Impact of traffic pollution on telomere length and chronic diseases: Results from the multi-ethnic study of atherosclerosis and the Mexican-American cohort study

Exposure to air pollutants in urban locales has been associated with increased risk for chronic diseases including cardiovascular disease (CVD) and pulmonary diseases in epidemiological studies. The exact mechanism explaining how air pollution affects chronic disease is still unknown. However, oxidative stress and inflammatory pathways have been posited as likely mechanisms. ^ Data from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Mexican-American Cohort Study (2003-2009) were used to examine the following aims, respectively: 1) to evaluate the association between long-term exposure to ambient particulate matter (PM) (PM10 and PM2.5) and nitrogen oxides (NO x) and telomere length (TL) among approximately 1,000 participants within MESA; and 2) to evaluate the association between traffic-related air pollution with self-reported asthma, diabetes, and hypertension among Mexican-Americans in Houston, Texas. ^ Our results from MESA were inconsistent regarding associations between long-term exposure to air pollution and shorter telomere length based on whether the participants came from New York (NY) or Los Angeles (LA). Although not statistically significant, we observed a negative association between long-term air pollution exposure and mean telomere length for NY participants, which was consistent with our hypothesis. Positive (statistically insignificant) associations were observed for LA participants. It is possible that our findings were more influenced by both outcome and exposure misclassification than by the absence of a relationship between pollution and TL. Future studies are needed that include longitudinal measures of telomere length as well as focus on effects of specific constituents of PM and other pollutant exposures on changes in telomere length over time. ^ This research provides support that Mexican-American adults who live near a major roadway or in close proximity to a dense street network have a higher prevalence of asthma. There was a non-significant trend towards an increased prevalence of adult asthma with increasing residential traffic exposure especially for residents who lived three or more years at their baseline address. Even though the prevalence of asthma is low in the Mexican-origin population, it is the fastest growing minority group in the U.S. and we would expect a growing number of Mexican-Americans who suffer from asthma in the future. Future studies are needed to better characterize risks for asthma associated with air pollution in this population.^

Impact of donor-recipient gender and race mismatching on patient survival in patients with end-stage liver diseases undergoing liver transplantation

Background. End-stage liver disease (ESLD) is an irreversible condition that leads to the imminent complete failure of the liver. Orthotopic liver transplantation (OLT) has been well accepted as the best curative option for patients with ESLD. Despite the progress in liver transplantation, the major limitation nowadays is the discrepancy between donor supply and organ demand. In an effort to alleviate this situation, mismatched donor and recipient gender or race livers are being used. However, the simultaneous impact of donor and recipient gender and race mismatching on patient survival after OLT remains unclear and relatively challenging to surgeons. ^ Objective. To examine the impact of donor and recipient gender and race mismatching on patient survival after OLT using the United Network for Organ Sharing (UNOS) database. ^ Methods. A total of 40,644 recipients who underwent OLT between 2002 and 2011 were included. Kaplan-Meier survival curves and the log-rank tests were used to compare the survival rates among different donor-recipient gender and race combinations. Univariate Cox regression analysis was used to assess the association of donor-recipient gender and race mismatching with patient survival after OLT. Multivariable Cox regression analysis was used to model the simultaneous impact of donor-recipient gender and race mismatching on patient survival after OLT adjusting for a list of other risk factors. Multivariable Cox regression analysis stratifying on recipient hepatitis C virus (HCV) status was also conducted to identify the variables that were differentially associated with patient survival in HCV + and HCV − recipients. ^ Results. In the univariate analysis, compared to male donors to male recipients, female donors to male recipients had a higher risk of patient mortality (HR, 1.122; 95% CI, 1.065–1.183), while in the multivariable analysis, male donors to female recipients experienced an increased mortality rates (adjusted HR, 1.114; 95% CI, 1.048–1.184). Compared to white donors to white recipients, Hispanic donors to black recipients had a higher risk of patient mortality (HR, 1.527; 95% CI, 1.293–1.804) in the univariate analysis, and similar result (adjusted HR, 1.553; 95% CI, 1.314–1.836) was noted in multivariable analysis. After the stratification on recipient HCV status in the multivariable analysis, HCV + mismatched recipients appeared to be at greater risk of mortality than HCV − mismatched recipients. Female donors to female HCV − recipients (adjusted HR, 0.843; 95% CI, 0.769–0.923), and Hispanic HCV + recipients receiving livers from black donors (adjusted HR, 0.758; 95% CI, 0.598–0.960) had a protective effect on patient survival after OLT. ^ Conclusion. Donor-recipient gender and race mismatching adversely affect patient survival after OLT, both independently and after the adjustment for other risk factors. Female recipient HCV status is an important effect modifier in the association between donor-recipient gender combination and patient survival.^

