Functional Dysregulations in CA1 Hippocampal Networks of a 3-Hit Mouse Model of Schizophrenia

For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABA_A receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.     

Electrical stimulation of the medial prefrontal cortex increases dopamine release in the striatum

Exogenous and endogenous glutamate has been shown to evoke dopamine (DA) release in the striatum using both in vitro and in vivo techniques. We hypothesized that stimulation of the prefrontal cortex (PFC) would phasically enhance striatal DA release via the glutamatergic corticostriatal pathway. To test this hypothesis, in vivo brain microdialysis was employed to measure extracellular concentrations of DA in the striatum during electrical stimulation of the PFC. Five rats were implanted with bilateral electrodes located in the medial PFC and dialysis probes in the dorsal striatum. Two days later the PFC of these awake, freely moving rats was stimulated first at 50 microA and then at 100 microA for 20 minutes at 2-hour intervals. Both currents significantly increased DA release. Extracellular DA rose rapidly during stimulation, peaked immediately afterward, and then slowly returned to baseline values. Dopamine reached 118% of baseline values with 50 microA stimulation and 138% with 100 microA stimulation. Histologic analysis using the fluorescent retrograde dye Fluoro Gold confirmed that cells projecting to the vicinity of the striatal dialysis probe originated in the vicinity of the PFC electrodes. These results provide direct evidence for phasic, excitatory modulation of striatal DA release by the PFC.     

Improved atrial function in bicaval versus standard orthotopic techniques in cardiac transplantation

Atrial geometry is preserved in the bicaval technique of cardiac transplantation. Using Doppler echocardiography, we investigated the impact of this technique on preservation of atrial function and found that echocardiographic indexes of atrial function are improved in bicaval cardiac transplants versus the standard orthotopic transplants.     

The effects of attrition on baseline comparability in randomized experiments in education: A meta-analysis.

Using meta-analysis, randomized experiments in education that either clearly did or clearly did not experience student attrition were examined for the baseline comparability of groups. Results from 35 studies suggested that after attrition, the observed measures of baseline comparability of groups did not differ more than would be expected given sampling error. The degree of either overall or differential attrition did not relate to baseline comparability, a finding that held under sensitivity analyses. Also, both overall and differential attrition rates were unrelated to posttest effect sizes. All of these analyses, however, lacked sufficient statistical power to detect small but potentially meaningful effects. Results suggest caution is warranted when applying quality scales and other blanket rules pertaining to attrition that are meant to either serve as inclusion-exclusion criteria or in scoring study quality. Much greater attention is needed to both the reporting of attrition in primary studies and to the development of conceptual and empirical models of the attrition process. These developments would aid further investigation of the relation between attrition and study outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Widespread microsatellite instability in sebaceous tumours of patients with the Muir-Torre syndrome

OBJECTIVE: Thoracic injury remains a major source of morbidity and mortality in urban trauma centers. With the advent and increasing expertise in video assisted thoracic surgery, this modality has become an attractive alternative in the management of patients with thoracic injury. This report will review our experience with video assisted thoracic surgery at a level I trauma center and attempt to further delineate the indications for and timing of thoracoscopy in thoracic trauma. METHODS: We identified 16 patients who had undergone video assisted thoracic surgery following chest trauma between July 1991 and June 1994. There were 15 penetrating and one blunt trauma. All 16 patients were initially treated with tube thoracostomy. From 0-20 days post-injury, video assisted thoracic surgery was attempted with either diagnostic or therapeutic intentions. RESULTS: Twelve of the 16 patients (75%) had successful thoracoscopy. Three patients had diaphragmatic injury excluded and nine patients had successful evacuation of clotted hemothoraces. Evacuation of clotted hemothorax up to 7 days post-injury was safe and easily accomplished. Four patients (25%) had unsuccessful thoracoscopy and were converted to standard thoracotomy; failure was attributed to either suboptimal single lung ventilation or severe pleural inflammatory reaction. The only death in the entire group occurred 10 days after a thoracotomy for retained hemothorax. The median post-operative hospital stay following successful video assisted thoracic surgery was 3.5 days. CONCLUSIONS: Video assisted thoracic surgery can be utilized as an effective and safe method for the initial diagnostic evaluation and surgical management of stable patients with penetrating thoracic trauma.     

