Gene deficiency in activating Fcγ receptors influences the macrophage phenotypic balance and reduces atherosclerosis in mice

Immunity contributes to arterial inflammation during atherosclerosis. Oxidized low-density lipoproteins induce an autoimmune response characterized by specific antibodies and immune complexes in atherosclerotic patients. We hypothesize that specific Fcγ receptors for IgG constant region participate in atherogenesis by regulating the inflammatory state of lesional macrophages. In vivo we examined the role of activating Fcγ receptors in atherosclerosis progression using bone marrow transplantation from mice deficient in γ-chain (the common signaling subunit of activating Fcγ receptors) to hyperlipidemic mice. Hematopoietic deficiency of Fcγ receptors significantly reduced atherosclerotic lesion size, which was associated with decreased number of macrophages and T lymphocytes, and increased T regulatory cell function. Lesions of Fcγ receptor deficient mice exhibited increased plaque stability, as evidenced by higher collagen and smooth muscle cell content and decreased apoptosis. These effects were independent of changes in serum lipids and antibody response to oxidized low-density lipoproteins. Activating Fcγ receptor deficiency reduced pro-inflammatory gene expression, nuclear factor-κB activity, and M1 macrophages at the lesion site, while increasing anti-inflammatory genes and M2 macrophages. The decreased inflammation in the lesions was mirrored by a reduced number of classical inflammatory monocytes in blood. In vitro, lack of activating Fcγ receptors attenuated foam cell formation, oxidative stress and pro-inflammatory gene expression, and increased M2-associated genes in murine macrophages. Our study demonstrates that activating Fcγ receptors influence the macrophage phenotypic balance in the artery wall of atherosclerotic mice and suggests that modulation of Fcγ receptor-mediated inflammatory responses could effectively suppress atherosclerosis

Serum levels and removal by haemodialysis and haemodiafiltration of tryptophan-derived uremic toxins in ESKD patients

Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, -0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (-72%, -39%, -43%, respectively), serum tryptophan levels increased, resulting in negative RR (-8%) towards the end of the dialysis session (p < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses

Mucosal immunoglobulins at respiratory surfaces mark an ancient association that predates the emergence of tetrapods

Gas-exchange structures are critical for acquiring oxygen, but they also represent portals for pathogen entry. Local mucosal immunoglobulin responses against pathogens in specialized respiratory organs have only been described in tetrapods. Since fish gills are considered a mucosal surface, we hypothesized that a dedicated mucosal immunoglobulin response would be generated within its mucosa on microbial exposure. Supporting this hypothesis, here we demonstrate that following pathogen exposure, IgT(+) B cells proliferate and generate pathogen-specific IgT within the gills of fish, thus providing the first example of locally induced immunoglobulin in the mucosa of a cold-blooded species. Moreover, we demonstrate that gill microbiota is predominantly coated with IgT, thus providing previously unappreciated evidence that the microbiota present at a respiratory surface of a vertebrate is recognized by a mucosal immunoglobulin. Our findings indicate that respiratory surfaces and mucosal immunoglobulins are part of an ancient association that predates the emergence of tetrapods

Impact in hospitalization costs of a cardiovascular risk management program in Colombia: a propensity score matching model

Cardiovascular diseases (CVD) are the leading cause of death and burden of disease in Colombia and globally. In 2017, CVD represented the 12% of total DALYs. CVD is a costly disease from patient, family and societal perspectives. Effective prevention and risk management programs reduces the incidence of CVD by as much as 80%. We aimed to estimate the impact of direct medical hospitalization costs related to adherence in a risk management program in Colombia, 2018. We retrospectively collected data from 6,243 patients with data of enrollment in a cardiovascular risk management program (DTC, in Spanish) of a subsidized insurer, who presented arterial hypertension (AH) or AH+ type 2 diabetes mellitus (DM2). 1,065 were identified adherent to the program (treated) and 5.178 non adherent (controls). We designed a propensity score matching model adjusted with confounding variables to estimate the effect of treatment (program adherence) over hospitalization cost. Costs were calculated based on hospitalization invoices and expressed in Colombian pesos (COP) 2018. DTC has an average negative effect on cost of treated population. Being treated avoids hospitalization costs; these results were statistically significant at the 5% and 10% level (with 95%CI that goes through zero). Hence, being in the DTC program reduces hospital costs that ranges from COP-$11,346,372 to -$ 799,259 (95%CI) compared to the average cost. The overall impact on program costs is a significant saving of COP583,670 per event-year. If all members of the DTC program fulfilled its activities by more than 80%, the savings generated by the program would be close to COP$ 6.85 billion. DTC risk management program reduces direct hospitalization costs of events associated to CVD. Our results are important to design policies focused on the cost and risk management of patients with CVD in poor population

Using GPUs in Real-Time Applications: A Review of Techniques for Analyzing and Optimizing the Timing Parameters

