Iron-Based Nanovehicle Delivering Fin56 for Hyperthermia-Boosted Ferroptosis Therapy Against Osteosarcoma.

Background: Although systemic chemotherapy is a standard approach for osteosarcoma (OS) treatment, its efficacy is limited by the inherent or acquired resistance to apoptosis of tumor cells. Ferroptosis is considered as an effective strategy capable of stimulating alternative pathways of cancer cell demise. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy. Methods and Results: A novel nanovehicle composed of arginine-glycine-aspartate (RGD) modified mesoporous silica-coated iron oxide loading Fin56 was rationally prepared (FSR-Fin56). With the RGD-mediated targeting affinity, FSR-Fin56 could achieve selective accumulation and accurate delivery of cargos into cancer cells. Upon exposure to NIR light, the nanovehicle could generate localized hyperthermia and disintegrate to liberate the therapeutic payload. The released Fin56 triggered the degradation of GPX4, while Fe3+ depleted the intracellular GSH pool, producing Fe2+ as a Fenton agent. The local rise in temperature, in conjunction with Fe2+-mediated Fenton reaction, led to a rapid and significant accumulation of ROS, culminating in LPOs and ferroptotic death. The outstanding therapeutic efficacy and safety of the nanovehicle were validated both in vitro and in vivo. Conclusion: The Fin56-loaded FSR nanovehicle could effectively disturb the redox balance in cancer cells. Coupled with NIR laser irradiation, the cooperative CDT and PTT achieved a boosted ferroptosis-inducing therapy. Taken together, this study offers a compelling strategy for cancer treatment, particularly for ferroptosis-sensitive tumors like osteosarcoma.

[End of life at home, guiding relatives on what to do in case of dyspnea]. / Fin de vie à domicile, guider les proches sur les conduites à tenir en cas de dyspnée.

Respiratory difficulties presented by a loved one at the end of life at home can leave those around him or her unable to cope and lead to emergency hospitalizations that are not clinically justified in this context. This is why the educational role of nurses is so important. They contribute, through anticipated explanations and indications, to allow adapted attitudes likely to reduce anguish, even panic, and to make it possible to continue to live at home.

[Implementation of a multimodal strategy for information and collection of advance directives in a comprehensive cancer center]. / Mise en place d'une stratégie multimodale d'information et de recueil des directives anticipées dans un Centre de lutte contre le cancer (CLCC).

INTRODUCTION: In France, advance directives (AD) remain unknown and underused by healthcare users and professionals. This is particularly true in oncology. This work was carried out with patients and caregivers of a Comprehensive Cancer Center to improve their appropriation and information. METHODS: The project, built by the Ethics Committee, the Patients Committee and the Palliative Care Team, made it possible to develop over 6 months a training program, an information procedure and several original documents. RESULTS: A total of 34 one-hour training courses for all professionals were organized. A procedure for making information available, including the right to draft ADs, has been implemented. This procedure is personalized, gradual and multi-professional. When a patient wishes to write his AD, he is accompanied by a dedicated team and benefits from a specific form, which enlighten values and preferences before addressing the desired level of therapeutic commitment. Communication elements were diffused, and a specific training on "anticipated discussions" was created. A dedicated space in the computerized chart makes it possible to locate the existence of ADs and to display them instantaneously. DISCUSSION - CONCLUSION: Based on the observation of the obstacles to the use of ADs, the strategy we implemented aims to provide information that is both efficient and ethically respectful for both patients and caregivers. ADs are only one element facilitating autonomy and anticipation, and must be associated with a shared continuous definition of the project and of the goals of care.

[Delirium Management in Palliative Care]. / Delirmanagement in der Palliative Care.

Delirium Management in Palliative Care Abstract. Delirium is one of the most common neuropsychiatric complications in patients with advanced incurable disease. End-of-life delirium is common but is often overlooked, undiagnosed or incorrectly diagnosed/untreated. Delirium should also be treated in a palliative situation - as far as possible - because persistent delirious states increase the patient's fragility, limit physical functionality and shorten the lifespan. In addition, acute states of confusion trigger high levels of distress in affected patients and their relatives, impair the quality of life and a dignified dying process. While hallucinations and visions at the end of life are interpreted as delirium in medicine and treated as such, this phenomenon is interpreted by philosophical and theological hermeneutics as a resource that can help patients and their relatives to reconcile with past life events and to deal with the process of dying. However, the occurrence of end-of-life visions as opposed to delirium has not yet been studied very much and requires more detailed exploration.

A nontoxic fungal natural product modulates fin regeneration in zebrafish larvae upstream of FGF-WNT developmental signaling.

