Plasma lipoprotein-associated phospholipase A2 activity in Alzheimer's disease, amnestic mild cognitive impairment, and cognitively healthy elderly subjects: a cross-sectional study.

ABSTRACT: INTRODUCTION: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulating enzyme with pro-inflammatory and oxidative activities associated with cardiovascular disease and ischemic stroke. While high plasma Lp-PLA2 activity was reported as a risk factor for dementia in the Rotterdam study, no association between Lp-PLA2 mass and dementia or Alzheimer's disease (AD) was detected in the Framingham study. The objectives of the current study were to explore the relationship of plasma Lp-PLA2 activity with cognitive diagnoses (AD, amnestic mild cognitive impairment (aMCI), and cognitively healthy subjects), cardiovascular markers, cerebrospinal fluid (CSF) markers of AD, and apolipoprotein E (APOE) genotype. METHODS: Subjects with mild AD (n = 78) and aMCI (n = 59) were recruited from the Memory Clinic, University Hospital, Basel, Switzerland; cognitively healthy subjects (n = 66) were recruited from the community. Subjects underwent standardised medical, neurological, neuropsychological, imaging, genetic, blood and CSF evaluation. Differences in Lp-PLA2 activity between the cognitive diagnosis groups were tested with ANOVA and in multiple linear regression models with adjustment for covariates. Associations between Lp-PLA2 and markers of cardiovascular disease and AD were explored with Spearman's correlation coefficients. RESULTS: There was no significant difference in plasma Lp-PLA2 activity between AD (197.1 (standard deviation, SD 38.4) nmol/min/ml) and controls (195.4 (SD 41.9)). Gender, statin use and low-density lipoprotein cholesterol (LDL) were independently associated with Lp-PLA2 activity in multiple regression models. Lp-PLA2 activity was correlated with LDL and inversely correlated with high-density lipoprotein (HDL). AD subjects with APOE-ε4 had higher Lp-PLA2 activity (207.9 (SD 41.2)) than AD subjects lacking APOE-ε4 (181.6 (SD 26.0), P = 0.003) although this was attenuated by adjustment for LDL (P = 0.09). No strong correlations were detected for Lp-PLA2 activity and CSF markers of AD. CONCLUSION: Plasma Lp-PLA2 was not associated with a diagnosis of AD or aMCI in this cross-sectional study. The main clinical correlates of Lp-PLA2 activity in AD, aMCI and cognitively healthy subjects were variables associated with lipid metabolism.

La forma lògica de les oracions d'acció i la tesi d'Anscombe

This paper has three sections. In the first one, I expose and discuss Davidson's semantic account of adverbial sentences: the basic idea is that these sentences involve quantification over events, and I defend that view from opposing perspectives like the theory of adverbs as predicate modifiers. In the second section I defend the claim that in english constructions following the scheme: ¿X did V by T-ings¿, we are referring to the same action of X; what is sometimes called ¿The Anscombe Thesis¿. Again I discuss competing theories only to conclude that the Anscombe Thesis is true. In the third section, however, it is shown that to assume as premisses these two theses -Davidson's account and the Anscombe Thesis- leads to a serious conflict. Alternative solutions are worked out and rejected. It is also argued that the only tenable solution depends on certain metaphysical assumptions. Finally, however, I will cast doubt on this solution.

PPARβ/δ activation blocks lipid-induced inflammatory pathways in mouse heart and human cardiac cells.

Owing to its high fat content, the classical Western diet has a range of adverse effects on the heart, including enhanced inflammation, hypertrophy, and contractile dysfunction. Proinflammatory factors secreted by cardiac cells, which are under the transcriptional control of nuclear factor-κB (NF-κB), may contribute to heart failure and dilated cardiomyopathy. The underlying mechanisms are complex, since they are linked to systemic metabolic abnormalities and changes in cardiomyocyte phenotype. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate metabolism and are capable of limiting myocardial inflammation and hypertrophy via inhibition of NF-κB. Since PPARβ/δ is the most prevalent PPAR isoform in the heart, we analyzed the effects of the PPARβ/δ agonist GW501516 on inflammatory parameters. A high-fat diet induced the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-6, and enhanced the activity of NF-κB in the heart of mice. GW501516 abrogated this enhanced proinflammatory profile. Similar results were obtained when human cardiac AC16 cells exposed to palmitate were coincubated with GW501516. PPARβ/δ activation by GW501516 enhanced the physical interaction between PPARβ/δ and p65, which suggests that this mechanism may also interfere NF-κB transactivation capacity in the heart. GW501516-induced PPARβ/δ activation can attenuate the inflammatory response induced in human cardiac AC16 cells exposed to the saturated fatty acid palmitate and in mice fed a high-fat diet. This is relevant, especially taking into account that PPARβ/δ has been postulated as a potential target in the treatment of obesity and the insulin resistance state.

