Little is known about genetic regulation of the development of white matter. This knowledge is critical in understanding the pathophysiology of neurodevelopmental syndromes associated with altered cognition as well as in elucidating the genetics of normal human cognition. The hemideletion of Ϸ25 genes on chromosome 7q11.23 that causes Williams syndrome (WS) includes genes that regulate cytoskeletal dynamics in neurons, especially LIMK1 and CYLN2, and therefore offers the opportunity to investigate the role of these genes in the formation of white matter tracts. We used diffusion tensor imaging to demonstrate alteration in white matter fiber directionality, deviation in posterior fiber tract course, and reduced lateralization of fiber coherence in WS. These abnormalities are consistent with an alteration of the late stages of neuronal migration, define alterations of white matter structures underlying dissociable behavioral phenotypes in WS, and provide human in vivo information about genetic control of white matter tract formation.development ͉ LIMK1 ͉ neuronal growth cone ͉ neuronal migration ͉ tractography

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Background:Intraoperative administration of opiates for postoperative analgesia requires a dosing strategy without clear indicators of pain in an anesthetized patient. Preoperative patient characteristics such as body mass index (BMI), gender, age, and other patient characteristics may provide important information regarding opiate requirements.This study intends to determine if there is an association between gender or BMI and the immediate postoperative pain scores after undergoing an open reduction and internal fixation (ORIF) of an ankle fracture with general anesthesia and morphine only analgesia.Materials and Methods:Using a retrospective cohort design, the perioperative records were reviewed at a university healthcare hospital. One hundred and thirty-seven cases met all inclusion and no exclusion criteria. Postanesthesia care unit (PACU) records were reviewed for pain scores at first report and 30 min later as well as PACU opiate requirements. T-test, chi-square, and Mann-Whitney tests compared univariate data and multivariate analysis was performed by linear regression.Results:There were no statistically significant PACU pain score group differences based on gender or BMI. Post hoc analysis revealed that in the setting of similar pain scores, obese patients received a similar weight based intraoperative morphine dose when using adjusted body weight (ABW) compared to nonobese subjects. A further finding revealed a negative correlation between age and pain score (P = 0.001).Conclusion:This study did not find an association between obesity or gender and postoperative pain when receiving morphine only preemptive analgesia. This study does support the use of ABW as a means to calculate morphine dosing for obese patients and that age is associated with lower immediate pain scores.

Data from our chronic pain clinic support a potential association of QTc prolongation during the initiation of methadone, but this effect is small and short lived. We believe larger scale studies to further characterize the safety profile of low-dose methadone are warranted.