RESUMEN
Tumor necrosis factor alpha (TNF-alpha) has been shown to have a protective role in the eyes and brains of herpes simplex virus type 1 (HSV-1)-infected mice. To determine whether overexpression of TNF-alpha affected the course of virus infection following uniocular anterior chamber inoculation, a recombinant of HSV-1 that produces TNF-alpha constitutively (KOSTNF) was constructed. BALB/c mice were injected with the TNF-alpha recombinant, a recombinant containing the pCI plasmid, a recombinant rescue virus, or the parental virus. Flow cytometry and immunohistochemistry were used to identify virus-infected cells and to determine the numbers and types of infiltrating inflammatory cells in the uninjected eyes. Virus titers were determined by plaque assay. There were no differences among the groups in virus titers or the route and timing of virus spread in the injected eyes or in the suprachiasmatic nuclei. However, in the uninjected eyes of KOSTNF-infected mice, TNF-alpha expression was increased and there were more viral antigen-positive cells and immune inflammatory cells. There was earlier microscopic evidence of retinal infection and destruction in these mice, and the titers of virus in the uninjected eyes were significantly increased in KOSTNF-infected mice on day 7 postinfection compared with those of KOSpCI-, KOS6beta rescue-, or KOS6beta-infected mice. The results suggest that instead of moderating infection and reducing virus spread, overexpression of TNF-alpha has deleterious effects due to increased inflammation and virus infection that result in earlier destruction of the retina of the uninoculated eye.
Asunto(s)
Oftalmopatías/inmunología , Herpes Simple/inmunología , Herpesvirus Humano 1/crecimiento & desarrollo , Herpesvirus Humano 1/inmunología , Retina/patología , Retina/virología , Factor de Necrosis Tumoral alfa/biosíntesis , Animales , Chlorocebus aethiops , Oftalmopatías/patología , Oftalmopatías/virología , Citometría de Flujo , Herpes Simple/patología , Herpes Simple/virología , Herpesvirus Humano 1/genética , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Retinitis/inmunología , Retinitis/patología , Retinitis/virología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/genética , Células Vero , Ensayo de Placa ViralRESUMEN
Problemgambling is thought to be comorbid with attention-deficit hyperactivity disorder (ADHD). We tested whether gamblers and ADHD patients exhibit similar reward-related brain activity in response to feedback in a gambling task. A series of brain electrical responses can be observed in the electroencephalogram (EEG) and the stimulus-locked event-related potentials (ERP), when participants in a gambling task are given feedback regardless of winning or losing the previous bet. Here, we used a simplified computerized version of the Iowa Gambling Task (IGT) to assess differences in reinforcement-driven choice adaptation between unmedicated ADHD patients with or without problem gambling traits and contrasted with a sex- and age-matched control group. EEG was recorded from the participants while they were engaged in the task which contained two choice options with different net payouts and win/loss probabilities. Learning trend which shows the ability to acquire and use knowledge of the reward outcomes to obtain a positive financial outcome was not observed in ADHD gamblers versus nongamblers. Induced theta-band (4-8Hz) power over frontal cortex was significantly higher in gamblers versus nongamblers in all different high-risk/low-risk win/lose conditions. Whereas induced low alpha (9-11Hz) power at frontal electrodes could only differentiate high-risk lose between gamblers and nongamblers but not the other three conditions between the two groups. The results indicate that ADHD nongamblers do not share with problem gamblers underlying deficits in reward learning. These pilot data highlight the need for studies of ADHD in gambling to elucidate how motivational states are represented during feedback processing.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Lóbulo Frontal/fisiopatología , Juego de Azar/fisiopatología , Recompensa , Ritmo Teta , Adulto , Ritmo alfa , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Corteza Cerebral/fisiopatología , Conducta de Elección , Electroencefalografía , Femenino , Juego de Azar/complicaciones , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Remote-telementored ultrasound involves novice examiners being remotely guided by experts using informatic-technologies. However, requiring a novice to perform ultrasound is a cognitively demanding task exacerbated by unfamiliarity with ultrasound-machine controls. We incorporated a randomized evaluation of using remote control of the ultrasound functionality (knobology) within a study in which the images generated by distant naive examiners were viewed on an ultrasound graphic user interface (GUI) display viewed on laptop computers by mentors in different cities. METHODS: Fire-fighters in Edmonton (101) were remotely mentored from Calgary (n = 65), Nanaimo (n = 19), and Memphis (n = 17) to examine an ultrasound phantom randomized to contain free fluid or not. Remote mentors (2 surgeons, 1 internist, and 1 ED physician) were randomly assigned to use GUI knobology control during mentoring (GUIK+/GUIK-). RESULTS: Remote-telementored ultrasound was feasible in all cases. Overall accuracy for fluid detection was 97% (confidence interval = 91 to 99%) with 3 false negatives (FNs). Positive/negative likelihood ratios were infinity/0.0625. One FN occurred with the GUIK+ and 2 without (GUIK-). There were no statistical test performance differences in either group (GUIK+ and GUIK-). CONCLUSIONS: Ultrasound-naive 1st responders can be remotely mentored with high accuracy, although providing basic remote control of the knobology did not affect outcomes.
