Evaluation of Chestnut Susceptibility to Cryphonectria parasitica: Screening under Controlled Conditions

Cryphonectria parasitica (Murrill) M.E. Barr (Sordariomycetes, Valsaceae) is the causal agent of chestnut blight. This disease is a major concern for chestnut cultivation in Europe. The fungus colonizes vascular tissues and evolves generating cankers causing severe dieback and the death of the tree. Excised and debarked well-lignified shoots of 28 C. sativa genotypes (assay A) and of 10 progenies (assay B) were inoculated with C. parasitica strain FMT3bc2 (vcg: EU2). Fungal growth was measured along the longitudinal axis on the 3rd and 6th days after inoculation. Results indicated the inoculation methodology works and the results were clear after 6 days. Differences in susceptibility to chestnut blight among C. sativa trees of Montseny have been detected both at the individual genotype level and at the progeny level. Nineteen genotypes and four progenies showed a susceptibility to Blight not significantly different from C. mollissima. The methodology was easy to apply in extensive/preliminary selection screenings to assess the susceptibility of C. sativa materials to the Blight.info:eu-repo/semantics/publishedVersio

El quart boom? Tendències de consum de recursos naturals a les Illes Balears

Neus ANDREU, Macià BLÁQUEZ, Sofia LÓPEZ, Llorenç MAS, Jaume MATEU, Felip MORRELL, Ivan MURRAY, Glòria TRUYOLS Departament de Ciències de la Terra, Universitat de les illes Balears. Centre d'Investigació i Tecnologies Turístique de les illes Balears [email protected], [email protected] EL QUART BOOM? TENDÈNCIES DE CONSUM DE RECURSOS NATURALS A LES ILLES BALEARS RESUM La dialèctica entre el desenvolupament econòmic, l'especialització turística i la conservació dels recursos naturals té un immillorable laboratori a les Illes Balears. Als anys seixanta s'inicia el primer boom turístic, i a partir de llavors succeeixen els booms, interromputs per períodes de recessió. Com a mesura de les disjuncions entre el model econòmic i el límit dels ecosistemes s'han definit els indicadors de sostenibilitat, amb l'objectiu de mesurar l'eficiència posant en relació l'augment del creixement econòmic amb els costos ambientals. S'han escollit variables relacionades amb el consum dels recursos naturals i la producció de residus durant el període 1989-2000, per definir les seves tendències i projecció futura, a paritr de tècniques de regressió linial, i s'han ponderat en relació amb el PIB i l'índex de pressió humana (IPH). La tendència estimada per al quart boom es dirigeix cap a un procés de desmaterialització local de l'economia, amb l'exportació de les externalitats negatives de l'activitat econòmica cap a altres territoris i en formes de contaminació no tan visibles com els impactes territorials de la urbanització. Paraules clau: Illes Balears, sostenibilitat, eficiència, PIB, recursos natural

Población introducida de tritón alpino (Mesotriton alpestris) en el Prepirineo catalán

Peer reviewe

Photosensitivity to Triflusal: Formation of a Photoadduct with Ubiquitin Demonstrated by Photophysical and Proteomic Techniques