An integrated encyclopedia of DNA elements in the human genome.

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

Influência da idade dos ovos de Helicoverpa zea (Boddie) no parasitismo de Trichogramma pretiosum Riley

Entre os agentes de controle biológico, os parasitóides do gênero Trichogramma representam um dos mais importantes grupos, pois controlam diversas pragas na agricultura. Este trabalho teve por objetivo determinar a melhor idade dos ovos de Helicoverpa zea (Boddie) para que Trichogramma pretiosum Riley tenha uma melhor eficiência no controle dessa praga. Ovos com um, dois, três e quatro dias foram oferecidos para o parasitismo, por um período de 24 horas a 25 ± 1ºC, umidade relativa de 70 ± 10% e fotofase de 14 horas. Ovos de um dia de idade apresentaram a maior taxa de parasitismo, viabilidade e número de descendentes por fêmea. A mais alta eficiência de T. pretiosum será alçancada no campo, quando for observado maior densidade de ovos de H. zea com, no máximo, dois dias de desenvolvimento embrionário.

This is YOUR Highway Commission,1968

Before the Iowa Department of Transportation (DOT) was established by legislation in July 1974, there were several state agencies that handled the tasks that are now the responsibility of an integrated, multimodal Iowa DOT. Among those agencies was the Iowa State Highway Commission (IHC). You are invited to read a brief history of the Iowa DOT here:http://www.iowadot.gov/about/organizationalhistory.htm The IHC operated as an independent state agency between 1913 and 1974. In 1968, the IHC created and released This is YOUR Highway Commission, a 24 ½- minute film that showcased the responsibilities and functions of the IHC. The narrator describes the activities of various offices and employees, and explains how those activities benefited Iowa’s citizens and motorists. The film journeys through all areas of IHC responsibility to Iowa’s roadways, including administration, planning, design, bidding, right of way, materials, construction, maintenance and facilities. As part of the Iowa DOT’s effort to preserve and archive its historical resources, the original 16mm film was professionally cleaned, restored and digitized so that it could be made available via this website. The Iowa DOT is currently researching and compiling information necessary to prepare detailed biographies of the IHC employees identified in the film. Included in each biography will be still frames taken from the film, as well as other images from the Iowa DOT’s archives. This more comprehensive description of the film will be available in the future. In the meantime, below is a list of the IHC employees who have been identified. The list is arranged in the order in which each employee first appears in the film. There remain numerous unidentified employees in the film, and the Iowa DOT would greatly appreciate any assistance in identifying them. If you recognize an IHC employee in the film who is not on this list, please contactbeth.collins@dot.iowa.gov with any information you feel would be useful. Identified employees: Joseph Coupal, Jr.—Director of Highways Harry Bradley—Commissioner Derby Thompson—Commissioner John Hansen—Commissioner Koert Voorhees—Commissioner Harold Shiel—Engineer Howard Gunnerson—Chief engineer Martha Groth—Commission Secretary Robert Barry—Commissioner Nancy Groomes—Director’s Secretary Russell Moreland—Planning C.B. Anderson—Planning Gus Anderson—Engineer Carl Schach—Deputy chief engineer Raymond Kassel—Hearings engineer (later director of Transportation) Bob Given—Deputy chief engineer Don McLean—Director of Engineering Howard Thielen—Surveying (using rod) John Huss—Surveying (using leveling transit) John “Harley” McCoy—Surveying (taking notes) Jim Smith—Right of Way Keith Davis—Contracts Sherrill P. Freed—Sign Shop Olav Smedal—Director of Public Information

Influência da idade dos ovos de Oxydia vesulia no parasitismo de Trichogramma maxacalii

Trichogramma é um dos gêneros de insetos mais importantes no controle biológico. Este trabalho avaliou o potencial de parasitismo de Trichogramma maxacalii em ovos de Oxydia vesulia, em diferentes estágios embrionários. Vinte e cinco ovos de O. vesulia, com um, três, cinco e sete dias de idade foram oferecidos a uma fêmea de T. maxacalii, em ensaio com 15 repetições, por um período de 24 horas. Não houve influência da idade dos ovos de O. vesulia na porcentagem de parasitismo, na viabilidade, na razão sexual e na porcentagem de fêmeas que parasitaram. Foram encontradas baixas taxas de parasitismo (de 6% a 10%) de T. maxacalii em ovos de O. vesulia, embora mais de 70% das fêmeas desse parasitóide tenham realizado o parasitismo em ovos de até cinco dias de idade.

