Extended access cocaine self-administration differentially activates dorsal raphe and amygdala corticotropin-releasing factor systems in rats.

Cocaine-induced neuroadaptation of stress-related circuitry and increased access to cocaine each putatively contribute to the transition from cocaine use to cocaine dependence. The present study tested the hypothesis that rats receiving extended versus brief daily access to cocaine would exhibit regional differences in levels of the stress-regulatory neuropeptide corticotropin-releasing factor (CRF). A secondary goal was to explore how CRF levels change in relation to the time since cocaine self-administration. Male Wistar rats acquired operant self-administration of cocaine and were assigned to receive daily long access (6 hours/day, LgA, n = 20) or short access (1 hour/day, ShA, n = 18) to intravenous cocaine self-administration (fixed ratio 1, ∼0.50 mg/kg/infusion). After at least 3 weeks, tissue CRF immunoreactivity was measured at one of three timepoints: pre-session, post-session or 3 hours post-session. LgA, but not ShA, rats showed increased total session and first-hour cocaine intake. CRF immunoreactivity increased within the dorsal raphe (DR) and basolateral, but not central, nucleus of the amygdala (BLA, CeA) of ShA rats from pre-session to 3 hours post-session. In LgA rats, CRF immunoreactivity increased from pre-session to 3 hours post-session within the CeA and DR but tended to decrease in the BLA. LgA rats showed higher CRF levels than ShA rats in the DR and, pre-session, in the BLA. Thus, voluntary cocaine intake engages stress-regulatory CRF systems of the DR and amygdala. Increased availability of cocaine promotes greater tissue CRF levels in these extrahypothalamic brain regions, changes associated here with a model of cocaine dependence.

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What is a virtual person? What is it used for? What is its added value? Virtual persons sometimes describe avatars and new forms of identities in online games. They also appear in other contexts; some authors use them in the legal domain. Within FIDIS, the concept of virtual person has been extended in order to better describe and understand new forms of identities in the Information Society in relation to rights, duties, obligations and responsibilities. Virtual persons, as other virtual entities, exist in the virtual world, the collection of all (abstract) entities which are or have been the product of the mind or imagination. The virtual world -not to be confused with the digital world- allows a unified description of many identity-related concepts that are usually defined separately without taking into consideration their similarities: avatars, pseudonyms, categories, profiles, legal persons, etc. The legal system has a long experience of using abstract entities to define rules, categories, etc., in order to associate legal rights, obligations, and responsibilities to persons that can be considered instances of these abstract entities in specific situations. The model developed within FIDIS intentionally uses a similar construction. n this chapter, after having explained the model, we apply it to pseudonyms. Then we explore the concept of virtual persons from a legal perspective. Eventually, we introduce trust in the light of virtual persons.

Intraocular implants for extended drug delivery: therapeutic applications.

An overview of ocular implants with therapeutic application potentials is provided. Various types of implants can be used as slow release devices delivering locally the needed drug for an extended period of time. Thus, multiple periocular or intraocular injections of the drug can be circumvented and secondary complications minimized. The various compositions of polymers fulfilling specific delivery goals are described. Several of these implants are undergoing clinical trials while a few are already commercialized. Despite the paramount progress in design, safety and efficacy, the place of these implants in our clinical therapeutic arsenal remains limited. Miniaturization of the implants allowing for their direct injection without the need for a complicated surgery is a necessary development avenue. Particulate systems which can be engineered to target specifically certain cells or tissues are another promising alternative. For ocular diseases affecting the choroid and outer retina, transscleral or intrasscleral implants are gaining momentum.

New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration.

BACKGROUND: Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. METHODS: Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na L-lactate (2 µl of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 µmol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. RESULTS: Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p < 0.05) and 14 days after ischaemia (median = 0, min = 0, max = 3, n = 7 vs. median = 3, min = 0.5, max = 3, n = 7, p = 0.05). Reduced tissue damage was demonstrated by attenuated hemispheric atrophy at 14 days (1.3 ± 4.0 mm(3), n = 7 vs. 12.1 ± 3.8 mm(3), n = 5, p < 0.05) in lactate-treated animals. Systemic intravenous lactate administration was also neuroprotective and attenuated the deficit (median = 1, min = 0, max = 2.5, n = 12) compared to vehicle treatment (median = 1.5, min = 1, max = 8, n = 12, p < 0.05) as well as the lesion volume at 48 h (13.7 ± 12.2 mm(3), n = 12 vs. 29.6 ± 25.4 mm(3), n = 12, p < 0.05). CONCLUSIONS: The beneficial effect of lactate is long-lasting: lactate protects the mouse brain against ischaemic damage when supplied intracerebroventricularly during reperfusion with behavioural and histological benefits persisting 2 weeks after ischaemia. Importantly, lactate also protects after systemic intravenous administration, a more suitable route of administration in a clinical emergency setting. These findings provide further steps to bring this physiological, commonly available and inexpensive neuroprotectant closer to clinical translation for stroke.

Theory of mind impairment in patients with behavioural variant fronto-temporal dementia (bv-FTD) increases caregiver burden.

