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Barrios acknowledges support of the Spanish Ministry of "Educacion y Ciencia" (Program "Ramon y Cajal"). K. B. Gylfason acknowledges support of the Steinmaur Foundation, Liechtenstein. ...doi:10.1364/ol.33.000708 pmid:18382525 fatcat:pgrqd2ij5nfyfdketurxigtvja
β1-tubulin plays a major role in proplatelet formation and platelet shape maintenance, and pathogenic variants in TUBB1 lead to thrombocytopenia and platelet anisocytosis (TUBB1-RT). To date, the reported number of pedigrees with TUBB1-RT and of rare TUBB1 variants with experimental demonstration of pathogenicity is limited. Here, we report 9 unrelated families presenting with thrombocytopenia carrying six β1-tubulin variants: p.Cys12Leufs12*, p.Thr107Pro, p.Gln423*, p.Arg359Trp, p.Gly109Glu,doi:10.1182/bloodadvances.2020004057 pmid:34516618 pmcid:PMC8714720 fatcat:77zzvrova5gbnoxx6lkk7gkwhe
more »... d p.Gly269Asp, the last of which novel. Segregation studies showed incomplete penetrance of these variants for platelet traits. Indeed, most carriers showed macrothrombocytopenia, some only increased platelet size and a minority no abnormalities. Moreover, only homozygous carriers of the p.Gly109Glu variant, displayed macrothrombocytopenia, highlighting the importance of allele burden in the phenotypic expression of TUBB1-RT. The p.Arg359Trp, p.Gly269Asp and p.Gly109Glu variants deranged β1-tubulin incorporation into the microtubular marginal ring in platelets, while had negligible effect on platelet activation, secretion or spreading, suggesting that β1-tubulin is dispensable for these processes. Transfection of TUBB1 missense variants in CHO cells altered β1-tubulin incorporation into the microtubular network. In addition, TUBB1 variants markedly impaired proplatelet formation from peripheral blood CD34+ cell-derived megakaryocytes. Our study, using in vitro modeling, molecular characterization, and clinical investigations provides a deeper insight into the pathogenicity of rare TUBB1 variants. These novel data expand the genetic spectrum of TUBB1-RT and highlight a remarkable heterogeneity in its clinical presentation, indicating that allelic burden or combination with other genetic or environmental factors modulate the phenotypic impact of rare TUBB1 variants.
a B S t r a c t Crataegus sp. has been used in the traditional medicine of Mexico as well as other countries for the treatment of several respiratory diseases, such as flu, cough and asthma. The tracheal relaxant effect of the leaves of C. mexicana is investigated here for the first time, through a bioassay-guided study by using isolated tracheal rings of guinea-pig as an experimental model. the hexane extract was the most active compared to dichloromethane and methanol. an active fraction wasdoi:10.1016/s0975-3575(10)80008-2 fatcat:kr2pzgio6fhxhdi4q7degarmmy
more »... btained from the hexane extract. Assays by HPLC-MS reveal that at least 14 compounds may exist in it. In addition, the results suggest that relaxant effect of the effective fraction was in part related to the activity of β-adrenergic receptors and not to K + atP channels. This study represents the first in which the relaxant effect of leaves of C. mexicana on tracheal rings of guinea pig was clearly demonstrated. More studies are required to correctly identify the bioactive compounds that contribute to the relaxant effects of Crataegus mexicana, and to know the mechanisms of action of these compounds.
Prostate segmentations are required for an ever-increasing number of medical applications, such as image-based lesion detection, fusion-guided biopsy and focal therapies. However, obtaining accurate segmentations is laborious, requires expertise and, even then, the inter-observer variability remains high. In this paper, a robust, accurate and generalizable model for Magnetic Resonance (MR) and three-dimensional (3D) Ultrasound (US) prostate image segmentation is proposed. It uses adoi:10.3390/app11020844 fatcat:opg2md7cs5eb7cctxyxk5agdqe
more »... et-based Convolutional Neural Network (CNN) combined with techniques such as deep supervision, checkpoint ensembling and Neural Resolution Enhancement. The MR prostate segmentation model was trained with five challenging and heterogeneous MR prostate datasets (and two US datasets), with segmentations from many different experts with varying segmentation criteria. The model achieves a consistently strong performance in all datasets independently (mean Dice Similarity Coefficient -DSC- above 0.91 for all datasets except for one), outperforming the inter-expert variability significantly in MR (mean DSC of 0.9099 vs. 0.8794). When evaluated on the publicly available Promise12 challenge dataset, it attains a similar performance to the best entries. In summary, the model has the potential of having a significant impact on current prostate procedures, undercutting, and even eliminating, the need of manual segmentations through improvements in terms of robustness, generalizability and output resolution.
