What if sharing music as a language is the key to meeting halfway? Absolute pitch, pitch discrimination and Autism Spectrum Disorder.

BACKGROUND: Absolute pitch is the ability to identify a given note in the absence of a reference note. The prevalence of absolute pitch in autism is between 5% and 11% and autism involves notably enhanced abilities in pitch discrimination. OBJECTIVES: To summarize the evidence about the role and the meaning of these special skills in autism. METHODS: Systematic electronic database searches were conducted using Pubmed, Scopus, Psycinfo, and Web of Science. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRI-SMA) guideline was followed, and, after thorough screening by two independent reviewers, 17 articles remained eligible for inclusion in this study. RESULTS: We have two different groups of results. Eight case-control studies discuss pitch discrimination and autism. The second group included four case reports about autistic individuals with absolute pitch and five case-control studies. These results strongly suggest that music elicits special attention for children with autism, and taken together, this evidence supports a major frequency of AP in autistic children. CONCLUSION: Based on this evidence, future perspectives could include studies aiming to detect absolute pitch at an early age and to use this special skill to stimulate joint attention, as well as socio-communicative skills.

LIF/Raman/XRF non-invasive microanalysis of frescoes from St. Alexander catacombs in Rome.

Laser-induced fluorescence (LIF), Raman spectroscopy and X-ray (XRF) fluorescence were used to study two frescoes at the S. Alexander catacombs complex, in Rome. LIF analysis has shown the presence of a transparent protective material probably deposited in previous restoration treatments and allowed to clearly distinguish the areas undergoing the current restoration process from the ones which still have to be treated. Raman and XRF analysis allowed to non-destructively characterizing most of the pictorial materials used for the artworks, including calcite (CaCO3), red ochre (Fe2O3), minium (Pb3O4), yellow ochre (α-FeOOH) and others. Therefore, thanks to the complementarity of the above-mentioned techniques, it was possible to obtain a detailed characterization of the studied frescoes. Finally, the whole ensemble of results constituted a valid tool to effectively plan the restoration of the frescoes.

Causas y curas de las dermatosis en la obra de Hildegarda de Bingen / Causes and Cures of Skin Diseases in the Work of Hildegard of Bingen

No disponible

Role of DWI assessing nodal involvement and response to neoadjuvant chemotherapy in advanced breast cancer.

OBJECTIVE: To explore the role of diffusion-weighted imaging (DWI) in the staging of axillary lymph nodes and the restaging after neoadjuvant chemotherapy (NAD) in advanced breast cancer. PATIENTS AND METHODS: MRI examinations of forty-two patients diagnosed with advanced breast cancer addressed to NAD and axillary lymph node dissection (ALND) were reviewed. Apparent diffusion coefficients (ADC) of each visible node in DWI in the pathologic axilla (PA) and healthy axilla (HA) were measured at the time of diagnosis (t0) and after chemotherapy (t1); mean values of the ADC were calculated. Patients were classified as responders (R), non-responders (NR), macrometastasis (MA), micrometastasis (Mi). RESULTS: Mean ADC was 0.92 ± 0.07 x 10-3 mm2/sec at t0 and 0.97 ± 0.06 x 10-3 mm2/sec at t1 (p = 0.284) in PA, 0.89 ± 0.06 x 10-3 mm2/sec at t0 and 0.92 ± 0.06 x 10-3 mm2/sec at t1 (p = 0.403) in HA, 0.95 ± 0.111 x 10-3 mm2/sec at t0 and 0.95 ± 0.14 x 10-3 mm2/sec at t1 (p = 0.954) in R group, 0.90 ± 0.09 x 10-3 mm2/sec at t0 and 0.97 ± 0.07 x 10-3 mm2/sec at t1 (p = 0.085) in NR group, 0.86 ± 0.10 x 10-3 mm2/sec at t0 and 0.99 ± 0.09 x 10-3 mm2/sec at t1 (p = 0.055) in MA, and 0.99 ± 0.23 x 10-3 mm2/sec at t0 and 0.95 ± 0.15 x 10-3 mm2/sec at t1 in Mi (p = 0.667). CONCLUSIONS: Mean ADC between PA and HA, R and NR, MA and Mi did not significantly differ at t0 and t1 (p > 0.05). Variation in mean ADC between t0 and t1 was not significant in all groups (p > 0.05), except for a trend toward significance (p = 0.055) in MA. DWI has a potential role in restaging of macrometastatic axillary nodes after NAD.

Infantile and childhood onset PLA2G6-associated neurodegeneration in a large North African cohort.

