Dynamic photopolymerization produces complex microstructures on hydrogels in a moldless approach to generate a 3D intestinal tissue model

Epithelial tissues contain three-dimensional (3D) complex microtopographies that are essential for proper performance. These microstructures provide cells with the physicochemical cues needed to guide their self-organization into functional tissue structures. However, most in vitro models do not implement these 3D architectural features. The main problem is the availability of simple fabrication techniques that can reproduce the complex geometries found in native tissues on the soft polymeric materials required as cell culture substrates. In this study reaction-diffusion mediated photolithography is used to fabricate 3D microstructures with complex geometries on poly(ethylene glycol)-based hydrogels in a single step and moldless approach. By controlling fabrication parameters such as the oxygen diffusion/depletion timescales, the distance to the light source and the exposure dose, the dimensions and geometry of the microstructures can be well-defined. In addition, copolymerization of poly(ethylene glycol) with acrylic acid improves control of the dynamic reaction-diffusion processes that govern the free-radical polymerization of highly-diluted polymeric solutions. Moreover, acrylic acid allows adjusting the density of cell adhesive ligands while preserving the mechanical properties of the hydrogels. The method proposed is a simple, single-step, and cost-effective strategy for producing models of intestinal epithelium that can be easily integrated into standard cell culture platfor

Results from the INMUNOSUN-SOGUG trial: a prospective phase II study of sunitinib as a second-line therapy in patients with metastatic renal cell carcinoma after immune checkpoint-based combination therapy

Immune checkpoint inhibitors; Metastatic renal carcinoma; Second-line treatmentInhibidors del punt de control immunitari; Carcinoma renal metastàtic; Tractament de segona líniaInhibidores del punto de control inmunitario; Carcinoma renal metastásico; Tratamiento de segunda líneaBackground: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. Patients and methods: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. Results: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. Conclusion: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens.This work was supported by Pfizer, S.L.U. (Madrid, Spain). Pfizer, S.L.U. provided an unrestricted research grant with drug funding and drug supply to conduct the study (no grant number)

Croyances populaires sur l’apprentissage précoce d’une langue étrangère

Ce travail analyse les croyances populaires à propos des jeunes enfants qui apprennent une langue étrangère. C’est la demande croissante dans notre société d’un enseignement précoce de l’anglais, c’est-à-dire avant l’introduction obligatoire de cette langue dans le système éducatif espagnol (à partir de huit ans), qui a suscité cette réflexion. L’analyse de quarante entretiens réalisés auprès de parents d’enfants apprenant l’anglais dans deux communautés distinctes – l’une monolingue (Madrid) et l’autre bilingue (Barcelone) – a permis d’identifier trente et une affirmations, qui sont mises en lumière tout au long de cette étude. Ces idées reçues tournent autour de trois grands axes : la supériorité de l’enfant par rapport à l’adulte, le type de formation que doit recevoir l’enfant à l’école, les opinions sur l’apprentissage d’une troisième langue dans une communauté bilingue. On retiendra surtout la forte dose de projection des expériences personnelles des parents sur leurs enfants, ainsi que les différences décelées entre les deux communautés observées.We analyse the set of popular beliefs which hold children to be more gifted language-learners than adults. The reason behind the study lies in the ever-increasing demand in Spanish society for early English language teaching before the age of 8, when English is officially incorporated into the course. Forty interviews with parents of children learning English in a monolingual community (Madrid) and a bilingual community (Barcelona) were analysed, which allowed us to identify thirty-one popularly-held beliefs concerning three broad areas : (i) the child is a better learner than the the adult ; (ii) the type of teaching suitable for the young child ; (iii) the value of a third language in a bilingual community. Two major phenomena are worth mentioning, namely, the way the parents’opinions are influenced by their own language-learning experience, and certain clear differences between the two types of community

Hepatic metastases from colorectal cancer: preoperative detectiona and assessment of resectability with helical CT