[EN] Triflusal is a platelet aggregation inhibitor chemically related to acetylsalicylic acid, which is used for the prevention and/or treatment of vascular thromboembolisms, which acts as a prodrug. Actually, after oral administration it is absorbed primarily in the small intestine, binds to plasma proteins (99%) and is rapidly biotransformed in the liver into its deacetylated active metabolite 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). In healthy humans, the half-life of triflusal is ca. 0.5 h, whereas for HTB it is ca. 35 h. From a pharmacological point of view, it is interesting to note that HTB is itself highly active as a platelet anti-aggregant agent. Indeed, studies on the clinical profile of both drug and metabolite have shown no significant differences between them. It has been evidenced that HTB displays ability to induce photoallergy in humans. This phenomenon involves a cell-mediated immune response, which is initiated by covalent binding of a light-activated photosensitizer (or a species derived therefrom) to a protein. In this context, small proteins like ubiquitin could be appropriate models for investigating covalent binding by means of MS/MS and peptide fingerprint analysis. In previous work, it was shown that HTB forms covalent photoadducts with isolated lysine. Interestingly, ubiquitin contains seven lysine residues that could be modified by a similar reaction. With this background, the aim of the present work is to explore adduct formation between the triflusal metabolite and ubiquitin as model protein upon sunlight irradiation, combining proteomic and photophysical (fluorescence and laser flash photolysis) techniques. Photophysical and proteomic analysis demonstrates monoadduct formation as the major outcome of the reaction. Interestingly, addition can take place at any of the E-amino groups of the lysine residues of the protein and involves replacement of the trifluoromethyl moiety with a new amide function. This process can in principle occur with other trifluoroaromatic compounds and may be responsible for the appearance of undesired photoallergic side effects.Financial support from the Generalitat Valenciana (Prometeo Program), the Spanish Government (MINECO CTQ2015-70164-P to VL-V and SAF2012-36519 to DP-S) and the Carlos III Institute of Health (Grant RIRAAF, RETICS program, RD12/0013/0009 to MM and RD12/0013/0008 to DP-S, and Miguel Servet Contract CP11/00154 for IA) is gratefully acknowledged.Nuin Pla, NE.; Pérez-Sala, D.; Lhiaubet-Vallet, VL.; Andreu Ros, MI.; Miranda Alonso, MÁ. (2016). Photosensitivity to Triflusal: Formation of a Photoadduct with Ubiquitin Demonstrated by Photophysical and Proteomic Techniques. Frontiers in Pharmacology. 7(277). https://doi.org/10.3389/fphar.2016.00277S727

Prevalence of altered passive eruption in orthodontically treated and untreated patients

Background: some authors have reported that after orthodontic treatment (OT), a 'gummy smile' might develop. Nevertheless, there are no studies in the literature that investigate whether OT increases the presence of altered passive eruption (APE). The primary aim of this cross-sectional study is to evaluate the prevalence of APE after OT (OT group) and compare it with patients who never received OT (control group). A secondary aim is to identify which variables are related to APE. Methods: the study population consisted of 190 patients (95 patients each in the control and OT groups), providing 1,140 anterior teeth for the clinical examination. The following clinical parameters were assessed: presence or absence of APE, clinical crown length, and gingival biotype, which was divided into three categories: thin-scalloped, thick-flat, and thick-scalloped. Results: twenty-eight patients (29.5%) were diagnosed with APE in the control group and 40 (42.1%) in the OT group, although this difference was not statistically significant (P = 0.07). Furthermore, 34 (75.6%) patients with thick-flat biotype were diagnosed with APE, whereas 30 (31.3%) and four (8.2%) with thick-scalloped and thin-scalloped biotypes, respectively, had APE. These differences were statistically significant (P <0.001). Conclusions: it was concluded that: 1) the prevalence of APE is higher after OT but not to a statistically significant degree and 2) APE is more common in individuals with a thick-flat gingival biotype

Female Employees’ Perception of Breastfeeding Support in the Workplace, Public Universities in Spain: A Multicentric Comparative Study

Despite scientific recommendations for exclusive breastfeeding until 6 months of age and complementary breastfeeding to 2 years of age, breastfeeding abandonment rates increase with time, and one of the main reasons is that women go back to work. Aim: To analyze the perception of support of breastfeeding workers to continue breastfeeding at two Spanish universities, and associated factors. Methods: A multicenter retrospective cross-sectional comparative study conducted in a population of 777 female workers at the Universidad de Sevilla (US) and the Universitat Jaume I (UJI) in Spain using an online questionnaire. Results: The response rate was 38.74% (n = 301). Of all the participants, 57.8% continued breastfeeding after returning to work. The factors associated with continuing breastfeeding for longer were the university having a breastfeeding support policy and special accommodation (p < 0.001); participating in breastfeeding support groups (p < 0.001); intending to continue breastfeeding after returning to work (p < 0.001); knowing the occupational legislation in force (p = 0.009); having a female supervisor (p = 0.04). Conclusion: Breastfeeding support initiatives and having special accommodation to pump and preserve breast milk after returning to work are associated with a longer duration of female workers’ breastfeeding.The Equality Unit of the Universidad de Sevilla, Spain Grant 17102/2016University of Jaume I, Spain Grant UJI-A2019-0