Substrate-induced conformational change in a trimeric ornithine transcarbamoylase

The crystal structure of Escherichia coli ornithine transcarbamoylase (OTCase, EC 2.1.3.3) complexed with the bisubstrate analog N-(phosphonacetyl)-L-ornithine (PALO) has been determined at 2.8-A resolution. This research on the structure of a transcarbamoylase catalytic trimer with a substrate analog bound provides new insights into the linkages between substrate binding, protein-protein interactions, and conformational change. The structure was solved by molecular replacement with the Pseudomonas aeruginosa catabolic OTCase catalytic trimer (Villeret, V., Tricot, C., Stalon, V. & Dideberg, O. (1995) Proc. Natl. Acad. Sci. USA 92, 10762-10766; Protein Data Bank reference pdb 1otc) as the model and refined to a crystallographic R value of 21.3%. Each polypeptide chain folds into two domains, a carbamoyl phosphate binding domain and an L-ornithine binding domain. The bound inhibitor interacts with the side chains and/or backbone atoms of Lys-53, Ser-55, Thr-56, Arg-57, Thr-58, Arg-106, His-133, Asn-167, Asp-231, Met-236, Leu-274, Arg-319 as well as Gln-82 and Lys-86 from an adjacent chain. Comparison with the unligated P. aeruginosa catabolic OTCase structure indicates that binding of the substrate analog results in closure of the two domains of each chain. As in E. coli aspartate transcarbamoylase, the 240s loop undergoes the largest conformational change upon substrate binding. The clinical implications for human OTCase deficiency are discussed.     

Cerebellar deficient folia (cdf): a new mutation on mouse chromosome 6

OBJECTIVE: To discuss the case of an 8-yr-old boy with an aneurysmal bone cyst of the right proximal humerus, including the features imaged on plain film radiography, computed tomography (CT), magnetic resonance imaging (MRI), including spin echo and fast field echo imaging. CLINICAL FEATURES: The patient suffered for 1 yr from intermittent but progressive pain in his right upper arm and shoulder area. There was no history of trauma or known systemic disease. There was decreased range of motion in abduction of the glenohumeral joint and pain on focal pressure along the deltoid muscle. A complete imaging evaluation consisting of plain film radiography, CT and MRI was performed, which revealed the classical imaging features of an aneurysmal bone cyst. An additional cystic lesion was detected by the MRI that was not appreciated on the plain films or CT. INTERVENTION AND OUTCOME: The patient was referred for biopsy to confirm the preliminary diagnosis of aneurysmal bone cyst. No treatment was instituted. CONCLUSION: Evaluation of aneurysmal bone cyst may be completed with CT scanning and more specifically with MRI MRI coronal T2, weighted images are advantageous for visualization of the main cystic lesion and any additional cysts. Fast field echo images show a better contrast between the cyst and bone marrow with extension of the cyst into the epiphysis as evident in this case. Follow-up studies revealed complete healing of the cyst with only residual densities in the humeral metaphyseal area.     

Evaluation of the completion of influenza vaccination

OBJECTIVE: To find the reasons which determine failures to comply with anti-flu vaccinations, so that these can be corrected and the coverage of this preventive action be increased. DESIGN: Observational crossover study, done by means of a telephone survey of people over 65. A questionnaire with closed questions, composed after a pilot study and validated by Cronbach's alpha. SETTING: Primary Care Centre (PCC). PATIENTS: We calculated a population sample for qualitative variables (_ = 0.05; p = 0.60; e = 0.05) of 294 people over 65, chosen from the PCC records, by means of random sampling (K = 4) stratified for age and discounting the telephone selection bias. MEASUREMENTS AND RESULTS: The proportion of vaccinated patients (60.9%) obtained in our study did not significantly differ from that in the general population. The percentage of patients included in the programme for the first time was 14%. Level of satisfaction among those vaccinated was 89.4%, with 8.9% of problems detected being light. Main causes of non-vaccination were: thinking that they didn't need it (63.5%), ignorance of the campaign (35.7%), fear of the reaction (24.3%), forgetting (10.4%). The main form of access to the campaign information was from the PCC, both through individuals and posters. Lack of information was statistically significant (p < 0.00001) as a determinant of non-vaccination, without other factors (age, sex, associated pathologies...) explaining these differences. CONCLUSIONS: Individualised and on-going health education by the PCC is fundamental. This would enable the identification of the group not vaccinated due to their express refusal and the recovery of non-vaccinated patients.