Una introducción al pensamiento de Anthony Giddens

1 archivo PDF (135 páginas)Este trabajo tiene como objetivo presentar a los alumnos avanzados de la licenciatura en sociología, y especialmente a los que cursan la UEA Teoría Sociológica IV, un material original que posibilite el acercamiento a la obra de uno de los más importantes sociólogos contemporáneos: Anthony Giddens. El texto pretende ante todo servir como introducción al pensamiento del autor, propiciar el debate en torno a sus ideas y fomentar el interés por profundizar en el conocimiento de los temas y problemas que desarrolla en su obra

Estudio de factibilidad para la creación del centro de acompañamiento académico “La Nave Maestra” en los niños del cantón La Maná, año 2023.

The present research had as general objective, to develop a feasibility study for the creation of the academic accompaniment center "La Nave Maestra", in order to achieve the proposed objectives it was necessary to collect primary information through field research, by using the survey technique directed to the owners of the existing academic support centers and the legal representatives of the students up to the basic average. The research had a quantitative approach and a descriptive level, with regard to the methodology, the logical and deductive historical methods were used. The results obtained revealed the existence of a current offer of 7.680 hours per year and an unsatisfied demand of 445.317,12 hours, evidencing a wide market for the proposal, around which it was projected to capture 2% equivalent to 10,368 hours per year. Through the technical study, the location was determined, in a macro, meso and micro way, as well as the flow charts of the service, the infrastructure distribution, and the organizational structure. The total investment required was $51,744.04, from which 8$980.29) will be financed with own capital and 92% ($11,000) by a 24-month loan. The net profit to be obtained for the first year was$10.950,48 with an IRR of 28%, a C/B ratio of $1,56 and a PRI of 2 years, 2 months and 8 days; For this reason, it is vitally important to recommend the creation of an academic monitoring center that benefits the social and economic sphere of the canton La Maná.La presente investigación tuvo como objetivo general, desarrollar un estudio de factibilidad para la creación del centro de acompañamiento académico “La Nave Maestra”, con el propósito de alcanzar los objetivos propuestos fue necesario recopilar información primaria a través de la investigación de campo, con el uso de la técnica de la encuesta dirigidas a los propietarios de los centros de acompañamiento académico existentes y los representantes legales de los estudiantes hasta la básica media. La investigación tuvo un enfoque cuantitativo y un nivel descriptivo, en lo que respecta a la metodología se empleó los métodos histórico lógico y deductivo. Los resultados obtenidos permitieron conocer la existencia de una oferta actual de 7.680 horas anuales y una demanda insatisfecha de 445.317,12 horas, evidenciando un amplio mercado para la propuesta, de los cuales se proyectó captar el 2$51.744,04 de los cuales el 8% ($980,29) será financiado con capital propio y el 92$11.000) por un crédito a 24 meses. La utilidad neta a obtener para el primer año fue $10.950,48 con una TIR del 28$1,56 y un PRI de 2 años, 2 meses y 8 días; por lo cual se recomienda la creación del centro de acompañamiento académico que beneficia en el ámbito social y económico del cantón La Maná

Two Novel Variants in YARS2 Gene Are Responsible for an Extended MLASA Phenotype with Pancreatic Insufficiency

Pathogenic variants in the mitochondrial tyrosyl-tRNA synthetase gene (YARS2) were associated with myopathy, lactic acidosis, and sideroblastic anemia (MLASA). However, patients can present mitochondrial myopathy, with exercise intolerance and muscle weakness, leading from mild to lethal phenotypes. Genes implicated in mtDNA replication were studied by Next Gener ation Sequencing (NGS) and whole exome sequence with the TruSeq Rapid Exome kit (Illumina, San Diego, CA, USA). Mitochondrial protein translation was studied following the Sasarman and Shoubridge protocol and oxygen consumption rates with Agilent Seahorse XF24 Analyzer Mi tostress Test, (Agilent, Santa Clara, CA, USA). We report two siblings with two novel compound heterozygous pathogenic variants in YARS2 gene: a single nucleotide deletion in exon 1, c.314delG (p.(Gly105Alafs*4)), which creates a premature stop codon in the amino acid 109, and a single nu cleotide change in exon 5 c.1391T>C (p.(Ile464Thr)), that cause a missense variant in amino acid 464. We demonstrate the pathogenicity of these new variants associated with reduced YARS2 mRNA transcript, reduced mitochondrial protein translation and dysfunctional organelle function. These pathogenic variants are responsible for late onset MLASA, herein accompanied by pancreatic insuf ficiency, observed in both brothers, clinically considered as Pearson's syndrome. Molecular study of YARS2 gene should be considered in patients presenting Pearson's syndrome characteristics and MLASA related phenotypes