"Snorkelling" vs. "diving" in mixed micelles probed by means of a molecular bathymeter

[EN] A photoactive bathymeter based on a carboxylic acid moiety covalently linked to a signalling methoxynaphthalene (MNP) fluorophore has been designed to prove the concept of "snorkelling" vs. "diving" in mixed micelles (MM). The carboxylic acid "floats" on the MM surface, while the MNP unit sinks deep in MM. The rate constants of MNP fluorescence quenching by iodide, which remains basically in water, consistently decrease with increasing spacer length, revealing different regions. This is associated with the distance MNP should "dive" in MM to achieve protection from aqueous reactants. Unequivocal proof of the exergonic photoinduced electron transfer was obtained from the UV-visible spectral signature of I-3(-) upon steady-state photolysis. The applicability of the bathymeter was examined upon testing a family of MNP derivatives. The obtained results were validated by comparison with different lipophilicity tests: (i) a modified version of the K-ow partition coefficient and (ii) the retention factor on thin layer chromatography. This concept could potentially be extended to test drugs or pharmacophores exhibiting any photoactive moiety.Financial support from the Spanish Government (SEV-2016-0683), Red RETICS de Investigacion de Reacciones Adversas a Alergenos y Farmacos (RIRAAF), Instituto de Salud Carlos III (RD012/0013, RD16/0006/0030, FIS PI16/01877), VLC-Campus and the Generalitat Valenciana (Prometeo Program) is gratefully acknowledged.Rodríguez Muñiz, GM.; Gomez Mendoza, M.; Nuin Pla, NE.; Andreu Ros, MI.; Marín García, ML.; Miranda Alonso, MÁ. (2017). "Snorkelling" vs. "diving" in mixed micelles probed by means of a molecular bathymeter. Organic & Biomolecular Chemistry. 15(48):10281-10288. https://doi.org/10.1039/c7ob02595eS10281102881548Porter, C. J. H., Trevaskis, N. L., & Charman, W. N. (2007). Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nature Reviews Drug Discovery, 6(3), 231-248. doi:10.1038/nrd2197Hammad, M. ., & Müller, B. . (1998). Increasing drug solubility by means of bile salt–phosphatidylcholine-based mixed micelles. European Journal of Pharmaceutics and Biopharmaceutics, 46(3), 361-367. doi:10.1016/s0939-6411(98)00037-xNagadome, S., Numata, O., Sugihara, G., Sasaki, Y., & Igimi, H. (1995). Solubilization and precipitation of cholesterol in aqueous solution of bile salts and their mixtures. Colloid & Polymer Science, 273(7), 675-680. doi:10.1007/bf00652260Hofmann, A. F. (1999). The Continuing Importance of Bile Acids in Liver and Intestinal Disease. Archives of Internal Medicine, 159(22), 2647. doi:10.1001/archinte.159.22.2647Ding, J., Sun, Y., Li, J., Wang, H., & Mao, S. (2017). Enhanced blood–brain barrier transport of vinpocetine by oral delivery of mixed micelles in combination with a message guider. Journal of Drug Targeting, 25(6), 532-540. doi:10.1080/1061186x.2017.1289541Lasic, D. D. (1992). Mixed micelles in drug delivery. Nature, 355(6357), 279-280. doi:10.1038/355279a0Cheng, L., Kamkaew, A., Sun, H., Jiang, D., Valdovinos, H. F., Gong, H., … Cai, W. (2016). Dual-Modality Positron Emission Tomography/Optical Image-Guided Photodynamic Cancer Therapy with