Effect of titanium carbide coating on the osseointegration response in vitro and in vivo

Titanium has limitations in its clinical performance in dental and orthopaedic applications. This study describes a coating process using pulsed laser deposition (PLD) technology to produce surfaces of titanium carbide (TiC) on titanium substrates and evaluates the biological response both in vitro and in vivo. X-ray photoelectron spectroscopy (XPS) analysis revealed the presence of 18.6-21.5% TiC in the surface layer, accompanied by oxides of titanium 78.5-81.4% in the following concentrations: 11.1-13.0% Ti(2)O(3), 50.8-55.8% TiO(2), 14.5-14.7% TiO. Expression of genes central to osteoblast differentiation (alkaline phosphatase, A2 pro-collagen type 1, osteocalcin, BMP-4, TGFbeta and Cbfa-1) were up-regulated in all cell lines (primary human osteoblasts, hFOB1.19 and ROS.MER#14) grown on TiC compared with uncoated titanium when measured by semiquantitative PCR and real time-PCR, whilst genes involved in modulation of osteoclastogenesis and osteoclast activity (IL-6 and M-CSF) were unchanged. Bone density was shown to be greater around TiC-coated implants after 2 and 4 weeks in sheep and both 4 and 8 weeks in rabbits compared to uncoated titanium. Rapid bone deposition was demonstrated after only 2 weeks in the rabbit model when visualized with intravital staining. It is concluded that coating with TiC will, in comparison to uncoated titanium, improve implant hardness, biocompatibility through surface stability and osseointegration through improved bone growth.     

Hepatocellular carcinoma cell supernatants increase expansion and function of CD4(+)CD25(+) regulatory T cells

Dysfunction of the host immune system in cancer patients can be due to a number of factors, including suppression of tumor-associated antigen reactive lymphocytes by CD4(+)CD25(+) regulatory T (Treg) cells. Several studies suggest that Tregs are elevated in cancer patients and that depletion of Tregs may enhance the antitumor immunity of host, but the pathogenic and mechanistic relationship between cancer and Tregs is still unclear. In this report, we show that Tregs are increased in peripheral blood mononuclear cells (PBMCs) from hepatocellular carcinoma (HCC) patients and positively correlate with tumor burden. When PBMCs are co-cultured with human hepatoma cell lines Huh7, HepG2, and Hclone5, CD4(+)CD25(+)-T cell populations increase in frequency and undergo phenotypic and functional changes. CD45RA, CD45RO, CD69, CD62L, GITR, CTLA-4, Ki67, granzyme A, granzyme B, and FOXP3 expression were upregulated in CD4(+)CD25(+) cells after in vitro exposure to HCC cell lines. CD4(+)CD25(+) T cells from PBMCs that were co-cultured with Huh7 cells also have higher suppressor ability compared to that of the CD4(+)CD25(+) T cells from control PBMC. Huh7 culture supernatants appear to promote CD4(+)CD25(+) T-cell proliferation and inhibit CD4(+)CD25(-) T-cell proliferation. In conclusion, these results strongly suggest that tumor-related factors not only induce and expand CD4(+)CD25(+) cells, but also enhance their suppressor ability.     

Anatomical measurements of the orbitofrontal cortex in child and adolescent patients with bipolar disorder

Imaging studies indicate smaller orbitofrontal cortex (OFC) volume in mood disorder patients compared with healthy subjects. We sought to determine whether child and adolescent patients with bipolar disorder have smaller OFC volumes than healthy controls. Fourteen children and adolescents meeting DSM-IV criteria for bipolar disorder (six males and eight females with a mean age+/-S.D.=15.5+/-3.2 years) and 20 healthy controls (11 males and nine females with mean age+/-S.D.=16.9+/-3.8 years) were studied. Orbitofrontal cortex volume was measured using magnetic resonance imaging. Male bipolar patients had smaller gray matter volumes in medial (p=0.044), right medial (0.037) and right (p=0.032) lateral OFC subdivisions compared to male controls. In contrast, female patients had larger gray matter volumes in left (p=0.03), lateral (p=0.012), left lateral (p=0.007), and trends for larger volumes in right lateral and left medial OFC subdivisions compared with female controls. Male patients exhibit smaller gray matter volumes, while female patients exhibit larger volumes in some OFC sub-regions. Gender differences in OFC abnormalities may be involved in illness pathophysiology among young bipolar patients.     

Comparison between a built-in "dual side" chest imaging device and a standard "single side" CR

An integrated readout computed radiography system (Fuji XU-D1) incorporating dual-side imaging plates (ST-55BD) was analyzed in terms of modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) for standard beam qualities RQA 9 and RQA 5. NPS and DQE were assessed using a detector entrance air kerma consistent with clinical practice for chest radiography. Similar investigation was performed on a standard reader (Fuji FCR 5000) using single-side imaging plates (ST-VI). Negligible differences were found between the MTFs of the two imaging systems for RQA 9, whereas for RQA 5 the single-side system exhibited slightly superior MTF. Regarding noise response, the dual-side system turned out to be better performing for both beam qualities over a wide range of frequencies. For RQA 9, at 8 microGy, the DQE of the dual-side system was moderately higher over the whole frequency range, whereas for RQA 5, at 10 microGy, significant improvement was found at low- and midrange frequencies. As an example, at 1 cycle/mm, the following improvements in the DQE of the dual-side system were observed: +22% (RQA 9, at 8 microGy), +50% (RQA 9, at 30 microGy), and +45% (RQA 5, at 10 microGy).     

