Hypocretin/orexin antagonism enhances sleep-related adenosine and GABA neurotransmission in rat basal forebrain.

Hypocretin/orexin (HCRT) neurons provide excitatory input to wake-promoting brain regions including the basal forebrain (BF). The dual HCRT receptor antagonist almorexant (ALM) decreases waking and increases sleep. We hypothesized that HCRT antagonists induce sleep, in part, through disfacilitation of BF neurons; consequently, ALM should have reduced efficacy in BF-lesioned (BFx) animals. To test this hypothesis, rats were given bilateral IgG-192-saporin injections, which predominantly targets cholinergic BF neurons. BFx and intact rats were then given oral ALM, the benzodiazepine agonist zolpidem (ZOL) or vehicle (VEH) at lights-out. ALM was less effective than ZOL at inducing sleep in BFx rats compared to controls. BF adenosine (ADO), γ-amino-butyric acid (GABA), and glutamate levels were then determined via microdialysis from intact, freely behaving rats following oral ALM, ZOL or VEH. ALM increased BF ADO and GABA levels during waking and mixed vigilance states, and preserved sleep-associated increases in GABA under low and high sleep pressure conditions. ALM infusion into the BF also enhanced cortical ADO release, demonstrating that HCRT input is critical for ADO signaling in the BF. In contrast, oral ZOL and BF-infused ZOL had no effect on ADO levels in either BF or cortex. ALM increased BF ADO (an endogenous sleep-promoting substance) and GABA (which is increased during normal sleep), and required an intact BF for maximal efficacy, whereas ZOL blocked sleep-associated BF GABA release, and required no functional contribution from the BF to induce sleep. ALM thus induces sleep by facilitating the neural mechanisms underlying the normal transition to sleep.

Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex.

Generation of distinct cortical projection neuron subtypes during development relies in part on repression of alternative neuron identities. It was reported that the special AT-rich sequence-binding protein 2 (Satb2) is required for proper development of callosal neuron identity and represses expression of genes that are essential for subcerebral axon development. Surprisingly, Satb2 has recently been shown to be necessary for subcerebral axon development. Here, we unravel a previously unidentified mechanism underlying this paradox. We show that SATB2 directly activates transcription of forebrain embryonic zinc finger 2 (Fezf2) and SRY-box 5 (Sox5), genes essential for subcerebral neuron development. We find that the mutual regulation between Satb2 and Fezf2 enables Satb2 to promote subcerebral neuron identity in layer 5 neurons, and to repress subcerebral characters in callosal neurons. Thus, Satb2 promotes the development of callosal and subcerebral neurons in a cell context-dependent manner.

Exploration of the attitudes of nursing students to peer physical examination and physical examination of patients.

BACKGROUND: The use of peer physical examination (PPE) in early clinical skills has been studied amongst medical students. The majority of students are comfortable with using peer physical examination, when sensitive areas are excluded. Students' attitudes are related to their personal characteristics: gender, age, religious faith, and ethnicity. There is no data on nursing students' attitudes to peer physical examination. OBJECTIVES: Identify and explore: DESIGN: Dual cohort, cross-sectional, anonymous survey. SETTING: Three-year undergraduate nursing programme, skills centre and service clinical learning. METHODS: All first and third year nursing students were asked to complete a modified Examining Fellow Students questionnaire at the end of 2008. The questionnaire asked students to indicate which of 12 body areas they would not be willing to examine/have examined by a peer of the same/opposite gender. This study also asked students which of the 12 body areas they felt uncomfortable examining on patients. RESULTS: The response rate was 76% (128/168). The students were predominantly female (93% female; 7% male). Most students were comfortable with examining non-sensitive body regions of peers (78.2%-100% willing) and patients (92.3-100% willing). Male gender was significantly associated with willingness to examine and be examined by peers (p=0.001); Asian students were significantly less willing to engage in peer physical examination with opposite gender (p<0.007). Year 3 students were significantly more comfortable than Year 1 in examining patients of either gender (p<0.001). DISCUSSION AND CONCLUSIONS: In spite of the male gender findings, this predominantly female population expresses similar attitudes to the gender-balanced medical student studies - high acceptability for non-sensitive areas. The role of characteristics and attitudes to peer physical examination shows similarities and differences to other studies. Student characteristics were not related to patient examination attitudes.