HPLC-HRMS Global Metabolomics Approach for the Diagnosis of “Olive Quick Decline Syndrome” Markers in Olive Trees Leaves

Olive quick decline syndrome (OQDS) is a multifactorial disease affecting olive plants. The onset of this economically devastating disease has been associated with a Gram-negative plant pathogen called Xylella fastidiosa (Xf). Liquid chromatography separation coupled to high-resolution mass spectrometry detection is one the most widely applied technologies in metabolomics, as it provides a blend of rapid, sensitive, and selective qualitative and quantitative analyses with the ability to identify metabolites. The purpose of this work is the development of a global metabolomics mass spectrometry assay able to identify OQDS molecular markers that could discriminate between healthy (HP) and infected (OP) olive tree leaves. Results obtained via multivariate analysis through an HPLC-ESI HRMS platform (LTQ-Orbitrap from Thermo Scientific) show a clear separation between HP and OP samples. Among the differentially expressed metabolites, 18 different organic compounds highly expressed in the OP group were annotated; results obtained by this metabolomic approach could be used as a fast and reliable method for the biochemical characterization of OQDS and to develop targeted MS approaches for OQDS detection by foliage analysis

Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas

Multiple osteochondromas is an autosomal dominant skeletal disorder characterized by the formation of multiple cartilage-capped tumours. Two causal genes have been identified, EXT1 and EXT2, which account for 65% and 30% of cases, respectively. We have undertaken a mutation analysis of the EXT1 and EXT2 genes in 39 unrelated Spanish patients, most of them with moderate phenotype, and looked for genotype-phenotype correlations. We found the mutant allele in 37 patients, 29 in EXT1 and 8 in EXT2. Five of the EXT1 mutations were deletions identified by MLPA. Two cases of mosaicism were documented. We detected a lower number of exostoses in patients with missense mutation versus other kinds of mutations. In conclusion, we found a mutation in EXT1 or in EXT2 in 95% of the Spanish patients. Eighteen of the mutations were novel.Fil: Sarrión, P.. Universidad de Barcelona; EspañaFil: Sangorrin, A.. Hospital Sant Joan de Déu; EspañaFil: Urreizti, R.. Universidad de Barcelona; EspañaFil: Delgado, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Artuch, R.. Hospital Sant Joan de Déu; EspañaFil: Martorell, L.. Hospital Sant Joan de Déu; EspañaFil: Armstrong, J.. Hospital Sant Joan de Déu; EspañaFil: Anton, J.. Hospital Sant Joan de Déu; EspañaFil: Torner, F.. Hospital Sant Joan de Déu; EspañaFil: Vilaseca, M. A.. Hospital Sant Joan de Déu; EspañaFil: Nevado, J.. Hospital Universitario La Paz; EspañaFil: Lapunzina, P.. Hospital Universitario La Paz; EspañaFil: Asteggiano, Carla Gabriela. Universidad Nacional de Córdoba; Argentina. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Balcells, S.. Universidad de Barcelona; EspañaFil: Grinberg, D.. Universidad de Barcelona; Españ

Pilot Study on Quantitative Cervical Cord and Muscular MRI in Spinal Muscular Atrophy: Promising Biomarkers of Disease Evolution and Treatment?

Introduction: Nusinersen is a recent promising therapy approved for the treatment of spinal muscular atrophy (SMA), a rare disease characterized by the degeneration of alpha motor neurons (αMN) in the spinal cord (SC) leading to progressive muscle atrophy and dysfunction. Muscle and cervical SC quantitative magnetic resonance imaging (qMRI) has never been used to monitor drug treatment in SMA. The aim of this pilot study is to investigate whether qMRI can provide useful biomarkers for monitoring treatment efficacy in SMA. Methods: Three adult SMA 3a patients under treatment with nusinersen underwent longitudinal clinical and qMRI examinations every 4 months from baseline to 21-month follow-up. The qMRI protocol aimed to quantify thigh muscle fat fraction (FF) and water-T2 (w-T2) and to characterize SC volumes and microstructure. Eleven healthy controls underwent the same SC protocol (single time point). We evaluated clinical and imaging outcomes of SMA patients longitudinally and compared SC data between groups transversally. Results: Patient motor function was stable, with only Patient 2 showing moderate improvements. Average muscle FF was already high at baseline (50%) and progressed over time (57%). w-T2 was also slightly higher than previously published data at baseline and slightly decreased over time. Cross-sectional area of the whole SC, gray matter (GM), and ventral horns (VHs) of Patients 1 and 3 were reduced compared to controls and remained stable over time, while GM and VHs areas of Patient 2 slightly increased. We found altered diffusion and magnetization transfer parameters in SC structures of SMA patients compared to controls, thus suggesting changes in tissue microstructure and myelin content. Conclusion: In this pilot study, we found a progression of FF in thigh muscles of SMA 3a patients during nusinersen therapy and a concurrent slight reduction of w-T2 over time. The SC qMRI analysis confirmed previous imaging and histopathological studies suggesting degeneration of αMN of the VHs, resulting in GM atrophy and demyelination. Our longitudinal data suggest that qMRI could represent a feasible technique for capturing microstructural changes induced by SMA in vivo and a candidate methodology for monitoring the effects of treatment, once replicated on a larger cohort