Chlorin e6-Containing Nanomicelles. ACS Nano, 10(8), 7721-7730. doi:10.1021/acsnano.6b03074Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 23(1-3), 3-25. doi:10.1016/s0169-409x(96)00423-1Beaumont, K., Schmid, E., & Smith, D. A. (2005). Oral delivery of G protein-coupled receptor modulators: An explanation for the observed class difference. Bioorganic & Medicinal Chemistry Letters, 15(16), 3658-3664. doi:10.1016/j.bmcl.2005.05.042Al-Abdul-Wahid, M. S., Neale, C., Pomès, R., & Prosser, R. S. (2009). A Solution NMR Approach to the Measurement of Amphiphile Immersion Depth and Orientation in Membrane Model Systems. Journal of the American Chemical Society, 131(18), 6452-6459. doi:10.1021/ja808964eAfri, M., Frimer, A. A., & Cohen, Y. (2004). Active oxygen chemistry within the liposomal bilayer. Chemistry and Physics of Lipids, 131(1), 123-133. doi:10.1016/j.chemphyslip.2004.04.006Cohen, Y., Bodner, E., Richman, M., Afri, M., & Frimer, A. A. (2008). NMR-based molecular ruler for determining the depth of intercalants within the lipid bilayer. Chemistry and Physics of Lipids, 155(2), 98-113. doi:10.1016/j.chemphyslip.2008.07.004Cohen, Y., Afri, M., & Frimer, A. A. (2008). NMR-based molecular ruler for determining the depth of intercalants within the lipid bilayer. Chemistry and Physics of Lipids, 155(2), 114-119. doi:10.1016/j.chemphyslip.2008.07.007Afri, M., Alexenberg, C., Aped, P., Bodner, E., Cohen, S., Ejgenburg, M., … Frimer, A. A. (2014). NMR-based molecular ruler for determining the depth of intercalants within the lipid bilayer. Chemistry and Physics of Lipids, 184, 105-118. doi:10.1016/j.chemphyslip.2014.07.007Afri, M., Naqqash, M. E., & Frimer, A. A. (2011). Using fluorescence to locate intercalants within the lipid bilayer of liposomes, bioliposomes and erythrocyte ghosts. Chemistry and Physics of Lipids, 164(8), 759-765. doi:10.1016/j.chemphyslip.2011.09.002Bodner, E., Afri, M., & Frimer, A. A. (2010). Determining radical penetration into membranes using ESR splitting constants. Free Radical Biology and Medicine, 49(3), 427-436. doi:10.1016/j.freeradbiomed.2010.04.029Laguerre, M., López Giraldo, L. J., Lecomte, J., Figueroa-Espinoza, M.-C., Baréa, B., Weiss, J., … Villeneuve, P. (2009). Chain Length Affects Antioxidant Properties of Chlorogenate Esters in Emulsion: The Cutoff Theory Behind the Polar Paradox. Journal of Agricultural and Food Chemistry, 57(23), 11335-11342. doi:10.1021/jf9026266Laguerre, M., López Giraldo, L. J., Lecomte, J., Figueroa-Espinoza, M.-C., Baréa, B., Weiss, J., … Villeneuve, P. (2010). Relationship between Hydrophobicity and Antioxidant Ability of «Phenolipids» in Emulsion: A Parabolic Effect of the Chain Length of Rosmarinate Esters. Journal of Agricultural and Food Chemistry, 58(5), 2869-2876. doi:10.1021/jf904119vAliaga, C., Bravo-Moraga, F., Gonzalez-Nilo, D., Márquez, S., Lühr, S., Mena, G., & Rezende, M. C. (2016). Location of TEMPO derivatives in micelles: subtle effect of the probe orientation. Food Chemistry, 192, 395-401. doi:10.1016/j.foodchem.2015.07.036Aliaga, C., López de Arbina, A., & Rezende, M. C. (2016). «Cut-off» effect of antioxidants and/or probes of variable lipophilicity in microheterogeneous media. Food Chemistry, 206, 