Prognostic significance of p53 and p63 immunolocalisation in primary and matched lymph node metastasis in oral squamous cell carcinoma

This study evaluates the prognostic significance of p53 and p63 immunolocalisation in oral squamous cell carcinoma samples from 45 matched primary tumors (PT) and lymph node metastases (LNM). Data regarding patient age, gender, primary site, histological differentiation, metastasis, disease-free survival (DFS) and overall survival (OS) were available. p53 and p63 immunolabeling was detected in 17 (37.8%) and 23 (51.1%) of the PT, respectively. For LNM, there was p53 and p63 labeling in 23 (51.1%) and 26 (57.8%) cases, respectively. Most cases showed similar labeling in PT and the corresponding LNM (73.3% for p53 and 53.3% for p63, respectively). No statistically significant associations were found between p53 and p63 immunolabeling and histological differentiation; p63 positive tumors showed higher DFS (p=0.006) and OS (p=0.049); and p53-negative tumors had a higher DFS interval (p=0.009). Our findings suggest that initially p53-negative tumors and initially p63-positive tumors that retain this labeling pattern may follow less aggressive biological courses and present better prognoses.     

The CDC2 I-G-T haplotype associated with the APOE epsilon4 allele increases the risk of sporadic Alzheimer's disease in Sicily

The cell division cycle 2 (CDC2) gene is a candidate susceptibility gene for Alzheimer's disease (AD). We investigated the CDC2 genotype, and allele and haplotype frequencies in AD patients and matched controls, distinguishing between apolipoprotein E (APOE) epsilon4 allele carriers and non-carriers. APOE epsilon4 is an established predictor of AD risk. APOE and CDC2 genotypes were examined in 109 sporadic AD patients and in 110 healthy age- and sex-matched controls from Sicily. The epsilon4 allele of APOE was predictive of AD risk in our study group (odds ratio: 5.37, 95% CI 2.77-10.41; P<0.0001). Genotype and allele frequencies of the three tested CDC2 polymorphisms (Ex6+7I/D, Ex7-15 G>A, Ex7-14 T>A) were not significantly different between AD patients and controls. However, a significant different distribution of a specific CDC2 haplotype (I-G-T) was found between AD patients and controls when analyzing APOE epsilon4-positive subjects (P=0.0288). Moreover, the combined presence of the I-G-T haplotype and the epsilon4 allele almost doubled the risk of AD (odds ratio: 10.09, 95% CI 3.88-26.25; P<0.0001) compared to carriers of epsilon4 alone. This study suggests that the I-G-T haplotype of the CDC2 gene increases the risk of AD in APOE epsilon4 carriers.     

Sortase A utilizes an ancillary protein anchor for efficient cell wall anchoring of pili in Streptococcus agalactiae

Pili are putative virulence factors and promising vaccine candidates in Streptococcus agalactiae (group B Streptococcus [GBS]) infection, a leading cause of neonatal sepsis and meningitis. The genes necessary for pilus synthesis and assembly are clustered in pilus islands (PI). Each gene encodes three structural subunits (a backbone and two ancillary proteins) bearing a C-terminal LPXTG motif and two subfamily C sortases (SrtC) involved in covalent polymerization of the subunits. GBS strains also possess the conserved “housekeeping” sortase A (SrtA), but its role in pilus assembly is unclear. To address this issue, pilus expression and cell wall anchoring were analyzed in srtA deletion mutants. Loss of SrtA did not affect pilus polymerization. However, pilus expression on the cell surface was reduced, and pili accumulated in the culture supernatant. Furthermore, cell-associated pili could be readily released by detergent treatment, indicating that SrtA is involved in covalent anchoring of pili to the cell wall. When each of the genes comprising PI-2a was systematically deleted, only the absence of ancillary subunit GBS150 or the SrtC required for incorporation of GBS150 into pili mimicked the srtA mutant phenotype. Thus, from these data a model for GBS pilus assembly can be proposed in which PI sortases are responsible for polymerization of the pilus structure, while SrtA is required to covalently attach it to the cell wall, utilizing ancillary pilus subunit GBS150 as the anchor protein.     

EEG and fMRI Coregistration to Investigate the Cortical Oscillatory Activities During Finger Movement

Electroencephalography combined with functional magnetic resonance imaging (EEG-fMRI) may be used to identify blood oxygenation level dependent (BOLD) signal changes associated with physiological and pathological EEG event. In this study we used EEG-fMRI to determine the possible correlation between topographical movement-related EEG changes in brain oscillatory activity recorded from EEG electrodes over the scalp and fMRI-BOLD cortical responses in motor areas during finger movement. Thirty-two channels of EEG were recorded in 9 subjects during eyes-open condition inside a 1.5 T magnetic resonance (MR) scanner using a MR-compatible EEG recording system. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during␣fMRI acquisition. For EEG data analysis we used the event-related-synchronization/desynchronization (ERS/ERD) approach to investigate where movement-related decreases in alpha and beta power are located. For image statistical analysis we used a general linear model (GLM) approach. There was a significant correlation between the positive-negative ratio of BOLD signal peaks and ERD values in the electrodes over the region of activation. We conclude that combined EEG-fMRI may be used to investigate movement-related oscillations of the human brain inside an MRI scanner and the movement-related changes in the EMG or EEG signals are useful to identify the brain activation sources responsible for BOLD-signal changes.