BACKGROUND: Theory of mind (ToM), the capacity to infer the intention, beliefs and emotional states of others, is frequently impaired in behavioural variant fronto-temporal dementia patients (bv-FTDp); however, its impact on caregiver burden is unexplored. SETTING: National Institute of Neurological Disorders and Stroke, National Institutes of Health. SUBJECTS: bv-FTDp (n = 28), a subgroup of their caregivers (n = 20) and healthy controls (n = 32). METHODS: we applied a faux-pas (FP) task as a ToM measure in bv-FTDp and healthy controls and the Zarit Burden Interview as a measure of burden in patients' caregivers. Patients underwent structural MRI; we used voxel-based morphometry to examine relationships between regional atrophy and ToM impairment and caregiver burden. RESULTS: FP task performance was impaired in bv-FTDp and negatively associated with caregiver burden. Atrophy was found in areas involved in ToM. Caregiver burden increased with greater atrophy in left lateral premotor cortex, a region associated in animal models with the presence of mirror neurons, possibly involved in empathy. CONCLUSION: ToM impairment in bv-FTDp is associated with increased caregiver burden.

'And the best essay is...' : Extended contact and cross-group friendships at school

We conducted one experimental intervention based on extended contact principles aimed at fostering the formation of cross-group friendships within educational settings. Italian school children took part in a school competition for the best essay on personal experiences of cross-group friendships with immigrants, to be written in small groups. This manipulation was intended to favour the exchange of personal positive cross-group experiences, thus capitalizing on the benefits of extended contact. In the control condition, participants wrote an essay on friendship, without reference to cross-group relations. Results revealed that children who took part in the intervention reported a higher number of outgroup friends 3 months later. This indirect effect was sequentially mediated by pro-contact ingroup and outgroup norms and by outgroup contact behavioural intentions. This study provides experimental evidence that interventions based on extended contact can foster cross-group friendship formation. Theoretical and practical implications of the findings are discussed.

Jevons, Mill and the Private Laboratory of the Mind

In this paper the rift between Jevons and Mill over the method of political economy serves as a prehistory to recent attempts of behavioural economists to once again explain economic behaviour by taking recourse to mankind's physiology. While Mill relied on the association psychology and its introspective method to establish indubitable first principles, Jevons scorned all recourse to introspection. As exemplified for Jevons's theory of labour, psychophysiology gave Jevons the means to think about economic behaviour in terms of functional form, and promised its assessment by means of experiments. Thus levelling down the Victorian distinction between mind and matter, Jevons turned political economy into social physics.

Mind the Gap. Do Proportional Electoral Systems Foster a More Equal Representation of Women and Men, Poor and Rich ?

Female gender and low income are two markers for groups that have been historically disadvantaged within most societies. The study explores two research questions related to their political representation: 1) Are parties ideologically biased towards the ideological preferences of male and rich citizens? 2) Does the proportionality of the electoral system moderate the degree of underrepresentation of women and poor citizens in the party system? A multilevel analysis of survey data from 24 parliamentary democracies indicates that there is some bias against those with low income and, at a much smaller rate, women. This has systemic consequences for the quality of representation, as the preferences of the complementary groups differ. The proportionality of the electoral system influences the degree of underrepresentation: specifically, larger district magnitudes help closing the considerable gap between rich and poor.

Transabdominal-pelvic-perineal (TAPP) anterolateral thigh flap: A new reconstructive technique for complex defects following extended abdominoperineal resection.

BACKGROUND: Abdominoperineal resection (APR) following radiotherapy is associated with a high rate of perineal wound complications. The anterolateral thigh (ALT) flap, combined with the vastus lateralis (VL) muscle, can cover complex perineal and pelvic anteroposterior defects. This is used for the first time transabdominally through the pelvis and the perineum (TAPP) in the infero-posterior directions; this technique has been described and illustrated in this study. METHODS: Among over 90 patients who underwent perineal reconstruction between May 2004 and June 2011, six patients presented high-grade tumours invading perineum, pelvis and sacrum, thereby resulting in a continuous anteroposterior defect. ALT + VL TAPP reconstructions were performed after extended APR and, subsequently, sacrectomy. Patients were examined retrospectively to determine demographics, operative time, complications (general and flap-related), time to complete healing and length of hospital stay. Long-term flap coverage, flap volume stability and functional and aesthetic outcomes were assessed. RESULTS: Mean operating time of the reconstruction was 290 min. No deaths occurred. One patient presented partial flap necrosis. Another patient presented a novel wound dehiscence after flap healing, due to secondary skin dissemination of the primary tumour. Following volumetric flap analysis on serial post-operative CT scans, no significant flap atrophy was observed. All flaps fully covered the defects. No late complications such as fistulas or perineal hernias occurred. Donor-site recovery was uneventful with no functional deficits. CONCLUSIONS: The use of the ALT + VL flap transabdominally is an innovative method to reconstruct exceptionally complex perineal and pelvic defects extending up to the lower back. This flap guarantees superior bulk, obliterating all pelvic dead space, with the fascia lata (FL) supporting the pelvic floor.