Desenvolvimento do predador Podisus nigrispinus alimentado com Spodoptera frugiperda e Tenebrio molitor

Ninfas de Podisus nigrispinus (Heteroptera: Pentatomidae) têm sido criadas em laboratório com larvas de Tenebrio molitor L. (Coleoptera: Tenebrionidae). No entanto, não existem relatos sobre a predação, no campo ou em laboratório, de P. nigrispinus em Spodoptera frugiperda (Lepidoptera: Noctuidae), uma das principais pragas de inúmeras culturas no Brasil. Este trabalho teve o objetivo de avaliar o desenvolvimento ninfal e características reprodutivas do percevejo predador P. nigrispinus em lagartas de S. frugiperda e em larvas de T. molitor, em laboratório. A presa S. frugiperda proporcionou ao predador menor longevidade, maior produção e viabilidade de ovos do que as larvas de T. molitor. Esses resultados demonstram que a lagarta S. frugiperda melhora as características reprodutivas de P. nigrispinus, de forma que a sua utilização como presa alternativa pode servir para incrementar a produção massal desse inimigo natural.

PPARβ/δ attenuates palmitate-induced endoplasmic reticulum stress and induces autophagic markers in human cardiac cells.

BACKGROUND: Chronic endoplasmic reticulum (ER) stress contributes to the apoptotic cell death in the myocardium, thereby playing a critical role in the development of cardiomyopathy. ER stress has been reported to be induced after high-fat diet feeding in mice and also after saturated fatty acid treatment in vitro. Therefore, since several studies have shown that peroxisome proliferator-activated receptor (PPAR)β/δ inhibits ER stress, the main goal of this study consisted in investigating whether activation of this nuclear receptor was able to prevent lipid-induced ER stress in cardiac cells. METHODS AND RESULTS: Wild-type and transgenic mice with reduced PPARβ/δ expression were fed a standard diet or a high-fat diet for two months. For in vitro studies, a cardiomyocyte cell line of human origin, AC16, was treated with palmitate and the PPARβ/δ agonist GW501516. Our results demonstrate that palmitate induced ER stress in AC16 cells, a fact which was prevented after PPARβ/δ activation with GW501516. Interestingly, the effect of GW501516 on ER stress occurred in an AMPK-independent manner. The most striking result of this study is that GW501516 treatment also upregulated the protein levels of beclin 1 and LC3II, two well-known markers of autophagy. In accordance with this, feeding on a high-fat diet or suppression of PPARβ/δ in knockout mice induced ER stress in the heart. Moreover, PPARβ/δ knockout mice also displayed a reduction in autophagic markers. CONCLUSION: Our data indicate that PPARβ/δ activation might be useful to prevent the harmful effects of ER stress induced by saturated fatty acids in the heart by inducing autophagy.

TraumaHawk: Improving Treatment for Crash Victims Using Photos and a Smartphone App

Photographic documentation of crashed vehicles at the scene can be used to improve triage of crash victims. A U.S. expert panel developed field triage rules to determine the likelihood of occupants sustaining serious injuries based on vehicle damage that would require transport to a trauma center (Sasser et al., 2011). The use of photographs for assessing vehicle damage and occupant compartment intrusion as it correlates to increased injury severity has been validated (Davidson et al., 2014). Providing trauma staff with crash scene photos remotely could assist them in predicting injuries. This would allow trauma care providers to assess the appropriate transport, as well as develop mental models of treatment options prior to patient arrival at the emergency department (ED). Crash-scene medical response has improved tremendously in the past 20-30 years. This is in part due to the increasing number of paramedics who now have advanced life support (ALS) training that allows independence in the field. However, while this advanced training provides a more streamlined field treatment protocol, it also means that paramedics focused on treating crash victims may not have time to communicate with trauma centers regarding crash injury mechanisms. As a result, trauma centers may not learn about severe trauma patients until just a few minutes before they arrive. The information transmitted by the TraumaHawk app allows interpretation of injury mechanisms from crash scene photos at the trauma center, providing clues about the type and severity of injury. With strategic crash scene photo documentation, trained trauma professionals can assess the severity and patterns of injury based on exterior crush and occupant intrusion. Intrusion increases the force experienced by vehicle occupants, which translates into a higher level of injury severity (Tencer et al., 2005; Assal et al., 2002; Mandell et al., 2010). First responders have the unique opportunity to assess the damaged vehicle at the crash scene, but often the mechanism of injury is limited or not even relayed to ED trauma staff. To integrate photographic and scene information, an app called TraumaHawk was created to capture images of crash vehicles and send them electronically to the trauma center. If efficiently implemented, it provides the potential advantage of increasing lead-time for preparation at the trauma center through the crash scene photos. Ideally, the result is better treatment outcomes for crash victims. The objective of this analysis was to examine if the extra lead-time granted by the TraumaHawk app could improve trauma team activation time over the current conventional communication method.

A high-resolution anatomical atlas of the transcriptome in the mouse embryo.

Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.

Oral rivaroxaban for symptomatic venous thromboembolism.

BACKGROUND: Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring. METHODS: We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study. RESULTS: The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11). CONCLUSIONS: Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193 and NCT00439725.).