OBJECTIVES The goal of this study was to determine the functional impact of paradoxical low-gradient aortic stenosis (PLGAS) and clarify whether the relevance of the valvular obstruction is related to baseline flow. BACKGROUND Establishing the significance of PLGAS is particularly challenging. METHODS Twenty symptomatic patients (77 AE 6 years of age; 17 female subjects) with PLGAS (mean gradient 28 AE 6 mm Hg; aortic valve area 0.8 AE 0.1 cm 2 ; ejection fraction 66 AE 7%) underwentdoi:10.1016/j.jcmg.2016.03.018 pmid:27568118 fatcat:24vfdxvoorcfzmplaelstnx35u
more »... nary exercise testing combined with right-heart catheterization and Doppler echocardiographic measurements. RESULTS Aortic valve area increased by 84 AE 23% (p < 0.001) and, in 70% of subjects, it reached values >1.0 cm 2 at peak exercise. Stroke volume index and blood pressure increased by 83 AE 56% and 26 AE 16%, respectively (both p < 0.0001). Peak oxygen consumption inversely correlated with the rate of increase in pulmonary capillary wedge pressure (PCWP) (PCWP slope: R ¼ -0.61; p ¼ 0.004). In turn, the PCWP slope was determined by changes in the valvular and vascular load but not by the rest of the indices of aortic stenosis. The functional impact of PLGAS was also not related to baseline flow. Agreement between Doppler echocardiography and the Fick technique was good up to intermediate workload. CONCLUSIONS In symptomatic patients with PLGAS, the capacity to dynamically reduce vascular and valvular loads determines the effect of exercise on PCWP, which, in turn, conditions the functional status. A critically fixed valvular obstruction may not be the main mechanism of functional impairment in a large proportion of patients with PLGAS. A lmost one-third of patients with aortic stenosis (AS) and normal left ventricular (LV) ejection fraction are considered to have severe AS based on aortic valve area (AVA) (<1 cm 2 and <0.6 cm 2 /m 2 of body surface area), but their pressure gradients are below cutoff values considered to identify severity. This condition is designated paradoxical low-gradient aortic stenosis (PLGAS) (1). Although it has been recommended to further distinguish low-flow PLGAS from normal-flow PLGAS (2),
Archivos de Bronconeumologia
COVID-19: intervencionismo diagnóstico torácico en tiempos difíciles
COVID-19: intervencionismo diagnóstico torácico en tiempos difíciles
G Model ARBRES-2508; No. of Pages 3 Arch Bronconeumol. 2020;xxx(xx):xxx-xxx w w w . a r c h b r o n c o n e u m o l . o r gdoi:10.1016/j.arbres.2020.05.019 pmid:32586699 pmcid:PMC7261459 fatcat:6fleatbayffhzfk2q7uqlre3sa
SEBS block copolymers were treated under mild conditions in an ozone atmosphere, producing very slightly chemically-modified surfaces. The thermal stability was analysed by chemiluminescence and related to morphological changes observed by AFM. The intrinsic thermal stability was diminished by ozone exposure, but the oxidation induction times were delayed which indicates an enhancement of thermal stability under oxidative conditions. Also, chemiluminescence analysis showed the presence of adoi:10.1016/j.polymdegradstab.2010.03.018 fatcat:x52pbkx4frg37ebfiwduti6twe
more »... cal orderedisorder transition at temperatures around 120 C. Two different sets of samples which showed different morphological patterns were imaged by AFM. The effects of micro-domain separation and inter-domain structure on thermal properties are discussed and explained by a coarsening of the internal interface induced by ozone. A detailed 2D Fourier transformed analysis of AFM images allowed us to identify a regular wrinkled nano-pattern induced by uniaxial strain combined with ozone treatment, offering new opportunities in applications ranging from organic electronics to bio-patterning.
