Cerebral perfusion mapping during retrieval of spatial memory in rats.

Studies of brain functional activation during spatial navigation using electrophysiology and immediate-early gene responses have typically targeted a limited number of brain regions. Our study provides the first whole brain analysis of cerebral activation during retrieval of spatial memory in the freely-moving rat. Rats (LEARNERS) were trained in the Barnes maze, an allocentric spatial navigation task, while CONTROLS received passive exposure. After 19 days, functional brain mapping was performed during recall by bolus intravenous injection of [14C]-iodoantipyrine using a novel subcutaneous minipump triggered by remote activation. Regional cerebral blood flow (rCBF)-related tissue radioactivity was analyzed by statistical parametric mapping from autoradiographic images of the three-dimensionally reconstructed brains. Functional connectivity was examined between regions of the spatial navigation circuit through interregional correlation analysis. Significant rCBF increases were noted in LEARNERS compared to CONTROLS broadly across the spatial navigation circuit, including the hippocampus (anterior dorsal CA1, posterior ventral CA1-3), subiculum, thalamus, striatum, medial septum, cerebral cortex, with decreases noted in the mammillary nucleus, amygdala and insula. LEARNERS showed a significantly greater positive correlation of rCBF of the ventral hippocampus with retrosplenial, lateral orbital, parietal and primary visual cortex, and a significantly more negative correlation with the mammillary nucleus, amygdala, posterior entorhinal cortex, and anterior thalamic nucleus. The complex sensory component of the spatial navigation task was underscored by broad activation across visual, somatosensory, olfactory, auditory and vestibular circuits which was enhanced in LEARNERS. Brain mapping facilitated by an implantable minipump represents a powerful tool for evaluation of mammalian behaviors dependent on locomotion.

Silver doped titanium dioxide nanoparticles as antimicrobial additives to dental polymers.

OBJECTIVE: The objectives of this in vitro study were to produce a filled resin containing Ag-TiO2 filler particles and to test its antibacterial properties. METHODS: Ag-TiO2 particles were manufactured using the ball milling method and incorporated into an epoxy resin using a high speed centrifugal mixer. Using UV/vis spectrophotometry investigations were performed to assess how the photocatalytic properties of the Ag-TiO2 particles are affected when encased in resin. Adopting the bacteria colony counting technique, the antibacterial properties of Ag-TiO2 particles and Ag-TiO2 containing resins were assessed using Streptococcus mutans under varying lighting conditions. RESULTS: Ag doping of TiO2 results in a band gap shift towards the visible spectrum enabling Ag-TiO2 to exhibit photocatalytic properties when exposed to visible light. Small quantities of Ag-TiO2 were able to produce a bactericidal effect when in contact with S. mutans under visible light conditions. When incorporated into the bulk of an epoxy resin, the photocatalytic properties of the Ag-TiO2 particles were significantly reduced. However, a potent bactericidal effect was still achieved against S. mutans. SIGNIFICANCE: Ag-TiO2 filled resin shows promising antimicrobial properties, which could potentially be used clinically.

Gleason grading after neoadjuvant hormonal therapy retains prognostic value for systemic progression following radical prostatectomy.

BACKGROUND: The Gleason grading system in prostatectomy specimens following receipt of neoadjuvant therapy has been considered inaccurate. However, with continuing expansion of novel therapeutics, it is important to understand whether the Gleason system can be effectively utilized in this setting. The aim of this study was to assess the ability of the Gleason grading system to predict systemic progression among prostatectomy specimens treated with neoadjuvant hormone therapy (NHT). METHODS: This was a single-institution retrospective analysis from 1987 to 2009 of 13,427 patients who underwent radical prostatectomy (RP) without NHT and 1148 patients with NHT. NHT consisted of leuprolide alone (n = 415), antiandrogen therapy alone (n = 400) and combined treatment (n = 333). Kaplan-Meier analysis estimated 15-year systemic progression-free survival among NHT and non-NHT patients. Cox proportional hazard regression models estimated risk of systemic progression following RP according to NHT use and nonuse. RESULTS: Median duration of NHT was 3 months (interquartile range (IQR) 2-4) whereas median follow-up after RP was 8.3 years (IQR 5-10.8). NHT patients were more likely to be D'Amico high risk, have locally advanced pathologic T stage (≥ pT3), pathologic Gleason scores (GS) of 8-10 and lymph node involvement (P<0.0001 for all). NHT use was associated with lower rates of positive surgical margins, more downgrading to pT0 and less GS upgrading from biopsy (P ≤ 0.001 for all). GS could not be assigned to only 3% of NHT patients. On multivariate analysis, pathologic GS remained a predictor of systemic progression (SP) following NHT (hazard ratio (HR) 1.6, P = 0.005), but the association was less strong compared with non-NHT patients (HR 2.9, P < 0.0001). CONCLUSIONS: Utilization of the Gleason system appears feasible among hormonally pretreated prostatectomy specimens and shows continued prognostication for systemic progression. Confirmatory investigations are needed before the Gleason system can be reliably applied in the setting of neoadjuvant therapy.

Does variation in either age at start of therapy or duration of therapy make chemoprevention with finasteride cost-effective?

BACKGROUND: Incremental cost-effectiveness ratios (ICERs) of finasteride for prostate cancer prevention are consistent with estimates beyond $100 000 per quality-adjusted life-year (QALY). The majority of these analyses are based on chemoprevention starting in men aged 50-55 years. We sought to evaluate the impact of varying both age at commencement of therapy and length of therapy on the cost-effectiveness of finasteride. METHODS: A probabilistic Markov model was designed to estimate lifetime prostate health-related costs and quality-adjusted survival for men receiving or not receiving chemoprevention with finasteride. ICERs across scenarios varying age at start of therapy and duration of chemoprevention were compared. RESULTS: The ICER for men starting chemoprevention at age 50 and continuing to age 75 was $88 800 per QALY when assuming finasteride causes a constant risk reduction across all tumor grades (base case 1) and $142 300 per QALY when assuming a differential treatment effect according to Gleason score (base case 2). When starting age is increased, the ICERs trend downward and nadir at 65 years to $64 700 per QALY (base case 1) and $118 600 per QALY (base case 2). Altering duration of therapy had minimal impact. Patient-level experiences with finasteride and BPH significantly influenced the cost-effectiveness of chemoprevention. CONCLUSIONS: Initiating chemoprevention at ages when prostate cancer incidence is higher improves its cost-effectiveness profile. Only when assuming a constant risk reduction for all tumor grades, did finasteride fall below $100 000 per QALY, but this finding was not upheld when accounting for side effects associated with the drug.