Influenza vaccination as a primary or secondary prevention for cardiovascular diseases: A systematic review of the literature

Background: Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. CVD mainly comprise of coronary heart disease and stroke and were ranked first and fourth respectively amongst leading causes of death in the United States. Influenza (flu) causes annual outbreaks and pandemics and is increasingly recognized as an important trigger for acute coronary syndromes and stroke. Influenza vaccination is an inexpensive and effective strategy for prevention of influenza related complications in high risk individuals. Though it is recommended for all CVD patients, Influenza vaccine is still used at suboptimal levels in these patients owing to prevailing controversy related to its effectiveness in preventing CVD. This review was undertaken to critically assess the effectiveness of influenza vaccination as a primary or secondary prevention method for CVD. ^ Methods: A systematic review was conducted using electronic databases OVID MEDLINE, PUBMED (National Library of Medicine), EMBASE, GOOGLE SCHOLAR and TRIP (Turning Research into Practice). The study search was limited to peer-reviewed articles published in English language from January 1970 through May 2012. The case control studies, cohort studies and randomized controlled trials related to influenza vaccination and CVD, with data on at least one of the outcomes were identified. In the review, only population-based epidemiologic studies in all ethnic groups and of either sex and with age limitation of 30 yrs or above, with clinical CVD outcomes of interest were included. ^ Results: Of the 16 studies (8 case control studies, 6 cohort studies and 2 randomized controlled trials) that met the inclusion criteria, 14 studies reported that there was a significant benefit in u influenza vaccination as primary or secondary prevention method for preventing new cardiovascular events. In contrary to the above findings, two studies mentioned that there was no significant benefit of vaccination in CVD prevention. ^ Conclusion: The available body of evidence in the review elucidates that vaccination against influenza is associated with reduction in the risk of new CVD events, hospitalization for coronary heart disease and stroke and as well as the risk of death. The study findings disclose that the influenza vaccination is very effective in CVD prevention and should be encouraged for the high risk population. However, larger and more future studies like randomized control trials are needed to further evaluate and confirm these findings. ^

THE NATURAL AND ORTHOGONAL INTERACTION (NOIA) MODELS FOR QUANTITATIVE TRAITS (QTs) AND COMPLEX DISEASES

My dissertation focuses on developing methods for gene-gene/environment interactions and imprinting effect detections for human complex diseases and quantitative traits. It includes three sections: (1) generalizing the Natural and Orthogonal interaction (NOIA) model for the coding technique originally developed for gene-gene (GxG) interaction and also to reduced models; (2) developing a novel statistical approach that allows for modeling gene-environment (GxE) interactions influencing disease risk, and (3) developing a statistical approach for modeling genetic variants displaying parent-of-origin effects (POEs), such as imprinting. In the past decade, genetic researchers have identified a large number of causal variants for human genetic diseases and traits by single-locus analysis, and interaction has now become a hot topic in the effort to search for the complex network between multiple genes or environmental exposures contributing to the outcome. Epistasis, also known as gene-gene interaction is the departure from additive genetic effects from several genes to a trait, which means that the same alleles of one gene could display different genetic effects under different genetic backgrounds. In this study, we propose to implement the NOIA model for association studies along with interaction for human complex traits and diseases. We compare the performance of the new statistical models we developed and the usual functional model by both simulation study and real data analysis. Both simulation and real data analysis revealed higher power of the NOIA GxG interaction model for detecting both main genetic effects and interaction effects. Through application on a melanoma dataset, we confirmed the previously identified significant regions for melanoma risk at 15q13.1, 16q24.3 and 9p21.3. We also identified potential interactions with these significant regions that contribute to melanoma risk. Based on the NOIA model, we developed a novel statistical approach that allows us to model effects from a genetic factor and binary environmental exposure that are jointly influencing disease risk. Both simulation and real data analyses revealed higher power of the NOIA model for detecting both main genetic effects and interaction effects for both quantitative and binary traits. We also found that estimates of the parameters from logistic regression for binary traits are no longer statistically uncorrelated under the alternative model when there is an association. Applying our novel approach to a lung cancer dataset, we confirmed four SNPs in 5p15 and 15q25 region to be significantly associated with lung cancer risk in Caucasians population: rs2736100, rs402710, rs16969968 and rs8034191. We also validated that rs16969968 and rs8034191 in 15q25 region are significantly interacting with smoking in Caucasian population. Our approach identified the potential interactions of SNP rs2256543 in 6p21 with smoking on contributing to lung cancer risk. Genetic imprinting is the most well-known cause for parent-of-origin effect (POE) whereby a gene is differentially expressed depending on the parental origin of the same alleles. Genetic imprinting affects several human disorders, including diabetes, breast cancer, alcoholism, and obesity. This phenomenon has been shown to be important for normal embryonic development in mammals. Traditional association approaches ignore this important genetic phenomenon. In this study, we propose a NOIA framework for a single locus association study that estimates both main allelic effects and POEs. We develop statistical (Stat-POE) and functional (Func-POE) models, and demonstrate conditions for orthogonality of the Stat-POE model. We conducted simulations for both quantitative and qualitative traits to evaluate the performance of the statistical and functional models with different levels of POEs. Our results showed that the newly proposed Stat-POE model, which ensures orthogonality of variance components if Hardy-Weinberg Equilibrium (HWE) or equal minor and major allele frequencies is satisfied, had greater power for detecting the main allelic additive effect than a Func-POE model, which codes according to allelic substitutions, for both quantitative and qualitative traits. The power for detecting the POE was the same for the Stat-POE and Func-POE models under HWE for quantitative traits.