[EN] Autonomous driving is attracting an increasing attention in industry, not only in the automotive sector, but also in the transport of people or goods by road or railway and in more controlled manufacturing environments. The cyber-physical systems that are being proposed for this type of applications require a large computing capacity (hardware architectures with several cores, GPUs, NPUs...) to be able to attend and react to a multiple and complex amount of sensors (cameras, radar, LiDAR, measure of distance, etc.). On the other hand, this type of system must meet both safety and real-time requirements. This last aspect poses challenges on which intensive work is being done and on which there are still many open issues. In this work, a review of the most recent literature on the use of heterogeneous architectures with GPUs in real-time applications is made. These works mainly propose some solutions to the estimation of bounds to the execution times and response times, and consider different optimization strategies emphasising memory interference mitigation.[ES] La conducción autónoma despierta un interés cada vez mayor en la industria, no solo en el sector de la automoción, sino también en el transporte de personas o mercancías por carretera o ferrocarril y en entornos de fabricación más controlados. Los sistemas ciber-físicos que se están proponiendo para este tipo de aplicaciones requieren de una gran capacidad de cómputo (arquitecturas hardware con varios núcleos, GPUs, NPUs ) para poder atender y reaccionar a una múltiple y compleja cantidad de sensores (cámaras, radar, LiDAR, medida de distancia, etc.). Por otro lado, este tipo de sistemas debe atender a requisitos de seguridad funcional y también de tiempo real. Este último aspecto plantea retos en los que se está trabajando intensamente y en los que aún quedan muchas cuestiones por resolver. En este trabajo, se hace una revisión de la literatura más reciente del uso de arquitecturas heterogéneas con GPUs en aplicaciones de tiempo real. Estos trabajos proponen soluciones para la estimación de cotas de tiempos de ejecución y respuesta temporal, proponiendo diferentes estrategias de optimización destacando la mitigación de interferencia en la memoria.Este trabajo ha sido parcialmente financiado por MCIN/AEI /10.13039/501100011033/ FEDER “Una manera de hacer Europa” a través de las subvenciones PID2021-124502OB-C42 y PID2021-124502OB-C44 (PRESECREL).Gomez, I.; Díaz De Cerio, U.; Parra, J.; Rivas, JM.; Gutiérrez, JJ. (2023). Uso de GPUs en aplicaciones de tiempo real: Una revisión de técnicas para el análisis y optimización de parámetros temporales. Revista Iberoamericana de Automática e Informática industrial. 21(1):1-16. https://doi.org/10.4995/riai.2023.2032111621

Effectiveness of a cardiovascular risk management program in the incidence of cardiovascular events in a low-income population from the caribbean region of Colombia

Methods This was a retrospective cohort study. Patients with 20 to 76 years affiliated to insurer company and enrolled to the DTC program were considered as the study population. The data source was an administrative database of all 128,263 patients between Jan 2015 and Dec 2018. The main outcome was the reduction in the risk of a CVE (stroke, AMI or CHF) based in the time-person exposed to the intervention. Four different time thresholds were considered for stablishing exposure status: six months, one year, two years and four years. Propensity score-weighted Cox regression models were used to evaluate the association between exposure to the program and the incidence of CVE

Comparative epigenomics in distantly related teleost species identifies conserved cis-regulatory nodes active during the vertebrate phylotypic period

The complex relationship between ontogeny and phylogeny has been the subject of attention and controversy since von Baer’s formulations in the 19th century. The classic concept that embryogenesis progresses from clade general features to species-specific characters has often been revisited. It has become accepted that embryos from a clade show maximum morphological similarity at the so-called phylotypic period (i.e., during mid-embryogenesis). According to the hourglass model, body plan conservation would depend on constrained molecular mechanisms operating at this period. More recently, comparative transcriptomic analyses have provided conclusive evidence that such molecular constraints exist. Examining cis-regulatory architecture during the phylotypic period is essential to understand the evolutionary source of body plan stability. Here we compare transcriptomes and key epigenetic marks (H3K4me3 and H3K27ac) from medaka (Oryzias latipes) and zebrafish (Danio rerio), two distantly related teleosts separated by an evolutionary distance of 115-200 Myr. We show that comparison of transcriptome profiles correlates with anatomical similarities and heterochronies observed at the phylotypic stage. Through comparative epigenomics, we uncover a pool of conserved regulatory regions (approximate to 700), which are active during the vertebrate phylotypic period in both species. Moreover, we show that their neighboring genes encode mainly transcription factors with fundamental roles in tissue specification. We postulate that these regulatory regions, active in both teleost genomes, represent key constrained nodes of the gene networks that sustain the vertebrate body plan

Estimating Genetic Ancestry Proportions from Faces

Ethnicity can be a means by which people identify themselves and others. This type of identification mediates many kinds of social interactions and may reflect adaptations to a long history of group living in humans. Recent admixture in the US between groups from different continents, and the historically strong emphasis on phenotypic differences between members of these groups, presents an opportunity to examine the degree of concordance between estimates of group membership based on genetic markers and on visually-based estimates of facial features. We first measured the degree of Native American, European, African and East Asian genetic admixture in a sample of 14 self-identified Hispanic individuals, chosen to cover a broad range of Native American and European genetic admixture proportions. We showed frontal and side-view photographs of the 14 individuals to 241 subjects living in New Mexico, and asked them to estimate the degree of NA admixture for each individual. We assess the overall concordance for each observer based on an aggregated measure of the difference between the observer and the genetic estimates. We find that observers reach a significantly higher degree of concordance than expected by chance, and that the degree of concordance as well as the direction of the discrepancy in estimates differs based on the ethnicity of the observer, but not on the observers' age or sex. This study highlights the potentially high degree of discordance between physical appearance and genetic measures of ethnicity, as well as how perceptions of ethnic affiliation are context-specific. We compare our findings to those of previous studies and discuss their implications

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201