Asunto(s)
Líquidos Corporales/diagnóstico por imagen , Servicios Médicos de Urgencia/métodos , Bomberos/educación , Telemedicina/métodos , Ultrasonografía/instrumentación , Heridas y Lesiones/diagnóstico , Intervalos de Confianza , Método Doble Ciego , Humanos , Maniquíes , Estudios Prospectivos , Consulta Remota/métodos , Análisis y Desempeño de Tareas , Heridas y Lesiones/terapiaRESUMEN
Problem gambling is thought to be highly comorbid with attention-deficit hyperactivity disorder (ADHD). We propose that the neurobiological pathologies underlying problem gambling overlap with those in ADHD. In this study, we used a simplified computerized version of the Iowa Gambling Task (IGT) to assess differences in reinforcement-driven choice adaptation among participants with pathological gambling and/or ADHD. The task contained two choice options with different net payouts over the session; a good bet that resulted in a win of +50 points on 60% of trials (and -50 points on 40%), and a bad bet that resulted in +100 points on 40% of the trials (and -100 points on 60%). We quantified participants' preference for the good bet over the session and their sensitivity to reinforcement. Both the control subjects and medicated ADHD nongamblers significantly increased the proportion of good bets over the 400-trial session. Subjects with problem gambling performed worse than controls and ADHD nongamblers, but better than our limited sample of unmedicated ADHD gamblers. Control subjects, medicated ADHD nongamblers, and unmedicated ADHD nongamblers tended to tolerate losses following good bets, whereas unmedicated ADHD gamblers tended to tolerate losses following bad bets. These data reveal that ADHD, particularly when treated with medication, is not associated with poor choices on the IGT, but may exacerbate pathological choices in problem gamblers. It seems that stabilization of dopamine signaling that occurs when ADHD is treated is itself also a treatment for certain forms of problem gambling.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/psicología , Juego de Azar/complicaciones , Juego de Azar/psicología , Aprendizaje , Recompensa , Adaptación Psicológica , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Conducta de Elección , Femenino , Humanos , Masculino , Probabilidad , Pruebas Psicológicas , Adulto JovenRESUMEN
Problem gambling (PG) is increasingly conceptualized as an addiction akin to substance abuse, rather than an impulse control disorder, however the mechanism of addiction remains unclear. Neuroimaging investigations have supported a "reward deficiency" hypothesis for PG by suggesting a blunted response to gambling, particularly in the striatum. Here we describe electrophysiological evidence of a hypersensitive response to gambling feedback in problem gamblers. Previous research in healthy participants has shown that feedback during gambling tasks triggers stereotypical neural responses including the Feedback-Related Mediofrontal Negativity (FRN), the feedback-related P300, and an increase in induced theta-band (4-8 Hz) power. We tested the theory that abnormal feedback processing characterizes brain activity in problem gamblers while gambling. EEG was recorded from non-gamblers and self-identified gamblers as they engaged in a computerized version of the Iowa Gambling Task. Feedback about valence (win vs. loss) triggered a FRN in both groups, but in gamblers this was preceded by an early-latency hypersensitive fronto-central difference to feedback. This early FRN was correlated with gambling severity and was localized to medial frontal cortex using distributed source imaging (CLARA). Gamblers also differed in responses to risk, showing a blunted P300 component and less EEG power in the theta band. Here we suggest that a more nuanced interpretation of reward deficiency is called for with respect to PG. For certain aspects of brain function, gamblers may exhibit hypersensitivity to reward feedback more akin to drug sensitization than reward deficiency. Our results also suggest that the neurologically normal brain employs dissociable systems in the processing of feedback from tasks involving risky decision making.