A genetic-epidemiologic study of Alzheimer’s disease

Alzheimer's disease (AD) is the most frequent cause of dementia and thus is a major public-health problem. Age and genetic predisposition to the disease are the most important risk factors. In 2001 more than 24 million people in the western world had dementia. This number is expected to double every 20 years up to 81 million in 2040 because of the anticipated increase in life expectancy. Genetically, AD is a heterogeneous disorder with both familial and sporadic forms. Chapter 1 is a general introduction on epidemiological and genetic factors of AD and also describes the different studies performed in this thesis. In chapter 2 the linkage studies are presented. Chapter 2.1 describes a whole genome screen on 112 AD patients and their first-degree relatives from the Genetics Research in Isolated Populations (GRIP) study. Of the 112 patients, 103 could be connected into an extremely large and complex pedigree. This pedigree cannot be analyzed with available linkage software. In this study, we developed an algorithm for splitting complex pedigrees to allow us to conduct linkage analysis. Then we determined genome wide significance thresholds for linkage analysis using the sub pedigrees obtained by our pedigree cutting algorithm and finally, we performed linkage analys

La apropiación social del conocimiento como base para la clasificación de las Instituciones de Educación Superior colombianas

 Las instituciones de educación superior (IES) colombianas están permanente sometidas a esquemas de clasificación que le otorgan mayor o menor visibilidad en el ámbito académico. Esto genera grandes expectativas y por ello la reciente publicación de la clasificación de la IES colombianas, basado en apropiación social del conocimiento (ASC), es controversial. Las clasificaciones, como cualquier estrategia que pretende establecer un orden no suelen ser completamente objetivas y se pueden confi­gurar como un dispositivo ideológico y político que promueven la estigmatización y exclusión

La Fibroscopia Nasal Preoperatoria. ¿Puede reducir la intubación en paciente despierto?

Los pacientes con patología en la Vía Aérea Superior son un reto para el anestesiólogo, requiriendo, por lo general, técnicas de intubación con el paciente despierto, para disminuir el riesgo. El objetivo primario de este artículo es valorar si el realizar un examen endoscópico nasal previo a la cirugía podría variar el abordaje en el manejo de esa vía aérea

Fibroscopia intranasal preoperatoria en una paciente con compresión de la vía aérea por bocio

Tras analizar si la Fibroscopia Nasal Preoperatoria podría reducir la necesidad de realizar intubación en el paciente despierto, presentamos el caso clínico de una mujer diagnosticada de BOCIO TOXICO DIFUSO COMPRESIVO, que se encuentra pendiente de cirugía

Developmentally Sensitive Interaction Effects of Genes and the Social Environment on Total and Subcortical Brain Volumes

Contains fulltext : 167721.PDF (publisher's version ) (Open Access)Smaller total brain and subcortical volumes have been linked to psychopathology including attention-deficit/hyperactivity disorder (ADHD). Identifying mechanisms underlying these alterations, therefore, is of great importance. We investigated the role of gene-environment interactions (GxE) in interindividual variability of total gray matter (GM), caudate, and putamen volumes. Brain volumes were derived from structural magnetic resonance imaging scans in participants with (N = 312) and without ADHD (N = 437) from N = 402 families (age M = 17.00, SD = 3.60). GxE effects between DAT1, 5-HTT, and DRD4 and social environments (maternal expressed warmth and criticism; positive and deviant peer affiliation) as well as the possible moderating effect of age were examined using linear mixed modeling. We also tested whether findings depended on ADHD severity. Deviant peer affiliation was associated with lower caudate volume. Participants with low deviant peer affiliations had larger total GM volumes with increasing age. Likewise, developmentally sensitive GxE effects were found on total GM and putamen volume. For total GM, differential age effects were found for DAT1 9-repeat and HTTLPR L/L genotypes, depending on the amount of positive peer affiliation. For putamen volume, DRD4 7-repeat carriers and DAT1 10/10 homozygotes showed opposite age relations depending on positive peer affiliation and maternal criticism, respectively. All results were independent of ADHD severity. The presence of differential age-dependent GxE effects might explain the diverse and sometimes opposing results of environmental and genetic effects on brain volumes observed so far

