Magnetic resonance elastography with guided pressure waves

Magnetic resonance elastography aims to non-invasively and remotely characterize the mechanical properties of living tissues. To quantitatively and regionally map the shear viscoelastic moduli in vivo, the technique must achieve proper mechanical excitation throughout the targeted tissues. Although it is straightforward, ante manibus, in close organs such as the liver or the breast, which practitioners clinically palpate already, it is somewhat fortunately highly challenging to trick the natural protective barriers of remote organs such as the brain. So far, mechanical waves have been induced in the latter by shaking the surrounding cranial bones. Here, the skull was circumvented by guiding pressure waves inside the subject's buccal cavity so mechanical waves could propagate from within through the brainstem up to the brain. Repeatable, reproducible and robust displacement fields were recorded in phantoms and in vivo by magnetic resonance elastography with guided pressure waves such that quantitative mechanical outcomes were extracted in the human brain.     

Importance of community size in practice location decisions of final year residents

Final year residents in training in Louisiana were surveyed regarding plans for medical practice and their perceptions of the importance of various factors in choosing practice locations. Most specialty groups selected smaller communities at similar rates. Growing up in small towns is associated with wanting to practice in small towns while concerns about opportunities for the family and income of the region are associated with wanting to practice in a larger city.This study was supported by the Louisiana Council for Statewide Planning for Physician Manpower through Contract No. 23058, Louisiana Department of Health and Human Resources.Ms. Samaha is a data analyst for the Louisiana Council for Statewide Planning for Physician Manpower; Robert R. Franklin, M.D. is Executive Secretary of the Council and Assistant Professor, Department of Biostatistics and Epidemiolgy, Tulane University School of Public Health and Tropical Medicine; Janet C. Rice is Assistant Pofessor, Department of Biostatistics and Epidemiology at the Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana 70112.     

Amphetamine maintenance therapy during intermittent cocaine self-administration in rats attenuates psychomotor and dopamine sensitization and reduces addiction-like behavior

D-amphetamine maintenance therapy shows promise as a treatment for people with cocaine addiction. Preclinical studies using Long Access (LgA) cocaine self-administration procedures suggest D-amphetamine may act by preventing tolerance to cocaine’s effects at the dopamine transporter (DAT). However, Intermittent Access (IntA) cocaine self-administration better reflects human patterns of use, is especially effective in promoting addiction-relevant behaviors, and instead of tolerance, produces psychomotor, incentive, and neural sensitization. We asked, therefore, how D-amphetamine maintenance during IntA influences cocaine use and cocaine’s potency at the DAT. Male rats self-administered cocaine intermittently (5 min ON, 25 min OFF x10; 5-h/session) for 14 sessions, with or without concomitant D-amphetamine maintenance therapy during these 14 sessions (5 mg/kg/day via s.c. osmotic minipump). We then assessed responding for cocaine under a progressive ratio schedule, responding under extinction and cocaine-primed reinstatement of drug seeking. We also assessed the ability of cocaine to inhibit dopamine uptake in the nucleus accumbens core using fast scan cyclic voltammetry ex vivo. IntA cocaine self-administration produced psychomotor (locomotor) sensitization, strong motivation to take and seek cocaine, and it increased cocaine’s potency at the DAT. D-amphetamine co-administration suppressed the psychomotor sensitization produced by IntA cocaine experience. After cessation of D-amphetamine treatment, the motivation to take and seek cocaine was also reduced, and sensitization of cocaine’s actions at the DAT was reversed. Thus, treatment with D-amphetamine might reduce cocaine use by preventing sensitization-related changes in cocaine potency at the DAT, consistent with an incentive-sensitization view of addiction.Subject terms: Diagnostic markers, Reward, Behavioural methods, Addiction, Predictive markers     

Amphetamine or cocaine limits the ability of later experience to promote structural plasticity in the neocortex and nucleus accumbens

Drugs of abuse and many other kinds of experiences share the ability to alter the morphology of neuronal dendrites and spines, the primary site of excitatory synapses in the brain. We hypothesized, therefore, that exposure to psychostimulant drugs might influence later experience-dependent structural plasticity. We tested this hypothesis by treating rats repeatedly with amphetamine or cocaine and then housing them in either a complex environment or standard laboratory cages for 3-3.5 mo. The brains were processed for Golgi-Cox staining, and the number of dendritic branches and the density of dendritic spines on medium spiny neurons in the nucleus accumbens and pyramidal cells in the parietal cortex were quantified. On most measures, prior treatment with amphetamine or cocaine interfered with the ability of experience in a complex environment to increase dendritic arborization and spine density. We conclude that in some brain regions, repeated exposure to psychomotor-stimulant drugs limits the ability of later experience to produce this form of synaptic plasticity, which may contribute to the persistent behavioral and cognitive deficits associated with drug abuse.     