Identification and evaluation of candidate genes for inherited retinal -degenerative diseases

Although more than 100 genes associated with inherited retinal disease have been mapped to chromosomal locations, less than half of these genes have been cloned. This text includes identification and evaluation of candidate genes for three autosomal dominant forms of inherited retinal degeneration: atypical vitelliform macular dystrophy (VMD1), cone-rod dystrophy (CORD), and retinitis pigmentosa (RP). ^ VMD1 is a disorder characterized by complete penetrance but extremely variable expressivity, and includes macular or peripheral retinal lesions and peripappilary abnormalitites. In 1984, linkage was reported between VMD1 and soluble glutamate-pyruvate transaminase GPT); however, placement of GPT to 8q24 on linkage maps had been debated, and VMD1 did not show linkage to microsatellite markers in that region. This study excluded linkage between the loci by cloning GPT, identifying the nucleotide substitution associated with the GPT sozymes, and by assaying VMD1 family samples with an RFLP designed to detect the substitution. In addition, linkage of VMD1 to the known dominant macular degeneration loci was excluded. ^ CORD is characterized by early onset of color-vision deficiency, and decreased visual acuity, However, this retinal degeneration progresses to no light perception, severe macular lesion, and “bone-spicule” accumulations in the peripheral retina. In this study, the disorder in a large Texan family was mapped to the CORD2 locus of 19q13, and a mutation in the retina/pineal-specific cone-rod homeobox gene (CRX) was identified as the disease cause. In addition, mutations in CRX were associated with significantly different retinal disease phenotypes, including retinitis pigmentosa and Leber congenital amaurosis. ^ Many of the mutations leading to inherited retinal disorders have been identified in genes like CRX, which are expressed predominantly in the retina and pineal gland. Therefore, a combination of database analysis and laboratory investigation was used to identify 26 novel retina/pineal-specific expressed sequence tag (EST) clusters as candidate genes for inherited retinal disorders. Eight of these genes were mapped into the candidate regions of inherited retinal degeneration loci. ^ Two of the eight clusters mapped into the retinitis pigmentosa RP13 candidate region of 17p13, and were both determined to represent a single gene that is highly expressed in photoreceptors. This gene, the Ah receptor-interacting like protein-1 (AIPL1), was cloned, characterized, and screened for mutations in RP13 patient DNA samples. ^