BACKGROUND: The regeneration of larvae zebrafish fin emerged as a new model of regeneration in the last decade. In contrast to genetic tools to study fin regeneration, chemical probes to modulate and interrogate regeneration processes are not well developed. RESULTS: We set up a zebrafish larvae fin regeneration assay system and tested activities of natural product compounds and extracts, prepared from various microbes. Colomitide C, a recently isolated product from a fungus obtained from Antarctica, inhibited larvae fin regeneration. Using fluorescent reporter transgenic lines, we show that colomitide C inhibited fibroblast growth factor (FGF) signaling and WNT/ß-catenin signaling, which were activated after larvae fin amputation. By using the endothelial cell reporter line and immunofluorescence, we showed that colomitide C did not affect migration of the blood vessel and nerve into the injured larvae fin. Colomitide C did not show any cytotoxic activities when tested against FGF receptor-amplified human cancer cell lines. CONCLUSION: Colomitide C, a natural product, modulated larvae fin regeneration likely acting upstream of FGF and WNT signaling. Colomitide C may serve as a template for developing new chemical probes to study regeneration and other biological processes.

Sentidos de vida e morte: reflexões de pacientes em cuidados paliativos / Sentidos de vida y muerte: reflexiones de pacientes en cuidados paliativos / Sens de la vie et de la mort: réflexions de patients en soins palliatifs / Meanings of life and death: reflections of patients in palliative care

Resumo Cuidados paliativos visam amenizar o sofrimento de pacientes com doenças crônicas e ameaçadoras da vida nas dimensões: física, social, psicológica e espiritual. Na dimensão espiritual, procura-se imbuir de sentido aspectos transcendentais, como vida e morte. Conhecer esses sentidos é o objetivo deste estudo, que se trata de pesquisa qualitativa de caráter exploratório e faz uso de entrevistas semiestruturadas para a coleta de dados e análise do discurso. Foram entrevistados quatro pacientes e identificadas três categorias de significado: recursos de enfrentamento relativos à finitude; sofrimentos relativos à finitude; sentidos atribuídos à vida e à morte. Percebeu-se como maior sofrimento não a finitude em si, mas o que decorre dela, como perda funcional, preocupação com a família e ameaça de valores. A dificuldade em se falar sobre a morte não necessariamente se encontra em si mesma, mas em identificar o sentido que ela tem para a pessoa e os sofrimentos subjacentes.

Resumen Los cuidados paliativos se proponen mitigar el sufrimiento de pacientes con enfermedades crónicas y amenazadoras de vida en cuatro dimensiones: física, social, psicológica y espiritual. En la dimensión espiritural se pretende llenar de sentido con aspectos trascendentales, como vida y muerte. Este estudio tiene como objetivo conocer estos sentidos. Para ello, se utilizó el método cualitativo de carácter exploratorio y aplicó entrevistas semiestructuradas para recopilar los datos y el análisis del discurso. Se entrevistaron a cuatro pacientes, y se identificó tres categorías de significado: recursos de afrontamiento relacionados con la finitud, sufrimientos relacionados con la finitud y sentidos atribuidos a la vida y la muerte. Se observó que el mayor sufrimiento no era la finitud en sí, sino lo que deriva de ella, como la pérdida funcional, la preocupación por la familia y la amenza de valores. La dificultad de hablar acerca de la muerte no reside necesariamente en sí misma, sino en identificar el sentido que tiene para la persona y los sufrimientos subyacentes.

Résumé Les soins palliatifs visent à soulanger les souffrances des patients atteints de maladies chroniques et potentiellement mortelles dans quatre domaines: physique, social, psychologique et spirituel. Ce dernier renvoie au sens que l'on peut donner à des aspects transcendants tels que la vie et la mort. Explorer ces différentes facettes est l'objective de cette étude. Il s'agit d'une recherche qualitative de nature exploratoire, menée à partir d'entretiens semi-directifs pour la collecte de données et l'analyse du discours. Quatre patients ont été interrogés et trois catégories de signification ont été identifiées: les ressources d'adaptation liées à la finitude, la souffrance associées à la finitude, et les sens attribué à la vie et à la mort. Il en ressort que la plus grande souffrance n'est pas l'idée de finitude en soi, mais ce qui en découle, comme la perte d'autonomie fonctionnelle, l'anxiété à l'égard de la famille et la remise en question des valeurs. La difficulté de parler de la mort ne réside cependant pas nécessairement dans le fait de parler de la mort elle-même, mais dans l'identification du sens qu'elle revêt pour la personne concernée et dans l'identification des souffrances sous-jacentes.

