Investigación de defectos genéticos en el sistema de la fosforilasa hepática en pacientes argentinos. Definición nosológica mediante una estrategia de análisis molecular. Investigation of genetic defects in the hepatic phosphorylase system in Argentinean patients. Nosological definition by molecular analysis strategy.

Las Enfermedades de Atesoramiento de Glucógeno (EAGs) también llamadas Glucogenosis comprenden un grupo de entidades causadas por una deficiencia enzimática específica relacionada con la vía de síntesis o degradación de esta macromolécula. La heterogeneidad fenotípica de los pacientes afectados dificulta la identificación de las diferentes variantes de EAG y por ende la correcta definición nosológica. En el Centro de Estudio de las Metabolopatías Congénitas, CEMECO, se fueron definiendo los diferentes tipos de Glucogenosis a través de una estrategia multidisciplinaria que integra distintos niveles de investigación clínica y complementaria, laboratorio metabólico especializado, enzimático, histomorfológico y de análisis molecular. Sin embargo, en algunos enfermos, entre los que se encuentran aquellos con defectos en el sistema de la fosforilasa hepática (EAG-VI y EAG-IX), la exacta definición nosológica aún no está resulta. La EAG-VI se refiere a un defecto en la fosforilasa hepática, enzima codificada por el gen PYGL, mientras que la EAG-IX es causada por un defecto genético en una de las subunidades de la fosforilasa b quinasa hepática codicadas por los genes PHKA2, PHKB y PHKG2, respectivamente. El objetivo del presente trabajo es propender a la definición nosológica de pacientes con defectos en el sistema de la fosforilasa mediante una estrategia de análisis molecular investigando los genes PYGL, PHKA2, PHKB y PHKG2. Los pacientes incluidos en este estudio deberán ser compatibles de padecer una EAG-VI o EAG-IX sobre la base de síntomas clínicos y hallazgos bioquímicos. La metodología incluirá la determinación de la enzima fosforilasa b quinasa en glóbulos rojos y dentro del análisis molecular la extracción de DNA genómico a partir de sangre entera para la amplificación por PCR de los exones más las uniones exon/intron de los genes PHKG2 y PYGL y la extracción de RNA total y obtención de cDNA para posterior amplificación de los cDNA PHKA2 y PHKB. Todos los fragmentos amplificados serán sometidos a análisis de secuencia de nucleótidos. Resultados esperados. Este trabajo, primero en Argentina, permitirá establecer las bases moleculares de los defectos del sistema de la fosforilasa hepática (EAG-VI y EAG-IX). El poder lograr este nivel de investigación traerá aparejado, una oferta integrativa en el vasto capítulo de las glucogenosis hepáticas, con extraordinaria significación en la práctica asistencial para el manejo, pronóstico y correspondiente asesoramiento genético. Hepatic glycogen storage diseases (GSDs) are a group of disorders produced by a deficiency in a specific protein involved in the metabolism of glycogen causing different types of GSDs. Phenotypic heterogeneity of affected patients difficult to identify the different GSD variants and therefore the correct definition of the disease. In the “Centro de Estudio de las Metabolopatías Congénitas”, CEMECO, were defined the different GSD types by a protocol which included complex gradual levels of clinical, biochemical, enzymatic and morphological investigation. However, in some patients, like those one with defects in the hepatic phosphorylase system (GSD-VI and GSD-IX) the exact definition of the disease has not yet been resolved. The GSD-VI is produced by a defect in the PYGL gen that encode the liver phosphorylase, while the GSD-IX is caused by a genetic defect in one of the Phosphorylase b kinase subunits, encoded by the PHKA2, PHKB and PHKG2 genes, respectively. The aim of the present study is to define the phosphorylase system defects in argentinian patients through a molecular strategy that involve the investigation of PYGL, PHKA2, PHKB and PHKG2 genes. Patients included in the present study must be compatible with a GSD-VI or GSD-IX on the bases of clinical symptoms and biochemical findings. The phosphorylase b kinase activity will be assay on in blood red cells. The molecular study will include genomic DNA extraction for the amplification of PHKG2 and PYGL genes and the total RNA extraction for amplification of the PHKA2 and PHKB cDNA by PCR. All PCR-amplified fragments will be subjected to direct nucleotide sequencing. This work, first in Argentina, will make possible to establish the molecular basis of the defects on the hepatic phosphorylase system (GSD-VI and GSD IX). To achieve this level of research will entail advance in the study of the hepatic glycogen storage disease, with extraordinary significance in the treatment, prognosis and the genetic counselling.

Polish immigrants in Ireland's black economy: a phenomenological investigation

The purpose of this thesis is to answer the research question ‗why do some Polish migrants engage in shadow employment in the Republic of Ireland?‘ The individual and group interviews, which were conducted in August 2011 with thirteen Polish migrants, living and working in Ireland, generated the answer to the research question. Interviewees‘ responses were analysed from the point of view of the literature that examines the various factors within the topics of migration and the black economy. The thesis begins with theoretical background information regarding the enlargement of the European Union and the economic situation of Poland and Ireland. Then migration theories are explained and Polish and Irish migration history is presented. Next, the issue of the black economy and shadow employment is developed with a focus on its presence in Poland and Ireland. The following section is dedicated to the research methodology that was adopted to ensure effective collection of the information. The issues of the qualitative and quantitative research, phenomenological approach to the research and interviews as data collection are raised in that section. The last part of the thesis is based on an analysis of the respondents‘ statements. It explores interviewees‘ experience of life and work in Ireland. The main part of that section develops the reasons why do Polish workers engage in shadow employment in the Republic of Ireland. Simultaneously, it provides the answers to the research question of this thesis.

Does the provision of full day care improve the quality of life for children and their parents

This study sought to explore and examine if the provision of full day care improves the quality of life for children and their parents. Owing to the effects of the Celtic Tiger, life in Ireland has changed considerably over the past five to ten years. Because of the booming economy there are now 60.8% of women employed in the workforce. This means many changes for children, parents and families. Findings in the literature review are based on international studies. The researcher utilised both qualitative and quantitative research methodologies for the study. She interviewed 31 respondents; 27 childcare managers; 3 politicians and the chairperson of a childcare committee. Furthermore, 325 questionnaires were completed in a survey by working parents in the statutory and voluntary sectors in and around Sligo town and in two childcare facilities in Letterkenny, Co. Donegal. Babies as young as 4 months are being cared for in childcare facilities from 6.45am until 6.pm daily, 5 days per week. Some children are spending up to 11 hours per day in childcare facilities. The study has not categorically concluded that full day care is either positive or negative for children. Childcare facilities are providing good quality childcare encompassing various services; however, 25 out of 27 childcare managers reported to the researcher that they would not leave their child in full day care. Parents are finding it difficult to manage work life balance. Health dominated quality of life issues. Two hundred and thirty five (235) parents reported being stressed. The study also found that 315 working parents feel that the government is not doing enough to support working parents. On a positive note, 241 parents said they are happy in general with the quality of life for them, their family and their children. In addition, the researcher has identified a number of recommendations for future changes in policy and further study.