Deciphering Multiple Sclerosis Progression

Esclerosi múltiple; NeurodegeneracióEsclerosis múltiple; NeurodegeneraciónMultiple sclerosis; NneurodegenerationMultiple sclerosis (MS) is primarily an inflammatory and degenerative disease of the central nervous system, triggered by unknown environmental factors in patients with predisposing genetic risk profiles. The prevention of neurological disability is one of the essential goals to be achieved in a patient with MS. However, the pathogenic mechanisms driving the progressive phase of the disease remain unknown. It was described that the pathophysiological mechanisms associated with disease progression are present from disease onset. In daily practice, there is a lack of clinical, radiological, or biological markers that favor an early detection of the disease's progression. Different definitions of disability progression were used in clinical trials. According to the most descriptive, progression was defined as a minimum increase in the Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 from a baseline level of 0, 1.0–5.0, and 5.5, respectively. Nevertheless, the EDSS is not the most sensitive scale to assess progression, and there is no consensus regarding any specific diagnostic criteria for disability progression. This review document discusses the current pathophysiological concepts associated with MS progression, the different measurement strategies, the biomarkers associated with disability progression, and the available pharmacologic therapeutic approaches

Minimally invasive lung tissue differentiation using electrical impedance spectroscopy: a comparison of the 3- and 4-electrode methods

Multiple imaging techniques are used for the diagnosis of lung diseases. The choice of a technique depends on the suspected diagnosis. Computed tomography (CT) of the thorax and positron emission tomography (PET) are imaging techniques used for the detection, characterization, staging and follow-up of lung cancer, and these techniques use ionizing radiation and are radiologist-dependent. Electrical impedance spectroscopy (EIS) performed through a bronchoscopic process could serve as a minimally invasive non-ionizing method complementary to CT and PET to characterize lung tissue. The aim of this study was to analyse the feasibility and ability of minimally invasive EIS bioimpedance measures to differentiate among healthy lung, bronchial and neoplastic lung tissues through bronchoscopy using the 3- and 4-electrode methods. Tissue differentiation was performed in 13 patients using the 4-electrode method (13 healthy lung, 12 bronchial and 3 neoplastic lung tissues) and the 3-electrode method (9 healthy lung, 10 bronchial and 2 neoplastic lung tissues). One-way analysis of variance (ANOVA) showed a statistically significant difference (P < 0.001) between bronchial and healthy lung tissues for both the 3- and 4-electrode methods. The 3-electrode method seemed to differentiate cancer types through changes in the cellular structures of the tissues by both the reactance (Xc) and the resistance (R). Minimally invasive measurements obtained using the 3-electrode method seem to be most suitable for differentiating between healthy and bronchial lung tissues. In the future, EIS using the 3-electrode method could be a method complementary to PET/CT and biopsy in lung pathology diagnosis.Peer ReviewedPostprint (author's final draft

Differentiation using minimally-invasive bioimpedance measurements of healthy and pathological lung tissue through bronchoscopy

Purpose: To use minimally-invasive transcatheter electrical impedance spectroscopy measurements for tissue differentiation among healthy lung tissue and pathologic lung tissue from patients with different respiratory diseases (neoplasm, fibrosis, pneumonia and emphysema) to complement the diagnosis at real time during bronchoscopic procedures. Methods: Multi-frequency bioimpedance measurements were performed in 102 patients. The two most discriminative frequencies for impedance modulus (|Z|), phase angle (PA), resistance (R) and reactance (Xc) were selected based on the maximum mean pair-wise Euclidean distances between paired groups. One-way ANOVA for parametric variables and Kruskal–Wallis for non-parametric data tests have been performed with post-hoc tests. Discriminant analysis has also been performed to find a linear combination of features to separate among tissue groups. Results: We found statistically significant differences for all the parameters between: neoplasm and pneumonia (p¿¿0.05) are found between neoplasm and fibrosis; fibrosis and pneumonia; and between healthy lung tissue and emphysema. Conclusion: The application of minimally-invasive electrical impedance spectroscopy measurements in lung tissue have proven to be useful for tissue differentiation between those pathologies that leads increased tissue and inflammatory cells and those ones that contain more air and destruction of alveolar septa, which could help clinicians to improve diagnosis.Peer ReviewedPostprint (published version