Abstract Palliative care seeks to alleviate the suffering of patients with chronic and life-threatening diseases in the physical, social, psychological and spiritual dimensions. In the spiritual dimension, it seeks to imbue transcendental aspects, such as life and death, with meaning. Knowing these senses is the objective of this study, which is a qualitative research of exploratory character, and uses semi-structured interviews for data collection and discourse analysis. Four patients were interviewed and three categories of meaning were identified: finitude coping resources; sufferings related to finitude; meanings attributed to life and death. We noticed the greater suffering was not the finitude itself, but what arises from it, such as functional loss, concern for the family and threat of values. The difficulty in talking about death is not necessarily in itself, but in identifying the meaning it has for the person and the underlying sufferings.

[Virtual reality and palliative care, a complement in the care provision]. / Réalité virtuelle et soins palliatifs, un complément dans la prise en charge.

Commonplace in the world of gaming or the cinema, virtual reality headsets have made their appearance in the hospital over recent years. A nursing team in Lyon shares its feedback regarding the benefit of these tools as a complement to the care provided to patients in a palliative care unit.

Characterization of carbonate fraction of the Atlantic bluefin tuna fin spine bone matrix for stable isotope analysis.

The mineral component of fish otoliths (ear bones), which is aragonitic calcium carbonate (CaCO3), makes this structure the preferred sample choice for measuring biological carbon and oxygen-stable isotopes in order to address fundamental questions in fish ecology and fisheries science. The main drawback is that the removal of otoliths requires sacrificing the specimen, which is particularly impractical for endangered and commercially valuable species such as Atlantic bluefin tuna (Thunnus thynnus) (ABFT). This study explores the suitability of using the first dorsal fin spine bone of ABFT as a non-lethal alternative to otolith analysis or as a complementary hard structure. The fin spines of freshly caught ABFT were collected to identify carbonate ions within the mineral matrix (i.e., hydroxyapatite) and to determine the nature of the carbonate substitution within the crystal lattice, knowledge which is crucial for correct measurement and ecological interpretation of oxygen and carbon stable isotopes of carbonates. Fin spine sections were analyzed via X-ray Photoelectron Spectroscopy (XPS), Raman Spectroscopy, and Fourier Transform InfraRed (FTIR). The XPS survey analysis showed signals of Ca, O, and P (three compositional elements that comprise hydroxyapatite). The Raman and FTIR techniques showed evidence of carbonate ions within the hydroxyapatite matrix, with the IR spectra being the most powerful for identifying the type B carbonate substitution as shown by the carbonate band in the v 2 CO3 2- domain at ∼872 cm-1. The results of this study confirmed the presence of carbonate ions within the mineral matrix of the fin spine bone of ABFT, showing the feasibility of using this calcified structure for analysis of stable isotopes. Overall, our findings will facilitate new approaches to safeguarding commercially valuable and endangered/protected fish species and will open new research avenues to improve fisheries management and species conservation strategies.

[Music therapy in paediatric oncology]. / Interventions musicales en oncopédiatrie.

At Gustave Roussy Institute in Villejuif, musicians regularly work with hospitalised children. Music offers young patients and their family a moment of wellbeing. The caregivers also appreciate this tool which can help to facilitate difficult care procedures.

Osteotoxicity of 3-methylcholanthrene in fish.

Many chemicals produced by human activities end up in the aquatic ecosystem causing adverse developmental and reproductive effects in aquatic organisms. There is evidence that some anthropogenic chemicals disturb bone formation and skeletal development but the lack of suitable in vitro and in vivo systems for testing has hindered the identification of underlying mechanisms of osteotoxicity. Several fish systems - an in vitro cell system to study extracellular matrix mineralization and in vivo systems to evaluate bone formation and skeletogenesis - were combined to collect data on the osteotoxic activity of 3-methylcholanthrene (3-MC), a polycyclic aromatic hydrocarbon. Anti-mineralogenic effects, increased incidence of skeletal deformities and reduced bone formation and regeneration were observed in zebrafish upon exposure to 3-MC. Pathway reporter array revealed the role of the aryl hydrocarbon receptor 2 (Ahr2) in the mechanisms underlying 3-MC osteotoxicity in mineralogenic cell lines. Analysis of gene expression in zebrafish larvae confirmed the role of Ahr2 in the signaling of 3-MC toxicity. It also indicated a possible complementary action of the pregnane X receptor (Pxr) in the regulation of genes involved in bone cell activity and differentiation but also in xenobiotic metabolism. Data reported here demonstrated the osteotoxicity of 3-MC but also confirmed the suitability of fish systems to gain insights into the toxic mechanisms of compounds affecting skeletal and bone formation.