Rescate de patashte (Theobroma bicolor Humb & Bonpl.) y cushta (Theobroma angustifolium) dos especies promisorias en peligro de extinción en El Salvador

En El Salvador existen especies vegetales como el patashte (Theobroma bicolor) y la cushta (Theobroma angustifolium) parientes silvestres del cacao, con alto potencial nutritivo para la alimentación y como materia prima para la agroindustria y el desarrollo de productos como chocolate, atoles, snack, entre otros, no obstante, estas especies están en peligro de extinción, por lo que no se cuenta con mucha información técnica. Por tal motivo se realizaron giras de colecta de estas especies, en municipios, con tradición en la producción de cacao a fin de incluir ambas especies en los bancos de germoplasma de cacao que se establecieron como parte del proyecto de rescate de recursos genéticos de cacao. Sin embargo, la situación de ambas especies es crítica por el alto grado de erosión genética, ya que, solamente se lograron obtener muestras de frutos en el cantón Cangrejera, Izalco, Sonsonate. Estas muestras se llevaron al Laboratorio de Química Agrícola de la Facultad de Ciencias Agronómicas de La Universidad de El Salvador (UES), a fin de realizar análisis bromatológicos y conocer de manera preliminar su composición química. Asimismo, desarrollar viveros con ambas especies para siembra en las colecciones de la UES. Como resultado se encontraron concentraciones para patashte y cushta de 16.04 y 4.48% de proteína; de 33.81 y 23.93% de grasa; 35.02 y 44.75% de carbohidratos respectivamente. Por otra parte se establecieron plantas de patashte y cushta en el banco de germoplasma del campus universitario, Estación Experimental y de Prácticas (EEP), San Pedro Nonualco y La cooperativa Hacienda Santa Clara, procurando contribuir al rescate de las mismas. Se concluye que ambas especies tienen potencial para consumo directo con preparaciones artesanales y materia prima para elaboración de muchos productos alimenticios nutritivos, e incluirlos en programas de Seguridad Alimentaria y Nutricional (SAN), por lo que es importante y urgente, proponer y ejecutar estrategias de conservación in situ y ex situ

Encuesta sobre hipoglucemia en pacientes con diabetes tratados con insulina: la población colombiana del International Operations Hypoglycemia Assessment Tool

Introduction: The non-interventional International Operations Hypoglycemia Assessment Tool (IO-HAT) study assessed the incidence of hypoglycemia in patients with insulin-treated diabetes across nine countries, including a cohort of patients in Colombia.Materials and methods: Hypoglycemia incidence among patients with insulin-treated diabetes was assessed across 26 sites in Colombia. Hypoglycaemic events (any, nocturnal or severe) were reported in self-assessment questionnaires (SAQ) and patient diaries based on capillary blood glucose measurement or symptoms. Retrospective events (severe events 6 months before baseline and any event 4 weeks before baseline) were recorded in SAQ, Part 1, and prospective events (4 weeks from baseline) were recorded in SAQ, Part 2, and patient diaries. Differences in hypoglycemia incidence reported in the retrospective and prospective periods were assessed using two-sided tests.Results: Of the 664 patients assessed, 213 had type 1 diabetes (T1D) and 451 had type 2 diabetes (T2D). Nearly all patients experienced at least one hypoglycaemic event in the prospective period (97.1% T1D; 93.3% T2D). Rates of hypoglycemia (events per personyear, PPY) were higher prospectively than retrospectively for any hypoglycemia (T1D: 121.6 vs. 83.2, p<0.001; T2D: 28.1 vs. 24.6, p=0.127) and severe hypoglycemia (T1D: 15.3 vs. 9.2, p=0.605; T2D: 9.5 vs. 3.5 p=0.040).Conclusion: These results, the first from a patient-reported dataset on hypoglycemia in insulin-treated patients with diabetes in Colombia, show that patients reported higher rates of any hypoglycemia during the prospective period. Clinical trial registration number: NCT02306681Introducción. En el estudio no intervencionista International Operations Hypoglycemia Assessment Tool (IO-HAT), se evalúo la incidencia de hipoglucemia en pacientes diabéticos tratados con insulina en nueve países, incluido Colombia.Materiales y métodos. La incidencia de hipoglucemia entre pacientes diabéticos tratados con insulina se evaluó en 26 centros médicos en Colombia. Los episodios de hipoglucemia determinados con base en la medición de la glucemia capilar o en los síntomas se reportaron en el cuestionario de autoevaluación (Self-Assessment Questionnaire, SAQ) y en el diario del paciente. Los episodios retrospectivos (episodios graves y cualquiera ocurrido 6 meses y 4 semanas antes del inicio del estudio, respectivamente) se registraron en el SAQ, parte 1, y los eventos prospectivos (4 semanas desde el inicio), en el SAQ, parte 2, y en el diario del paciente. Las diferencias en la incidencia de la hipoglucemia entre los períodos retrospectivo y prospectivo se evaluaron mediante una prueba de dos colas.Resultados. De los 664 pacientes evaluados, 213 tenían diabetes de tipo 1 y 451 tenían diabetes de tipo 2. Casi todos los pacientes experimentaron al menos un episodio de hipoglucemia en el período prospectivo (97,1 %, diabetes de tipo 1, y 93,3 %, diabetes de tipo 2). Los índices de hipoglucemia (episodios año-persona) fueron mayores prospectivamente que retrospectivamente para cualquier tipo de hipoglucemia (diabetes de tipo 1: 121,6 Vs. 83,2; p<0,001; la diabetes de tipo 2: 28,1 Vs. 24,6; p=0,127) y para la hipoglucemia grave (diabetes de tipo 1: 15,3 Vs. 9,2; p=0,605; diabetes de tipo 2: 9,5 Vs. 3,5; p=0,040).Conclusión. Estos resultados, que constituyen el primer conjunto de datos sobre hipoglucemia informados por pacientes diabéticos colombianos tratados con insulina, evidenciaron tasas más altas para ambos tipos de hipoglucemia durante el período prospectivo. Número de registro del ensayo clínico: NCT0230668

