Over-engagement of the mesolimbic dopamine system is thought to enhance motivation in adolescents. Whereas human neuroimaging has characterized event-evoked responses of the mesolimbic system in adolescents, research has yet to characterize state-dependent engagement (i.e., seconds to minutes) of this system in goal-relevant contexts. In the current longitudinal study, we characterized age-related changes in state-dependent coupling in male and female human participants ranging in age from adolescence to adulthood. Analyses focused on two key regions of the mesolimbic dopamine system, the ventral tegmental area (VTA) and nucleus accumbens (NAcc). Although there were no differences in VTA-NAcc functional coupling in a resting-state context, VTA-NAcc functional coupling was enhanced in preadolescence/early adolescence and decreased into adulthood in a motivational context, in which individuals had to translate goal-relevant cues into instrumental actions. Furthermore, we found that task-related activation in orbitofrontal cortex, middle temporal gyrus, and visual association cortex partially mediated age-related changes in state-dependent VTA-NAcc functional coupling. These results extend prior models of neurodevelopment by showing a relationship between cortical event-evoked activation and state-dependent increases in subcortical engagement of mesolimbic systems. Adolescence is characterized by increased motivated behavior, which is thought to result from an over-engagement of mesolimbic dopamine systems. Rodent models show increases in state-dependent engagement of mesolimbic systems in adolescence. However, human neuroimaging research has mainly focused on event-evoked responses (i.e., reward cues). We show that in motivational contexts, there is increased state-dependent coupling across mesolimbic systems in preadolescence/early adolescence that decreases into adulthood and is further predicted by event-evoked cortical responses. Critically, these developmental trajectories were specific to motivationally relevant contexts and were not apparent during resting state. These findings extend emerging models of human development and suggest that state-dependent increases in dopamine signaling may underlie heightened motivation.
Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP.
Primary cutaneous blastomycosis is a rare presentation of infection caused by direct inoculation of a wound. We present a 61-year-old male with an extensive history of wound dehiscence and wound care noncompliance after a bite from a brown recluse spider on the left thigh while on vacation in Cape Cod in September of 2020. After antibiotic therapy and culture, treatment involved debridement, split thickness skin grafting, strict wound vacuum-assisted closure care, and oral itraconazole. This brief demonstrates a case of blastomycosis arising from trauma in a non-endemic region for infection and serves as an example of successful management of the longstanding wound.
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