The association of the alpha-5 subunit of the nicotinic acetylcholine receptor gene and the brain-derived neurotrophic factor gene with different aspects of smoking behavior

Recent studies show that different aspects of smoking behavior are associated with the α-5 subunit of the nicotinic acetylcholine receptor (CHRNA5) gene and the gene coding for brain-derived neurotrophic factor (BDNF). This raises the question whether the amount of cigarettes smoked per day has a different genetic background than smoking initiation and what other smoking phenotypes may be relevant. The aim of this study was to replicate these associations in a large population-based sample. We investigated the association with smoking initiation and the number of cigarettes used per day and additional smoking phenotypes in a population-based sample of 2166 participants of Dutch origin. Rs6265 in BDNF was not associated with smoking initiation. This single nucleotide polymorphism was associated with smoking cessation. Rs16969968 in CHRNA5 was associated with the amount of nicotine used and in particular smoking 25 cigarettes or more per day. Overall, the results confirm the involvement of the CHRNA5 gene in the amount of nicotine use and further suggest involvement of the BDNF gene in smoking behavior.     

Medial frontal negativity reflects learning from positive feedback

The ability to learn from the consequences of our actions is crucial for adaptive goal-directed behavior. We learn to avoid actions that lead to unfavorable outcomes and pursue actions that lead to desirable results. By recording event-related potentials (ERPs), we show that neural reinforcement learning signals associated with positive outcomes are predictive of subsequent learning of a sequence of motor actions: Positive feedback to a response that was later correctly repeated was associated with a larger medial frontal negativity (MFN) compared to when it was not correctly repeated on a subsequent encounter. This finding adds to recent evidence suggesting that the function of the anterior cingulate cortex is to establish associations between actions and their outcomes, both positive and negative.     

The effect of ultrasound on osteogenesis in the vertically distracted edentulous mandible: a double-blind trial

Whether low intensity pulsed ultrasound therapy stimulates osteogenesis in mandibular distraction was investigated in a double-blind trial. Nine patients underwent a vertical mandibular distraction over a distance of 5.1+/-1.2mm. Ultrasound or placebo therapy was started daily from the first day of distraction. After 46+/-8.1 days consolidation, two endosseous implants were inserted and a transmandibular biopsy was taken. Ultrasonographs were taken regularly to follow osteogenesis inside the gap. There were no complications during the 44+/-7.1 months of follow-up. Microradiographic measurements of the biopsies revealed no differences in the area of mineralized tissue in the distraction gap. The cranially distracted bone segment appeared significantly more radiolucent than the caudal bone. Histological examination showed large lacunae inside the cranially distracted bone segment, filled with clusters of osteoclasts and surrounded by clear tetracycline double labels. Within the distraction gap, woven bone was present, with no apparent differences between the treatment groups. Ultrasonographic follow-up revealed that osteogenesis inside the distraction gap progresses from 4 to 20 weeks post distraction, with no differences between the ultrasound and the placebo groups. In summary, ultrasound treatment does not appear to stimulate bone formation in the severely resorbed vertical distracted mandible.     

A comparison of micro-CT, microradiography and histomorphometry in bone research

OBJECTIVE: Intraobserver reliability and agreement were determined for microradiography (MR), micro-computed tomography (microCT) and histomorphometry (HM). These three modalities were compared for quantitative measurements of bone formation and graft modelling in rat mandibular defects and grafts. DESIGN: Twelve rats were randomly selected from a larger experiment, evaluating bone formation in rat mandibular defects and bone modelling in grafts. Twelve lateral microradiographs were taken of the grafts. microCT images were obtained from all defects and grafts (24 specimens). Defects and grafts were cut perpendicularly through their centre. Microradiographs, microCT images and histological sections were obtained from the resulting 48 specimens. New bone volume and graft volume were measured using image analysis software on MR and microCT images. Defect width and graft width were measured using images from HM, MR and microCT. The results were compared to each other. RESULTS: The intraobserver reliabilities for the measurements of new bone volume by microCT, and the measurement of graft modelling by MR and graft volume by microCT were high. The differences between MR, HM and microCT were larger in defect width measurements than in graft width measurement. MR measured smaller defects than HM and microCT. The 95% confidence interval was larger in defect width measurements compared to graft width measurements. CONCLUSIONS: The methods of MR and microCT image analysis are reliable but preferably should be used in combination as to obtain valid conclusions. HM, MR and microCT for graft widths measurements showed more agreement than for defect width measurements. MR appears to overestimate bone formation.     

Optimal Doses of Specific Antipsychotics for Relapse Prevention in a Nationwide Cohort of Patients with Schizophrenia

Background and HypothesisOptimal doses of most antipsychotics in the maintenance treatment of schizophrenia are unknown. We aimed to study the risk of severe relapse indicated by rehospitalization for different dose categories of 15 most frequently used antipsychotics in monotherapy in Finland. Study MethodsWe studied the risk of rehospitalization (Adjusted Hazard Ratio, aHR) associated with six antipsychotic monotherapy dose categories (as time-varying dose, measured in defined daily dose, DDDs/day) in a nationwide cohort of persons diagnosed with schizophrenia (n = 61 889), using within-individual analyses to eliminate selection bias. Study ResultsAmong the 15 most widely used antipsychotics, 13 had a U- or J-shaped dose-response curve, showing the lowest risks of relapse for doses of 0.6–<1.1 DDDs/day vs nonuse of antipsychotics. The exceptions were oral perphenazine (aHR = 0.72, 95% CI = 0.68–0.76, <0.6 DDDs/day), and olanzapine-long-acting injectable (LAI), which had the lowest aHR of any antipsychotic (aHR = 0.17, 95% CI = 0.11–0.25, 1.4–<1.6 DDDs/day). Certain risperidone and perphenazine doses <0.9 DDD/day were associated with 21%–45% lower risk of rehospitalization (P < .001) than the standard dose of 0.9–1.1 DDD/day (ie, 5 mg for risperidone and 30 mg for perphenazine). ConclusionsFor most antipsychotics, the risk of severe relapse was the lowest during use of standard dose. Our results suggest that olanzapine LAI is highly effective in dose ranges >0.9 DDD/day, and especially at 1.4–<1.6 DDDs/day (405 mg/4 weeks) associated with substantially lower risk of rehospitalization than any dose of any other antipsychotic. The current WHO standard dose definitions appear to be clearly too high for perphenazine and somewhat too high for risperidone.     

Lactate dehydrogenase and creatine kinase activities in isolated edema fluid and peripheral blood in cold-induced brain edema

A study of the alterations in lactate dehydrogenase and creatine kinase isoenzyme patterns in isolated grey and white matter edema fluid and in peripheral blood is described with a view to possible clinical use in severe brain-injury.The breakdown of the blood-brain barrier, caused by the infliction of a cold injury to the cerebral cortex of cats, resulted in a shift in the LD isoenzyme distribution in favour of the faster moving fractions and the appearance of brain-type CK in the peripheral blood. Total lactate dehydrogenase activity demonstrated no statistical significant changes during the experiment and total creatine kinase showed only slight increased values in the samples collected simultaneously with the infliction of a cold lesion. This strongly suggest that measurements of these parameters in peripheral blood are of little value as indicators of brain damage.Alterations in isoenzyme patterns observed in edema fluids are reflected in peripheral blood. The presence, therefore, of brain-type creatine kinase acompanied by a relative high amount of lactate dehydrogenase H-sub unit in peripheral blood, can be considered as adequate indices of severe brain damage.