A subset of anti-rotavirus antibodies directed against the viral protein VP7 predicts the onset of celiac disease and induces typical features of the disease in the intestinal epithelial cell line T84

Celiac disease (CD) is an autoimmune disorder of the small intestine triggered by environmental factors in genetically predisposed individuals. A strong association between type 1 diabetes (T1DM) and CD has been reported. We have previously shown that rotavirus infection may be involved in the pathogenesis of CD through a mechanism of molecular mimicry. Indeed, we identified a subset of anti-transglutaminase IgA antibodies that recognize the rotavirus viral protein VP7. In this study, we aimed at evaluating whether such antibodies may predict the onset of CD in children affected by T1DM. Moreover, to further analyze the link between rotavirus infection and pathogenesis of CD, we analyzed the effect of anti-rotavirus VP7 antibodies on T84 intestinal epithelial cells using the gene-array technique, complemented by the analysis of molecules secreted in the supernatant of stimulated cells. We found that anti-rotavirus VP7 antibodies are present in the vast majority (81 %) of T1DM-CD tested sera, but are detectable also in a fraction (27 %) of T1DM children without CD. Moreover, we found that anti-rotavirus VP7 antibodies are present before the CD onset, preceding the detection of anti-tTG and anti-endomysium antibodies. The gene-array analysis showed that purified anti-rotavirus VP7 antibodies modulate genes that are involved in apoptosis, inflammation, and alteration of the epithelial barrier integrity in intestinal epithelial cells, all typical features of CD. Taken together, these new data further support the involvement of rotavirus infection in the pathogenesis of CD and suggest a predictive role of anti-rotavirus VP7 antibodies.     

Greek language processing in naive and skilled readers: Functional properties of the VWFA investigated with ERPs

Neuroimaging studies have provided evidence that the orthographic properties of linguistic stimuli are processed within the visual word form area (VWFA) localised in the left inferotemporal cortex (Cohen & Dehaene, 2004). It is not, however, clear in the literature whether this region responds preferentially to words, distinguishing them from pseudowords, or whether the pseudowords are distinguished from letter-strings on the basis of their orthographic regularity, or again, whether the VWFA distinguishes letters from numbers or from visual stimuli such as chequerboards. Very recently, it has been claimed that there is no evidence that the ill-named VWFA changes its responsiveness during or after reading acquisition (Price & Devlin, 2004). In order to simulate a condition of pre-reading ability in adult readers, we performed this study, in which we compared processing of Greek words and legal pseudowords in mother-tongue Greeks (skilled readers) and monolingual Italian individuals (naive readers) who had no familiarity with the Greek alphabet. ERPs were recorded while volunteers were engaged in a task involving the identification and response to target letters contained within Greek words or pseudowords. The response speed was identical in the two groups (550 vs. 557 ms). ERP data showed that at 165 ms post-stimulus (N1 component) the left lateral-occipital scalp area, probably corresponding to the left ventral occipitotemporal sulcus, discriminates letters of a familiar alphabet, while an unknown alphabet also activates the homologous right-hemispheric region more than 100 ms later. This suggests that the VWFA discriminates nonalphabetic symbols from letter-strings. An analysis of the N2 component showed an increase in the activation of the same region at about 285 ms post-stimulus during the processing of words rather than pseudowords in skilled readers, thus supporting the view that the VWFA discriminates words on the basis of their familiarity. The data seem to suggest that the VWFA is alphabet-specific and that it is based on the shaping of visual area activity during acquisition of the ability to read a given symbolic code.     

Hot topics in coagulation testing: Important considerations for testing children for bleeding/thrombotic disorders

The accurate use and interpretation of diagnostic investigations are essential for safe and effective patient care. Appropriate application and interpretation of coagulation testing can be challenging, and many controversies exist relating to the standardization of testing procedures, the application of relevant tests to different patient populations and the interpretation of test results. We present a list of the most prominent controversies in coagulation testing and have selected three specific examples (age‐appropriate reference ranges, therapeutic anticoagulation monitoring and tests of thrombin generation) for closer discussion, highlighting examples with a paediatric framework. We discuss the limitations of discrete age‐partitioned reference intervals, given the established principle of developmental haemostasis; the difficulties in establishing normative data across different laboratories; important pre‐analytical variables affecting coagulation testing; the challenges in interpreting APTT and anti‐Xa assays for monitoring unfractionated heparin therapy in different clinical situations; and the limitations in interpreting tests of thrombin generation due to current available thrombin‐specific substrates and the complicating factor of variable alpha2‐macroglobulin levels. These controversies are demonstrated using paediatric examples, but raise important implications for coagulation testing in patients of all ages and highlight the pressing need for further research in these areas.     

Molecular and Serological Diversity of Neisseria meningitidis Carrier Strains Isolated from Italian Students Aged 14 to 22 Years

Neisseria meningitidis is an obligate human commensal that commonly colonizes the oropharyngeal mucosa. Carriage is age dependent and very common in young adults. The relationships between carriage and invasive disease are not completely understood. In this work, we performed a longitudinal carrier study in adolescents and young adults (173 subjects). Overall, 32 subjects (18.5%) had results that were positive for meningococcal carriage in at least one visit (average monthly carriage rate, 12.1%). Only five subjects tested positive at all four visits. All meningococcal isolates were characterized by molecular and serological techniques. Multilocus sequence typing, PorA typing, and sequencing of the 4CMenB vaccine antigens were used to assess strain diversity. The majority of positive subjects were colonized by capsule null (34.4%) and capsular group B strains (28.1%), accounting for 23.5% and 29.4% of the total number of isolates, respectively. The fHbp and nhba genes were present in all isolates, while the nadA gene was present in 5% of the isolates. The genetic variability of the 4CMenB vaccine antigens in this collection was relatively high compared with that of other disease-causing strain panels. Indications about the persistence of the carriage state were limited to the time span of the study. All strains isolated from the same subject were identical or cumulated minor changes over time. The expression levels and antigenicities of the 4CMenB vaccine antigens in each strain were analyzed by the meningococcal antigen typing system (MATS), which revealed that expression can change over time in the same individual. Future analysis of antigen variability and expression in carrier strains after the introduction of the MenB vaccine will allow for a definition of its impact on nasopharyngeal/oropharyngeal carriage.     

Locoregional recurrence in patients with HER2 positive breast cancer

Literature shows that HER2/neu positive breast cancer cells are more sensitive to radiation-induced apoptosis by targeting the epidermal growth factor receptor family tyrosine kinase. We selected 466 patients with pT1-2 HER2/neu positive tumors who received adjuvant trastuzumab for primary invasive breast cancer. Patients were divided into three groups [Quadrantectomy followed by conventional radiotherapy vs Quadrantectomy followed by Intra-operative radiotherapy with electrons vs Mastectomy without radiotherapy]. After a median follow-up of 52 months, the 5-year cumulative incidence of locoregional recurrence (LRR) was 1.9%, 11.5% and 5.0% respectively (p < 0.01). At the multivariate analysis, extensive perivascular invasion, Luminal B HER2/Progesterone Receptor (PgR) negative status and Quadrantectomy followed by Intra-operative radiotherapy with electrons have significantly increased the risk of LRR. Our results suggest that HER2/neu positive breast cancer might have better outcomes when treated simultaneously with external radiotherapy and trastuzumab. Moreover, we underline the importance of PgR and further new stratification of risk among luminal subtypes.