Using temporal electrical impedance spectroscopy measures to differentiate lung pathologies with the 3-electrode method

Minimally invasive lung bioimpedance measurements could serve in the future diagnosis of lung pathologies complementing biopsies and imaging techniques. Through the electrical impedance spectroscopy (EIS) technique using the 3-electrode method, distinction of lung pathologies could be possible depending on the state of the tissue. Since now, only averaged information has been used for the analysis of bioimpedance data in lungs. The aim of this study is to use temporal information to evaluate changes in the impedance signal due to the mechanism of ventilation and perfusion produced by the lungs. Preliminary results show: 1) correlation between ventilation and perfusion with the bioimpedance signal and 2) changes in the amplitude of the bioimpedance time signal depending on the pathology. As conclusion, together with cycled averaged data, temporal data could be useful for lung pathologies distinction.Postprint (published version

Effect of calibration for tissue differentiation between healthy and neoplasm lung using minimally invasive electrical impedance spectroscopy

his study proposes a calibration method and analyses the effect of this calibration in lung measures, using minimally invasive electrical impedance spectroscopy with the 3-electrode method, for tissue differentiation between healthy and neoplasm lung tissue. Tissue measurements were performed in 99 patients [54 healthy tissue and 15 neoplastic tissue samples obtained] with an indicated bronchoscopy. Statistically significant difference (P < 0.001) were found between healthy lung tissue and neoplasm lung tissue in bioimpedance parameters. The calibration of the bioimpedance measures with respect to a measure performed in bronchi reduces the inter-patient dispersion, increasing the sensitivity, decreasing the specificity and increasing the area below the ROC curve for three out of four impedance-derived estimators. Results also show that there are no significant differences between healthy lung tissue among smoker, non-smoker and ex-smoker samples, which was initially stated as a possible cause of EIS measurement dispersion in lungs.Peer ReviewedPostprint (published version

All in One High Quality Genomic DNA and Total RNA Extraction From Nematode Induced Galls for High Throughput Sequencing Purposes

Meloidogyne spp. are plant-parasitic nematodes that form a very complex pseudo-organ, called gall, which contains the giant cells (GCs) to nourish them. During the last decade, several groups have been studying the molecular processes accompanying the formation of these structures, combining both transcriptomics and cellular biology. Among others, it was confirmed that a generalized gene repression is a hallmark of early developing GCs formed by Meloidogyne javanica in Arabidopsis and tomato. One of the main mechanisms behind this gene repression involve small RNAs (sRNAs) directed gene silencing. This is supported not only by the described action of several microRNAs differentially expressed in galls, but by the differential abundance of 24-nucleotide sRNAs in early developing Arabidopsis galls, particularly those rasiRNAs which are mostly involved in RNA-directed DNA methylation. Their accumulation strongly correlates to the repression of several retrotransposons at pericentromeric regions of Arabidopsis chromosomes in early galls. However, the contribution of this global gene repression to GCs/galls formation and maintenance is still not fully understood. Further detailed studies, as the correlation between gene expression profiles and the methylation state of the chromatin in galls are essential to raise testable working hypotheses. A high quality of isolated DNA and RNA is a requirement to obtain non-biased and comprehensive results. Frequently, the isolation of DNA and RNA is performed from different samples of the same type of biological material. However, subtle differences on epigenetic processes are frequent even among independent biological replicates of the same tissue and may not correlate to those changes on the mRNA population obtained from different biological replicates. Herein, we describe a method that allows the simultaneous extraction and purification of genomic DNA and total RNA from the same biological sample adapted to our biological system. The quality of both nucleic acids from Arabidopsis galls formed by M. javanica was high and adequate to construct RNA and DNA libraries for high throughput sequencing used for transcriptomic and epigenetic studies, such as the analysis of the methylation state of the genomic DNA in galls (MethylC-seq) and RNA sequencing (RNAseq). The protocol presents guidance on the described procedure, key notes and troubleshooting