Leigh syndrome associated with TRMU gene mutations

Insuficiència hepàtica aguda: Síndrome de Leigh; TRMUInsuficiencia hepática aguda; Síndrome de Leigh; TRMUAcute liver failure; Leigh syndrome; TRMUtRNA 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) deficiency causes an early onset potentially reversible acute liver failure, so far reported in less than 30 patients. We describe two new unrelated patients with an acute liver failure and a neuroimaging compatible with Leigh syndrome (LS) due to TRMU deficiency, a combination not previously reported. Our report enlarges the phenotypical spectrum of TRMU disease.This work was partially supported by the Spanish Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias and cofounded with ERDF funds (Grant No. FIS PI15/01428, PI19/01772)

Leigh Syndrome Associated with TRMU Gene Mutations

tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) deficiency causes an early onset potentially reversible acute liver failure, so far reported in less than 30 patients. We describe two new unrelated patients with an acute liver failure and a neuroimaging compatible with Leigh syndrome (LS) due to TRMU deficiency, a combination not previously reported. Our report enlarges the phenotypical spectrum of TRMU diseaseThe Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), is an initiative of the Instituto de Salud Carlos III (Ministerio de Ciencia e Innovacion, Spain). This study was supported by the Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) (2014: SGR 393) and the CERCA Programme/Generalitat de Catalunya. The present study was supported by the Department de Salut, Generalitat de Catalunya (URDCAT project, SLT002/16/00174

Leigh syndrome associated with TRMU gene mutations

tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) deficiency causes an early onset potentially reversible acute liver failure, so far reported in less than 30 patients. We describe two new unrelated patients with an acute liver failure and a neuroimaging compatible with Leigh syndrome (LS) due to TRMU deficiency, a combination not previously reported. Our report enlarges the phenotypical spectrum of TRMU disease

Efficacy, Safety and Cost-Effectiveness of Methotrexate, Adalimumab or Their Combination in Non-infectious Non-anterior Uveitis: A Protocol for a Multicentre, Randomised, Parallel Three Arms, Active-Controlled, Phase III Open Label With Blinded Outcome Assessment Study

[Abstract] Introduction: Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet. Methods and analysis: The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects’ subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers. Ethics and dissemination: The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation. Trial registration number: 2020-000130-18; NCT04798755.This work was supported by the Instituto de Salud Carlos III, grant number [ICI19/00020]. Sponsor: Fundación para la Investigacion Biomédica del Hospital Clínico San Carlos. Executive Committee: Administrative and executive arm of the clinical trial, providing overall oversight for the study and making decisions on day-to-day operational issues (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Spanish Clinical Trial Network (Amanda López Picado), and 5 Site Directors (these seats will be rotatory, with changes every 6 months months)); Data Coordinating and Analysis Committee: Supervising data collection,management and quality control, designing the statistical analysis plan, performing unmasked data analysis and preparing interim and final reports for the Data Security Monitoring Board and the Executy Committee (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Spanish Clinical Trial Network (Amanda López Picado) and Ester Carreño); Biobank and Biomarker Identification Committee (Maintaining an up-to-date manual of operations for blood extraction, processing and storage, and monitoring procedures adherence, supervising biological sample collection, sample shipment coordination, coordinating the phamacogenetic and proteomic analysis (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Instituto de Salud Carlos III Biobank Platform (Elena Molino), a representative the Instituto de Investigación Biomédica de A Coruña, a representative from, the Data Coordinating and Analysis Committee); Data Security Monitoring Committee (PierGiogio Neri, Andrew Dick, Loreto Carmona

