Biomarker combination is necessary for the assessment of Gaucher disease?

Biomarkers are useful tools to help in disease diagnosis and follow-up. According to the US Food & Drug Administration, biomarkers are defined as measurable elements that can be used as indicators in normal biological and pathological processes, or in response to an exposure or therapeutic interventions. Molecular, histologic, radiographic or physiological characteristics are some of those biomarkers (www.fda.gov). The term biomarker is currently being applied to molecular markers that define a specific biological status (1). Considering these factors, the “ideal” biomarker should fulfill susceptibility/risk, be reliable, and can be used for diagnosis, monitoring, prognosis, prediction and pharmacodynamic response. Some useful biomarkers such as the number of BCR/ABL transcripts in chronic myeloid leukemia serve as sensitive indicators that help in the monitoring of the molecular response, a quantitative instrument to monitor the long-term molecular response to therapy (2) or for example the serum concentration of M-component in monoclonal gammopathies ..

Inferring resilience to fragmentation-induced changes in plant communities in a semi-arid Mediterranean ecosystem

Predicting the capacity of ecosystems to absorb impacts from disturbance events (resilience), including land-use intensification and landscape fragmentation, is challenging in the face of global change. Little is known about the impacts of fragmentation on ecosystem functioning from a multi-dimensional perspective (multiple traits). This study used 58 500-m linear transects to quantify changes in the functional composition and resilience of vascular plant communities in response to an increase in landscape fragmentation in 18 natural scrubland fragments embedded within a matrix of abandoned crop fields in Cabo de Gata-Níjar Natural Park, Almería, Spain. Changes in functional community composition were measured using functional diversity indices (functional richness and functional dispersion) that were based on 12 plant traits. Resilience was evaluated using the functional redundancy and response diversity from the perspective of plant dispersal, which is important, particularly, in fragmented landscapes. Scrubland fragmentation was measured using the Integral Index of Connectivity (IIC). The functional richness of the plant communities was higher in the most fragmented scrubland. Conversely, the functional dispersion (i.e., spread) of trait values among species in the functional trait space was lower at the most fragmented sites; consequently, the ecological tolerance of the vegetation to scrubland fragmentation decreased. Classifying the plant species into four functional groups indicated that fragmentation favoured an increase in functional redundancy in the 'short basal annual forbs and perennial forbs' group, most of which are species adapted to degraded soils. An assessment based on the traits associated with plant dispersal indicated that the resilience of 'woody plants ', an important component in the Mediterranean scrubland, and habitat fragmentation were negatively correlated; however, the correlation was positive in the 'short basal annual forbs and perennial forbs ' and the 'grasses' groups. © 2015 de Frutos et al.We are grateful to Beatriz Bueno, Elena Lahoz, Benjamin Komac, and Virginia Pascual for assisting with the collection of field data. We thank Luis Villar for his help in translating the biological types. María Felipe, Maite Gartzia, Bruce MacWhirter, and two referees provided critical comments and helpful suggestions on the manuscript.Peer Reviewe

Reference frames in General Relativity and the galactic rotation curves

The physical interpretation of the exact solutions of the Einstein field equations is, in general, a challenging task, part of the difficulties lying in the significance of the coordinate system. We discuss the extension of the International Astronomical Union (IAU) reference system to the exact theory. It is seen that such an extension, retaining some of its crucial properties, can be achieved in a special class of spacetimes, admitting non-shearing congruences of observers which, at infinity, have zero vorticity and acceleration. As applications, we consider the FLRW, Kerr and NUT spacetimes, the van Stockum rotating dust cylinder, spinning cosmic strings and, finally, we debunk the so-called Balasin-Grumiller (BG) model, and the claims that the galaxies' rotation curves can be explained through gravitomagnetic effects without the need for Dark Matter. The BG spacetime is shown to be completely inappropriate as a galactic model: its dust is actually static with respect to the asymptotic inertial frame, its gravitomagnetic effects arise from unphysical singularities along the axis (a pair of NUT rods, combined with a spinning cosmic string), and the rotation curves obtained are merely down to an invalid choice of reference frame -- the congruence of zero angular momentum observers, which are being dragged by the singularities.Comment: 29 pages, 10 figures. Slightly improved version, typos corrected, references added. Supplemental material is provided in the ancillary Mathematica files "NUTmetrics.nb" and "BGmetric.nb". Version to be submitte

Allelic and phenotypic characterization of CYP2D6 and its encoded P450 cytochrome enzyme in a serie of Spanish type 1 Gaucher disease patients

