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Sanctionner le pape sans rompre avec le Siège apostolique ? Retour sur la condamnation de Vigile prononcée par le concile oecuménique de Constantinople II (553)
Full text linkDuring Late Antiquity, a pope does not usually go personally to a council convoked by the emperor. But, being present in Constantinople from 547, Vigilius can’t argue about the need to stay in his city. He has to find other reasons. For he already knows that synodal decisions will end with an Three Chapters condamnationunbearable to West. He does not want either to represent the renouncement to pontifical program conceived by Leo. So he chooses not to take part to the synod and to publish an alternative decision (first constitutum). As a consequence, under imperial instructions, the council decides to put the maximum pressure on him and to suspend him while, so is it said, maintaining communion with Rome. Remarkable judgement, which reveals the strength of the confrontation, also interestingly attested by two successive forms of conciliar acts preserved in latin
CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum
Full text linkPURPOSE: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD).
METHODS: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function.
RESULTS: The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits.
CONCLUSION: We significantly broaden the mutational and clinical spectrum of CTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila
Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives
Full text linkRhenium-188 (Re) is a high energy beta-emitting radioisotope with a short 16.9 h physical half-life, which has been shown to be a very attractive candidate for use in therapeutic nuclear medicine. The high beta emission has an average energy of 784 keV and a maximum energy of 2.12 MeV, sufficient to penetrate and destroy targeted abnormal tissues. In addition, the low-abundant gamma emission of 155 keV (15%) is efficient for imaging and for dosimetric calculations. These key characteristics identify Re as an important therapeutic radioisotope for routine clinical use. Moreover, the highly reproducible on-demand availability of Re from the W/Re generator system is an important feature and permits installation in hospital-based or central radiopharmacies for cost-effective availability of no-carrier-added (NCA) Re. Rhenium-188 and technetium-99 m exhibit similar chemical properties and represent a "theranostic pair." Thus, preparation and targeting of Re agents for therapy is similar to imaging agents prepared with Tc, the most commonly used diagnostic radionuclide. Over the last three decades, radiopharmaceuticals based on Re-labeled small molecules, including peptides, antibodies, Lipiodol and particulates have been reported. The successful application of these Re-labeled therapeutic radiopharmaceuticals has been reported in multiple early phase clinical trials for the management of various primary tumors, bone metastasis, rheumatoid arthritis, and endocoronary interventions. This article reviews the use of Re-radiopharmaceuticals which have been investigated in patients for cancer treatment, demonstrating that Re represents a cost effective alternative for routine clinical use in comparison to more expensive and/or less readily available therapeutic radioisotopes
Assessment of the risk and characterization of non-melanoma skin cancer in Kindler syndrome: study of a series of 91 patients
Full text linkBACKGROUND: Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of squamous cell carcinoma (SCC) in these patients. SCC developed in 13 of the 91 patients.
RESULTS: The youngest case arose in a 29-year-old patient; however, the cumulative risk of SCC increased to 66.7% in patients over 60 years of age. The highly aggressive nature of SCCs in KS was confirmed showing that 53.8% of the patients bearing SCCs develop metastatic disease. Our data also showed there are no specific mutations that correlate directly with the development of SCC; however, the mutational distribution along the gene appears to be different in patients bearing SCC from SCC-free patients. The body distribution of the tumor appearance was also unique and different from other bullous diseases, being concentrated in the hands and around the oral cavity, which are areas of high inflammation in this disease.
CONCLUSIONS: This study characterizes SCCs in the largest series of KS patients reported so far, showing the high frequency and aggressiveness of these tumors. It also describes their particular body distribution and their relationship with mutations in the FERMT-1 gene. These data reinforce the need for close monitoring of premalignant or malignant lesions in KS patients
CD45RC Expression of Circulating CD8 T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients
Full text linkPredictive biomarkers of acute rejection (AR) are lacking. Pre-transplant expression of CD45RC on blood CD8 T cells has been shown to predict AR in kidney transplant (KT) patients. The objective of the present study was to study CD45RC expression in a large cohort of KT recipients exposed to modern immunosuppressive regimens. CD45RC expression on T cells was analyzed in 128 KT patients, where 31 patients developed AR, of which 24 were found to be T-cell mediated (TCMR). Pre-transplant CD4 and CD8 CR45RC T cell proportions were significantly higher in patients with AR. The frequency of CD45RC T cells was significantly associated with age at transplantation but was not significantly different according to gender, history of transplantation, pre-transplant immunization, and de novo donor specific anti-Human Leucocyte Antigen (HLA) antibody. Survival-free AR was significantly better in patients with CD8 CD45RC T cells below 58.4% (p = 0.0005), but not different according to CD4 T cells (p = 0.073). According to multivariate analysis, CD8 CD45RC T cells above 58.4% increased the risk of AR 4-fold (HR 3.96, p = 0.003). Thus, pre-transplant CD45RC expression on CD8 T cells predicted AR, mainly TCMR, in KT patients under modern immunosuppressive therapies. We suggest that CD45RC expression should be evaluated in a prospective study to validate its usefulness to quantify the pre-transplant risk of AR
Compte rendu du livre de Fabrice Galtier, L'empreinte des morts, : relations entre mort, mémoire et reconnaissance dans la 'Pharsale' de Lucain. Collection d'études anciennes. Série latine, 82. Paris : Les Belles Lettres, 2018.