119-123. doi:10.1016/j.foodchem.2016.03.024Lopez de Arbina, A., Rezende, M. C., & Aliaga, C. (2017). Cut-off effect of radical TEMPO derivatives in olive oil-in-water emulsions. Food Chemistry, 224, 342-346. doi:10.1016/j.foodchem.2016.12.058Agostinis, P., Berg, K., Cengel, K. A., Foster, T. H., Girotti, A. W., Gollnick, S. O., … Golab, J. (2011). Photodynamic therapy of cancer: An update. CA: A Cancer Journal for Clinicians, 61(4), 250-281. doi:10.3322/caac.20114Kamkaew, A., Lim, S. H., Lee, H. B., Kiew, L. V., Chung, L. Y., & Burgess, K. (2013). BODIPY dyes in photodynamic therapy. Chem. Soc. Rev., 42(1), 77-88. doi:10.1039/c2cs35216hYano, S., Hirohara, S., Obata, M., Hagiya, Y., Ogura, S., Ikeda, A., … Joh, T. (2011). Current states and future views in photodynamic therapy. Journal of Photochemistry and Photobiology C: Photochemistry Reviews, 12(1), 46-67. doi:10.1016/j.jphotochemrev.2011.06.001Dolmans, D. E. J. G. J., Fukumura, D., & Jain, R. K. (2003). Photodynamic therapy for cancer. Nature Reviews Cancer, 3(5), 380-387. doi:10.1038/nrc1071Bronshtein, I., Afri, M., Weitman, H., Frimer, A. A., Smith, K. M., & Ehrenberg, B. (2004). Porphyrin Depth in Lipid Bilayers as Determined by Iodide and Parallax Fluorescence Quenching Methods and Its Effect on Photosensitizing Efficiency. Biophysical Journal, 87(2), 1155-1164. doi:10.1529/biophysj.104.041434Lavi, A., Weitman, H., Holmes, R. T., Smith, K. M., & Ehrenberg, B. (2002). The Depth of Porphyrin in a Membrane and the Membrane’s Physical Properties Affect the Photosensitizing Efficiency. Biophysical Journal, 82(4), 2101-2110. doi:10.1016/s0006-3495(02)75557-4Chattopadhyay, A., & London, E. (1987). Parallax method for direct measurement of membrane penetration depth utilizing fluorescence quenching by spin-labeled phospholipids. Biochemistry, 26(1), 39-45. doi:10.1021/bi00375a006Nuin, E., Gómez-Mendoza, M., Andreu, I., Marin, M. L., & Miranda, M. A. (2012). New Photoactive Compounds To Probe Cholic Acid and Cholesterol inside Mixed Micelles. Organic Letters, 15(2), 298-301. doi:10.1021/ol303201yNuin, E., Gomez-Mendoza, M., Marin, M. L., Andreu, I., & Miranda, M. A. (2013). Influence of Drug Encapsulation within Mixed Micelles on the Excited State Dynamics and Accessibility to Ionic Quenchers. The Journal of Physical Chemistry B, 117(32), 9327-9332. doi:10.1021/jp404353uGomez-Mendoza, M., Nuin, E., Andreu, I., Marin, M. L., & Miranda, M. A. (2012). Photophysical Probes To Assess the Potential of Cholic Acid Aggregates as Drug Carriers. The Journal of Physical Chemistry B, 116(34), 10213-10218. doi:10.1021/jp304708yBoschloo, G., & Hagfeldt, A. (2009). Characteristics of the Iodide/Triiodide Redox Mediator in Dye-Sensitized Solar Cells. Accounts of Chemical Research, 42(11), 1819-1826. doi:10.1021/ar900138mGardner, J. M., Abrahamsson, M., Farnum, B. H., & Meyer, G. J. (2009). Visible Light Generation of Iodine Atoms and I−I Bonds: Sensitized I−Oxidation and I3−Photodissociation. Journal of the American Chemical Society, 131(44), 16206-16214. doi:10.1021/ja905021cSangster, J. (1989). Octanol‐Water Partition Coefficients of Simple Organic Compounds. Journal of Physical and Chemical Reference Data, 18(3), 1111-1229. doi:10.1063/1.55583

