A genome-wide analysis in cluster headache points to neprilysin and PACAP receptor gene variants

Background: Cluster Headache (CH) is a severe primary headache, with a poorly understood pathophysiology. Complex genetic factors are likely to play a role in CH etiology; however, no confirmed gene associations have been identified. The aim of this study is to identify genetic variants influencing risk to CH and to explore the potential pathogenic mechanisms. Methods: We have performed a genome-wide association study (GWAS) in a clinically well-defined cohort of 99 Italian patients with CH and in a control sample of 360 age-matched sigarette smoking healthy individuals, using the Infinium PsychArray (Illumina), which combines common highly-informative genome-wide tag SNPs and exonic SNPs. Genotype data were used to carry out a genome-wide single marker case-control association analysis using common SNPs, and a gene-based association analysis focussing on rare protein altering variants in 745 candidate genes with a putative role in CH. Results: Although no single variant showed statistically significant association at the genome-wide threshold, we identified an interesting suggestive association (P = 9.1 7 10 126) with a common variant of the PACAP receptor gene (ADCYAP1R1). Furthermore, gene-based analysis provided significant evidence of association (P = 2.5 7 10 125) for a rare potentially damaging missense variant in the MME gene, encoding for the membrane metallo-endopeptidase neprilysin. Conclusions: Our study represents the first genome-wide association study of common SNPs and rare exonic variants influencing risk for CH. The most interesting results implicate ADCYAP1R1 and MME gene variants in CH susceptibility and point to a role for genes involved in pain processing. These findings provide new insights into the pathogenesis of CH that need further investigation and replication in larger CH samples

Evaluation of environmental sustainability in additive manufacturing processes for orthopaedic devices production

Sustainability impact assessment of additive manufacturing represents one of the work packages (WP5) of the European Union Horizon 2020 project “Driving up Reliability and Efficiency of Additive Manufacturing” (DREAM). Additive manufacturing is a versatile technology consisting in melting metallic powders to produce objects from 3D data, layer upon layer. Additive manufacturing applications in industry range from automotive, biomedical (e.g. prosthetic implants for dentistry and orthopedics), aeronautics and others. One of the main target of WP5 is to assess the environmental sustainability of DREAM products and processes, conducted with laser-based powder bed fusion additive manufacturing systems through Life Cycle Assessment (LCA) methodology. Environmental impacts on different impact and damage categories due to manufacturing, use and end of life of the designed solution have been assessed adopting IMPACT 2002+ method

Altitudinal training sets of pollen rain – vegetation cover and modelled climate as a tool for the interpretation of paleoecological records

To improve our ability to reconstruct past environments and climate from fossil pollen records, modern proxy calibration studies along climatic and ecological gradients are needed. Here we present the first training set of modern pollen rain, vegetation, climate and terrain parameters developed along a 1700m-high transect in the western Italian Alps. The accurate knowledge on the relationships between these factors is essential for robust and sound reconstructions of past ecosystems based on microscopic plant remains

O015. Evaluation of the genetic polymorphism of the α3 (CHRNA3) and α5 (CHRNA5) nicotinic receptor subunits, in patients with cluster headache

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House Dust Mite Allergy and the Der p1 Conundrum: A Literature Review and Case Series

The house dustmite (HDM) is globally ubiquitous in human habitats. Thirty-two allergens for Dermatophagoides farinae and 21 for Dermatophagoides pteronyssinus have been detected so far. The present minireview summarizes information about the role of Der p 1 as a key coordinator of the HDM-induced allergic response and reports on a series of Italian patients who are allergic to HDMs. We studied the specific IgE profiles in a population of patients with allergic asthma and rhinitis screened for specific immunotherapy (SIT) for HDMallergies, with the aim of obtaining insights into the pathogenic role of Der p1. Patients co-sensitized to other airborne allergens showed a higher prevalence of asthma (9/12 (75%) vs. 2/7 (29%); p < 0.05) than did HDMmono-sensitized patients. The latter group showed higher Der p1 concentrations than that of the co-sensitized group (p = 0.0360), and a direct correlation between Der p1 and Der p2 (r = 0.93; p = 0.0003) was observed. In conclusion, our study offers insights into the role of Der p1 in a population of patients with allergic rhinitis and asthma who were candidates for SIT. Interestingly, Der p1 positivity was associated with bronchial asthma and co-sensitization

