Differential roles of caudate nucleus and putamen during instrumental learning

The dorsal striatum is crucial for the acquisition and consolidation of instrumental behaviour, but the underlying computations and internal dynamics remain elusive. To address this issue, we combined a model of key computations supporting decision-making during instrumental learning with human behavioural and functional magnetic resonance imaging (fMRI) data. The results showed that the associative and sensorimotor dorsal striatum host complementary computations that, we suggest, may differentially support goal-directed and habitual processes. The anterior caudate nucleus integrates information about performance and cognitive control demands, whereas the putamen tracks how likely the conditioning stimuli lead to correct response. Contrary to current models, the putamen is recruited during initial acquisition. As the exploratory phase proceeds, the relative contribution of the caudate nucleus becomes dominant over the putamen. During early consolidation, caudate nucleus and putamen settle to asymptotic values and share control. We then investigated how dorsal striatal computations may affect decision-making. We found that portion of reaction times' variance parallels the combined cost associated with the dorsal striatal computations. Overall, our findings provide a deeper insight into the functional heterogeneity within the dorsal striatum and suggest that the dynamic interplay between caudate nucleus and putamen, rather than their serial recruitment, underlies the acquisition and early consolidation of instrumental behaviours.     

Sclerosing epithelioid fibrosarcoma. A case report

Sclerosing epithelioid fibrosarcoma is a rare variant of fibrosarcomas, which was recently identified as a separate entity due to specific histologic and immunohistochemistry features and its poor prognosis. We report a case of sclerosing epithelioid fibrosarcoma of soft tissues, which developed in a 37-year-old woman who presented a tumor involving the posteromedial aspect of the left knee and which progressed in size for one year. Imaging revealed a well-delimited tumor process measuring 8 cm in its largest diameter and situated in the medial compartment of the left knee. Histology of the tumorectomy specimen and the immunohistochemistry study led to the diagnosis of sclerosing epithelioid fibrosarcoma of soft tissues. This new case illustrates the characteristic features of this tumor and recalls the difficult pathological diagnosis.     

Prehension movements in the macaque monkey: effects of perturbation of object size and location

While the neural bases of prehension have been extensively studied in monkeys, a few kinematic studies have examined their prehension behavior. Recently (Roy et al. 2000, 2002), we have described the kinematics of reaching and grasping in freely behaving monkeys under normal conditions by applying the high-resolution recording techniques (Optotrak^® system) and behavioral paradigms used in humans. Here we determined whether online movement reorganization observed in monkeys following sudden changes of either object size or location at movement onset is similar to that observed in humans. We found that changing object size led to rapid on-flight re-calibration of the different movement parameters, eventually preserving the unitary aspect of the movement with a minor time cost. By contrast, a shift in object location triggered a massive time-consuming reorganization. Re-directed movements appeared as a concatenation of two sub-movements: a first one directed to the initial object and a second one directed to the new object location. These findings first complement our earlier studies in providing further evidence of the similarities between monkey and human prehension. Second, they suggest that the two components of prehension, reaching and grasping, interact through coordination mechanisms that are more efficient to correct for size than for location perturbation. This difference may reflect a hierarchical organization in which reaching would be the subordinate of grasping in both primate species.     

Health care providers’ requests to Teratogen Information Services on medication use during pregnancy and lactation

Background  Medication use during pregnancy and lactation is prevalent. However, current knowledge of the risks and benefits of medication use during pregnancy and lactation is incomplete as the best available evidence has been obtained from cohort studies of inadvertent exposures and registries. This situtation may partly explain health care providers’ (HCP) risk perceptions and thus the increasing number of calls to Teratogen Information Services (TIS). Objectives  The objectives of this study were (1) to identify the medication classes for which HCP are seeking counseling from the IMAGe center, a Quebec TIS; (2) to identify the medical conditions for which medication classes were used during pregnancy and lactation; (3) to identify and quantify predictors of medication information requests during pregnancy and lactation. Methods  A retrospective analysis of data was conducted within the population served by the IMAGe center, a TIS based at CHU Ste-Justine in Montreal, Quebec, Canada, that serves the French population of Canada. To be included, calls had to be received between January 1, 2004 and April 30, 2007, and the subject of the call had to be directly associated with the exposure, or not, of a pregnant or breastfeeding woman to medication. Multivariate generalized estimating equation (GEE) regression models were performed to identify the predictors of medication requests. Results  A total of 11, 076 requests regarding medication exposure during pregnancy, 12 055 requests regarding pregnant women before the exposure took place, and 13, 364 requests regarding lactation were included for analyses. Pregnant women were most frequently exposed to antidepressants (17.3), antibiotics (6.3%), and benzodiazepines (5.3%). Prior to drug exposure, the most frequent inquiries by HCP were on antibiotics (11.0%), anti-inflammatory drugs (6.0%), and antiemetics (5.1%). Inquiries concerning lactating women most frequently requested information on the drug classes of antidepressants (10.8%), antibiotics (9.1%), and anti-inflammatory drugs (7.8%). Depressive disorders were an indication of antidepressant, benzodiazepine and antipsychotic exposures reported to IMAGe. Associations were found between medication use and maternal age, previous pregnancies, trimester of pregnancy at the time of the call and lifestyle habits. Conclusions  The IMAGe received frequent inquiries on antidepressant, antibiotic, and benzodiazepine exposures, with depressive disorders being the most frequently declared indication. Predictors of medication requests were identified among exposed women during pregnancy, and breastfeeding women. These results emphasize the need for effective studies on drug use during pregnancy and lactation and for better knowledge transfer programs.     