Background: Cytochrome p450 is the main drug metabolic pathway. CYP2D6 is a highly polymorphic gene that encodes a cytochrome p450 enzyme with three activity levels: null, reduced and normal. Apart from another type of mutations CYP2D6 can suffer duplications and deletions of the entire gene. This is the pathway to metabolize one of the Gaucher disease treatments, whose dose administration is regulated according to the metabolizer phenotype, this being one of the administration limitations. Objectives: The aim of this paper is to evaluate the allelic frequencies and the metabolizer status of Gaucher type 1 patients in the Spanish population and compare it with the general Spanish population and other Gaucher disease groups. Methods: In this study, 109 type 1 Gaucher disease patients were analyzed with the xTAG®CYP2D6 kit to identify the CYP2D6 gene alleles. Results: We observed that eighty-seven patients could be classified as extensive, 14 as intermediate, 6 as poor and 2 as ultra-rapid metabolizers. The allelic duplication frequency is 5.5% and deletion is 4.5%. The most common allele is wild-type and the second is the null *4 allele. Intermediate phenotype frequency is higher than expected (p < 0.05). Conclusions: Our Spanish GD series shows an unexpected distribution of some alleles and phenotypic metabolizer status, in contrast to that previously reported in the Spanish population

Consensus on the Clinical Approach to Moderate-to-Severe Atopic Dermatitis in Spain: A Delphi Survey

Background. The purpose of this study was to gather information on the current assessment and management of patients with moderate-to-severe AD in routine daily practice. Methods. A cross-sectional two-round Delphi survey with the participation of dermatologists and allergologists throughout Spain was conducted. They completed a 46-item questionnaire, and consensus was defined when responses of >= 80% of participants coincided in the categories of a 5-point Likert scale for that item. Results. A total of 105 specialists (aged 40-59 years) completed the two rounds. Participants agreed regarding the consideration of AD as a multifaceted disease and the differences in clinical presentation of AD according to the patient's age. It is recommendable to perform a skin biopsy to exclude early stage T-cell cutaneous lymphoma, psoriasis, or dermatitis herpetiformis, among others (99.1%). Also, consensus was reached regarding the use of the SCORAD index to quantify the severity of the disease (86.7%), the use of wet wraps to increase the effect of topical corticosteroids (90.4%), the usefulness of proactive treatment during follow-up (85.6%) and tacrolimus ointment (91.2%) to reduce new flares, and the fact that crisaborole is not the treatment of choice for severe AD (92.4%). AD was not considered a contraindication for immunotherapy in patients with allergic respiratory diseases (92.4%). In patients with severe AD, the use of immune response modifier drugs (97.6%) or phototherapy (92.8%) does not sufficiently cover their treatment needs. Consensus was also obtained regarding the role of the new biologic drugs (93.6%) targeting cytokines involved in the Th2 inflammatory pathway (92.0%) and the potential role of dupilumab as first-line treatment (90.4%) in moderate-to-severe AD patients. Conclusion. This study contributes a reference framework to the care of AD patients. There is no diagnostic test or biomarkers to direct treatment or to assess the severity of the disease, and many therapeutic challenges remain

Molecular aspects in pathogen-fruit interactions: Virulence and resistance

Fruit losses during postharvest storage and handling due to pathogen infections are one of the major problems in the global food chain supply. The application of chemical fungicides to control diseases is currently limited by legislation in some countries and also raises concerns about food and environmental safety. Exploring molecular aspects of pathogen-fruit interactions therefore has biological and economic significance as a means to help develop rational alternatives for disease control. In this review we present the current knowledge of molecular aspects in pathogen-fruit interactions, addressing the following topics: the application of new “omics” technologies for studying these interactions; the molecular mechanisms of fungal pathogen attack; the regulation of virulence by exogenous factors; and, finally, fruit defense mechanisms.Work in Tian’s lab has been funded by the National Natural Science Foundation of China (31530057; 31371863). Work in the LGC lab has been funded by the Spanish Ministry of Economy and Competitiveness (AGL2011-30519-C03-01 and AGL2014-55802-R) and the Generalitat Valenciana (PrometeoII/2014/027). Work in the IRTA lab has been funded by the Spanish Ministry of Economy and Competitiveness by three national projects AGL2008-04828-C01/AGR, AGL2011-30519-C03/AGR and AGL2014-55287-C02.Peer reviewe

Fístula arteriovenosa postraumática: tratamiento endovascular. Revisión de la literatura y presentación de un caso clínico

ResumenLas fístulas arteriovenosas en la cabeza y el cuello son entidades poco frecuentes. La mayoría es secundaria a heridas penetrantes por arma blanca. Se describe el tratamiento exitoso mediante cirugía endovascular de una fístula postraumática tras una herida penetrante entre la arteria maxilar interna izquierda y la vena yugular externa. A través de este caso clínico y la revisión de la literatura se ilustran las causas, manifestaciones, estudio radiológico y tratamiento de una fístula postraumática entre la arteria maxilar interna y la vena yugular externa. A través de este caso clínico se demuestra la utilidad de los procedimientos endovasculares en el tratamiento de estas complicaciones.AbstractTraumatic arteriovenous fistulas of the head and neck region are uncommon. The majority are due to penetration of blunt injury. We describe a successful endovascular treatment of a posttraumatic fistula between the left maxillary artery and the external jugular vein due to a penetration injury. This case and a review of the literature illustrate the causes, manifestations, image studies and treatment for a posttraumatic fistula between the maxillary artery and the external jugular vein. This case demonstrate the utility of endovascular treatment of head and neck injuries complications