Purpose: to prospectively evaluate helical computed tomography (CT) in the preoperative detection of hepatic metastases and assessment of resectability with surgical, intraoperative ultrasonographic (US), and histopathologic correlation. Materials and methods: between October 1995 and December 1998, preoperative staging with helical CT (5-mm collimation; reconstruction interval, 5 mm) was performed in 157 patients with hepatic metastases. Iodinated contrast material was injected intravenously (160-170 mL; rate, 2.5-3.0 mL/sec); acquisition began at 60-70 seconds. Four radiologists prospectively assessed the metastatic involvement of the liver by indicating the number and location of the lesions; resection was indicated in 113 patients (119 instances). Helical CT findings were correlated with pathologic and surgical findings on a lesion-by-lesion basis. Results: intraoperative US, palpation, and histopathologic examination revealed 290 liver metastases; helical CT correctly depicted 247. Helical CT results were the following: overall detection rate, 85.1% (95% CI: 80.8%, 89.3%); positive predictive value, 96.1% (95% CI: 92.9%, 98.1%); and false-positive rate, 3.9% (10 of 257 findings; 95% CI: 1.9%, 7.1%). False-positive findings were related to hemangioendothelioma, hemangioma, hepatic peliosis, biliary adenoma, centrilobar hemorrhage, biliary hamartoma, periportal fibrosis, and normal liver parenchyma. Curative resection was performed in 112 instances with a resectability rate of 94.1%. Four-year patient survival rate was 58.6%. Conclusion: helical CT is a noninvasive, reliable, and accurate technique for imaging the liver and should be considered as the standard preoperative work-up of hepatic metastases from colorectal cancer

LITTORAL BENTHIC COMMUNITIES AS INDICATORS OF ENVIRONMENTAL QUALITY IN MEDITERRANEAN WATERS

ABSTRACT Sampling of benthic communities from the Catalonia rocky littoral (NW Mediterranean) was carried out in 1999-2000 to study the environmental quality of the waters, using the organisms as bioindicators, and DCA analysis as ordination method. Coverage of the main organisms was used as descriptors of the ecological state. Cystoseira mediterranea was the dominant species in the north coast, whilst the central and south coasts were mainly dominated by Corallina elongata and Mytilus galloprovincialis. Samples in reference zones (non-polluted areas, with almost nil human influence) were also introduced in the analysis to compare the water quality of the different stations in the Catalan coast with these of "pristine" areas. Our results are compared with previous data obtained in 1982. We observe changes in the structure of the littoral communities since 1982, with an apparent increase of the environmental quality. There is a decrease in the abundance of green-algae but we do not observe an increase in the abundance of Cystoseira. These changes can be related to the implementation of the management of the residual waters since 80's years

Croyances populaires sur l’apprentissage précoce d’une langue étrangère

Ce travail analyse les croyances populaires à propos des jeunes enfants qui apprennent une langue étrangère. C’est la demande croissante dans notre société d’un enseignement précoce de l’anglais, c’est-à-dire avant l’introduction obligatoire de cette langue dans le système éducatif espagnol (à partir de huit ans), qui a suscité cette réflexion. L’analyse de quarante entretiens réalisés auprès de parents d’enfants apprenant l’anglais dans deux communautés distinctes – l’une monolingue (Madrid) et l’autre bilingue (Barcelone) – a permis d’identifier trente et une affirmations, qui sont mises en lumière tout au long de cette étude. Ces idées reçues tournent autour de trois grands axes : la supériorité de l’enfant par rapport à l’adulte, le type de formation que doit recevoir l’enfant à l’école, les opinions sur l’apprentissage d’une troisième langue dans une communauté bilingue. On retiendra surtout la forte dose de projection des expériences personnelles des parents sur leurs enfants, ainsi que les différences décelées entre les deux communautés observées.We analyse the set of popular beliefs which hold children to be more gifted language-learners than adults. The reason behind the study lies in the ever-increasing demand in Spanish society for early English language teaching before the age of 8, when English is officially incorporated into the course. Forty interviews with parents of children learning English in a monolingual community (Madrid) and a bilingual community (Barcelona) were analysed, which allowed us to identify thirty-one popularly-held beliefs concerning three broad areas : (i) the child is a better learner than the the adult ; (ii) the type of teaching suitable for the young child ; (iii) the value of a third language in a bilingual community. Two major phenomena are worth mentioning, namely, the way the parents’opinions are influenced by their own language-learning experience, and certain clear differences between the two types of community

Extracapillary proliferation scoring correlates with renal outcome and contributes to stratification in adult patients with immunoglobulin A nephropathy

Background. The revised Oxford classification of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate the histological crescents and interstitial fibrosis and tubular atrophy (IFTA) subgrouping, and to investigate the additional value of the proportion of crescents (CatPE) in the prediction of renal outcome. Methods. Data were retrospectively collected over 10 years, from the time of diagnosis, by systematic review of medical records from 90 patients with renal biopsies recruited to cohorts from two hospitals in Spain. Patients were classified into three groups for the analysis: CatPE >25% (C2), CatPE 50% reduction in glomerular filtrate rate or end-stage renal disease. Results. Renal survival at 5 years was 90% in group C0, 81% in group C1 and 31% in group C2 (P 1⁄4 0.013). The presence of >25% crescents in the sample was associated with more severe disease when compared with 50% had poorer renal function compared with the other groups. Conclusions. We have confirmed the predictive value for renal survival of the revised Oxford classification in a two-centre study. We found worse renal outcome in patients with severe tubulointerstitial fibrosis and atrophy. Patients with extracapillary lesions >25% and IFTA >50% had a worse renal prognosis due to more severe kidney injury. These results contribute to patient stratification in immunoglobulin A nephropathy for therapeutic, epidemiological and basic research

Benchmarking bimanual cloth manipulation

© 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.Cloth manipulation is a challenging task that, despite its importance, has received relatively little attention compared to rigid object manipulation. In this paper, we provide three benchmarks for evaluation and comparison of different approaches towards three basic tasks in cloth manipulation: spreading a tablecloth over a table, folding a towel, and dressing. The tasks can be executed on any bimanual robotic platform and the objects involved in the tasks are standardized and easy to acquire. We provide several complexity levels for each task, and describe the quality measures to evaluate task execution. Furthermore, we provide baseline solutions for all the tasks and evaluate them according to the proposed metrics.Peer ReviewedPostprint (author's final draft

Traumatic brain injury in late adolescent rats : effects on adulthood memory and anxiety

This article may not exactly replicate the final version published in the APA journal. It is not the copy of record.The consequences of traumatic brain injury (TBI) sustained during late adolescence (7 weeks-old) on spontaneous object recognition memory and on anxiety-like behaviors in the elevated plus maze were tested in rats during adulthood. Testing took place at two different post injury times, in separate groups: three and six weeks, when animals were 10 and 13 weeks old, respectively. The rats were either submitted to controlled cortical impact injury, an experimental model of focal TBI with contusion, or were shamoperated. TBI animals failed to remember the familiar object and had a significantly lower performance than sham-operated animals, indicating memory disruption, when the retention delay was 24 h, but not when it was 3 h. TBI did not have any significant effect on the main anxiety-related behaviors, but it reduced time in the central platform of the elevated plus maze. The effects of TBI on memory and on anxiety-like behaviors were similar at the two post injury times. In both TBI and sham-operated groups, animals tested six weeks after surgery had lower anxiety-related indices than those tested at three weeks, an effect that might be indicative of reduced anxiety levels with increasing age. In summary, focal TBI with contusion sustained during late adolescence led to object recognition memory deficits in a 24-h test during adulthood, but did not have a major impact on anxiety-like behaviors. Memory deficits persisted for at least six weeks after injury, indicating that spontaneous modifications of these functional disturbances did not take place along this time span

Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa

Mounting evidence supports the importance of the intestinal epithelial barrier and its permeability both in physiological and pathological conditions. Conventional in vitro models to evaluate intestinal permeability rely on the formation of tightly packed epithelial monolayers grown on hard substrates. These two-dimensional (2D) models lack the cellular and mechanical components of the non-epithelial compartment of the intestinal barrier, the stroma, which are key contributors to the barrier permeability in vivo. Thus, advanced in vitro models approaching the in vivo tissue composition are fundamental to improve precision in drug absorption predictions, to provide a better understanding of the intestinal biology, and to faithfully represent related diseases. Here, we generate photo-crosslinked gelatine methacrylate (GelMA) - poly(ethylene glycol) diacrylate (PEGDA) hydrogel co-networks that provide the required mechanical and biochemical features to mimic both the epithelial and stromal compartments of the intestinal mucosa, i.e., they are soft, cell adhesive and cell-loading friendly, and suitable for long-term culturing. We show that fibroblasts can be embedded in the GelMA-PEGDA hydrogels while epithelial cells can grow on top to form a mature epithelial monolayer that exhibits barrier properties which closely mimic those of the intestinal barrier in vivo, as shown by the physiologically relevant transepithelial electrical resistance (TEER) and permeability values. The presence of fibroblasts in the artificial stroma compartment accelerates the formation of the epithelial monolayer and boosts the recovery of the epithelial integrity upon temporary barrier disruption, demonstrating that our system is capable of successfully reproducing the interaction between different cellular compartments. As such, our hydrogel co-networks offer a technologically simple yet sophisticated approach to produce functional three-dimensional (3D) in vitro models of epithelial barriers with epithelial and stromal cells arranged in a spatially relevant manner and near-physiological functionality