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Search Results: 1 - 10 of 94406 matches for " Alexandra I. Soto-Ortolaza "
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Evaluation of the Role of SNCA Variants in Survival without Neurological Disease
Michael G. Heckman, Alexandra I. Soto-Ortolaza, Nancy N. Diehl, Minerva M. Carrasquillo, Ryan J. Uitti, Zbigniew K. Wszolek, Neill R. Graff-Radford, Owen A. Ross
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042877
Abstract: Background A variety of definitions of successful aging have been proposed, many of which relate to longevity, freedom from disease and disability, or preservation of high physical and cognitive function. Many behavioral, biomedical, and psychological factors have been linked with these various measures of successful aging, however genetic predictors are less understood. Parkinson's disease (PD) is an age-related neurodegenerative disorder, and variants in the α-synuclein gene (SNCA) affect susceptibility to PD. This exploratory study examined whether SNCA variants may also promote successful aging as defined by survival without neurological disease. Methods We utilized 769 controls without neurological disease (Mean age: 79 years, Range: 33–99 years) and examined the frequency of 20 different SNCA variants across age groups using logistic regression models. We also included 426 PD cases to assess the effect of these variants on PD risk. Results There was a significant decline in the proportion of carriers of the minor allele of rs10014396 as age increased (P = 0.021), from 30% in controls younger than 60 to 14% in controls 90 years of age or older. Findings were similar for rs3775439, where the proportion of carriers of the minor allele declined from 32% in controls less than 60 years old to 19% in those 90 or older (P = 0.025). A number of SNCA variants, not including rs10014396 or rs3775439, were significantly associated with susceptibility to PD. Conclusions In addition to its documented roles in PD and α-synucleinopathies, our results suggest that SNCA has a role in survival free of neurological disease. Acknowledging that our findings would not have withstood correction for multiple testing, validation in an independent series of aged neurologically normal controls is needed.
NOTCH3 Variants and Risk of Ischemic Stroke
Owen A. Ross, Alexandra I. Soto-Ortolaza, Michael G. Heckman, Christophe Verbeeck, Daniel J. Serie, Sruti Rayaprolu, Stephen S. Rich, Michael A. Nalls, Andrew Singleton, Rita Guerreiro, Emma Kinsella, Zbigniew K. Wszolek, Thomas G. Brott, Robert D. Brown, Bradford B. Worrall, James F. Meschia
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075035
Abstract: Background Mutations within the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). CADASIL mutations appear to be restricted to the first twenty-four exons, resulting in the gain or loss of a cysteine amino acid. The role of other exonic NOTCH3 variation not involving cysteine residues and mutations in exons 25-33 in ischemic stroke remains unresolved. Methods All 33 exons of NOTCH3 were sequenced in 269 Caucasian probands from the Siblings With Ischemic Stroke Study (SWISS), a 70-center North American affected sibling pair study and 95 healthy Caucasian control subjects. Variants identified by sequencing in the SWISS probands were then tested for association with ischemic stroke using US Caucasian controls collected at the Mayo Clinic (n=654), and further assessed in a Caucasian (n=802) and African American (n=298) patient-control series collected through the Ischemic Stroke Genetics Study (ISGS). Results Sequencing of the 269 SWISS probands identified one (0.4%) with small vessel type stroke carrying a known CADASIL mutation (p.R558C; Exon 11). Of the 19 common NOTCH3 variants identified, the only variant significantly associated with ischemic stroke after multiple testing adjustment was p.R1560P (rs78501403; Exon 25) in the combined SWISS and ISGS Caucasian series (Odds Ratio [OR] 0.50, P=0.0022) where presence of the minor allele was protective against ischemic stroke. Although only significant prior to adjustment for multiple testing, p.T101T (rs3815188; Exon 3) was associated with an increased risk of small-vessel stroke (OR: 1.56, P=0.008) and p.P380P (rs61749020; Exon 7) was associated with decreased risk of large-vessel stroke (OR: 0.35, P=0.047) in Caucasians. No significant associations were observed in the small African American series. Conclusion Cysteine-affecting NOTCH3 mutations are rare in patients with typical ischemic stroke, however our observation that common NOTCH3 variants may be associated with risk of ischemic stroke warrants further study.
