Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation

The recent hypothesis that postnatal microglia are maintained independently of circulating monocytes by local precursors that colonize the brain before birth has relevant implications for the treatment of various neurological diseases, including lysosomal storage disorders (LSDs), for which hematopoietic cell transplantation (HCT) is applied to repopulate the recipient myeloid compartment, including microglia, with cells expressing the defective functional hydrolase. By studying wild-type and LSD mice at diverse time-points after HCT, we showed the occurrence of a short-term wave of brain infiltration by a fraction of the transplanted hematopoietic progenitors, independently from the administration of a preparatory regimen and from the presence of a disease state in the brain. However, only the use of a conditioning regimen capable of ablating functionally defined brain-resident myeloid precursors allowed turnover of microglia with the donor, mediated by local proliferation of early immigrants rather than entrance of mature cells from the circulation.     

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.     

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.     

Reading disorders in a language with shallow orthography: A multiple single-case study in Italian

Background: This study aimed (i) to verify whether the classical word-naming models developed for English-speaking participants also account for the performance of patients who speak a shallow-orthography language such as Italian, and (ii) to study the effects of word frequency, concreteness, and grammatical class on word naming. Methods & Procedures: A total of 90 Italian aphasic patients participated in two reading tasks. The first task contained four sets of items: (i) concrete nouns (natural objects and artefacts), (ii) abstract nouns, (iii) function words, (iv) morphologically simple legal nonwords. The second task (trisyllabic words with unpredictable stress position) was designed to test reading ability along the lexical route (the position of the major word stress is the only opaque variable in the Italian reading system). The patients' performances on the two tasks were analysed for strong dissociations, and to test the effect of grammatical class, concreteness, word frequency, and item length. The effect of age of acquisition was tested in a subsequent analysis. Outcomes & Results: Reading scores were pathological for all patients. The present sample reflected the entire spectrum of reading impairments: phonological (49), surface (4), undifferentiated (32), and letter-by-letter (5) dyslexia, which is in line with data reported for English-speaking aphasic patients. Only one of the phonological dyslexic patients made semantic errors (a reading impairment compatible with the diagnosis of deep dyslexia). The vast majority of Broca's aphasic patients suffered from phonological dyslexia (76%), while fluent aphasic patients were distributed more evenly across dyslexia types; all four surface dyslexic patients belonged to the fluent aphasia group. Overall, grammatical class (concrete nouns vs function words) had a significant effect on 14 patients (15.6%), concreteness (concrete vs abstract nouns) on 15 (16.7%), and word frequency on 5 (5.6%). Grammatical class and concreteness affected the performance of phonological and undifferentiated dyslexic patients, and seemed not to influence the scores of the surface dyslexic patients. Age of acquisition turned out to have a highly significant effect and may account for most of the lexical effects emerging from the first analysis. Conclusions: The entire spectrum of reading impairments was observed in this group of Italian aphasic patients, thus confirming the validity of contemporary reading models also for shallow-orthography languages. Concreteness and grammatical class effects, present in deep dyslexia, also affected the performance of patients suffering from other types of dyslexia, although both phenomena might derive from a confounding effect of age of acquisition.