BACKGROUND AND PURPOSE: Mutations in the PLA2G6 gene are causative of PLA2G6-associated neurodegeneration (PLAN), a spectrum of neurodegenerative conditions including infantile, childhood and adult onset forms. METHODS: Seventeen North African patients with a clinical suspicion of infantile-onset PLAN underwent clinical, neurophysiological and neuroimaging examinations, and PLA2G6 sequencing. Haplotype analysis was performed to date the identified founder mutation. RESULTS: All patients carried biallelic mutations in PLA2G6. Sixteen children had the commonest form of infantile-onset PLAN, with early onset of psychomotor regression, hypotonia, pyramidal and cerebellar signs, and abnormal ocular movements. The phenotype was highly homogeneous, with rapid development of severe spastic tetraparesis, cognitive impairment and optic atrophy. Neuroimaging showed cerebellar atrophy and claval hypertrophy to be the commonest and earliest signs, whilst cerebellar cortex hyperintensity and pallidal iron deposition were later findings. Motor or sensory-motor neuropathy and electroencephalogram fast rhythms were also frequent. Nine patients from six families shared the same founder mutation (p.V691del) which probably arose by the late seventeenth century. Only one patient fitted the diagnosis of the much rarer childhood-onset PLAN. Despite the early onset (18 months), clinical progression was slower, with behavioral disturbances and dystonia. Typical features of infantile-onset PLAN such as hypotonia, nystagmus/strabismus, optic atrophy, electroencephalogram fast rhythms and motor neuropathy were absent. Cerebellar atrophy, claval hypertrophy and pallidal hypointensity were evident at brain magnetic resonance imaging. This patient carried a missense variant predicted to be less deleterious. CONCLUSIONS: The PLAN-associated phenotypes and the challenges of diagnosing the childhood-onset form are delineated, and a common North African founder mutation is identifed.

Evaluation of the trade-offs encountered in planning and treating locally advanced head and neck cancer: intensity-modulated radiation therapy vs dual-arc volumetric-modulated arc therapy.

OBJECTIVE: The primary purpose of this study was to assess the practical trade-offs between intensity-modulated radiation therapy (IMRT) and dual-arc volumetric-modulated arc therapy (DA-VMAT) for locally advanced head and neck cancer (HNC). METHODS: For 15 locally advanced HNC data sets, nine-field step-and-shoot IMRT plans and two full-rotation DA-VMAT treatment plans were created in the Pinnacle(3) v. 9.0 (Philips Medical Systems, Fitchburg, WI) treatment planning environment and then delivered on a Clinac iX (Varian Medical Systems, Palo Alto, CA) to a cylindrical detector array. The treatment planning goals were organised into four groups based on their importance: (1) spinal cord, brainstem, optical structures; (2) planning target volumes; (3) parotids, mandible, larynx and brachial plexus; and (4) normal tissues. RESULTS: Compared with IMRT, DA-VMAT plans were of equal plan quality (p>0.05 for each group), able to be delivered in a shorter time (3.1 min vs 8.3 min, p<0.0001), delivered fewer monitor units (on average 28% fewer, p<0.0001) and produced similar delivery accuracy (p>0.05 at γ(2%/2mm) and γ(3%/3mm)). However, the VMAT plans took more planning time (28.9 min vs 7.7 min per cycle, p<0.0001) and required more data for a three-dimensional dose (20 times more, p<0.0001). CONCLUSIONS: Nine-field step-and-shoot IMRT and DA-VMAT are both capable of meeting the majority of planning goals for locally advanced HNC. The main trade-offs between the techniques are shorter treatment time for DA-VMAT but longer planning time and the additional resources required for implementation of a new technology. Based on this study, our clinic has incorporated DA-VMAT for locally advanced HNC. ADVANCES IN KNOWLEDGE: DA-VMAT is a suitable alternative to IMRT for locally advanced HNC.

High mobility group box 1 is a novel substrate of dipeptidyl peptidase-IV.

AIMS/HYPOTHESIS: High mobility group box 1 (HMGB1) is a cytokine with a key role in tissue regeneration and angiogenesis. Previous studies have shown that topical application of HMGB1 to skin wounds of mouse models of diabetes enhanced vessel density and accelerated wound healing, suggesting that diabetes may affect endogenous HMGB1 functions. Dipeptidyl peptidase IV (DPP-IV/CD26) is a protease whose activity is increased in diabetes and whose inhibition improves glucose tolerance. Since HMGB1 contains potential DPP-IV cleavage sites, we determined whether HMGB1 may be a substrate for DPP-IV and whether DPP-IV-mediated cleavage may alter the biological activity of HMGB1. METHODS: Reversed phase HPLC, mass spectrometry and western blot analyses were performed to analyse and identify HMGB1 peptides generated following DPP-IV digestion. HMGB1 angiogenic functions in the presence of DPP-IV were evaluated in vitro and in vivo. HMGB1 protein was detected in the serum of type 2 diabetic patients before and after treatment with DPP-IV inhibitors. RESULTS: DPP-IV cleaved HMGB1 at its N-terminal region and affected its angiogenic functions. Specifically, DPP-IV inhibited HMGB1-induced endothelial cell migration and capillary-like structure formation, as well as HMGB1-mediated vascular network formation in Matrigel implants in mice. We had previously found that HMGB1 promoted endothelial cell migration through activation of extracellular regulated kinase signalling pathway. Here we showed that such an effect was abolished in the presence of DPP-IV. Finally, the N-terminal truncated form of HMGB1 was detected in the serum of type 2 diabetic patients, in whom DPP-IV inhibitors enhanced the levels of full-length HMGB1. CONCLUSIONS/INTERPRETATION: DPP-IV cleaves HMGB1 and, via this mechanism, inhibits HMGB1 angiogenic activity. Treatment with DPP-IV inhibitors may enhance HMGB1 activity in diabetic patients, thereby improving angiogenesis in this condition.