Glutathione S-transferase omega genes in Alzheimer and Parkinson disease risk, age-at-diagnosis and brain gene expression: an association study with mechanistic implications
Mariet Allen, Fanggeng Zou, High Chai, Curtis S Younkin, Richard Miles, Asha A Nair, Julia E Crook, V Pankratz, Minerva M Carrasquillo, Christopher N Rowley, Thuy Nguyen, Li Ma, Kimberly G Malphrus, Gina Bisceglio, Alexandra I Ortolaza, Ryan Palusak, Sumit Middha, Sooraj Maharjan, Constantin Georgescu, Debra Schultz, Fariborz Rakhshan, Christopher P Kolbert, Jin Jen, Sigrid B Sando, Jan O Aasly, Maria Barcikowska, Ryan J Uitti, Zbigniew K Wszolek, Owen A Ross, Ronald C Petersen, Neill R Graff-Radford, Dennis W Dickson, Steven G Younkin, Nilüfer Ertekin-Taner
Molecular Neurodegeneration , 2012, DOI: 10.1186/1750-1326-7-13
Abstract: We found that rs156697 minor allele associates with significantly increased risk (odds ratio = 1.14, p = 0.038) in the older ADs with age-at-diagnosis > 80 years. The minor allele of GSTO1 rs4925 associates with decreased risk in familial PD (odds ratio = 0.78, p = 0.034). There was no other association with disease risk or age-at-diagnosis. The minor alleles of both GSTO SNPs associate with lower brain levels of GSTO2 (p = 4.7 × 10-11-1.9 × 10-27), but not GSTO1. Pathway analysis of significant genes in our brain expression GWAS, identified significant enrichment for glutathione metabolism genes (p = 0.003).These results suggest that GSTO locus variants may lower brain GSTO2 levels and consequently confer AD risk in older age. Other glutathione metabolism genes should be assessed for their effects on AD and other chronic, neurologic diseases.Glutathione S-Transferase (GST) family of genes have been implicated in multiple neuropsychiatric [1-4] and neurodegenerative diseases [5-11]; where altered levels or function of these enzymes is thought to impact levels of oxidative stress and/or inflammation in a way that contributes to disease susceptibility. A linkage locus on chromosome 10q that has been implicated in both Alzheimer's (AD)[11-13] and Parkinson's disease (PD)[13] harbors two GST genes of the omega class: GSTO1 and GSTO2, which are approximately 75 kb apart.GSTOs have enzymatic activities as thioltransferases and dehydroascorbate reductases that promote antioxidant activity and can also function in metabolism of drugs and toxins[14]. Additionally, GSTO1 was shown to promote activation of the pro-inflammatory cytokine, interleukin-1β (IL-1β) by post-translational processing[15]. Given their location and function, they have been studied as candidate genes in AD and PD[5,6,9,11,14,16-18]. Li et al. compared hippocampal gene expression levels in 6 AD vs. 2 control brains and identified significantly lower GSTO1 levels in the AD hippocampi[5]. This group studied
La calidad de vida relacionada con la salud como medida de resultados en pacientes con cardiopatía isquémica
Soto,M.; Failde,I.;
Revista de la Sociedad Espa?ola del Dolor , 2004,
Abstract: the term health-related quality of life (hrql) is a concept related to the assessment of how the individual perceives health and that covers both objective and subjective aspects. despite the lack of consensus about its definition, several tools have been developed for the measurement of hrql in different pathologies, such as in the ischemic cardiopathy. these tools take into consideration different dimensions of the hrql and are usually classified as generic or specific questionnaires. these tools must have certain features in order to be considered useful, allowing to record patient perceptions in a quantitative or semi-quantitatively way that might be communicated and used to describe, assess or compare. the assessment of hrql is important due to the high relevance of this disease in terms of epidemiology and health care, and also in terms of the related psychological aspects that are not always duly considered by clinicians. we describe the most widely used generic and specific hrql questionnaires in ischemic cardiopathy, indicating the dimensions covered by each of them. finally, the main uses of the measurement of hrql in the ischemic cardiopathy for the assessment of outcomes are reviewed, with reference to clinical trials and cardiac rehabilitation. it is stressed that the assessment of hrql in the ischemic cardiopathy provides us with a final health outcome focused on the individual instead of the disease; focused on how the patient feels, regardless the clinical data. hence, the assessment of hrql in the ischemic cardiopathy is a tool aimed to promote a patient-focused health care and to provide information that complements the traditional clinical assessment. for this purpose, the clinical interpretability of the different assessment questionnaires should be further improved.