The study of calcified atherosclerotic arteries: an alternative to evaluate the composition of a problematic tissue reveals new insight including metakaryotic cells

Background Calcifications of atherosclerotic plaques represent a controversial issue as they either lead to the stabilization or rupture of the lesion. However, the cellular key players involved in the progression of the calcified plaques have not yet been described. The primary reason for this lacuna is that decalcification procedures impair protein and nucleic acids contained in the calcified tissue. The aim of our study was to preserve the cellular content of heavily calcified plaques with a new rapid fixation in order to simplify the study of calcifications. Methods Here we applied a fixation method for fresh calcified tissue using the Carnoy’s solution followed by an enzymatic tissue digestion with type II collagenase. Immunohistochemistry was performed to verify the preservation of nuclear and cytoplasmic antigens. DNA content and RNA preservation was evaluated respectively with Feulgen staining and RT-PCR. A checklist of steps for successful image analysis was provided. To present the basic features of the F-DNA analysis we used descriptive statistics, skewness and kurtosis. Differences in DNA content were analysed with Kruskal-Wallis and Dunn’s post tests. The value of P < 0.05 was considered significant. Results Twenty-four vascular adult tissues, sorted as calcified (14) or uncalcified (10), were processed and 17 fetal tissues were used as controls (9 soft and 8 hard). Cells composing the calcified carotid plaques were positive to Desmin, Vimentin, Osteocalcin or Ki-67; the cellular population included smooth muscle cells, osteoblasts and osteoclasts-like cells and metakaryotic cells. The DNA content of each cell type found in the calcified carotid artery was successfully quantified in 7 selected samples. Notably the protocol revealed that DNA content in osteoblasts in fetal control tissues exhibits about half (3.0 ng) of the normal nuclear DNA content (6.0 ng). Conclusion Together with standard histology, this technique could give additional information on the cellular content of calcified plaques and help clarify the calcification process during atherosclerosis.United Therapeutics Corporatio

New Chromane-Based Derivatives as Inhibitors of Mycobacterium tuberculosis Salicylate Synthase (MbtI): Preliminary Biological Evaluation and Molecular Modeling Studies

Tuberculosis is the leading cause of death from a single infectious agent worldwide; therefore, the need for new antitubercular drugs is desperate. The recently validated target salicylate synthase MbtI is the first enzyme involved in the biosynthesis of mycobactins, compounds able to chelate iron, an essential cofactor for the survival of Mycobacterium tuberculosis in the host. Here, we report on the synthesis and biological evaluation of chromane-based compounds as new potential inhibitors of MbtI. Our approach successfully allowed the identification of a novel lead compound (1), endowed with a promising activity against this enzyme (IC50 = 55 μM). Molecular modeling studies were performed in order to evaluate the binding mode of 1 and rationalize the preliminary structure-activity relationships, thus providing crucial information to carry out further optimization studies

Colonización, inmigración y etnicidad en la provincia de Misiones, Argentina. Etapa II. Cartografia etnografica de la plurietnicidad en Misiones. Argentina. 16H237