A broad spectrum of genomic changes in latinamerican patients with EXT1/EXT2-CDG

Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). In contrast, solitary osteochondroma (SO) is a non-hereditary condition. EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). Sixty-three percent of all MO cases presented severe phenotype and two malignant transformations to chondrosarcoma (7%). We found the mutant allele in 78% of MO patients. Ten mutations were novel. The disease-causing mutations remained unknown in 22% of the MO patients and in all SO patients. No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. Neither EXT1 nor EXT2 protein could be detected in this sample. This is the first Latin American research program on EXT1/EXT2-CDG.Fil: Delgado, M. A.. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Martinez Domenech, G.. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Sarrión, P.. Universidad de Barcelona; EspañaFil: Urreizti, R.. Universidad de Barcelona; EspañaFil: Zecchini, L.. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Robledo, H. H.. Hospital de Niños de la Santísima Trinidad; ArgentinaFil: Segura, F.. Universidad Nacional de Córdoba; ArgentinaFil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Balcells, S.. Universidad de Barcelona; EspañaFil: Grinberg, D.. Universidad de Barcelona; EspañaFil: Asteggiano, Carla Gabriela. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Est.de Las Metabolopatias Congenitas. Cátedra de Clinica Pediatrica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

A broad spectrum of genomic changes in Latinamerican patients with EXT1/EXT2-CDG

Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). In contrast, solitary osteochondroma (SO) is a non-hereditary condition. EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). Sixty-three percent of all MO cases presented severe phenotype and two malignant transformations to chondrosarcoma (7%). We found the mutant allele in 78% of MO patients. Ten mutations were novel. The disease-causing mutations remained unknown in 22% of the MO patients and in all SO patients. No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. Neither EXT1 nor EXT2 protein could be detected in this sample. This is the first Latin American research program on EXT1/EXT2-CDG

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC)

Peer reviewe

2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)

info:eu-repo/semantics/publishe

Standardized assessment of evidence supporting the adoption of mobile health solutions: A Clinical Consensus Statement of the ESC Regulatory Affairs Committee

Mobile health (mHealth) solutions have the potential to improve self-management and clinical care. For successful integration into routine clinical practice, healthcare professionals (HCPs) need accepted criteria helping the mHealth solutions’ selection, while patients require transparency to trust their use. Information about their evidence, safety and security may be hard to obtain and consensus is lacking on the level of required evidence. The new Medical Device Regulation is more stringent than its predecessor, yet its scope does not span all intended uses and several difficulties remain. The European Society of Cardiology Regulatory Affairs Committee set up a Task Force to explore existing assessment frameworks and clinical and cost-effectiveness evidence. This knowledge was used to propose criteria with which HCPs could evaluate mHealth solutions spanning diagnostic support, therapeutics, remote follow-up and education, specifically for cardiac rhythm management, heart failure and preventive cardiology. While curated national libraries of health apps may be helpful, their requirements and rigour in initial and follow-up assessments may vary significantly. The recently developed CEN-ISO/TS 82304-2 health app quality assessment framework has the potential to address this issue and to become a widely used and efficient tool to help drive decision-making internationally. The Task Force would like to stress the importance of co-development of solutions with relevant stakeholders, and maintenance of health information in apps to ensure these remain evidence-based and consistent with best practice. Several general and domain-specific criteria are advised to assist HCPs in their assessment of clinical evidence to provide informed advice to patients about mHealth utilization