Configuración de una estrategia para la identificación genético-molecular de pacientes con enfermedad mitocondrial

Las enfermedades mitocondriales son un grupo de trastornos hereditarios de metabolismo caracterizados por la alteración de la función mitocondrial, que en la mayor parte de los casos derivan en una disfunción en el sistema de fosforilación oxidativa. Este grupo de enfermedades es muy heterogéneo tanto clínica como genéticamente, debido a su implicación multiorgánica y a su origen genético dual. Debido a que por lo general no hay correlación entre fenotipo y genotipo en los pacientes con sospecha de enfermedad mitocondrial, en la mayor parte de los casos es difícil realizar un diagnóstico molecular definitivo. La integración de las técnicas de secuenciación masiva en este diagnóstico permite mejorar su eficacia, así como asociar nuevos fenotipos a genes ya descritos como implicados en estas enfermedades o incluso asociar nuevos genes a fenotipos clínicos. Durante el desarrollo de este trabajo, se ha integrado la secuenciación masiva en el diagnóstico de pacientes con fenotipo clínico de enfermedad mitocondrial. En primer lugar, se ha puesto a punto la secuenciación del ADNmt completo, así como se ha diseñado y validado un panel de genes a la carta incluyendo aquellos genes implicados en el mantenimiento del ADNmt, para su posterior uso en el diagnóstico; además, junto a dos aproximaciones, se ha aplicado el exoma clínico y el exoma completo a este diagnóstico. Finalmente, se han caracterizado variantes potencialmente patogénicas no descritas anteriormente, y se han estudiado posibles variables modificadoras del fenotipo en pacientes con sordera neurosensorial no sindrómica portadores de la variante homoplasmica m.1555A>G. Se ha obtenido un alto rendimiento diagnostico incluyendo diferentes técnicas de secuenciación masiva en la rutina diagnóstica de pacientes con enfermedad mitocondrial, sobretodo en pacientes bien caracterizados clínicamente. La secuenciación del ADNmt ha permitido la detección de variantes patogénicas en muy bajo porcentaje de heteroplasmia, así como el diagnóstico de pacientes con variantes no asociadas comúnmente a sus fenotipos. La aplicación del panel de genes a la carta ha permitido realizar el diagnóstico genético de pacientes con deleciones múltiples en el ADNmt. Con la aplicación del exoma clínico y el exoma completo, hemos identificado variantes potencialmente patogénicas asociadas a pacientes con síndrome de Leigh y defectos en la actividad enzimática de los complejos OXPHOS; además, una de las variantes se ha encontrado en un gen donde no se han asociado mutaciones previamente a un fenotipo clínico, abriendo nuevas líneas de investigación. Además, se ha podido caracterizar la patogenicidad de las variantes patogénicas estudiadas, asociándolas a los fenotipos clínicos de los pacientes.The mitochondrial disorders (MD) are a group of inherited metabolic diseases characterized by an alteration in the correct function of the mitochondria, mainly due to deficiencies of the oxidative phosphorylation system. These diseases are genetically and clinical heterogenic, due to their dual genetic origin (they can be caused due to mutations in the nuclear and in the mitochondrial genome) and their great phenotypic variability (the disease can affect only one organ or it can be multisystemic). Many times this group of disorders lacks of a genotype-phenotype correlation, since the same mutation can generate different phenotypes, and one specific phenotype can be caused by mutations in different genes, and this fact hampers the genetic diagnose of these disorders. The hypothesis of this thesis proposes that the use of the next generation sequencing (NGS) technologies in the genetic diagnostic of the MD will improve its performance. The use of the NGS in the diagnostic of these diseases will allow the detection of new point mutations in genes already described. Furthermore, the diagnostic through NGS also will allow to associate genes related with a specific MD to new phenotypes, or even to discover new genes causing MD, thus expanding the genetic and phenotypic spectrum of MD and improving the performance of the genetic diagnostic. In the present work we have integrated massive sequencing analysis of mitochondrial and nuclear genes to the diagnostic of patients with MD. We have set up and validated the complete mitochondrial DNA (mtDNA) sequencing that has enabled us to detect low levels of mtDNA heteroplasmy. Furthermore, the covering homogeneity of the complete mtDNA molecule has been optimized. This methodology has allowed us to precisely determine the concrete deleted sequences in single mtDNA deletions. Additionally, we have designed à la carte and validated a panel of genes directly related to mtDNA maintenance for diagnostic purposes. In patients with MD the clinic (n=8) and complete (n=9) exomes have been studied and analyzed. In this regard, new potentially mutagenic variants in both nuclear and mitochondrial DNA genes have been completely characterized, as well as potential phenotypic modulator variants in Non-Syndromic Sensoryneural Hearing Loss patients carrying the homoplasmic m.1555A>G mutation in the MTRNR1 gene. The application of the massive sequencing analysis technique in the diagnosis of these MD has represented an increase in the diagnosis efficiency, specially in those patients that had been well characterized clinically. MtDNA sequencing has allowed the detection in peripheric blood samples of pathogenic variants with a very low degree of heteroplasmy that were not previously detected by the classic Sanger sequencing, reducing the necessity of performing a muscle biopsy. In the complete mtDNA sequencing study, we have detected pathogenic variants that had not been previously associated to the phenotype of the patients. Additionally, the application of the genes panel related with mtDNA maintenance has proven to be very efficient, specially in those patients with multiple mtDNA deletions, being the POLG and TK2 the most representative in those patients. The clinic exome study in patients with Leigh syndrome has allowed us to genetically diagnose 2 out of 6 patients studied. Finally, in two patients with multi-enzymatic deficit of the oxidative phosphorylation system, we have found new potentially pathogenic variants, one in a gene previously associated with the YARS2 clinical phenotype, while the other in a mitochondrial gene previously not associated to any MD

