Prevalence of Dementia in Older Latinos: The Influence of Type 2 Diabetes Mellitus, Stroke and Genetic Factors

To estimate dementia prevalence in older Mexican Americans, determine the distribution of dementia by etiology, and evaluate the contribution of type 2 diabetes mellitus, stroke, and apolipoprotein E (ApoE) genotype to dementia. DESIGN: Analysis of baseline data from an epidemiological cohort study. SETTING: Sacramento Valley, California. PARTICIPANTS: One thousand seven hundred eighty-nine Latinos aged 60 and older residing in targeted census tracts during 1998–99. MEASUREMENTS: Each subject was interviewed and screened for dementia and cardiovascular risk factors and diseases. Fasting blood samples were drawn for glucose, insulin, and lipids. Buccal cells were obtained for genetic analysis of ApoE. A three-stage process of screening was used to diagnose dementia, including cognitive testing, a clinical examination, and imaging to determine etiology. Presence of dementia was established according to National Institute of Neurological Disorders and Stroke/Alzheimers and Related Disorders Association criteria and California Alzheimer's Disease Diagnostic and Treatment Criteria. RESULTS: Overall dementia prevalence was 4.8%. Prevalence in those aged 85 and older was 31%. Education and Anglo cultural orientation was negatively associated with dementia risk. Risk of dementia was nearly eight times higher in those with both type 2 diabetes mellitus and stroke. Forty-three percent of dementia was attributable to type 2 diabetes mellitus, stroke, or a combination of the two. ApoE allele frequency was E2 5.9%, E3 90.1%, and E4 4%. Those with any E4 and 4–4 combinations had a higher risk for dementia than those with the E3–3 combination. CONCLUSIONS: Dementia prevalence in this ethnic group is similar to that reported in Canadian and European studies but lower than in Caribbean-Hispanics residing in the United States. The etiological fraction of dementia attributable to type 2 diabetes mellitus and stroke is substantial and points toward the need for intervention research and treatment with the goal of reducing neurological sequelae in groups with high prevalence of type 2 diabetes mellitus. The allele frequency of ApoE was similar to that in other published studies on Mexican Americans. The low frequency of the E4 allele may contribute to the difference in etiology of dementia in older Mexican Americans and older people of European background. Dementia in this ethnic group may be related to preventable causes, with a smaller genetic component than in Europeans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66237/1/j.1532-5415.2003.51054.x.pd

Staple-based paper electrochemical platform for celiac disease diagnosis

A staple-based electrochemical platform is proposed for the first time as a simple and low-cost detection system for paper-based devices. The system, that incorporates small and disposable stainless-steel staples as electrodes (modified with carbon ink in the case of the working electrode) is combined with a paper strip and is carefully optimized with ferrocene carboxylic acid. As a proof-of-concept, it was employed for the enzymatic (HRP-based) immunoelectroanalytical detection of human tissue anti-transglutaminase (anti-tTG), biomarker for celiac disease diagnosis. The intensity of the current due to the electrochemical reduction of TMB (HRP substrate) was recorded chronoamperometrically at -0.2 V in different paper areas. A linear relationship between the current measured at 30 s and the logarithm of the concentration of anti-tTG in the range comprised between 3 and 100 U.mL-1 was obtained. Negative and positive controls produced expected values. Results demonstrated that the paper/staple-combined platform is very convenient for the detection of electroactive analytes and other compounds that can be determined indirectly in bioassays.Fil: Nanni, Paula Inés. Universidad de Oviedo; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; ArgentinaFil: Gonzalez Lopez, Andrea. Universidad de Oviedo; EspañaFil: Nuñez Bajo, Estefanía. Universidad de Oviedo; EspañaFil: Madrid, Rossana Elena. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Fernandez Abedul, M. Teresa. Universidad de Oviedo; Españ

Proline cis-​trans isomerization and its implications for the dimerization of analogues of cyclopeptide stylostatin 1: a combined computational and experimental study