Characterization of anti -sulfatide autoantibodies in demyelinating diseases

Multiple sclerosis (MS) is the most common autoimmune disease of the central nerve system and Guillain Barré Syndrome (GBS) is an inflammatory neuropathy involving the peripheral nerves. Anti-myelin immunoglobins may play a role in the demyelination processes of the both diseases. Sulfatide is an abundant glycolipid on myelin and is a candidate target antigen for disease related autoantibodies. The objective of this study was to characterize anti-sulfatide antibodies and compare antibodies from GBS and MS patients with fetal antibodies. Our hypothesis is that some B cells producing disease-associated autoantibodies are derived from or related to B cells of the fetal repertoire. Here we report that reactivity of plasma IgM against sulfatide was elevated in twelve MS patients compared with twelve normal subjects. This result implies that anti-sulfatide antibodies are disease-related. A total of sixteen human B lymphocyte clones producing anti-sulfatide autoantibodies were isolated from MS patients, GBS patients and a human fetus. Seven of the clones were from three MS patients, four of the clones were from three GBS patients and five were from the spleen of a twenty-week human fetus. Sequences have been obtained for the heavy and light chain variable regions (VDJ and VJ regions) of all of the anti-sulfatide immunoglobulins. Seven of the sixteen antibodies used VH3 for the variable region gene of the heavy chain consistent with the rate of VH3 usage in randomly selected B cells. Somatic mutations were significantly more frequent in the patient antibodies than in the fetus and somatic mutations in CDR's (Complementarity Determining Region) were significantly more frequent than in framework regions. No significant difference was found between patients and fetus in length of VH CDRIII. However, it is reported that antibodies from randomly selected normal adult B cells have longer CDRIII lengths than those of the fetus (Sanz I, 1991 Journal of Immunology Sep 1;147(5):1720-9). Our results are consistent with derivation of the precursors of B cells producing these autoantibodies from B cells related to those of the fetal repertoire. These findings are consistent with a model in which quiescent B cells from clones produced early in development undergo proliferation in dysregulated disease states, accumulating somatic mutations and increasing in reactivity toward self-antigens. ^ Epitope mapping and molecular modeling were done to elucidate the relationships between antibody structure and binding characteristics. The autoantibodies were tested for binding activity to three different antigens: sulfatide, galactoceramide and ceramide. Molecular modeling suggests that antibodies with positive charge surrounded by or adjacent to hydrophobic groups in the binding pocket bind to the head of sulfatide via the sulfate group through electrostatic interactions. However, the antibodies with hydrophobic groups separated from positive charges appear to bind to the hydrophobic tail of sulfatide. This observation was supported by a study of the effect of NaCl concentration on antigen binding. The result suggested that electrostatic interactions played a major role in sulfate group binding and that hydrophobic interactions were of greater importance for binding to the ceramide group. Our three-dimensional structure data indicated that epitope specificity of these antibodies is more predictable at the level of tertiary than primary structure and suggested positive selection based on structure occurred in the. formation of those autoantibodies. ^

Smith K. M. - A texbook of plant virus diseases (New second edition) J. A. Churchill Ltd, Londres, Inglaterra

Fil: Pontis, Rafael E..

Cardiovascular risk assessment, body composition and incidence of chronic diseases in a group of Senior Quintero commune

Actualmente la población de adultos mayores va creciendo demográficamente a pasos agigantados "la preocupación por la situación de las personas adultas mayores forma parte de un amplio proceso de toma de conciencia a nivel mundial respecto del envejecimiento de las sociedades y los desafíos económicos, sociales, políticos y culturales que ello conlleva. El fenómeno del envejecimiento poblacional en América Latina viene ocurriendo de manera menos acentuada que en los países desarrollados, los cuales se enriquecieron antes de envejecer, mientras que los países en desarrollo están envejeciendo antes de aumentar su riqueza (OMS, 2002)". En el caso de esta investigación se evaluaron el Indice de cintura y cadera (ICC), el índice de masa corporal (IMC) y la incidencia de ECNT en un grupo de Adultosmayores pertenecientes a los programas de fomento del Deporte impartidos por la Ilustre Municipalidad de Quintero en la comuna. Las evidencias recopiladas demuestran altos índices de riesgo cardiovascular y de sobrepeso y obesidad en los adultos mayores evaluados. También se evidencia alta prevalencia de la Hipertensión arterial en este grupo de personas

Aspectos importantes de la anatomía funcional del abdomen para la actividad física

El propósito de ésta ponencia es analizar cuestiones que posiblemente estén estrechamente vinculadas con una problemática que actualmente sufre gran parte de la población, que son los dolores lumbares y cómo profesionales del campo de la Educación física, podemos aportar análisis, ideas y ejercicios concretos para su prevención. Pasando por una breve introducción de anatomía descriptiva y funcional de la zona, me enfocaré tanto en la filogénesis, como en la óntogenesis del ser humano y, a partir de allí, me detengo en destacar el papel fundamental que desarrollan los músculos intrínsecos, de sostén y estabilizadores del complejo lumbo pélvico y el hecho de generar engramas motores que anticipen la contracción (protección) de dichos músculos antes de cualquier movimiento en el que se requiera movimiento de grandes masas musculares

