Growth hormone nadir during oral glucose load depends on waist circumference, gender and age: normative data in 231 healthy subjects.

Objective  (i) To analyse the predictors of GH suppression after standard glucose load (oGTT) in the healthy population and (ii) to establish the 97th percentile of GH nadir post-oGTT according to these variables. Design  Analytical, retrospective. Measurements  GH nadir after oGTT. Subjects  Two hundred and thirty-one healthy subjects (113 women, 118 men 15-80 years) were studied. Results  The GH nadir after glucose load ranged from 0·01 (<assay detection limit) to 0·65 μg/l was higher in women and was inversely correlated with age, BMI, waist circumference, waist/hip, total cholesterol, triglycerides, basal and maximal glucose and basal insulin levels and directly correlated with basal GH levels, IGF-I SDS and HDL-cholesterol (P values ranging 0·004-<0·0001). On multistep regression analysis, the best predictors of nadir GH levels were waist circumference (t = -9·64, P < 0·0001), gender (t = -3·86, P = 0·0001) and age (t = -3·63, P = 0·0003). The results of comparative analysis among subjects grouped according to these variable showed different results in GH nadir in premenopausal women with waist circumference ≤88 cm (97th percentile 0·65 μg/l), in premenopausal women with waist circumference ≤88 cm and in men of any age with waist circumference ≤102 cm (97th percentile 0·33 μg/l) and in subjects of either gender and any age with waist circumference >88 cm in women and 102 cm in men (97th percentile 0·16 μg/l). Conclusions  The results of this study show that GH nadir after oGTT should be analysed according to gender, menopausal status and waist circumference. The GH cut-off should be limited to the assay used

Synchronous Lung Cancers: When Same Histological Types Feature Different Molecular Profiles and Response Phenotypes

We discuss the case of synchronous bilateral lung cancers which feature the same histological phenotype and a different EGFR mutational profile. Both histological and molecular characterizations were performed on specimens derived thorough CT-guided fine needle aspiration. A first-line chemotherapy was unsuccessful. Subsequent objective response to the EGFR inhibitor Erlotinib was clearly coherent with the sequencing data and the mutated nodule was effectively reduced (> 50%) after therapy, while the lesion assessed as EGFR wild type featured a slight response. This report has two relevant implications. It points out that in case of multiple malignant lesions at time of diagnosis, molecular profiling should be as extensive as possible and it might contribute to clarify the association between the lesions found. Besides the molecular analysis on cytology specimens could identify an accurate and safe diagnostic approach for clinical use

Targeting EGFR in non-small-cell lung cancer: Lessons, experiences, strategies

SummaryCancer is a genetic disease and this concept is now widely exploited by both scientists and clinicians to design new targeted molecules. Indeed many data have already allowed us to ameliorate not only our knowledge about cancer onset, but also about patients treatment. Correlation between mutations in cancer alleles and drug response is a key point to identify drugs that match the genetic profile of each individual tumors. On the other hand, experience derived from inhibition of tyrosine kinase receptors has pointed out that targeted treatment is really successful only in a small subset of tumors. The latter are eventually addicted to those genetic alterations which are responsible for receptors activation and for the continued expression of their signalling. Overall these observations provide a strong rationale for a molecular-based diagnosis and patients selection for targeted therapies.This review analyses the current state of the art of molecularly-tailored pharmacological approach to lung cancer, one of the biggest killers among human solid tumors. Main relevance is addressed to genetic lesions activating the EGFR pathway transducers, focusing on their role as markers of targeted drug response

Data for proteomic analysis of murine cardiomyocytic HL1 cells treated with siRNA against tissue factor

YesThis data article is related to the research article entitled Proteomics of Tissue Factor silencing in cardiomyocytic cells reveals a new role for this coagulation factor in splicing machinery control by Lento et al [1]. Tissue Factor (TF) is the key player in the coagulation cascade, but it has additional functions ranging from angiogenesis, tumor invasion and, in the heart, the maintenance of the integrity of cardiac cells. This article reports the nano-LC-MSE analysis of the cardiomyocytic HL-1 cell line proteome and describes the results obtained from a Gene Ontology analysis of those proteins affected by TF-gene silencing

Regional reductions of gray matter volume in familial dyslexia

An in vivo anatomic study of gray matter volume was performed in a group of familial dyslexic individuals, using an optimized method of voxel-based morphometry. Focal abnormalities in gray matter volume were observed bilaterally in the planum temporale, inferior temporal cortex, and cerebellar nuclei, suggesting that the underlying anatomic abnormalities may be responsible for defective written language acquisition in these subjects