No association of CDK5 genetic variants with Alzheimer's disease risk

<p>Abstract</p> <p>Background</p> <p>As cyclin-dependent kinase 5 (CDK5) has been implicated in the abnormal hyperphosphorylation of tau in Alzheimer's disease (AD) brain, and the development of neurofibrillary tangles, we examined the contribution of this gene to the susceptibility for AD.</p> <p>Methods</p> <p>We examined genetic variations of CDK5 by genotyping haplotype tagging SNPs (htSNPs) (rs9278, rs2069459, rs891507, rs2069454, rs1549759 and rs2069442) in a group of 408 Spanish AD cases and 444 controls.</p> <p>Results</p> <p>There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by APOE ε4 allele.</p> <p>Conclusion</p> <p>Our negative findings in the Spanish population argue against the hypothesis that CDK5 genetic variations are causally related to AD risk. Still, additional studies using different sets of patients and control subjects deserve further attention, since supporting evidence for association between CDK5 gene and AD risk in the Dutch population exists.</p

Infiltrating CD16 +

Our aim was to characterize glomerular monocytes (Mo) infiltration and to correlate them with peripheral circulating Mo subsets and severity of lupus nephritis (LN). Methods. We evaluated 48 LN biopsy samples from a referral hospital. Recognition of Mo cells was done using microscopic view and immunohistochemistry stain with CD14 and CD16. Based on the number of cells, we classified LN samples as low degree of diffuse infiltration (<5 cells) and high degree of diffuse infiltration (≥5 cells). Immunophenotyping of peripheral Mo subsets was done using flow cytometry. Results. Mean age was 34.0±11.7 years and the mean SLEDAI was 17.5±6.9. The most common SLE manifestations were proteinuria (91%) and hypocomplementemia (75%). Severe LN was found in 70% of patients (Class III, 27%; Class IV, 43%). Severe LN patients and patients with higher grade of CD16+ infiltration had lower levels of nonclassical (CD14+CD16++) Mo in peripheral blood. Conclusions. Our results might suggest that those patients with more severe forms of LN had a higher grade of CD14+CD16+ infiltration and lower peripheral levels of nonclassical (CD14+CD16++) Mo and might reflect a recruitment process in renal tissues. However, given the small sample, our results must be interpreted carefully