WWP2 confers risk to osteoarthritis by affecting cartilage matrix deposition via hypoxia associated genes.

OBJECTIVE: To explore the co-expression network of the osteoarthritis (OA) risk gene WWP2 in articular cartilage and study cartilage characteristics when mimicking the effect of OA risk allele rs1052429-A on WWP2 expression in a human 3D in vitro model of cartilage. METHOD: Co-expression behavior of WWP2 with genes expressed in lesioned OA articular cartilage (N = 35 samples) was explored. By applying lentiviral particle mediated WWP2 upregulation in 3D in vitro pellet cultures of human primary chondrocytes (N = 8 donors) the effects of upregulation on cartilage matrix deposition was evaluated. Finally, we transfected primary chondrocytes with miR-140 mimics to evaluate whether miR-140 and WWP2 are involved in similar pathways. RESULTS: Upon performing Spearman correlations in lesioned OA cartilage, 98 highly correlating genes (|ρ| > 0.7) were identified. Among these genes, we identified GJA1, GDF10, STC2, WDR1, and WNK4. Subsequent upregulation of WWP2 on 3D chondrocyte pellet cultures resulted in a decreased expression of COL2A1 and ACAN and an increase in EPAS1 expression. Additionally, we observed a decreased expression of GDF10, STC2, and GJA1. Proteomics analysis identified 42 proteins being differentially expressed with WWP2 upregulation, which were enriched for ubiquitin conjugating enzyme activity. Finally, upregulation of miR-140 in 2D chondrocytes resulted in significant upregulation of WWP2 and WDR1. CONCLUSIONS: Mimicking the effect of OA risk allele rs1052429-A on WWP2 expression initiates detrimental processes in the cartilage shown by a response in hypoxia associated genes EPAS1, GDF10, and GJA1 and a decrease in anabolic markers, COL2A1 and ACAN.

Are artificial intelligence systems useful in breast cancer screening programs? / ¿Son los sistemas de inteligencia artificial una herramienta útil para los programas de cribado de cáncer de mama?

Population-based breast cancer screening programs are efficacious in reducing the mortality due to breast cancer. These programs use mammography to screen the women who are invited to participate. Digital mammography makes it possible to develop computer-assisted diagnosis (CAD) systems that promise to reduce the workload of radiologists participating in screening programs. However, various studies have shown that CAD results in a high rate of false positive diagnoses. Systems based on artificial intelligence are being more widely implemented, and studies have shown that these systems have better diagnostic performance than traditional CAD systems. This article explains the fundamentals of artificial intelligence systems and an overview of possible applications of these systems within the framework of breast cancer screening programs.

Evaluation of the technical performance of three different commercial digital breast tomosynthesis systems in the clinical environment.

The aim of this work was to research and evaluate the performance of three different digital breast tomosynthesis (DBT) systems in the clinical environment (Siemens Mammomat Inspiration, Hologic Selenia Dimensions, and Fujifilm Amulet Innovality). The characterization included the study of the detector, the automatic exposure control, and the resolution of DBT projections and reconstructed planes. The modulation transfer function (MTF) of the DBT projections was measured with a 1mm thick steel edge, showing a strong anisotropy (30-40% lower MTF0.5 frequencies in the tube travel direction). The in-plane MTF0.5, measured with a 25µm tungsten wire, ranges from 1.3 to 1.8lp/mm in the tube-travel direction and between 2.4 and 3.7lp/mm in the chest wall-nipple. In the latter direction, the MTF peak shift is more emphasized for large angular range systems (2.0 versus 1.0lp/mm). In-depth resolution of the planes, via the full width at half maximum (FWHM) from the point spread function of a 25µm tungsten wire, is not only influenced by angular range and yields 1.3-4.6mm among systems. The artifact spread function from 1mm diameter tungsten beads depends mainly on angular range, yielding two tendencies whether large (FWHM is 4.5mm) or small (FWHM is 10mm) angular range is used. DBT delivers per scan a mean glandular dose between 1.4 and 2.7mGy for a 45mm thick polymethyl methacrylate (PMMA) block. In conclusion, we have identified and analysed specific metrics that can be used for quality assurance of DBT systems.