Are salmon-derived nutrients being incorporated in food webs of invaded streams? Evidence from southern Chile Les nutriments dérivés du saumon sont-ils incorporés dans les réseaux trophiques des cours d'eau envahis ? Un cas au sud du Chili.
Arismendi I.,Soto D.
Knowledge and Management of Aquatic Ecosystems , 2012, DOI: 10.1051/kmae/2012009
Abstract: Using stable isotope analyses of N and C we present preliminary evidence of marine-derived nutrients from introduced Chinook salmon (Oncorhynchus tshawytscha Walbaum) in stream food webs of Laguna Los Patos, NW Patagonia. Similar to values reported within Chinook salmon's native distributional range periphyton and aquatic insects are the trophic levels that show the greatest enrichment of δ15N (5–6‰). Since there is a rapid expansion of Chinook salmon in South America future effort is needed to elucidate the mechanisms and consequences of nutrients subsidies from salmon carcasses in those invaded ecosystems. En utilisant l’analyse des isotopes stables de N et C, nous présentons des données préliminaires indiquant que les éléments nutritifs provenant du saumon Chinook introduit (Oncorhynchus tshawytscha Walbaum) entrent dans le réseau trophique de la rivière Laguna Los Patos, NW Patagonie. Comme pour les valeurs rapportées dans l’aire de répartition d’origine du saumon Chinook, le périphyton et les insectes aquatiques sont les niveaux trophiques qui montrent le plus grand enrichissement de δ15N (5–6 ‰). Comme il s'agit d'une expansion rapide du saumon Chinook en Amérique du Sud, un effort de recherche est nécessaire pour comprendre les mécanismes et les conséquences des apports en substances nutritives provenant des carcasses de saumons dans ces écosystèmes envahis.
La calidad de vida relacionada con la salud como medida de resultados en pacientes con cardiopatía isquémica Health-related quality of life as an outcome measure in patients with ischemic cardiopathy
M. Soto,I. Failde
Revista de la Sociedad Espa?ola del Dolor , 2004,
Abstract: El término calidad de vida relacionada con la salud (CVRS) surge como un concepto que hace referencia a valoraciones de la percepción de la salud por parte del individuo, recogiendo tanto aspectos objetivos como subjetivos. Aunque no hay un consenso en su definición, se han desarrollado diversos instrumentos de medición de CVRS en diferentes patologías, entre ellas la cardiopatía isquémica. Los diversos instrumentos tienen en cuenta distintas dimensiones de la CVRS y suelen clasificarse en cuestionarios genéricos y específicos. Estos instrumentos deben cumplir una serie de características para ser considerados útiles, permitiendo la posibilidad de registrar las percepciones del paciente de una forma cuantitativa o semicuantitativa, que pueda comunicarse y utilizarse para describir, evaluar o comparar. La importancia de la medición de CVRS en cardiopatía isquémica radica en la magnitud del problema de esta enfermedad en términos epidemiológicos y de asistencia sanitaria, así como en los aspectos psicológicos relacionados con ella que en ocasiones no son debidamente tenidos en cuenta por los clínicos. Se describen los cuestionarios de CVRS tanto genéricos como específicos más utilizados en cardiopatía isquémica, mostrando las dimensiones contempladas por cada uno de ellos. Finalmente se analizan las principales aplicaciones de la medición de CVRS en cardiopatía isquémica en el campo de la evaluación de resultados, haciendo mención a los ensayos clínicos y a la rehabilitación cardiaca. Se pone de manifiesto que la evaluación de la CVRS en cardiopatía isquémica nos aporta un resultado final de salud que se centra en la persona, no en la enfermedad; en cómo se siente el paciente, independientemente de los datos clínicos. Se sitúa así la medición de CVRS en cardiopatía isquémica como un instrumento para promover la atención centrada en el paciente, proporcionando una información complementaria a la valoración clínica tradicional. Para ello será necesario seguir mejorando la interpretabilidad clínica de los diversos cuestionarios de medición. The term health-related quality of life (HRQL) is a concept related to the assessment of how the individual perceives health and that covers both objective and subjective aspects. Despite the lack of consensus about its definition, several tools have been developed for the measurement of HRQL in different pathologies, such as in the ischemic cardiopathy. These tools take into consideration different dimensions of the HRQL and are usually classified as generic or specific questionnaires. These tools must have certain featur
Discourse and Dominion in Chaucer’s Wife of Bath’s Prologue
Alexandra Lo?on?i
Journal for Communication and Culture , 2011,
Abstract: In the following paper we will investigate the power of discourse in medieval text, with a particular reference to a fragment of Geoffrey Chaucer’s Wife of Bath Prologue. In the context of the New Historicist paradigm of approaching the medieval text, our research explores the dialectic of selfhood and its discourse within the cultural and social constructs of the Middle Ages at the end of the fourteenth century in England. The focus is on the concept of authority in the medieval texts and the textualization of history in the context of the tension between the speaking subject and the objectified historical identity.
