Primary cilia (PC) are conserved structures in the adult thyroid gland of different mammals. It was recently described that in humans, PC are usually present as a single copy per follicular cell ...emerging from the follicular cell apex into the follicular lumen.
To understand the role developed by PC in thyroid hormonogenesis better, their changes in different human functional thyroid diseases (diffuse toxic hyperplasia/Graves' disease GD and nodular hyperplasia NH/nodular goiter), in comparison to normal thyroid tissue, were investigated using immunofluorescence, morphometry, and electron microscopy analyses.
Significantly decreased ciliary frequencies were found in both NH (51.16 ± 11.69%) and GD (44.43 ± 23.70%) compared to normal thyroid tissue (76.09 ± 7.31%). Similarly, PC lengths were also significantly decreased in both NH (2.02 ± 0.35 μm) and GD (2.4 ± 0.48 μm) compared to normal glands (3.93 ± 0.90 μm). Moreover, in GD patients, hyperactive-follicle foci always showed diminished ciliary frequency and length compared to any other thyroid follicle pattern, independent of their thyroid status. Finally, in GD, the percentage of thyrocytes exhibiting PC in the "normal-appearance areas" was significantly lower in correspondence with the subsistence of signs of thyroid biosynthetic hyperactivity after long-term antithyroid drug treatment.
The results suggest a direct relationship between ciliogenesis and both follicle activity and tissue heterogeneity in the functional pathology of the thyroid gland.
Triazole fungicides are widely used in the world, mainly in agriculture, but their abuse and possible toxic effects are being reported in some in vivo and in vitro studies that have demonstrated ...their danger to human health. This in vitro study evaluated the cytotoxicity, oxidative stress and proinflammation of EA.hy926 endothelial cells in response to ipconazole exposure. Using the MTT assay, ipconazole was found to produce a dose-dependent reduction (*** p < 0.001; concentrations of 20, 50 and 100 µM) of cell viability in EA.hy926 with an IC50 of 29 µM. Also, ipconazole induced a significant increase in ROS generation (** p < 0.01), caspase 3/7 (** p < 0.01), cell death (BAX, APAF1, BNIP3, CASP3 and AKT1) and proinflammatory (NLRP3, CASP1, IL1β, NFκB, IL6 and TNFα) biomarkers, as well as a reduction in antioxidant (NRF2 and GPx) biomarkers. These results demonstrated that oxidative stress, proinflammatory activity and cell death could be responsible for the cytotoxic effect produced by the fungicide ipconazole, such that this triazole compound should be considered as a possible risk factor in the development of alterations in cellular homeostasis.
18F-FDG PET/CT in pure testicular Yolk Sac Tumor in adult García-Gómez, Francisco Javier; Villar-Rodríguez, José Luis; Beato-Zambrano, Carmen ...
International Brazilian Journal of Urology,
01/2021, Letnik:
47, Številka:
1
Journal Article
Human Leukocyte Antigen (HLA) includes a large set of genes with important actions in immune response against viral infection. Numerous studies have revealed the existence of significant associations ...between certain HLA alleles and the susceptibility and prognosis of different infectious diseases. In this pilot study we analyse the binding affinity between 66 class I HLA alleles and SARS-CoV-2 viral peptides, and its association with the severity of the disease.
A total of 45 Spanish patients with mild, moderate and severe SARS-CoV-2 infection were typed for HLA class I; after that, we analysed if an in silico model of HLA I-viral peptide binding affinity and classical HLA supertypes could be correlated to the severity of the disease. Our results suggest that patients with mild disease present Class I HLA molecules with a higher theoretical capacity for binding SARS-Cov-2 peptides and showed greater heterozygosity when comparing them with moderate and severe groups. In this regard, identifying HLA-SARS-CoV-2 peptides binding differences between individuals would help to clarify the heterogeneity of clinical responses to the disease and will also be useful to guide a personalized treatment according to its particular risk.
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Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical ...control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/μL.
The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92μg/umeclidinium (UMEC) 55μg/vilanterol (VI) 22μg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia.
The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026.
The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.