Deaths in France: Characteristics, place of death, hospitalisations and use of palliative care during the year before death.

AIM: Only limited data are available concerning the diseases managed and the hospital pathway before death. The aim of this study was to describe diseases, hospitalisations, and use of palliative care one year before death as well as place of death in France. METHODS: French health insurance general scheme beneficiaries who died in 2013 were identified in the National Health Insurance Information System (SNIIRAM) with a selection of information concerning their various hospital stays, including hospital palliative care (HPC) and nursing home care. Diseases were identified by algorithms from reimbursement data recorded in the SNIIRAM database. RESULTS: A total of 347 253 people were included (61% of all deaths in France). The mean age of death was 77 years (SD 15.1). Diseases managed before death were cardiovascular/neurovascular diseases (56%), cancers (42%), neurological and degenerative diseases (25%), diabetes (21%) and chronic respiratory diseases (20%). Deaths occurred in hospital in 60% of cases: 51% in acute wards, 6% in rehabilitation units, 3% in hospital at home (HaH), and 13% in nursing homes. During the year preceding death, 84% of people were hospitalised at least once and 29% received HPC. People receiving HPC more often died in hospital than people not receiving HPC (69% vs. 44%). CONCLUSION: Health administrative data from the SNIIRAM database can refine our knowledge of the care pathway prior to death and of the use of hospital palliative care and can be useful to evaluate the new governmental palliative care plan recently deployed in France.

Batoid locomotion: effects of speed on pectoral fin deformation in the little skate, Leucoraja erinacea.

Most batoids have a unique swimming mode in which thrust is generated by either oscillating or undulating expanded pectoral fins that form a disc. Only one previous study of the freshwater stingray has quantified three-dimensional motions of the wing, and no comparable data are available for marine batoid species that may differ considerably in their mode of locomotion. Here, we investigate three-dimensional kinematics of the pectoral wing of the little skate, Leucoraja erinacea, swimming steadily at two speeds [1 and 2 body lengths (BL) s-1]. We measured the motion of nine points in three dimensions during wing oscillation and determined that there are significant differences in movement amplitude among wing locations, as well as significant differences as speed increases in body angle, wing beat frequency and speed of the traveling wave on the wing. In addition, we analyzed differences in wing curvature with swimming speed. At 1 BL s-1, the pectoral wing is convex in shape during the downstroke along the medio-lateral fin midline, but at 2 BL s-1 the pectoral fin at this location cups into the flow, indicating active curvature control and fin stiffening. Wing kinematics of the little skate differed considerably from previous work on the freshwater stingray, which does not show active cupping of the whole fin on the downstroke.

Hipnosis y magnetismo en la Revista Magnetológica (1897-1903) / Hypnotism and magnetism in revista magnetológica (1897-1903)

El objetivo de este artículo es analizar una fuente poco estudiada hasta el presente, la Revista Magnetológica publicada por una sociedad conformada principalmente por adherentes al espiritismo y la teosofía en Buenos Aires. El contenido de la revista ofrece evidencias muy valiosas sobre la manera en que actores sociales ajenos al campo médico tradicional abordaron teórica y prácticamente la hipnosis y el magnetismo en el cambio de siglo. En efecto, los magnetólogos de Buenos Aires no sólo elaboraron complejas conceptualizaciones sobre esos fenómenos, sino que también pusieron en práctica curaciones magnéticas cuyos detalles fueron difundidos des-de las páginas de la revista. Nuestro cometido es analizar algunos aspectos puntuales de esa publicación: de un lado, el modo en que los magnetólogos se posicionaron en relación a los médicos de la ciudad, y de otro, sus estrategias de autolegitimación.

The aim of this article is to analyze a source that has not been deeply studied yet: the Magnetologic Magazine (Revista Magnetológica)published by a society mainly composed of adherents of spiritualism and theosophy in Buenos Aires. The content of the magazine offers valuable evidence about the way in which social actors -who were foreign to the medical traditional field- theoretically and practically approached hypnosis and magnetism at the end of the century. In fact, magnetists from Buenos Aires not only developed complex conceptualizations of these phenomena, but also implemented magnetic cures which details were spread throughout the pages of the magazine. Our task is to analyze some specific aspects of this publication: on the one hand, how the magnetists were placed in relation to the doctors of the city, and on the other, their strategies of self-legitimation.

[The "wine bar", or a different way of caring]. / Le "bar à vin" ou une autre façon de prendre soin.