Effect of piezocision corticotomy on en-masse retraction:: A randomized controlled trial

ObjectivesTo compare the amount of en-masse retraction with or without piezocision corticotomy, to assess the type of tooth movement, to evaluate root integrity after retraction, and to record reported pain levels.Materials and MethodsThis randomized, controlled clinical trial included 26 orthodontic patients requiring premolar extraction. The patients were divided into two groups: (1) an extraction with piezocision corticotomy group (PCG) and (2) an extraction-only group, which served as the control group (CG). Cone-beam computed tomography images were acquired before and 4 months after the initiation of en-masse retraction utilizing miniscrews. The following variables were assessed: the amount of en-masse retraction, incisor inclination, incisor and canine root resorption, and patient-reported pain.ResultsTwelve and 11 participants completed the entire study in the PCG and CG, respectively. The amount of en-masse retraction was significantly greater in the PCG compared to the CG (mean = 4.8 ± 0.57 mm vs 2.4 ± 0.33 mm, respectively [P < .001]). There was also significantly less tipping and root resorption of incisors in the PCG (P < .05). The reported pain was significantly higher on the first day in the PCG compared to the CG (P < .001); however, it became similar between the groups after 24 hours.ConclusionsPiezocision corticotomy enhanced the amount of en-masse retraction two times more with less root resorption. However, future studies are required to assess the long-term effects of this technique.     

Emergency Presenting Colon Cancer Is an Independent Predictor of Adverse Disease-Free Survival

Twenty percent of colon cancers present as an emergency. However, the association between emergency presentation and disease-free survival (DFS) remains uncertain. Consecutive patients who underwent elective (CC) and emergent (eCC) resection for colon cancer were included in the analysis. Survival outcomes were compared between the 2 groups in univariate/multivariate analyses. A total of 439 patients underwent colonic resection for colon cancer during the interval 2000−2010; 97 (22.1%) presented as an emergency. eCC tumors were more often located at the splenic flexure (P = 0.017) and descending colon (P = 0.004). The eCC group displayed features of more advanced disease with a higher proportion of T4 (P = 0.009), N2 tumors (P < 0.01) and lymphovascular invasion (P< 0.01). eCC was associated with adverse locoregional recurrence (P = 0.02) and adverse DFS (P < 0.01 ) on univariate analysis. eCC remained an independent predictor of adverse locoregional recurrence (HR 1.86, 95% CI 1.50–3.30, P = 0.03) and DFS (HR 1.30, 95% CI 0.88–1.92, P = 0.05) on multivariate analysis. eCC was not associated with adverse overall survival and systemic recurrence. eCC is an independent predictor of adverse locoregional recurrence and DFS.Key words: Emergency presentation, Colon cancer, Disease free survival, Locoregional recurrenceColorectal cancer (CRC) is a significant cause of mortality, with over 40,000 new cases diagnosed annually in the UK contributing to over 16,000 deaths (Bowel Cancer UK).^1,2 Up to 20% of colon cancers (CC) present as an emergency (eCC) necessitating emergent surgery.^3,4 Although eCC has been shown to be associated with poorer overall survival (OS), much discrepancy exists in the literature regarding its association with disease-free survival (DFS).⁵⁻⁷Studies reporting the oncologic outcomes of CRC presenting as an emergency consist of heterogeneous populations of patients with colon and rectal cancers.^3,5 Colon and rectal cancers are 2 distinct entities with different molecular, clinical, pathologic, and biologic characteristics and treatment modalities.^8,4,9−11 Since the incorporation of combined multimodal treatment and total mesorectal excision the disparity in OS and DFS between colon and rectal cancer has increased.¹²⁻¹⁷ Rectal cancer patients may alter the impression of outcomes in emergency presenting colon cancer. Consequently, previous studies assessing outcomes in eCC may be flawed. Furthermore, the negative impact of eCC has previously been attributed to immediate postoperative complications with an inpatient hospital mortality of approximately 15%. Inclusion of such cases in studies assessing long-term outcomes may have overestimated the negative impact of eCC.¹⁸The aim of the current study was to determine the association between eCC and disease-free/overall survival.     

Arginase and α‐smooth muscle actin induction after hyperoxic exposure in a mouse model of bronchopulmonary dysplasia

The L‐arginine/NO pathway is an important regulator of pulmonary hypertension, the leading cause of mortality in patients with the chronic lung disease of prematurity, bronchopulmonary dysplasia. L‐arginine can be metabolized by NO synthase (NOS) to form L‐citrulline and NO, a potent vasodilator. Alternatively, L‐arginine can be metabolized by arginase to form urea and L‐ornithine, a precursor to collagen and proline formation important in vascular remodelling. In the current study, we hypothesized that C3H/HeN mice exposed to prolonged hyperoxia would have increased arginase expression and pulmonary vascular wall cell proliferation. C3H/HeN mice were exposed to 14 days of 85% O₂ or room air and lung homogenates analyzed by western blot for protein levels of arginase I, arginase II, endothelial NOS (eNOS), ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and α‐smooth muscle actin (α‐SMA). Hyperoxia did not change arginase I or eNOS protein levels. However, arginase II protein levels were 15‐fold greater after hyperoxia exposure than in lungs exposed to room air. Greater protein levels of ODC and OAT were found in lungs following hyperoxic exposure than in room air animals. α‐SMA protein levels were found to be 7‐fold greater in the hyperoxia exposed lungs than in room air lungs. In the hyperoxia exposed lungs there was evidence of greater pulmonary vascular wall cell proliferation by α‐SMA immunohistochemistry than in room air lungs. Taken together, these data are consistent with a more proliferative vascular phenotype, and may explain the propensity of patients with bronchopulmonary dysplasia to develop pulmonary hypertension.