Cerebellar mutism syndrome: from pathophysiology to rehabilitation

Cerebellar mutism syndrome (CMS) is a common complication following surgical resection of childhood tumors arising in the posterior fossa. Alteration of linguistic production, up to muteness and emotional lability, generally reported at least 24 h after the intervention, is the hallmark of post-operative CMS. Other associated traits include hypotonia and other cerebellar motor signs, cerebellar cognitive-affective syndrome, motor deficits from the involvement of the long pathways, and cranial neuropathies. Recovery usually takes 6 months, but most children are burdened with long-term residual deficits. The pathogenic mechanism is likely due to the damage occurring to the proximal efferent cerebellar pathway, including the dentate nucleus, the superior cerebellar peduncle, and its decussation in the mesencephalic tegmentum. Proven risk factors include brain stem invasion, diagnosis of medulloblastoma, midline localization, tumor size, invasion of the fourth ventricle, invasion of the superior cerebellar peduncle, left-handedness, and incision of the vermis. Currently, rehabilitation is the cornerstone of the treatment of patients with cerebellar mutism syndrome, and it must consider the three main impaired domains, namely speech, cognition/behavior, and movement

Open Philology at the University of Leipzig

The Open Philology Project at the University of Leipzig aspires to re-assert the value of philology in its broadest sense. Philology signifies the widest possible use of the linguistic record to enable a deep understanding of the complete lived experience of humanity. Pragmatically, we focus on Greek and Latin because (1) substantial collections and services are already available within these languages, (2) substantial user communities exist (c. 35,000 unique users a month at the Perseus Digital Library), and (3) a European-based project is better positioned to process extensive cultural heritage materials in these languages rather than in Chinese or Sanskrit. The Open Philology Project has been designed with the hope that it can contribute to any historical language that survives within the human record. It includes three tasks: (1) the creation of an open, extensible, repurposable collection of machine-readable linguistic sources; (2) the development of dynamic textbooks that use annotated corpora to customize the vocabulary and grammar of texts that learners want to read, and at the same time engage students in collaboratively producing new annotated data; (3) the establishment of new workflows for, and forms of, publication, from individual annotations with argumentation to traditional publications with integrated machine-actionable data

Linear Accelerator Test Facility at LNF Conceptual Design Report

Test beam and irradiation facilities are the key enabling infrastructures for research in high energy physics (HEP) and astro-particles. In the last 11 years the Beam-Test Facility (BTF) of the DA{\Phi}NE accelerator complex in the Frascati laboratory has gained an important role in the European infrastructures devoted to the development and testing of particle detectors. At the same time the BTF operation has been largely shadowed, in terms of resources, by the running of the DA{\Phi}NE electron-positron collider. The present proposal is aimed at improving the present performance of the facility from two different points of view: extending the range of application for the LINAC beam extracted to the BTF lines, in particular in the (in some sense opposite) directions of hosting fundamental physics and providing electron irradiation also for industrial users; extending the life of the LINAC beyond or independently from its use as injector of the DA{\Phi}NE collider, as it is also a key element of the electron/positron beam facility. The main lines of these two developments can be identified as: consolidation of the LINAC infrastructure, in order to guarantee a stable operation in the longer term; upgrade of the LINAC energy, in order to increase the facility capability (especially for the almost unique extracted positron beam); doubling of the BTF beam-lines, in order to cope with the signicant increase of users due to the much wider range of applications.Comment: 71 page

Overcome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides

The fragile histidine triad (FHIT) protein is a member of the large and ubiquitous histidine triad (HIT) family of proteins. On the basis of genetic evidence, it has been postulated that the FHIT protein may function as tumor suppressor, implying a role for the FHIT protein in carcinogenesis. Recently, Gaudio et al. reported that FHIT binds and delocalizes annexin A4 (ANXA4) from plasma membrane to cytosol in paclitaxel-resistant lung cancer cells, thus restoring their chemosensitivity to the drug. They also identified the smallest protein sequence of the FHIT still interacting with ANXA4, ranging fromposition 7 to 13: QHLIKPS. This short sequence of FHIT protein was not only able to bind ANXA4 but also to hold its target in the cytosol during paclitaxel treatment, thus avoiding ANXA4 translocation to the inner side of the cell membrane. Starting from these results, to obtain much information about structure requirements involved in the interaction of the peptide mentioned above, we synthetized a panel of seven peptides through an Ala-scan approach. In detail, to study the binding of FHIT derived peptides with ANXA4, we applied a combination of different biophysical techniques such as differential scanning fluorimetry (DSF), surface plasmon resonance (SPR), and microscale thermophoresis (MST). Circular dichroism (CD) and nuclear magnetic resonance (NMR) were used to determine the conformational structure of the lead peptide (7–13) and peptides generated from ala-scan technique. The application of different biophysical and structural techniques, integrated by a preliminary biological evaluation, allowed us to build a solid structure activity relationship on the synthesized peptides