No full textMetabolomic Profiling of Aqueous Humor in Glaucoma Points to Taurine and Spermine Deficiency: Findings from the Eye-D Study
Full text linkWe compared the metabolomic profile of aqueous humor from patients with primary open-angle glaucoma (POAG; n = 26) with that of a group of age- and sex-matched non-POAG controls (n = 26), all participants undergoing cataract surgery. Supervised paired partial least-squares discriminant analysis showed good predictive performance for test sets with a median area under the receiver operating characteristic of 0.89 and a p-value of 0.0087. Twenty-three metabolites allowed discrimination between the two groups. Univariate analysis after the Benjamini-Hochberg correction showed significant differences for 13 of these metabolites. The POAG metabolomic signature indicated reduced concentrations of taurine and spermine and increased concentrations of creatinine, carnitine, three short-chain acylcarnitines, 7 amino acids (glutamine, glycine, alanine, leucine, isoleucine, hydroxyl-proline, and acetyl-ornithine), 7 phosphatidylcholines, one lysophosphatidylcholine, and one sphingomyelin. This suggests an alteration of metabolites involved in osmoprotection (taurine and creatinine), neuroprotection (spermine, taurine, and carnitine), amino acid metabolism (7 amino acids and three acylcarnitines), and the remodeling of cell membranes drained by the aqueous humor (hydroxyproline and phospholipids). Five of these metabolic alterations, already reported in POAG plasma, concern spermine, C3 and C4 acylcarnitines, PC aa 34:2, and PC aa 36:4, thus highlighting their importance in the pathogenesis of glaucoma
How does access to luxury fashion challenge self-identity? Exploring women's practices of joint and non-ownership
Full text linkThis paper examines how the practices of access, borrowing, and sharing (including shared purchase) influence women\u27s self-identity in the world of luxury clothing and accessories. In the context of joint- or non-ownership, using 28 semi-structured interviews across three age groups, this qualitative research explores and contrasts the various practices of access, borrowing, and sharing (including shared purchase) with regard to the self–object relationship. The results underline the identification and appropriation process at stake in access to luxury fashion, which runs counter to prior research on access-based consumption. The research shows the liquid transformation of self-identity inherent in access, borrowing, and sharing practices (but not present in shared purchase), as well as the positive contamination of the owner\u27s image in the case of borrowing, sharing, and making shared purchases – but not in the case of access
Involvement of Medicago truncatula glutamate receptor-like channels in nitric oxide production under short-term water deficit stress
Full text linkEarly stages of plant development are highly susceptible to environmental cues, and seedlings have to develop sophisticated mechanisms to sense and respond to abiotic stresses. We have previously identified that abscisic acid (ABA), nitric oxide (NO) and modulation of nitrogen metabolism are involved in adaptive responses in Medicago truncatula seedlings under water deficit stress. Here, we investigated whether glutamate receptor-like channels (GLRs) played a role in the developmental physiological processes of Medicago seedlings during post-germination after a short-term water deficit stress. Twenty-nine independent MtGLR genes have been identified and then divided into four clades following a phylogenetic analysis; seventeen of them exhibited specific domains which are characteristic of animal ionotropic glutamate receptors. Under drought stress, ABA-induced NO accumulation was significantly reduced in presence of a GLR competitive antagonist, suggesting that this water deficit-induced endogenous NO production was mediated through a MtGLR-dependent pathway. Water deficit-induced inhibition of embryo axis elongation was strongly reduced whereas loss of water content was alleviated when MtGLRs were inhibited. These results suggest that glutamate receptors-like channels are required, through their involvement in NO production, in adaptive responses under short-term water-deficit stress during Medicago seedling establishment