Management systems efficiency estimation in tourism organizations
Alexandra I. Mikheyeva
European Researcher , 2011,
Abstract: The article is concerned with management systems efficiency estimation in tourism organizations, examines effective management systems requirements and characteristics in tourism organizations and takes into account principles of management systems formation.
Modeling Spatial Opportunity Structures and Youths’ Transitions from School to Training  [PDF]
Alexandra Wicht, Alexandra Nonnenmacher
Open Journal of Statistics (OJS) , 2017, DOI: 10.4236/ojs.2017.76071
Abstract: This paper examines the significance of spatial externalities for youths’ school-to-training transitions in Germany. For this purpose, it is necessary to address the methodological question of how an individual’s spatial context has to be operationalized with respect to both its extent and the problem of spatial autocorrelation. Our analyses show that the “zone of influence” comprises of the whole of Germany, not only close-by districts, and that these effects differ between structurally weak and strong regions. Consequently, assuming that only close proximity affects individual outcomes may disregard relevant contextual influences, and for spatial models that require an a priori definition of the weights for spatial units, it may be erroneous to make a decision based on this assumption. Concerning spatial autocorrelation, we found that neglecting local spatial autocorrelation at the context level causes considerable bias to the estimates, especially for districts that are close to the home district.
Changes in health related quality of life 3 months after an acute coronary syndrome
Inmaculada I Failde, Maria M Soto
BMC Public Health , 2006, DOI: 10.1186/1471-2458-6-18
Abstract: HRQL was assessed in 132 patients while they were admitted to the hospital and at 3 months after discharge, using the SF-36 health questionnaire. To identify the variables associated with the change, multiple linear regression models were constructed for two summary dimensions of the SF-36 (PCS and MCS) taking the change in the score of the dimension as dependent variable.There were no significant differences between the patients who completed the monitoring (n = 76) and those who were dropped out. After three months, a significant decrease was observed in the dimensions of physical functioning, general health, vitality, and Physical Summary Component (PCS). The variables revascularisation, age, and the interaction between previous history of coronary heart disease (CHD) and the presence of one or more risk factors explained 16.6% of the decrease in the PCS. The decrease in the PCS was 6.4 points less in the patients who had undergone revascularisation, 0.2 points less for each year of age, and 4.7 points less in the patients who had antecedents of the illness as well as one or more risk factors.The dimensions most affected at three months after an acute coronary episode were those related to the physical component. Undergoing revascularisation improved the PCS in patients, but in the younger patients and those without personal antecedents or risk factors, the PCS was affected more, perhaps due to greater expectations for recovery in these patients.Although the traditional measures of mortality and morbidity are frequently used as primary end points in coronary heart disease (CHD), they have limitations because they require prolonged periods of observations and are expensive to measure.Despite the obvious value of these measures, others like health related quality life (HRQL) are considered of great importance. [1]. HRQL seems to be useful for defining health both in terms of how individuals feel (distress and well-being) and in terms of how they evaluate their heal
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