Scenario-targeted toxicity assessment through multiple endpoint bioassays in a soil posing unacceptable environmental risk according to regulatory screening values.

Lanestosa is a chronically polluted site (derelict mine) where the soil (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity assessment was carried out on the basis of a multi-endpoint bioassay approach. Acute and chronic toxicity bioassays were conducted with selected test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates and with bioaccumulation studies in earthworms. Besides, the toxicity profile was compared with that of the mine runoff (RO) soil and of a fresh artificially polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange and/or release into the environment. Indeed, Pb and Zn were accumulated in earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri, vegetative and developmental cycles of D. discoideum and survival and juvenile production of E. fetida were severely affected. These results confirmed that LA soil had unacceptable environmental risk and demanded intervention. In contrast, although Pb and Zn concentrations in RO soil revealed also unacceptable risk, both metal extractability and toxicity were much lower than in LA soil. Thus, within the polluted site, the need for intervention varied between areas that posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal fraction, was the most toxic, ageing under in situ natural conditions seemingly contributed to attenuate LA soil risk. As a whole, combining multi-endpoint bioassays with scenario-targeted analysis (including leaching and ageing) provides reliable risk assessment in soils posing unacceptable environmental risk according to SVs, which is useful to optimise the required intervention measures.

Toxicity assessment through multiple endpoint bioassays in soils posing environmental risk according to regulatory screening values.

Toxicity profiles of two soils (a brownfield in Legazpi and an abandoned iron mine in Zugaztieta; Basque Country) contaminated with several metals (As, Zn, Pb and Cu in Legazpi; Zn, Pb, Cd and Cu in Zugaztieta) and petroleum hydrocarbons (in Legazpi) were determined using a multi-endpoint bioassay approach. Investigated soils exceeded screening values (SVs) of regulatory policies in force (Basque Country; Europe). Acute and chronic toxicity bioassays were conducted with a selected set of test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates, as well as with bioaccumulation studies in earthworms. The sensitivity of the test species and the toxicity endpoints varied depending on the soil. It was concluded that whilst Zugaztieta soil showed very little or no toxicity, Legazpi soil was toxic according to almost all the toxicity tests (solid phase Microtox, D. discoideum inhibition of fruiting body formation and developmental cycle solid phase assays, lettuce seed germination and root elongation test, earthworm acute toxicity and reproduction tests, D. discoideum cell viability and replication elutriate assays). Thus, albeit both soils had similar SVs, their ecotoxicological risk, and therefore the need for intervening, was different for each soil as unveiled after toxicity profiling based on multiple endpoint bioassays. Such a toxicity profiling approach is suitable to be applied for scenario-targeted soil risk assessment in those cases where applicable national/regional soil legislation based on SVs demands further toxicity assessment.

[Urticaria as a clinical manifestation of intestinal parasitism]. / Urticaria: como manifestación clínica del parasitismo intestinal.

The main goal of this paper is to call the attention of general practitioners and internists on the different affections which may involve urticaria as a clinical manifestations. A differential diagnosis of the causes of urticaria with an allergic and a nonallergic pathogenesis is made. Intestinal parasitism is among the first causes of urticaria. Six cases studied at the allergy service which had been referred from health areas or other hospital services are reviewed and reported. In these patients, a total regression of the clinical picture was achieved once intestinal parasitism was eradicated.

[IgE determination in a group of allergic patients in Cuba]. / Dosificación de IgE en un grupo de pacientes alérgicos en Cuba.

Because the importance of IgE in allergic phenomena and due to the fact that its measurement is not usual in our country, we decided to evaluate this immunoglobulin in 62 patients suffering one or more allergic symptoms. We used PRIST, the solid phase radioimmunoassay by the sandwich technique. IgE was increased in 75% of the patients. Factors influencing this find were analyzed: geographic, weather and environmental conditions, genetic and other factors.