Cis and trans proline conformers are often associated with dramatic changes in the biological function of peptides. A slow equilibrium between cis and trans Ile-Pro amide bond conformers occurs in constrained derivatives of the native marine cyclic heptapeptide stylostatin 1 (cyclo-(NSLAIPF)), a potential anticancer agent. In this work, four cyclopeptides, cyclo-(NSTAIPF), cyclo-(KSTAIPF), cyclo-(RSTAIPF) and cyclo-(DSTAIPF), which are structurally related to stylostatin 1, are experimentally and computationally examined in order to assess the effect of residue mutations on the cis-trans conformational ratio and the apparent capacity to form dimeric aggregates. Primarily, cyclo-(KSTAIPF) and cyclo-(RSTAIPF) showed specific trends in circular dichroism, MALDI-TOF and HPLC purification experiments, which suggests the occurrence of peptide dimerization. Meanwhile, the NMR spectrum of cyclo-(KSTAIPF) indicates that this cyclopeptide exists in the two slow-exchange families of conformations mentioned above. Molecular dynamics simulations combined with quantum mechanical calculations have shed light on the factors governing the cis/trans conformational ratio. In particular, we have found that residue mutations affect the internal hydrogen bond pattern which ultimately tunes the cis/trans conformational ratio and that only trans conformers are capable of aggregating due to the shape complementarity of the two subunits

Integrative analyses of speciation and divergence in Psammodromus hispanicus (Squamata: Lacertidae)

BackgroundGenetic, phenotypic and ecological divergence within a lineage is the result of past and ongoing evolutionary processes, which lead ultimately to diversification and speciation. Integrative analyses allow linking diversification to geological, climatic, and ecological events, and thus disentangling the relative importance of different evolutionary drivers in generating and maintaining current species richness.ResultsHere, we use phylogenetic, phenotypic, geographic, and environmental data to investigate diversification in the Spanish sand racer (Psammodromus hispanicus). Phylogenetic, molecular clock dating, and phenotypic analyses show that P. hispanicus consists of three lineages. One lineage from Western Spain diverged 8.3 (2.9-14.7) Mya from the ancestor of Psammodromus hispanicus edwardsianus and P. hispanicus hispanicus Central lineage. The latter diverged 4.8 (1.5-8.7) Mya. Molecular clock dating, together with population genetic analyses, indicate that the three lineages experienced northward range expansions from southern Iberian refugia during Pleistocene glacial periods. Ecological niche modelling shows that suitable habitat of the Western lineage and P. h. edwardsianus overlap over vast areas, but that a barrier may hinder dispersal and genetic mixing of populations of both lineages. P. h. hispanicus Central lineage inhabits an ecological niche that overlaps marginally with the other two lineages.ConclusionsOur results provide evidence for divergence in allopatry and niche conservatism between the Western lineage and the ancestor of P. h. edwardsianus and P. h. hispanicus Central lineage, whereas they suggest that niche divergence is involved in the origin of the latter two lineages. Both processes were temporally separated and may be responsible for the here documented genetic and phenotypic diversity of P. hispanicus. The temporal pattern is in line with those proposed for other animal lineages. It suggests that geographic isolation and vicariance played an important role in the early diversification of the group, and that lineage diversification was further amplified through ecological divergence

Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase.

Profound metabolic changes are characteristic of macrophages during classical activation and have been implicated in this phenotype. Here we demonstrate that nitric oxide (NO) produced by murine macrophages is responsible for TCA cycle alterations and citrate accumulation associated with polarization. 13C tracing and mitochondrial respiration experiments map NO-mediated suppression of metabolism to mitochondrial aconitase (ACO2). Moreover, we find that inflammatory macrophages reroute pyruvate away from pyruvate dehydrogenase (PDH) in an NO-dependent and hypoxia-inducible factor 1α (Hif1α)-independent manner, thereby promoting glutamine-based anaplerosis. Ultimately, NO accumulation leads to suppression and loss of mitochondrial electron transport chain (ETC) complexes. Our data reveal that macrophages metabolic rewiring, in vitro and in vivo, is dependent on NO targeting specific pathways, resulting in reduced production of inflammatory mediators. Our findings require modification to current models of macrophage biology and demonstrate that reprogramming of metabolism should be considered a result rather than a mediator of inflammatory polarization