Acknowledgements The authors thank Javier Zamora, from the biostatistics unit of Hospital Universitario Ramón y Cajal (Madrid, Spain), for reading and critically reviewing the manuscript; Marta Rosas and María ... Twitter Irene Carretero-Barrio @irenecarretero, Amparo Benito @AmparoBenito and Jose Palacios @jpalacioscalvo Figure 1 1 Figure 1 Vascular patterns in patients with COVID-19. (A) Normal lung H&E. ... ORCID iDs Irene Carretero-Barrio http:// orcid. org/ 0000-0003-1986-2965 Álvaro Caballero http:// orcid. org/ 0000-0003-1859-0662 Jose Palacios http:// orcid. org/ 0000-0002-6730-5066 ...doi:10.1136/thoraxjnl-2020-216714 pmid:33758071 fatcat:dkexr2rcz5f5njzglp3b3epbpi
Data in Brief
We are also grateful for a postdoctoral fellowship from ICyTDF from Mexico, now renamed SECITI, to María Esther Herrera-Aguirre. ... Acknowledgements We thank Conacyt from Mexico for the financial support of this project to Raul Mena and Juan Pedro Luna-Arias, as well as for a Ph.D. scholarship and a postdoctoral fellowship to Benito ...doi:10.1016/j.dib.2016.04.071 pmid:27257613 pmcid:PMC4878460 fatcat:zfllxgigd5hjnd5pbtjnflnlye
Aims The physiological determinants of RV diastolic function remain poorly understood. We aimed to quantify the contribution of elastic recoil to RV filling and determine its sensitivity to interventricular interaction. Methods and results High-fidelity pressure -volume loops and simultaneous 3-dimensional ultrasound sequences were obtained in 13 pigs undergoing inotropic modulation, volume overload, and acute pressure overload induced by endotoxin infusion. Using a validated method, wedoi:10.1093/cvr/cvv047 pmid:25691537 pmcid:PMC4560043 fatcat:hcpna4mxsbb4xk6rmommptj3ie
more »... elastic restoring forces from ongoing relaxation using conventional pressurevolume data. The RV contracted below the equilibrium volume in .75% of the data sets. Consequently, elastic recoil generated strong sub-atmospheric passive pressure at the onset of diastole [23 (24 to 22) mmHg at baseline]. Stronger restoring suction pressure was related to a shorter isovolumic relaxation period, a higher rapid filling fraction, and lower atrial pressures (all P , 0.05). Restoring forces were mostly determined by the position of operating volumes around the equilibrium volume. By this mechanism, the negative inotropic effect of beta-blockade reduced and sometimes abolished restoring forces. During acute pressure overload, restoring forces initially decreased, but recovered at advanced stages. This biphasic response was related to alterations of septal curvature induced by changes in the diastolic LV -RV pressure balance. The constant of elastic recoil was closely related to the constant of passive stiffness (R ¼ 0.69). Conclusion The RV works as a suction pump, exploiting contraction energy to facilitate filling by means of strong elastic recoil. Restoring forces are influenced by the inotropic state and RV conformational changes mediated by direct ventricular interdependence. ---
Cerro Ortega The Cerro Ortega burial site (Villanueva de la Fuente, Ciudad Real) was discovered by chance in 1997 by Barrio and Maquedano (2000) . ... Ana María Muñoz Amilibia in the 1960's was restricted to the outlying areas of the Iberian Peninsula; the Portuguese (western) and Millarense-Argaric (south-eastern) settlements and tombs, the Basque megaliths ...doi:10.1016/j.jasrep.2015.11.021 fatcat:3eomlp33yvfy5nq6yvdwkeczie
Disintegrin and metalloproteinase domain 17 (ADAM17) activates inflammatory and fibrotic processes through the shedding of various molecules such as Tumor Necrosis Factor-α (TNF-α) or Transforming Growht Factor-α (TGF-α). There is a well-recognised link between TNF-α, obesity, inflammation, and diabetes. In physiological situations, ADAM17 is expressed mainly in the distal tubular cell while, in renal damage, its expression increases throughout the kidney including the endothelium. The aim ofdoi:10.3390/ijms23010221 pmid:35008648 pmcid:PMC8745741 fatcat:jqy4ldanubgffc2zwf6ed2gveu
more »... is study was to characterize, for the first time, an experimental mouse model fed a high-fat diet (HFD) with a specific deletion of Adam17 in endothelial cells and to analyse the effects on different renal structures. Endothelial Adam17 knockout male mice and their controls were fed a high-fat diet, to induce obesity, or standard rodent chow, for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, macrophage infiltration, and galectin-3 levels were evaluated. Results showed that obese mice presented higher blood glucose levels, dysregulated glucose homeostasis, and higher body weight compared to control mice. In addition, obese wild-type mice presented an increased albumin-to-creatinine ratio; greater glomerular size and mesangial matrix expansion; and tubular fibrosis with increased galectin-3 expression. Adam17 deletion decreased the albumin-to-creatinine ratio, glomerular mesangial index, and tubular galectin-3 expression. Moreover, macrophage infiltration in the glomeruli of obese Adam17 knockout mice was reduced as compared to obese wild-type mice. In conclusion, the expression of ADAM17 in endothelial cells impacted renal inflammation, modulating the renal function and histology in an obese pre-diabetic mouse model.
