Plos One
-
Despite the life-long implications of social and communication dysfunction after pediatric traumatic brain injury, there is a poor understanding of these deficits in terms of their developmental trajectory and underlying mechanisms. In a well-characterized murine model of pediatric brain injury, we recently demonstrated that pronounced deficits in social interactions emerge across maturation to adulthood after injury at postnatal day (p) 21, approximating a toddler-aged child. Extending these findings, we here hypothesized that these social deficits are dependent upon brain maturation at the time of injury, and coincide with abnormal sociosexual behaviors and communication. ⋯ Contrary to the hypothesis that changes in white matter volume may underlie social dysfunction, injury at both p21 and p35 resulted in a similar degree of atrophy of the corpus callosum by adulthood. However, loss of hippocampal tissue was greater after p21 compared to p35 injury, suggesting that a longer period of lesion progression or differences in the kinetics of secondary pathogenesis after p21 injury may contribute to observed behavioral differences. Together, these findings indicate vulnerability of the developing brain to social dysfunction, and suggest that a younger age-at-insult results in poorer social and sociosexual outcomes.
-
The transient receptor potential family V1 channel (TRPV1) is activated by multiple stimuli, including capsaicin, acid, endovanilloids, and heat (>42C). Post-translational modifications to TRPV1 result in dynamic changes to the sensitivity of receptor activation. We have previously demonstrated that β-arrestin2 actively participates in a scaffolding mechanism to inhibit TRPV1 phosphorylation, thereby reducing TRPV1 sensitivity. ⋯ Conversely, herkinorin treatment has no effect on TRPV1 sensitivity. Additional behavioral studies indicate that GPCR-driven β-arrestin2 sequestration plays an important peripheral role in the development of thermal sensitivity. Taken together, the reported data identify a novel cross-talk mechanism between GPCRs and TRPV1 that may contribute to multiple clinical conditions.
-
Liver transplantation can prolong survival in patients with end-stage liver disease. We have proposed that the Sequential Organ Failure Assessment (SOFA) score calculated on post-transplant day 7 has a great discriminative power for predicting 1-year mortality after liver transplantation. The Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) score, a modified SOFA score, is a newly developed scoring system exclusively for patients with end-stage liver disease. This study was designed to compare the CLIF-SOFA score with other main scoring systems in outcome prediction for liver transplant patients. ⋯ The CLIF-SOFA score can increase the prediction accuracy of prognosis after transplantation. Moreover, the CLIF-SOFA score on post-transplantation day 7 had the best discriminative power for predicting 1-year mortality after liver transplantation.
-
Isometric contractions can influence the way that we perceive pain, but conclusions on the dose-response effect of force amplitude on pain perception are limited because previous studies have not held the duration of force contractions constant while varying force amplitude. To address this issue we designed an experiment that allowed us to accurately guide the amplitude of an isometric pinch grip force contraction on a trial-by-trial basis, while a thermal pain eliciting stimulus was simultaneously delivered for the same duration to the non-contracting hand. Our results show that an increase in the amplitude of force produced by one hand corresponded with a decrease in pain perception in the opposite hand. Our observations provide novel evidence that the centralized inhibitory response that underlies analgesia is sensitive to and enhanced by stronger isometric contractions.
-
To evaluate the utilization trends of advanced radiology, i.e. computed tomography (CT) and magnetic resonance imaging (MRI), examination in an emergency department (ED) of an academic medical center from 2001 to 2010. ⋯ We report a three-fold and nine-fold increase in the use of CT and MRI, respectively, during the study period. Additional studies will be required to understand the causes of this change and to determine the effect of advanced radiology utilization on the patient outcome.