Intensive groundwater development is a common circumstance in semiarid and arid areas. Often abstraction exceeds recharge, thus continuously depleting reserves. There is groundwater mining when the ...recovery of aquifer reserves needs more than 50years. The MASE project has been carried out to compile what is known about Spain and specifically about the south-eastern Iberian Peninsula and the Canary Islands. The objective was the synthetic analysis of available data on the hydrological, economic, managerial, social, and ethical aspects of groundwater mining. Since the mid-20th century, intensive use of groundwater in south-eastern Spain allowed extending and securing the areas with traditional surface water irrigation of cash crops and their extension to former dry lands, taking advantage of good soils and climate. This fostered a huge economic and social development. Intensive agriculture is a main activity, although tourism plays currently an increasing economic role in the coasts. Many aquifers are relatively high yielding small carbonate units where the total groundwater level drawdown may currently exceed 300m. Groundwater storage depletion is estimated about 15km3. This volume is close to the total contribution of the Tagus-Segura water transfer, but without large investments paid for with public funds. Seawater desalination complements urban supply and part of cash crop cultivation. Reclaimed urban waste water is used for irrigation. Groundwater mining produces benefits but associated to sometimes serious economic, administrative, legal and environmental problems. The use of an exhaustible vital resource raises ethical concerns. It cannot continue under the current legal conditions. A progressive change of water use paradigm is the way out, but this is not in the mind of most water managers and politicians. The positive and negative results observed in south-eastern Spain may help to analyse other areas under similar hydrogeological conditions in a less advanced stage of water use evolution.
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•Intensive use and mining of groundwater allow social development.•Groundwater mining is not sustainable, but is a valuable transient water resource.•Groundwater mining in south-eastern Spain is estimated to be 15km3.•Groundwater mining is not compatible with the European Water Framework Directive.•The intensive and mining uses of groundwater involve ethical and moral problems.
El estudio tiene como objetivo general analizar el cortometraje, como herramienta pedagógica para el trabajo colaborativo en los estudiantes que cursan la Licenciatura en Matemáticas orientada a la ...Educación Secundaria, en el ISFODOSU, Recinto Luis Napoleón Núñez Molina, República Dominicana, cuatrimestre enero- abril 2021. El abordaje metodológico se desarrolló con base al paradigma cualitativo, bajo el método investigación-acción. La población estuvo conformada por 19 estudiantes. El procedimiento de investigación, está basado en el método inductivo y para el modelo de investigación acción, se eligió el modelo de Kemmis. En los resultados se contrastaron las opiniones de los estudiantes, del equipo investigador y de las teorías consultadas, presentados mediante una matriz que contiene las similitudes y diferencias. Como conclusiones, se tiene que es pertinente mejorar la capacidad del trabajo colaborativo de los estudiantes mediante la estrategia de producción de cortometrajes, pues contribuye a la resolución de problemas y favorece su aprendizaje.
The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, ...to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality.
In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model.
Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 19% patients), phenotype B (1955 73%) and phenotype C (196 7%)—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 17% patients), phenotype B (1019 74%), and phenotype C (116 8%). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p<0·0001). The predicted phenotypes in the internal validation cohort and external validation cohort showed similar mortality rates to the assigned phenotypes (internal validation cohort: 5·3% 95% CI 3·4–8·1 for phenotype A, 31·3% 28·5–34·2 for phenotype B, and 59·5% 48·8–69·3 for phenotype C; external validation cohort: 3·7% 2·0–6·4 for phenotype A, 23·7% 21·8–25·7 for phenotype B, and 51·4% 41·9–60·7 for phenotype C).
Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated.
Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.
Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade,
-sialidase has become a pharmacological target for new anti-Chagas drugs. ...In this work, the aims were to design and find a new series of benzoic acid derivatives as
-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (
,
, and
) sharing a
-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC
) was <0.15 µM on the NINOA strain, and LC
< 0.22 µM on the INC-5 strain. Additionally, compound
showed a moderate inhibition (47%) on the
-sialidase enzyme and a binding model similar to DANA (pattern A).
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