[Clinicopathologic characteristics of low grade primary gastric non-Hodgkin's lymphomas: experience from a single center]. / Caractéristiques clinico-pathologiques des lymphomes gastriques primitifs de bas grade de malignité.

AIM: To report the clinicopathological data and the treatment outcomes in patients with primary gastric low grade non-Hodgkin's lymphoma. METHODS: We carried out a retrospective analysis of 16 consecutive patients (median age 46 and range 28-75 years) who presented to our department with histopathological diagnosis of primary gastric low grade non-Hodgkin's lymphoma. We analyzed clinical manifestations, endoscopic features, pathological features,Helicobacter pylori infection and treatment. RESULTS: Common symptoms included abdominal pain (87.5%),vomiting (62.5%), and gastrointestinal bleeding (25%). Endoscopic appearances were mainly ulcers and ulcerations (93.75%).Endoscopic biopsy confirmation rate reached 87.5% when biopsies were repeated. Helicobacter pylori detection rate was 75%. A total of 9 patients received surgeries. Three patients had chemotherapy and 8 patients had Helicobacter pylori eradication therapy. The range of follow-up was 2-74 months with a median of 27 months. A complete remission was obtained in 12 cases, whereas 1 patient died and 3 were lost of view. CONCLUSION: Eradication therapy may be offered as an initial treatment option in patients with low-grade gastric lymphoma.

Extra-mammary findings in breast MRI.

OBJECTIVES: Incidental extra-mammary findings in breast Magnetic Resonance Imaging (MRI) may be benign in nature, but may also represent a metastasis or another important lesion. We aimed to analyse the prevalence and clinical relevance of these unexpected findings. METHODS: A retrospective review of 1535 breast MRIs was conducted. Only axial sequences were reassessed. Confirmation examinations were obtained in all cases. RESULTS: 285 patients had a confirmed incidental finding, which were located in the liver (51.9%), lung (11.2%), bone (7%), mediastinal lymph nodes (4.2%) or consisted of pleural/pericardial effusion (15.4%). 20.4% of incidental findings were confirmed to be malignant. Positive predictive value for MRI to detect a metastatic lesion was high if located within the bone (89%), lymph nodes (83%) and lung (59%), while it was low if located within the liver (9%) or if it consisted of pleural/pericardial effusion (6%). The axial enhanced sequence showed superior sensitivity to unenhanced images in detecting metastatic lesions, especially if only smaller (≤10 mm.) lesions were considered. CONCLUSIONS: The prevalence of metastatic incidental extra-mammary findings is not negligible. Particular attention should be to incidental findings located within the lung, bone and mediastinal lymph nodes.

[Association of Sjögren's syndrome and Plummer Vinson syndrome]. / Association d'un syndrome de Gougerot Sjögren et d'un syndrome de Plummer Vinson.

Dysphagia is a common complaint of patients with Sjogren's syndrome, but its mechanism remains a subject of controversy. The association of Sjogren's syndrome with Plummer-Vinson syndrome remains uncommon. We report a 56-year-old women who presented both disorders. The diagnosis of the Plummer-Vinson syndrome was based on the classic triad of dysphagia, iron-deficiency anaemia and oesophageal webs. The diagnosis of Sjogren's syndrome was based on the presence of three Fox criteria. This association should incite us to search for common immuno-genetic pathogenic factors between these two syndromes.

Pathological and molecular characteristics distinguishing contralateral metastatic from new primary breast cancer.

BACKGROUND: Breast cancer patients have a cumulative lifetime risk of 2%-15% of developing a contralateral metastatic or ex novo primary cancer. From prognostic and therapeutic viewpoints, it is important to differentiate metastatic from second primary. To distinguish these entities, we investigated whether the pattern of X chromosome inactivation could determine whether the two tumors derived from different progenitor cells. MATERIALS AND METHODS: The clonality of bilateral breast cancer was evaluated through the X-inactivation analysis using the human androgen receptor gene (HUMARA) polymorphism and the histopathologic and molecular results were compared. A different or an identical pattern of X inactivation was considered as indicator of a second primary cancer or not informative, respectively. We considered morphological indicators of a new primary cancer the absence of concordance in the histological type or a better histological differentiation. RESULTS: Ten patients with bilateral breast cancer were evaluated. Morphological criteria indicated that eight were second primary, a conclusion confirmed by the X-inactivation analysis. Two cases classified as recurrence according to morphological criteria were classified as second tumor by molecular analysis. CONCLUSION: Our results show that the HUMARA clonality assay can improve the histological parameters in differentiating metastatic cancer from second primary cancer.