La provincia de Misiones constituye un área particularmente relevante para el estudio de los procesos migratorios. En un espacio que abarca 30.719 km2, cuyos límites de frontera alcanzan un 90% entre los países de Paraguay y Brasil, se asentaron pobladores de más de veinte nacionalidades diferentes, fenómeno que se constituye en un paisaje étnico particular y diverso para el estudio del poblamiento de la provincia. Poblamiento que se ha constituido desde fines del siglo XIX con población de la zona -paraguayos, correntinos, aborígenes- a los que se suman las colonizaciones que se dividen en oficiales y privadas, así como por el poblamiento espontáneo. A partir del análisis de lo antedicho, observamos que la influencia de las migraciones y asentamiento de población extranjera en Misiones prefigura particularidades vinculadas a: la organización del espacio geográfico, la gestación de la historia regional, los procesos de interculturización, la constitución de identidades culturales y las relaciones interétnicas e intraétnicas. Tan es así que entre las caracterizaciones de la Provincia, la mayoría de las publicaciones existentes, destacan esta particularidad desde la denominación de “Misiones crisol de razas” u otros como “provincia pluriétnica”. Frente a esta caracterización de Misiones, la elaboración de una “cartografía etnográfica” de los habitantes y de las colectividades ubicadas en la provincia será de gran utilidad para el conocimiento de: lugares de procedencia, periodización de los movimientos migratorios, lugares de asentamiento, relaciones (de trabajo, de parentesco, religiosas, etc.) establecidas entre los diferentes grupos étnicos, la población de origen y de fronteras de la zona. De la misma manera, conociendo la inserción en el medio de “los que llegaron” y la “descendencia” filial de los mismos, podremos reconstruir un mapa poblacional en cuanto a sus ascendencias y descendencias, hecho que sin dudas se convierte en un diacrítico interesante al momento de su caracterización.

Benefits of glucocorticoids in non-ambulant boys/men with Duchenne muscular dystrophy: A multicentric longitudinal study using the Performance of Upper Limb test

The aim of this study was to establish the possible effect of glucocorticoid treatment on upper limb function in a cohort of 91 non-ambulant DMD boys and adults of age between 11 and 26 years. All 91 were assessed using the Performance of Upper Limb test. Forty-eight were still on glucocorticoid after loss of ambulation, 25 stopped steroids at the time they lost ambulation and 18 were GC naive or had steroids while ambulant for less than a year. At baseline the total scores ranged between 0 and 74 (mean 41.20). The mean total scores were 47.92 in the glucocorticoid group, 36 in those who stopped at loss of ambulation and 30.5 in the naive group (p <0.001). The 12-month changes ranged between -20 and 4 (mean -4.4). The mean changes were -3.79 in the glucocorticoid group, -5.52 in those who stopped at loss of ambulation and -4.44 in the naive group. This was more obvious in the patients between 12 and 18 years and at shoulder and elbow levels. Our findings suggest that continuing glucocorticoids throughout teenage years and adulthood after loss of ambulation appears to have a beneficial effect on upper limb function. (C) 2015 The Authors. Published by Elsevier B.V

Timed rise from floor as a predictor of disease progression in Duchenne muscular dystrophy: An observational study

The role of timed items, and more specifically, of the time to rise from the floor, has been reported as an early prognostic factor for disease progression and loss of ambulation. The aim of our study was to investigate the possible effect of the time to rise from the floor test on the changes observed on the 6MWT over 12 months in a cohort of ambulant Duchenne boys.A total of 487 12-month data points were collected from 215 ambulant Duchenne boys. The age ranged between 5.0 and 20.0 years (mean 8.48 ±2.48 DS).The results of the time to rise from the floor at baseline ranged from 1.2 to 29.4 seconds in the boys who could perform the test. 49 patients were unable to perform the test at baseline and 87 at 12 month The 6MWT values ranged from 82 to 567 meters at baseline. 3 patients lost the ability to perform the 6mwt at 12 months. The correlation between time to rise from the floor and 6MWT at baseline was high (r = 0.6, p<0.01).Both time to rise from the floor and baseline 6MWT were relevant for predicting 6MWT changes in the group above the age of 7 years, with no interaction between the two measures, as the impact of time to rise from the floor on 6MWT change was similar in the patients below and above 350 m. Our results suggest that, time to rise from the floor can be considered an additional important prognostic factor of 12 month changes on the 6MWT and, more generally, of disease progression