Interleukin 28B polymorphism predicts pegylated interferon plus ribavirin treatment outcome in chronic hepatitis C genotype 4

Single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) region are the strongest baseline predictors of a sustained virologic response (SVR) to peg-interferon (PegIFN) and ribavirin (Rbv) in patients with hepatitis C virus (HCV) genotype 1 infection. Whether this holds true for HCV-4 patients too is unknown. The aim was to investigate the predictive power of the rs12979860 IL28B SNP for a response to Peg-IFN and Rbv in HCV-4 patients. All HCV-4 patients consecutively treated between September 2004 and June 2010 with PegIFN and Rbv at two liver centers at the Maggiore Hospital Milan (Italy) underwent TaqMan SNP Genotyping assays for testing rs12979860 genotype. Of 112 treated patients (98 males, 75 of Egyptian descent, 26 with cirrhosis) 103 were included in the final analysis; five discontinued treatment for nonvirologic reasons and four did not consent to genetic testing. Twenty-four (23%) were genotype CC, 65 (63%) CT, and 14 (14%) TT. Overall, 50 (49%) achieved an SVR: 21 (88%) CC patients versus 29 (37%) CT/TT (P < 0.0001). CC patients more often had a rapid virologic response (RVR) than CT/TT patients (12, 50% versus 23, 29%; P = 0.08), while also showing lower relapse rates (0% [0/21] versus 36% [16/45] P = 0.0013). In non-RVR patients, SVR rates were higher in CC than CT/TT patients (9 [75%] versus 13 [23%] P = 0.001). By logistic regression, the IL28B rs12979860 CC genotype was an independent predictor of SVR with an odds ratio of 8.0 (95% confidence interval 2.00-32.01; P = 0.003). CONCLUSION: The IL28B rs12979860 SNP may have an added value in the treatment algorithm of HCV-4 patients because it is the strongest predictor of an SVR to PegIFN/Rbv therapy.     

Their pain is not our pain: Brain and autonomic correlates of empathic resonance with the pain of same and different race individuals

Recent advances in social neuroscience research have unveiled the neurophysiological correlates of race and intergroup processing. However, little is known about the neural mechanisms underlying intergroup empathy. Combining event‐related fMRI with measurements of pupil dilation as an index of autonomic reactivity, we explored how race and group membership affect empathy‐related responses. White and Black subjects were presented with video clips depicting white, black, and unfamiliar violet‐skinned hands being either painfully penetrated by a syringe or being touched by a Q‐tip. Both hemodynamic activity within areas known to be involved in the processing of first and third‐person emotional experiences of pain, i.e., bilateral anterior insula, and autonomic reactivity were greater for the pain experienced by own‐race compared to that of other‐race and violet models. Interestingly, greater implicit racial bias predicted increased activity within the left anterior insula during the observation of own‐race pain relative to other‐race pain. Our findings highlight the close link between group‐based segregation and empathic processing. Moreover, they demonstrate the relative influence of culturally acquired implicit attitudes and perceived similarity/familiarity with the target in shaping emotional responses to others' physical pain. Hum Brain Mapp 34:3168–3181, 2013. © 2012 Wiley Periodicals, Inc.     

Brain plasticity for verbal and visual memories in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: An fMRI study

We aimed to identify the brain areas involved in verbal and visual memory processing in normal controls and patients with unilateral mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS) by means of functional magnetic resonance imaging (fMRI). The sample comprised nine normal controls, eight patients with right MTLE, and nine patients with left MTLE. All subjects underwent fMRI with verbal and visual memory paradigms, consisting of encoding and immediate recall of 17 abstract words and 17 abstract drawings. A complex network including parietal, temporal, and frontal cortices seems to be involved in verbal memory encoding and retrieval in normal controls. Although similar areas of activation were identified in both patient groups, the extension of such activations was larger in the left‐HS group. Patients with left HS also tended to exhibit more bilateral or right lateralized encoding related activations. This finding suggests a functional reorganization of verbal memory processing areas in these patients due to the failure of left MTL system. As regards visual memory encoding and retrieval, our findings support the hypothesis of a more diffuse and bilateral representation of this cognitive function in the brain. Compared to normal controls, encoding in the left‐HS group recruited more widespread cortical areas, which were even more widespread in the right‐HS group probably to compensate for their right mesial temporal dysfunction. In contrast, the right‐HS group exhibited fewer activated areas during immediate recall than the other two groups, probably related to their greater difficulty in dealing with visual memory content. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

In vivo microglia activation in very early dementia with Lewy bodies,comparison with Parkinson's disease

BackgroundReactive microgliosis, hallmark of neuroinflammation, may contribute to neuronal degeneration, as shown in several neurodegenerative diseases. We in vivo evaluated microglia activation in early dementia with Lewy bodies, still not reported, and compared with early Parkinson's disease, to assess possible differential pathological patterns.MethodsWe measured the [¹¹C]-PK11195 binding potentials with Positron Emission Tomography, using a simplified reference tissue model, as marker of microglia activation, and cerebral spinal fluid protein carbonylation levels, as marker of oxidative stress. Six dementia with Lewy bodies and 6 Parkinson's disease patients within a year from the onset, and eleven healthy controls were included. Clinical diagnosis was confirmed at a 4-year follow-up.ResultsIn dementia with Lewy bodies as well as in Parkinson's disease, we found significant (p < 0.001) [¹¹C]-PK11195 binding potential increases in the substantia nigra and putamen. Patients with Lewy bodies dementia had extensive additional microglia activation in several associative cortices. This was evident also at a single subject level. Significant increase of Cerebral Spinal Fluid protein carbonylation was shown in both patients' groups.Conclusions[¹¹C]-PK11195 Positron Emission Tomography imaging revealed neuroinflammation in dementia with Lewy bodies and Parkinson's disease, mirroring, even at a single subject level, the common and the different topographical distribution of neuropathological changes, yet in the earliest stages of the disease process. Focusing on those events that characterize parkinsonisms and Parkinson's disease may be the key to further advancing the understanding of pathogenesis and to taking these mechanisms forward as a means of defining targets for neuroprotection.     

Biomedical Ti–Mo Alloys with Surface Machined and Modified by Laser Beam: Biomechanical,Histological, and Histometric Analysis in Rabbits

Purpose: In vivo bone response was assessed by removal torque, hystological and histometrical analysis on a recently developed biomedical Ti‐15Mo alloy, after surface modification by laser beam irradiation, installed in the tibia of rabbits. Materials and Methods: A total of 32 wide cylindrical Ti‐15Mo dental implants were obtained (10 mm × 3.75 mm). The implants were divided into two groups: 1) control samples (Machined surface – MS) and 2) implants with their surface modified by Laser beam‐irradiation (Test samples – LS). Six implants of each surface were used for removal torque test and 10 of each surface for histological and histometrical analysis. The implants were placed in the tibial metaphyses of rabbits. Results: Average removal torque was 51.5 Ncm to MS and >90 Ncm to LS. Bone‐to‐implant‐contact percentage was significantly higher for LS implants both in the cortical and marrow regions. Conclusions: The present study demonstrated that laser treated Ti‐15Mo alloys are promising materials for biomedical application.     

Implantation of a completely subcutaneous ICD system: case report of a patient with Brugada syndrome and state of the art

Aims  

Complications of implantable cardioverter-defibrillator (ICD) therapy are often linked to transvenous lead insertion, lead failure, or infections. An entirely subcutaneous ICD system (S-ICD) avoids the need for the placement of electrodes within the heart and can provide clinical advantages.