Background and study aims Chromoendoscopy with targeted biopsy is the technique of choice for colorectal cancer screening in longstanding inflammatory bowel disease. We aimed to analyze results of a chromoendoscopy screening program and to assess the possibility of identifying low-risk dysplastic lesions by their endoscopic appearance in order to avoid histological analysis. Materials and methods We retrospectively reviewed chromoendoscopies performed between February 2011 and June 2017 indoi:10.1055/a-0839-4514 pmid:31157291 pmcid:PMC6524993 fatcat:2f3bmjffqbft5d6p62dyvdywjm
more »... Spanish hospitals in a standardized fashion. We analyzed the findings and the diagnostic yield of the Kudo pit pattern for predicting dysplasia. Results A total of 709 chromoendoscopies (569 patients) were reviewed. Median duration of disease was 16.7 years (SD 8.1); 80.4 % had ulcerative colitis. A total of 2025 lesions (3.56 lesions per patient) were found; two hundred and thirty-two lesions were neoplastic (11.5 %) (223 were LGD (96.1 %), eight were HGD (3.4 %), and one was colorectal cancer (0.5 %). The correlation between dysplasia and Kudo pit patterns predictors of dysplasia (≥ III) was low, with an area under the curve of 0.649. Kudo I and II lesions were correctly identified with a high negative predictive value (92 %), even by non-experts. Endoscopic activity, Paris 0-Is classification, and right colon localization were risk factors for dysplasia detection, while rectum or sigmoid localization were protective against dysplasia. Conclusions Chromoendoscopy in the real-life setting detected 11 % of dysplastic lesions with a low correlation with Kudo pit pattern. A high negative predictive value would prevent Kudo I and, probably, Kudo II biopsies in the left colon, reducing procedure time and avoiding complications.
The emergence of multi-parametric magnetic resonance imaging (mpMRI) has had a profound impact on the diagnosis of prostate cancers (PCa), which is the most prevalent malignancy in males in the western world, enabling a better selection of patients for confirmation biopsy. However, analyzing these images is complex even for experts, hence opening an opportunity for computer-aided diagnosis systems to seize. This paper proposes a fully automatic system based on Deep Learning that takes aarXiv:2103.12650v3 fatcat:leutbxtmsbcnvbqk4jewckn72e
more »... mpMRI from a PCa-suspect patient and, by leveraging the Retina U-Net detection framework, locates PCa lesions, segments them, and predicts their most likely Gleason grade group (GGG). It uses 490 mpMRIs for training/validation, and 75 patients for testing from two different datasets: ProstateX and IVO (Valencia Oncology Institute Foundation). In the test set, it achieves an excellent lesion-level AUC/sensitivity/specificity for the GGG≥2 significance criterion of 0.96/1.00/0.79 for the ProstateX dataset, and 0.95/1.00/0.80 for the IVO dataset. Evaluated at a patient level, the results are 0.87/1.00/0.375 in ProstateX, and 0.91/1.00/0.762 in IVO. Furthermore, on the online ProstateX grand challenge, the model obtained an AUC of 0.85 (0.87 when trained only on the ProstateX data, tying up with the original winner of the challenge). For expert comparison, IVO radiologist's PI-RADS 4 sensitivity/specificity were 0.88/0.56 at a lesion level, and 0.85/0.58 at a patient level. Additional subsystems for automatic prostate zonal segmentation and mpMRI non-rigid sequence registration were also employed to produce the final fully automated system. The code for the ProstateX-trained system has been made openly available at https://github.com/OscarPellicer/prostate_lesion_detection. We hope that this will represent a landmark for future research to use, compare and improve upon.
To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinaldoi:10.1111/aos.14905 pmid:34085771 fatcat:6txbsdphk5a7didmoagctwazai
more »... , on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice.
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