Drugs of abuse cause activation of the cyclic AMP response element binding protein (CREB) in the nucleus accumbens (NAc). Expression of active CREB in rat NAc medium spiny neurons (MSNs) increased their excitability, whereas dominant-negative CREB had the opposite effect. Decreasing excitability of NAc MSNs in vivo by overexpression of potassium channels enhanced locomotor responses to cocaine, suggesting that the increased NAc MSN excitability caused by CREB helped to limit behavioral sensitivity to cocaine.

GvHD is a rare and serious complication of organ transplantation. The literature is sparse following solid organ transplantation. The aim of this report was to review the literature of GvHD in paediatric solid organ transplantation. We searched PubMed for English-language full-text manuscripts between 1990 and 2015 for eligible studies. A total of 28 publications were found pertaining to paediatric GvHD following solid organ transplantation. GvHD had a mean incidence of 11% (range 8.3-13.4%) following SBTx and 1.5% following liver transplantation. Where described, the most common sites for presentation of GvHD were the skin (87%), the native GI tract (43%), the lungs (7%), the eyes (4%), HA (4%), and the kidneys (1%). Diagnosis was confirmed with biopsy (93%) and/or chimerism (41%). Treatments used include steroids (80%), of which 75% showed partial or complete resolution. Mortality was 33.3% (range 0-100%). Novel therapies include ECP and MSC therapy. GvHD is a rare but serious disease with high mortality. Novel therapies may offer hope in the future, but currently there is limited evidence for their efficacy in the context of intestinal or liver transplantation.

Background Phosphorylation plays an essential role in regulating the voltage-gated sodium (Nav) channels and excitability. Yet, a surprisingly limited number of kinases have been identified as regulators of Nav channels. Herein, we posited that glycogen synthase kinase 3 (GSK3), a critical kinase found associated with numerous brain disorders, might directly regulate neuronal Nav channels. Methods We used patch-clamp electrophysiology to record sodium currents from Nav1.2 channels stably expressed in HEK-293 cells. mRNA and protein levels were quantified with RT-PCR, Western blot, or confocal microscopy, and in vitro phosphorylation and mass spectrometry to identify phosphorylated residues. Results We found that exposure of cells to GSK3 inhibitor XIII significantly potentiates the peak current density of Nav1.2, a phenotype reproduced by silencing GSK3 with siRNA. Contrarily, overexpression of GSK3β suppressed Nav1.2-encoded currents. Neither mRNA nor total protein expression were changed upon GSK3 inhibition. Cell surface labeling of CD4-chimeric constructs expressing intracellular domains of the Nav1.2 channel indicates that cell surface expression of CD4-Nav1.2-Ctail was up-regulated upon pharmacological inhibition of GSK3, resulting in an increase of surface puncta at the plasma membrane. Finally, using in vitro phosphorylation in combination with high resolution mass spectrometry, we further demonstrate that GSK3β phosphorylates T1966 at the C-terminal tail of Nav1.2. Conclusion These findings provide evidence for a new mechanism by which GSK3 modulate Nav channel function via its C-terminal tail. General Significance These findings provide fundamental knowledge in understanding signaling dysfunction common in several neuropsychiatric disorders.

Purpose: This study examined the effects of a 6-week Nordic hamstring exercise (NHE) program in youth male soccer players of less mature (pre–peak height velocity [PHV]) or more mature (mid/post-PHV) status. Methods: Forty-eight participants were separated into pre-PHV (11.0 [0.9] y) or mid/post-PHV (13.9 [1.1]) groups and further divided into experimental (EXP) and control groups with eccentric hamstring strength assessed (NordBord) both before and after the training program. Participants in the EXP groups completed a periodized NHE program performed once or twice weekly over a 6-week period. Results: The NHE program resulted in moderate and small increases in relative eccentric hamstring strength (in newtons per kilogram) in the pre-PHV EXP (d = 0.83 [0.03–1.68]) and mid-PHV EXP (d = 0.53 [−0.06 to 1.12]) groups, respectively. Moderate increases in the same measure were also seen in the between-groups analyses in the pre-PHV (d = 1.03 [0.23–1.84]) and mid-PHV (d = 0.87 [0.22–1.51]) groups, with a greater effect observed in the former. Conclusion: The results from this study demonstrate that a 6-week NHE program can improve eccentric hamstring strength in male youth soccer players, with less-mature players achieving mostly greater benefits. The findings from this study can aid in the training prescription of NHE in youth male soccer players.