International psychometric validation of the Living with Chronic Illness Scale in Spanish-speaking patients with chronic obstructive pulmonary disease

Objectives To validate the Living with Chronic Illness (LW-CI) Scale in patients with chronic obstructive pulmonary disease (COPD). Design Observational, cross-sectional validation study with retest. Acceptability, reliability, precision and construct validity were tested. Setting The study took place in primary and secondary specialised units of public and private hospitals of Spain and Colombia. Participants The study included 612 patients with COPD assessed from May 2018 to May 2019. A consecutive cases sampling was done. Inclusion criteria included: (A) patients with a diagnosis of COPD; (B) native Spanish speaking; (C) able to read and understand questionnaires; and (D) able to provide informed consent. Exclusion criteria included: (A) cognitive deterioration and (B) pharmacological effect or disorder that could disrupt the assessment. Results The LW-CI-COPD presented satisfactory data quality, with no missing data or floor/ceiling effects, showing high internal consistency for all the domains (Cronbach's alpha for the total score 0.92). Test-retest reliability was satisfactory (intraclass correlation coefficient=0.92). The LW-CI-COPD correlated 0.52-0.64 with quality of life and social support measures. The scale demonstrated satisfactory known-groups validity, yielding signifi cantly different scores in patients grouped according to COPD severity levels. Conclusions This has been the first validation study of the LW-CI-COPD. It is a feasible, reliable, valid and precise self-reported scale to measure living with COPD in the Spanish-speaking population. Therefore, it could be recommended for research and clinical practice to measure this concept and evaluate the impact of centred-care interdisciplinary interventions based on the patients' perspective, focused on providing holistic and comprehensive care to patients with COPDMinistry of Science, Innovation and University (FEDER/Ministerio de Ciencia, Innovacion y Universidades -Agencia Estatal de Investigacion)||Universidad de la Saban

Fluoroquinolone photodegradation influences specific basophil activation

Fluoroquinolones (FQs) are photoreactive drugs, but it is not known whether laboratory light exposure can influence the induction of photoproducts and modify in vitro test results. The basophil activation test (BAT) has proven to be useful for evaluating immunoglobulin E (IgE)-mediated hypersensitivity to FQs, with a higher percentage of positive responders with ciprofloxacin (CIP) than with moxifloxacin (MOX). We studied the effect of laboratory light on CIP and MOX degradation, and drug-protein conjugate formation, and its influence on the BAT for evaluating IgE-mediated hypersensitivity to FQs. The results showed an important decrease in fluorescence emission intensity under light compared to dark conditions for MOX, and that BAT positivity was lower in light (17.9%) than in dark (35.7%) conditions. No changes were found for CIP in either fluorescence emission intensity or BAT results (46.4% in both conditions). We can conclude that light exposure is a critical factor in BAT results when photolabile drugs like MOX are used. Therefore, light is important when interpreting in vitro results. Copyright (C) 2012 S. Karger AG, BaselWe thank Ian Johnstone for his help with the English language version of the manuscript, and Jose Luis Rodriguez-Bada and Lidia Melendez for their technical support. This study was funded by the FIS-Thematic Networks and Co-operative Research Centres: RIRAAF (RD07/0064) and the Spanish Health Ministry (FIS PS09/01768, PI11/01416 and M Servet contract CP11/00154 for I.A.), the Andalusia Health Ministry (PI-0545-2010), and the Andalusia Economic Innovation and Science Ministry (CTS 06603).Mayorga, C.; Andreu Ros, MI.; Aranda, A.; Doña, I.; Montañez, MI.; Blanca-López, N.; Ariza, A.... (2013). Fluoroquinolone photodegradation influences specific basophil activation. International Archives of Allergy and Immunology. 160(4):377-382. https://doi.org/10.1159/000343023S3773821604Albini, A., & Monti, S. (2003). Photophysics and photochemistry of fluoroquinolones. Chemical Society Reviews, 32(4), 238. doi:10.1039/b209220bBelvedere, A., Boscá, F., Cuquerella, M. C., de Guidi, G., & Miranda, M. A. (2002). Photoinduced N-Demethylation of Rufloxacin and its Methyl Ester Under Aerobic Conditions¶. Photochemistry and Photobiology, 76(3), 252. doi:10.1562/0031-8655(2002)0762.0.co;2Dawe, R. S., Ibbotson, S. H., Sanderson, J. B., Thomson, E. M., & Ferguson, J. (2003). A randomized controlled trial (volunteer study) of sitafloxacin, enoxacin, levofloxacin and sparfloxacin phototoxicity. British Journal of Dermatology, 149(6), 1232-1241. doi:10.1111/j.1365-2133.2003.05582.xHayashi, N., Nakata, Y., & Yazaki, A. (2004). New Findings on the Structure-Phototoxicity Relationship and Photostability of Fluoroquinolones with Various Substituents at Position 1. Antimicrobial Agents and Chemotherapy, 48(3), 799-803. doi:10.1128/aac.48.3.799-803.2004Van Bambeke, F., & Tulkens, P. M. (2009). Safety Profile of the Respiratory Fluoroquinolone Moxifloxacin. Drug Safety, 32(5), 359-378. doi:10.2165/00002018-200932050-00001Sachs, B., Riegel, S., Seebeck, J., Beier, R., Schichler, D., Barger, A., … Erdmann, S. (2006). Fluoroquinolone-Associated Anaphylaxis in Spontaneous Adverse Drug Reaction Reports in Germany. Drug Safety, 29(11), 1087-1100. doi:10.2165/00002018-200629110-00008Manfredi, M., Severino, M., Testi, S., Macchia, D., Ermini, G., Pichler, W. J., & Campi, P. (2004). Detection of specific IgE to quinolones. Journal of Allergy and Clinical Immunology, 113(1), 155-160. doi:10.1016/j.jaci.2003.09.035Aranda, A., Mayorga, C., Ariza, A., Doña, I., Rosado, A., Blanca-Lopez, N., … Torres, M. J. (2010). In vitro evaluation of IgE-mediated hypersensitivity reactions to quinolones. Allergy, 66(2), 247-254. doi:10.1111/j.1398-9995.2010.02460.xAndreu, I., Mayorga, C., & Miranda, M. A. (2010). Generation of reactive intermediates in photoallergic dermatitis. Current Opinion in Allergy and Clinical Immunology, 10(4), 303-308. doi:10.1097/aci.0b013e32833bc68cAntunez, C., Fernandez, T., Blanca-Lopez, N., Torres, M. J., Mayorga, C., Canto, G., … Blanca, M. (2006). IgE antibodies to betalactams: relationship between the triggering hapten and the specificity of the immune response. Allergy, 61(8), 940-946. doi:10.1111/j.1398-9995.2006.01120.xTorres, M. J., Ariza, A., Mayorga, C., Doña, I., Blanca-Lopez, N., Rondon, C., & Blanca, M. (2010). Clavulanic acid can be the component in amoxicillin-clavulanic acid responsible for immediate hypersensitivity reactions. Journal of Allergy and Clinical Immunology, 125(2), 502-505.e2. doi:10.1016/j.jaci.2009.11.032Torres, M. J., & Blanca, M. (2010). The Complex Clinical Picture of β-Lactam Hypersensitivity: Penicillins, Cephalosporins, Monobactams, Carbapenems, and Clavams. Medical Clinics of North America, 94(4), 805-820. doi:10.1016/j.mcna.2010.04.00