Hepatic and serum branched-chain fatty acid profile in patients with nonalcoholic fatty liver disease: A case–control study

Objective Alterations in the hepatic lipidome are a crucial factor involved in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the serum and hepatic profile of branched-chain fatty acids (BCFAs) in patients with different stages of NAFLD. Methods This was a case–control study performed in 27 patients without NAFLD, 49 patients with nonalcoholic fatty liver, and 17 patients with nonalcoholic steatohepatitis, defined by liver biopsies. Serum and hepatic levels of BCFAs were analyzed by gas chromatography–mass spectrometry. The hepatic expression of genes involved in the endogenous synthesis of BCFAs was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Results A significant increase in hepatic BCFAs was found in subjects with NAFLD compared with those without NAFLD; no differences were observed in serum BCFAs between study groups. Trimethyl BCFAs, iso-BCFAs, and anteiso-BCFAs were increased in subjects with NAFLD (either nonalcoholic fatty liver or nonalcoholic steatohepatitis) compared with those without NAFLD. Correlation analysis showed a relationship between hepatic BCFAs and the histopathological diagnosis of NAFLD, as well as other histological and biochemical parameters related to this disease. Gene expression analysis in liver showed that the mRNA levels of BCAT1, BCAT2, and BCKDHA were upregulated in patients with NAFLD. Conclusions These results suggest that the increased production of liver BCFAs might be related to NAFLD development and progression.This work was funded by the Institute of Health “Carlos III” (ISCIII) and cofunded by the Fondo Europeo de Desarrollo Regional-FEDER (grant number PI20/00505). J.C.F-G was supported by an intensification research program (INT21/00078, ISCIII, Spain; cofunded by the Fondo Europeo de Desarrollo Regional-FEDER), M.A.M-S was supported by a PFIS predoctoral fellowship from the ISCIII (FI21/00003, ISCIII, Spain; cofunded by the Fondo Europeo de Desarrollo Regional-FEDER), and B.R-M was supported by the “Miguel Servet Type I” program (CP19/00098, ISCIII, Spain; cofunded by the Fondo Europeo de Desarrollo Regional-FEDER). The funding organizations played no role in the design of the study, review and interpretation of the data, or final approval of the manuscript. Funding for open access charge: Universidad de Málaga / CBU

Soft Skills y empleabilidad: Estudio de las habilidades blandas de los estudiantes en prácticas de la Facultad de Comercio y Turismo para su mejor inserción laboral

Estudio de las habilidades blandas de estudiantes en prácticas con el fin de identificar posibles limitaciones, ofrecer herramientas necesarias para transformarlas en habilidades empoderadoras en su perfil profesional y potenciar su empleabilidad

Validation of three predictive models for suboptimal cytoreductive surgery in advanced ovarian cancer

The standard treatment for advanced ovarian cancer (AOC) is cytoreduction surgery and adjuvant chemotherapy. Tumor volume after surgery is a major prognostic factor for these patients. The ability to perform complete cytoreduction depends on the extent of disease and the skills of the surgical team. Several predictive models have been proposed to evaluate the possibility of performing complete cytoreductive surgery (CCS). External validation of the prognostic value of three predictive models (Fagotti index and the R3 and R4 models) for predicting suboptimal cytoreductive surgery (SCS) in AOC was performed in this study. The scores of the 3 models were evaluated in one hundred and three consecutive patients diagnosed with AOC treated in a tertiary hospital were evaluated. Clinicopathological features were collected prospectively and analyzed retrospectively. The performance of the three models was evaluated, and calibration and discrimination were analyzed. The calibration of the Fagotti, R3 and R4 models showed odds ratios of obtaining SCSs of 1.5, 2.4 and 2.4, respectively, indicating good calibration. The discrimination of the Fagotti, R3 and R4 models showed an area under the ROC curve of 83%, 70% and 81%, respectively. The negative predictive values of the three models were higher than the positive predictive values for SCS. The three models were able to predict suboptimal cytoreductive surgery for advanced ovarian cancer, but they were more reliable for predicting CCS. The R4 model discriminated better because it includes the laparotomic evaluation of the peritoneal carcinomatosis index