The "wine bar" in the palliative care unit of Clermont-Ferrand general hospital is an example of a different way of providing care. It defends the right of patients at the end of life to treat themselves and others. Acknowledging that life is present right up until the end, patients are invited to drink wine at mealtimes and caregivers are encouraged to learn the basics of oenology.

Relato sobre el proceso psicoanalítico de un niño diagnosticado tempranamente: “¿y si Lucas tiene autismo? / A story about the psychoanalytic process of early diagnosis of a child: “what if lucas has autism?”

El artículo intenta transmitir una modalidad de trabajo clínico construida a partir de un modo de pensamiento psicoanalítico, a través del relato de un niño que fue diagnosticado a los dos años y seis meses con un retraso en su desarrollo. El recorrido da cuenta de un proceso analítico de cuatro años que llegó a su término incluyendo a los padres en dicho trabajo, pudiendo favorecer el crecimiento del niño, el despliegue del lenguaje verbal y la restitución de un vínculo tempranamente afectado.

The article attempts to transmit a form of clinical work built from a psychoanalyticway of thinking, through the story of a child who was diagnosed with adevelopmental delay at two and a half years of age. The journey conductsa four year analytical process that came to an end including parents in suchwork, being able to promote the growth of the child, the deployment of hisverbal language and the restoration of an earlier affected link.

L’article a l’objectif de transmettre une modalité de travail clinique construiteà partir d’un mode de pensée psychanalytique à travers le récit d’un enfantque fut diagnostiqué d’un retard dans son développement à l’âge de deuxans et six mois. Le parcours rend compte d’un procès analytique de quatreans qui est arrivé à son terme avec la inclusion de ses parents dans ce travail,permettant d’aider la croissance de l’enfant, le déploiement de la langueverbal et la restitution d’un lien affecté depuis très tôt.

Novel polymorphisms in UTR and coding region of inducible heat shock protein 70.1 gene in tropically adapted Indian zebu cattle (Bos indicus) and riverine buffalo (Bubalus bubalis).

Due to evolutionary divergence, cattle (taurine, and indicine) and buffalo are speculated to have different responses to heat stress condition. Variation in candidate genes associated with a heat-shock response may provide an insight into the dissimilarity and suggest targets for intervention. The present work was undertaken to characterize one of the inducible heat shock protein genes promoter and coding regions in diverse breeds of Indian zebu cattle and buffaloes. The genomic DNA from a panel of 117 unrelated animals representing 14 diversified native cattle breeds and 6 buffalo breeds were utilized to determine the complete sequence and gene diversity of HSP70.1 gene. The coding region of HSP70.1 gene in Indian zebu cattle, Bos taurus and buffalo was similar in length (1,926 bp) encoding a HSP70 protein of 641 amino acids with a calculated molecular weight (Mw) of 70.26 kDa. However buffalo had a longer 5' and 3' untranslated region (UTR) of 204 and 293 nucleotides respectively, in comparison to Indian zebu cattle and Bos taurus wherein length of 5' and 3'-UTR was 172 and 286 nucleotides, respectively. The increased length of buffalo HSP70.1 gene compared to indicine and taurine gene was due to two insertions each in 5' and 3'-UTR. Comparative sequence analysis of cattle (taurine and indicine) and buffalo HSP70.1 gene revealed a total of 54 gene variations (50 SNPs and 4 INDELs) among the three species in the HSP70.1 gene. The minor allele frequencies of these nucleotide variations varied from 0.03 to 0.5 with an average of 0.26. Among the 14 B. indicus cattle breeds studied, a total of 19 polymorphic sites were identified: 4 in the 5'-UTR and 15 in the coding region (of these 2 were non-synonymous). Analysis among buffalo breeds revealed 15 SNPs throughout the gene: 6 at the 5' flanking region and 9 in the coding region. In bubaline 5'-UTR, 2 additional putative transcription factor binding sites (Elk-1 and C-Re1) were identified, other than three common sites (CP2, HSE and Pax-4) observed across all the analyzed animals. No polymorphism was found within the 3'-UTR of Indian cattle or buffalo as it was found to be monomorphic. The promoter sequences generated in 117 individuals showed a rich array of sequence elements known to be involved in transcription regulation. A total of 11 nucleotide changes were observed in the promoter sequence across the analyzed species, 3 of these changes were located within the potential transcription factor binding domains. We also identified 4 microsatellite markers within the buffalo HSP70.1 gene and 3 microsatellites within bovine HSP70.1. The present study identified several distinct changes across indicine, taurine and bubaline HSP70.1 genes that could further be evaluated as molecular markers for thermotolerance.