Mutational spectrum by phenotype: panel-based NGS testing of patients with clinical suspition of RASopathy and children with multiple café-au-lait macules

Children with neurofibromatosis type 1 (NF1) may exhibit an incomplete clinical presentation, making difficult to reach a clinical diagnosis. A phenotypic overlap may exist in children with other RASopathies or with other genetic conditions if only multiple café‐au‐lait macules (CALMs) are present. The syndromes that can converge in these inconclusive phenotypes have different clinical courses. In this context, an early genetic testing has been proposed to be clinically useful to manage these patients. We present the validation and implementation into diagnostics of a custom NGS panel (I2HCP, ICO‐IMPPC Hereditary Cancer Panel) for testing patients with a clinical suspicion of a RASopathy (n = 48) and children presenting multiple CALMs (n = 102). We describe the mutational spectrum and the detection rates identified in these two groups of individuals. We identified pathogenic variants in 21 out of 48 patients with clinical suspicion of RASopathy, with mutations in NF1 accounting for 10% of cases. Furthermore, we identified pathogenic mutations mainly in the NF1 gene, but also in SPRED1, in more than 50% of children with multiple CALMs, exhibiting an NF1 mutational spectrum different from a group of clinically diagnosed NF1 patients (n = 80). An NGS panel strategy for the genetic testing of these two phenotype‐defined groups outperforms previous strategie