T regulatory cells in xenotransplantation

Abstract: The role of T regulatory cells (Treg) in the induction and maintenance of allograft tolerance is being studied to a great extent. In contrast, little is known on their potential to prevent graft rejection in the field of xenotransplantation, where acute vascular rejection mediated by cellular and humoral mechanisms and thrombotic microangiopathy still prevents long‐term graft survival. In this regard, the induction of donor‐specific tolerance through isolation and expansion of xenoantigen‐specific recipient Treg is currently becoming a focus of interest. This review will summarize the present knowledge concerning Treg and their potential use in xenotransplantation describing in particular CD4⁺CD25⁺Foxp3⁺ T cells, CD8⁺CD28^? Treg, double negative CD4^?CD8^? T cells, and natural killer Treg. Although only studied in vitro so far, human CD4⁺CD25⁺Foxp3⁺ Treg is currently the best characterized subpopulation of regulatory cells in xenotransplantation. CD8⁺CD28^? Treg and double negative CD4^?CD8^? Treg also seem to be implicated in tolerance maintenance of xenografts. Finally, one study revealing a role for natural killer CD4⁺Vα14⁺ Treg in the prolongation of xenograft survival needs further confirmation. To our opinion, CD4⁺CD25⁺Foxp3⁺ Treg are a promising candidate to protect xenografts. In contrast to cadaveric allotransplantation, the donor is known prior to xenotransplantation. This advantage allows the expansion of recipient Treg in a xenoantigen specific manner before transplantation.     

Differential regulation of the signaling and trafficking of the two prostaglandin D2 receptors, prostanoid DP receptor and CRTH2

Prostaglandin D2 (PGD2) exerts its actions on two G protein-coupled receptors, the prostanoid DP receptor and CRTH2 (chemoattractant homologous receptor expressed on TH2 cells). Here, we characterize the regulation of the signaling and trafficking of the prostanoid DP receptor and CRTH2. Time-course and dose-response curves showed that both receptors expressed in HEK293 cells internalized maximally after 2 h of stimulation with 1 microM PGD2. Co-expression of the G protein-coupled receptor kinases GRK2, GRK5 or GRK6 increased agonist-induced internalization of CRTH2, while only GRK2 had an effect on the internalization of the prostanoid DP receptor. Protein kinase C (PKC) activation stimulated the internalization of both receptors. Interestingly, only PGD2-induced internalization of CRTH2, and not of prostanoid DP receptor, was decreased by inhibition of PKC or protein kinase A (PKA). Our data also indicate that CRTH2 is subjected to basal phosphorylation by PKA, which appears to be involved in CRTH2 internalization. Prostanoid DP receptor internalization was promoted by co-expression of arrestin-2 and -3, while the internalization of CRTH2 was increased by co-expression of arrestin-3 only. The detection of prostanoid DP receptor and CRTH2 internalization was reduced by the co-expression of Rab4 and Rab11, respectively, suggesting differential regulation of receptor recycling. Moreover, immunofluorescence microscopy experiments showed that the prostanoid DP receptor specifically co-localized with Rab4, and CRTH2 with Rab11. The signaling of the prostanoid DP receptor was regulated by GRK2 overexpression, while that of CRTH2 was modulated by overexpression of GRK2, -5 and -6. Our results show a differential regulation of the prostanoid DP receptor and CRTH2, two receptors for PGD2.     

Non–surgical management of abdominal ectopic pregnancy with uterine artery embolization

Abdominal pregnancy is a rare but life-threatening variation of ectopic pregnancy that is often treated with laparoscopic management; however, we present a case successfully treated using only minimally invasive techniques. A 36-year-old female G1P0 with a history of infertility is diagnosed with 11-weeks abdominal pregnancy by transvaginal ultrasound. She presented with vaginal bleeding and abdominal pain, and her beta-human chorionic gonadotropin was 53,680 mIU/mL. The location of the fetal sac was not amenable to surgery or percutaneous injection. We performed bilateral uterine artery embolization and subsequent intramuscular methotrexate injection. The procedure was successful with no complications. The patient was followed at postoperative week 11, and beta-human chorionic gonadotropin was 2 mIU/mL, and at 3 months, a transvaginal ultrasound revealed resolution of the abdominal pregnancy.