[Monoclonal gammopathy and primary colonic mantle cell lymphoma]. / Une gammapathie monoclonale associée à un lymphome colique primitif à cellules du manteau.

The association of a monoclonal gammopathy (MG) with a B cell non-Hodgkin's lymphoma (NHL) is a well-known phenomenon. It has been recognized in many subtypes of primary gastrointestinal lymphoma but its association with primary colonic mantle cell lymphoma has never been yet described. We report a 65-year-old man who presented with an exudative ascites and constipation. Serum electrophoresis showed a monoclonal peak in the gamma region of 45g/L and immunoelectrophoresis confirmed the presence of monoclonal gammopathy of IgM kappa type. Bone marrow aspirate was normal. Radiologic and endoscopic investigations evidenced a primary colonic mantle cell lymphoma. Although the association of an MG with an NHL and, in particular, to a primitive digestive location appears a rare phenomenon, endoscopic investigations in patients with MG appears legitimate in the presence of any digestive sign.

Biological and clinical role of p73 in neuroblastoma.

The p73 gene is a p53 homologue localized at 1p36.3, a chromosomal region frequently deleted in neuroblastoma. p73 was originally considered an oncosuppressor gene. However, it was soon realized that its mode of action did not resemble that of a classic anti-oncogene. The recent discovery of N-terminal truncated isoforms, with oncogenic properties, showed that p73 has a 'two in one' structure. Indeed, the full-length variants are strong inducers of apoptosis while the truncated isoforms inhibit the pro-apoptotic activity of p53 and of the full-length p73. This review summarizes some aspects of p73 biology with particular reference to its possible role in neuroblastoma.

Magnetic resonance imaging in breast cancer recurrence.

PURPOSE: To determine the sensitivity, specificity and accuracy of magnetic resonance imaging (MRI) in detecting breast cancer recurrence. MATERIALS AND METHODS: Forty women conservatively treated for breast cancer underwent MRI and confirmation on histology and cytology of suspected local recurrence. In these patients both clinical and mammographic/ultrasound features of local recurrence were nonspecific or suspicious. All patients were examined at least 1 year after completion of radiation treatment. Dynamic magnetic resonance imaging was performed with a 1.5 T unit using a dedicated bilateral breast coil. Qualitative and quantitative data were obtained. Statistical analysis was also performed with the Student T-test. RESULTS: Breast cancer recurrence was confirmed on histology in 22 patients. MRI identified all the 22 breast recurrent cancers. False-positive contrast enhancement was seen in only two patients. In four patients recurrence was classified as multifocal. In one patient the tumor was detected in the contralateral breast. MRI showed 95% accuracy, 100% sensitivity, 88.8% specificity with 5% false-positives and 100% negative predictive value. CONCLUSION: Dynamic MRI appears a valuable technique for differentiation of post-treatment changes from recurrent carcinoma and for guiding the histological confirmation. Its high negative predictive value may have an impact on follow-up of treated breast.

Expression of DeltaNp73 is a molecular marker for adverse outcome in neuroblastoma patients.

The p73 gene is a p53 homologue which induces apoptosis and inhibits cell proliferation. Although p73 maps at 1p36.3 and is frequently deleted in neuroblastoma (NB), it does not act as a classic oncosuppressor gene. In developing sympathetic neurons of mice, p73 is predominantly expressed as a truncated anti-apoptotic isoform (DeltaNp73), which antagonizes both p53 and the full-length p73 protein (TAp73). This suggests that p73 may be part of a complex tumor-control mechanism. To determine the role of DeltaNp73 in NB we analyzed the pattern of expression of this gene in vivo and evaluated the prognostic significance of its expression. Our results indicate that DeltaNp73 expression is associated with reduced apoptosis in a NB tumor tissue. Expression of this variant in NB patients significantly correlates with age at diagnosis and VMA urinary excretion. Moreover it is strongly associated with reduced survival (HR=7.93; P<0.001) and progression-free survival (HR=5.3; P<0.001) and its role in predicting a poorer outcome is independent from age, primary tumor site, stage and MYCN amplification (OS: HR=5.24, P=0.012; PFS: HR=4.36, P=0.005). In conclusion our data seem to indicate that DeltaNp73 is a crucial gene in neuroblastoma pathogenesis.