical inhibition and up-modulation of motor evoked potential amplitudes, evaluated using mixed model, repeated measure regression. Our results show that both reward cues and reward receipt reduce short-interval cortical inhibition, and that baseline differences by diagnosis (less inhibition in attention-deficit/hyperactivity disorder) were no longer present when reward was cued or received. Similarly, both reward cues and reward receipt up-modulated motor evoked potential amplitudes, but, differentiating the two groups, this Task-Related-Up-Modulation was decreased in children with attention-deficit/hyperactivity disorder. Furthermore, more severe hyperactive/impulsive symptoms correlated significantly with less up-modulation with success in obtaining reward. These results suggest that in children with attention-deficit/hyperactivity disorder, short interval cortical inhibition may reflect baseline deficiencies as well as processes that normalize performance under rewarded conditions. Task-Related-Up-Modulation may reflect general hypo-responsiveness in attention-deficit/hyperactivity disorder to both reward cue and, especially in more hyperactive/impulsive children, to successful reward receipt. These findings support transcranial magnetic stimulation evoked cortical inhibition and task-induced excitability as biomarkers of clinically relevant domains of dysfunction in childhood attention-deficit/hyperactivity disorder.
ABSTRACT
Candida dubliniensis is an uncommon species of Candida which has been implicated in fungal pneumonia only very rarely. We present the case of a 75-year-old man with laryngeal cancer undergoing chemotherapy on broad-spectrum antibiotics and tuberculosis therapy with blood and endotracheal cultures positive for C. dubliniensis. Subsequent autopsy was performed with postmortem lung cultures positive for C. dubliniensis and lung histopathology demonstrating an invasive fungal infection. Molecular analysis of the lung tissue confirmed the identity of the fungi as C. dubliniensis. Since its discovery as a pathogen in the oral cavities of HIV-positive patients, C. dubliniensis has been identified in a wide spectrum of clinical scenarios and anatomic locations but manifests only rarely as pneumonia. This report represents a novel case of C. dubliniensis pneumonia confirmed by culture, histopathology, and molecular identification.