Electrochemical Detection for Isothermal Loop-Mediated Amplification of Pneumolysin Gene of Streptococcus pneumoniae Based on the Oxidation of Phenol Red Indicator

A highly sensitive electrochemical methodology for end-point detection of loop-mediated isothermal nucleic acid amplification reactions was developed. It is based on the oxidation process of phenol red (PR), commonly used as a visual indicator. The dependence of its redox process on pH, which changes during amplification, allows performing quantitative measurements. Thus, the change in the oxidation potential of PR during the amplification is used, for the first time, as the analytical signal that correlates with the number of initial DNA copies. As a proof-of-concept, the amplification of the pneumolysin gene from Streptococcus pneumoniae, one of the main pathogens causing community-acquired pneumonia, is performed. Combination of isothermal amplification with electrochemical detection, performed on small-size flexible electrodes, allows easy decentralization. Adaptation to the detection of other pathogens causing infectious diseases would be very useful in the prevention of future epidemics

Criptococosis pulmonar que simula un cáncer de pulmón

Cryptococcosis; Pulmonary malignancyCriptococcosi; Càncer de pulmóCriptococosis; Cáncer de pulmó

From “trust” to “trustworthiness”: Retheorizing dynamics of trust, distrust, and water security in North America

Assumptions of trust in water systems are widespread in higher-income countries, often linked to expectations of “modern water.” The current literature on water and trust also tends to reinforce a technoscientific approach, emphasizing the importance of aligning water user perceptions with expert assessments. Although such approaches can be useful to document instances of distrust, they often fail to explain why patterns differ over time, and across contexts and populations. Addressing these shortcomings, we offer a relational approach focused on the trustworthiness of hydro-social systems to contextualize water-trust dynamics in relation to broader practices and contexts. In doing so, we investigate three high-profile water crises in North America where examples of distrust are prevalent: Flint, Michigan; Kashechewan First Nation; and the Navajo Nation. Through our theoretical and empirical examination, we offer insights on these dynamics and find that distrust may at times be a warranted and understandable response to experiences of water insecurity and injustice. We examine the interconnected experiences of marginality and inequity, ontological and epistemological injustice, unequal governance and politics, and histories of water insecurity and harm as potential contributors to untrustworthiness in hydro-social systems. We close with recommendations for future directions to better understand water-trust dynamics and address water insecurity

Investigating particle acceleration in Protostellar Jets: The triple radio continuum source in serpens

While most protostellar jets present free-free emission at radio wavelengths, synchrotron emission has also been proposed to be present in a handful of these objects. The presence of nonthermal emission has been inferred by negative spectral indices at centimeter wavelengths. In one case (the HH 80-81 jet arising from a massive protostar), its synchrotron nature was confirmed by the detection of linearly polarized radio emission. One of the main consequences of these results is that synchrotron emission implies the presence of relativistic particles among the nonrelativistic material of these jets. Therefore, an acceleration mechanism should be taking place. The most probable scenario is that particles are accelerated when the jets strongly impact against the dense envelope surrounding the protostar. Here we present an analysis of radio observations obtained with the Very Large Array of the triple radio source in the Serpens star-forming region. This object is known to be a radio jet arising from an intermediate-mass protostar. It is also one of the first protostellar jets where the presence of nonthermal emission was proposed. We analyze the dynamics of the jet and the nature of the emission and discuss these issues in the context of the physical parameters of the jet and the particle acceleration phenomenon.Fil: Rodríguez Kamenetzky, Adriana Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Carrasco Gonzalez, Carlos Eugenio. Universidad Nacional Autónoma de México; MéxicoFil: Araudo, Anabella Teresa. University of Oxford. Department of Physics; Reino Unido. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Torrelles, Jose M.. Universidad de Barcelona; EspañaFil: Anglada, Guillem. Instituto de Astrofisica Andalucia; EspañaFil: Marti, Josep. Universidad de Jaén; EspañaFil: Luis Felipe Rodriguez. Universidad Nacional Autónoma de México; MéxicoFil: Valotto, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentin