ACS Omega

Neurotensin receptor 2 (NTS) is a well-known mediator of central opioid-independent analgesia. Seminal studies have highlighted NTS overexpression in a variety of tumors including prostate cancer, pancreas adenocarcinoma, and breast cancer. Herein, we describe the first radiometalated neurotensin analogue targeting NTS. JMV 7488 (DOTA-(βAla)-Lys-Lys-Pro-(D)Trp-Ile-TMSAla-OH) was prepared using solid-phase peptide synthesis, then purified, radiolabeled with Ga and In, and investigated on HT-29 cells and MCF-7 cells, respectively, and on HT-29 xenografts. [Ga]Ga-JMV 7488 and [In]In-JMV 7488 were quite hydrophilic (logD = -3.1 ± 0.2 and -2.7 ± 0.2, respectively, < 0.0001). Saturation binding studies showed good affinity toward NTS ( = 38 ± 17 nM for [Ga]Ga-JMV 7488 on HT-29 and 36 ± 10 nM on MCF-7 cells; = 36 ± 4 nM for [In]In-JMV 7488 on HT-29 and 46 ± 1 nM on MCF-7 cells) and good selectivity (no NTS binding up to 500 nM). On cell-based evaluation, [Ga]Ga-JMV 7488 and [In]In-JMV 7488 showed high and fast NTS-mediated internalization of 24 ± 5 and 25 ± 11% at 1 h for [In]In-JMV 7488, respectively, along with low NTS-membrane binding (<8%). Efflux was as high as 66 ± 9% at 45 min for [Ga]Ga-JMV 7488 on HT-29 and increased for [In]In-JMV 7488 up to 73 ± 16% on HT-29 and 78 ± 9% on MCF-7 cells at 2 h. Maximum intracellular calcium mobilization of JMV 7488 was 91 ± 11% to that of levocabastine, a known NTS agonist on HT-29 cells demonstrating the agonist behavior of JMV 7488. In nude mice bearing HT-29 xenograft, [Ga]Ga-JMV 7488 showed a moderate but promising significant tumor uptake in biodistribution studies that competes well with other nonmetalated radiotracers targeting NTS. Significant uptake was also depicted in lungs. Interestingly, mice prostate also demonstrated [Ga]Ga-JMV 7488 uptake although the mechanism was not NTS-mediated

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

La reconstruction de l’aréole et du mamelon

National audienceLa réfection du complexe aréolo-mamelonnaire est l’étape finale de la reconstruction mammaire. Elle restitue l’identité visuelle du sein. Les options les plus courantes pour refaire une aréole sont la dermopimentation, la greffe de peau totale de la racine interne de la cuisse et la greffe de peau totale prélevée sur l’aréole controlatérale. Les solutions de reconstruction mamelonnaire sont le dédoublement du mamelon controlatéral, le lambeau local, la greffe de peau totale et le tatouage en trompe l’œil. Le dédoublement du mamelon est la technique de choix parce qu’elle offre d’emblée une couleur, une texture et une projection optimales. La dermopigmentation aréolaire est la procédure la plus courante pour sa simplicité et sa reproductibilité

Constraints on the composition and temperature of LLSVPs from seismic properties of lower mantle minerals

Seismic observations have suggested the presence of two Large Low Shear Velocity Provinces (LLSVPs) in the lowermost mantle whose nature and origin are still debated. Several studies have tried to infer their potential composition using seismic observations with the hope to identify their formation mechanism. In particular, compositions enriched in iron (similar to 12-14 wt%) and bridgmanite (similar to 90 vol%) have been identified as promising candidates. Interestingly, these characteristics are somewhat consistent with the cumulates produced by the solidification of a primitive magma ocean, except that the iron enrichment should be much larger (> 20 wt%). Here, we provide a reappraisal of potential LLSVPs compositions based on an improved mineralogical model including, in particular, the effects of alumina. We systematically investigate the effects of six parameters: FeO and Al2O3 content, proportion of CaSiO3 and bridgmanite (so that the proportion of ferropericlase is implicitly investigated), Fe3+/Sigma Fe and temperature contrast between far-field mantle and LLSVPs. From the 81 millions cases studied, only 79000 cases explain the seismic observations. Nevertheless, these successful cases involve a large range of parameters with, for instance, FeO content between 12-25 wt% and Al2O3 content between 3-17 wt%. We then apply a principal component analysis (PCA) to these cases and find two robust results: (i) the proportion of ferropericlase should be low (<6 vol%); (ii) the formation of Fe3+-bearing bridgmanite is much more favored compared to other iron-bearing components. Following these results, we identify two endmember compositions: a Bm-rich and a CaPv-rich one. For each end-member composition, a large range of parameters is possible. We note, however, that a low temperature contrast (<500 K) is favored, and that a certain proportion between FeO content, Al2O3 and oxidation state should be maintained. Finally, we discuss different scenarios for the formation of LLSVPs and propose that investigating the mineral proportion produced by each scenario is the best way to evaluate their relevance. For instance, the solidification of a primitive magma ocean may produce FeO and Al2O3 contents similar to those suggested by our analysis. However, the mineral proportion of such reservoirs is not well-constrained and may contain a larger proportion of ferropericlase than what is allowed by our results. (C) 2020 Elsevier B.V. All rights reserved

The Transverse Musculocutaneous Gracilis Free Flap: Virtual Animation-Assisted Dissection and Application in Breast Reconstruction.

International audienceThe transverse musculocutaneous gracilis free flap is a valuable choice for autologous tissue, unilateral or bilateral breast reconstruction. This procedure is an excellent and customized option for immediate or delayed breast reconstruction in patients with small to moderate size breasts. Few descriptions of flap dissection and breast mound shaping are available. In this first educational video, the authors report the original dissection of the transverse musculocutaneous gracilis free flap used for breast reconstruction. Virtual animations insist on surgical key points and relevant details of the harvesting of the flap

Cleft alveolar bone graft materials: literature review

Introduction: Since the early stages of alveolar bone grafting development, multiple types of materials have been used. Iliac cancellous bone graft (ICBG) remains the gold standard.Design/Methods: A review of literature is conducted in order to describe the different bone filling possibilities, autologous or not, and to assess their effectiveness compared to ICBG. This review focused on studies reporting volumetric assessment of the alveolar cleft graft result (by computed tomography scan or cone beam computed tomography).Results: Grafting materials fall into 3 types: autologous bone grafts, ICBG supplementary material, and bone substitutes. Among autologous materials, no study showed the superiority of any other bone origin over iliac cancellous bone. Yet ICBG gives inconsistent results and presents donor site morbidity. Concerning supplementary material, only 3 studies could show a benefit of adding platelet-rich fibrin (1 study) or platelet-rich plasma (2 studies) to ICBG, which remains controversial in most studies. There is a lack of 3-dimensional (3D) assessment in most articles concerning the use of scaffolds. Only one study showed graft improvement when adding acellular dermal matrix to ICBG. Looking at bone substitutes highlights failures among bioceramics alone, side-effects with bone morphogenetic protein-2 composite materials, and difficulties in cell therapy setup. Studies assessing cell therapy–based substitutes show comparable efficacy with ICBG but remain too few.Conclusion: This review highlights the lack of 3D assessments in the alveolar bone graft materials field. Nothing dethroned ICBG from its position as the gold standard treatment at this time

Constraints on the composition and temperature of LLSVPs from seismic properties of lower mantle minerals

International audienceSeismic observations have suggested the presence of two Large Low Shear Velocity Provinces (LLSVPs) in the lowermost mantle whose nature and origin are still debated. Several studies have tried to infer their potential composition using seismic observations with the hope to identify their formation mechanism. In particular, compositions enriched in iron (∼12–14 wt%) and bridgmanite (∼90 vol%) have been identified as promising candidates. Interestingly, these characteristics are somewhat consistent with the cumulates produced by the solidification of a primitive magma ocean, except that the iron enrichment should be much larger (>20 wt%). Here, we provide a reappraisal of potential LLSVPs compositions based on an improved mineralogical model including, in particular, the effects of alumina. We systematically investigate the effects of six parameters: FeO and Al2O3 content, proportion of CaSiO3 and bridgmanite (so that the proportion of ferropericlase is implicitly investigated), Fe3+/∑Fe and temperature contrast between far-field mantle and LLSVPs. From the 81 millions cases studied, only 79000 cases explain the seismic observations. Nevertheless, these successful cases involve a large range of parameters with, for instance, FeO content between 12–25 wt% and Al2O3 content between 3–17 wt%. We then apply a principal component analysis (PCA) to these cases and find two robust results: (i) the proportion of ferropericlase should be low (<6 vol%); (ii) the formation of Fe3+-bearing bridgmanite is much more favored compared to other iron-bearing components. Following these results, we identify two end-member compositions: a Bm-rich and a CaPv-rich one. For each end-member composition, a large range of parameters is possible. We note, however, that a low temperature contrast (<500 K) is favored, and that a certain proportion between FeO content, Al2O3 and oxidation state should be maintained. Finally, we discuss different scenarios for the formation of LLSVPs and propose that investigating the mineral proportion produced by each scenario is the best way to evaluate their relevance. For instance, the solidification of a primitive magma ocean may produce FeO and Al2O3 contents similar to those suggested by our analysis. However, the mineral proportion of such reservoirs is not well-constrained and may contain a larger proportion of ferropericlase than what is allowed by our results.

Risk factors for de Quervain's disease in a French working population.

International audienceOBJECTIVE: De Quervain's disease (DQD) is a significant cause of musculoskeletal pain among workers. The aim of this study was to assess the relative importance of personal and occupational risk factors for DQD in a working population. METHODS: A total of 3710 workers from a French region were randomly included in the cross-sectional study between 2002-2005. There were 45 subjects with DQD (of these, 5 subjects had a bilateral condition), diagnosed by 83 trained occupational physicians performing a standardized physical examination. Individual factors and work exposure were assessed by a standardized physical and a self-administered questionnaire. Statistical associations between DQD and individual and occupational factors were analyzed using logistic regression modeling in the whole sample and among women. RESULTS: The prevalence rates of uni- or bilateral DQD for the whole, male and female working populations were 1.2% [95% confidence interval (95% CI) 0.9-1.6], 0.6% (95% CI 0.3-0.9) and 2.1% (95% CI 1.4-2.8), respectively. Personal risk factors for DQD were mainly age (1.1 for 1-year increase in age) and female gender [odds ratio (OR) 4.9, 95% CI 2.4-10.1]. Work-related factors were workpace dependent on (i) technical organization (OR 2.0, 95% CI 1.0-4.0), (ii) repeated or sustained wrist bending in extreme posture (OR 2.6, 95% CI 1.3-5.3) and (iii) repeated movements associated with the twisting or driving of screws (OR 3.4, 95% CI 1.7-7.1). No association was found with psychosocial factors. CONCLUSIONS: Personal and work-related factors were associated with DQD in the working population; wrist bending and movements associated with the twisting or driving of screws were the most significant of the work-related factors

Forest vegetation dynamics in French mountain forests : impact of climatic change

National audienc