Caracterización clínica y ecográfica de pacientes con diagnóstico ultrasonográfico de litiasis vesicular en Potosí, Bolivia Clinical and ultrasonographic characterization of patients presenting vesicular lithiasis in Potosi, Bolivia

Se realizó un estudio observacional, descriptivo y trasversal para analizar clínica y epidemiológicamente a los pacientes diagnosticados de manera ecográfica de litiasis vesicular en Potosí, Bolivia. El universo estuvo constituido por los 7890 pacientes que acudieron al servicio de ecografía de tres hospitales integrales comunitarios desde junio de 2006 a mayo de 2008. La muestra estuvo conformada por 952 pacientes a los cuales se les diagnosticó ecográficamente litiasis vesicular. Fue más frecuente la afección en el sexo femenino y el grupo de edades de 60 años y más. La mayoría de los pacientes no presentó síntomas ni signos, pero entre los sintomáticos el dolor en hipocondrio derecho resultó ser el síntoma más referido. Según el número de cálculos presentes predominó la litiasis múltiple. La colecistitis aguda fue la complicación más frecuentemente observada.<br>An observational, descriptive and cross-sectional study was carried out to characterize the patients ultrasonographic and clinically presenting vesicular lithiasis in Potosi, Bolivia. The target group included 7890 patients attending to the ultrasonographic services of three Community Comprehensive Hospitals from June 2006 to May 2008. The sample was comprised of 952 patients which ultrasonographic diagnosis revealed vesicular lithiasis. Female sex showed the highest frequency and ages from 60 years old or more prevailed. The majority of patients presented neither symptoms nor signs, those presenting symptoms complained of pain in the right hypochondriac region. Multiple lithiases prevailed regarding the number of calculi. Acute cholelithiasis was the most frequent complication found