Cardiovascular risk assessment, body composition and incidence of chronic diseases in a group of Senior Quintero commune

Actualmente la población de adultos mayores va creciendo demográficamente a pasos agigantados "la preocupación por la situación de las personas adultas mayores forma parte de un amplio proceso de toma de conciencia a nivel mundial respecto del envejecimiento de las sociedades y los desafíos económicos, sociales, políticos y culturales que ello conlleva. El fenómeno del envejecimiento poblacional en América Latina viene ocurriendo de manera menos acentuada que en los países desarrollados, los cuales se enriquecieron antes de envejecer, mientras que los países en desarrollo están envejeciendo antes de aumentar su riqueza (OMS, 2002)". En el caso de esta investigación se evaluaron el Indice de cintura y cadera (ICC), el índice de masa corporal (IMC) y la incidencia de ECNT en un grupo de Adultosmayores pertenecientes a los programas de fomento del Deporte impartidos por la Ilustre Municipalidad de Quintero en la comuna. Las evidencias recopiladas demuestran altos índices de riesgo cardiovascular y de sobrepeso y obesidad en los adultos mayores evaluados. También se evidencia alta prevalencia de la Hipertensión arterial en este grupo de personas

Aspectos importantes de la anatomía funcional del abdomen para la actividad física

El propósito de ésta ponencia es analizar cuestiones que posiblemente estén estrechamente vinculadas con una problemática que actualmente sufre gran parte de la población, que son los dolores lumbares y cómo profesionales del campo de la Educación física, podemos aportar análisis, ideas y ejercicios concretos para su prevención. Pasando por una breve introducción de anatomía descriptiva y funcional de la zona, me enfocaré tanto en la filogénesis, como en la óntogenesis del ser humano y, a partir de allí, me detengo en destacar el papel fundamental que desarrollan los músculos intrínsecos, de sostén y estabilizadores del complejo lumbo pélvico y el hecho de generar engramas motores que anticipen la contracción (protección) de dichos músculos antes de cualquier movimiento en el que se requiera movimiento de grandes masas musculares

Cardiovascular risk assessment, body composition and incidence of chronic diseases in a group of Senior Quintero commune

Actualmente la población de adultos mayores va creciendo demográficamente a pasos agigantados "la preocupación por la situación de las personas adultas mayores forma parte de un amplio proceso de toma de conciencia a nivel mundial respecto del envejecimiento de las sociedades y los desafíos económicos, sociales, políticos y culturales que ello conlleva. El fenómeno del envejecimiento poblacional en América Latina viene ocurriendo de manera menos acentuada que en los países desarrollados, los cuales se enriquecieron antes de envejecer, mientras que los países en desarrollo están envejeciendo antes de aumentar su riqueza (OMS, 2002)". En el caso de esta investigación se evaluaron el Indice de cintura y cadera (ICC), el índice de masa corporal (IMC) y la incidencia de ECNT en un grupo de Adultosmayores pertenecientes a los programas de fomento del Deporte impartidos por la Ilustre Municipalidad de Quintero en la comuna. Las evidencias recopiladas demuestran altos índices de riesgo cardiovascular y de sobrepeso y obesidad en los adultos mayores evaluados. También se evidencia alta prevalencia de la Hipertensión arterial en este grupo de personas

Aspectos importantes de la anatomía funcional del abdomen para la actividad física

El propósito de ésta ponencia es analizar cuestiones que posiblemente estén estrechamente vinculadas con una problemática que actualmente sufre gran parte de la población, que son los dolores lumbares y cómo profesionales del campo de la Educación física, podemos aportar análisis, ideas y ejercicios concretos para su prevención. Pasando por una breve introducción de anatomía descriptiva y funcional de la zona, me enfocaré tanto en la filogénesis, como en la óntogenesis del ser humano y, a partir de allí, me detengo en destacar el papel fundamental que desarrollan los músculos intrínsecos, de sostén y estabilizadores del complejo lumbo pélvico y el hecho de generar engramas motores que anticipen la contracción (protección) de dichos músculos antes de cualquier movimiento en el que se requiera movimiento de grandes masas musculares