Bone and Cytokine Markers Associated With Bone Disease in Systemic Mastocytosis

Background Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown. Objective To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis. Methods A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n = 46), (2) significant bone loss (n = 47), and (3) diffuse bone sclerosis (n = 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis. Results Bone loss was associated with significantly higher levels of serum baseline tryptase (P = .01), IFN-γ (P = .05), IL-1β (P = .05), and IL-6 (P = .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P < .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P = .01), together with lower IFN-γ (P = .03) and RANK-ligand (P = .04) plasma levels versus healthy bone cases. Conclusions SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.This study was supported by grants from the Instituto de Salud Carlos III (ISCIII, Spain) (PI19/01166, CIBERONC: CB16/12/00400) and Fondo Europeo de Desarrollo Regional (FEDER) (EQC2019-005419-P), within the Subprograma Estatal de Infraestructuras de Investigación y Equipamiento Científico Técnico de 2019 del Ministerio de Ciencia, Innovación y Universidades, Fundación Española de Mastocitosis (FEM, Madrid, Spain ref.: FEM2019-MAGPIX and FEM2021-SAM); Asociación Española de Mastocitosis y Enfermedades Relacionadas (AEDM-CTMC-2019). We also thank the Biobank at the Hospital Virgen de la Salud (BioB-HVS) No. B.0000520, Toledo, Spain. TAR was supported by the 2019 European Academy of Allergy and Clinical Immunology Research Fellowship award. We thank our patients for their willingness to participate in this study

Mastocytosis presenting with mast cell-mediator release-associated symptoms elicited by cyclo oxygenase inhibitors: prevalence, clinical, and laboratory features

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently avoided in mastocytosis, because of a potential increased risk for drug hypersensitivity reactions (DHRs) due to inhibition of cyclo-oxygenase (COX), subsequent depletion of prostaglandin E2 and release of leukotrienes. Objectives: Here, we aimed at determining the prevalence of mast cell (MC) mediator release symptoms triggered by NSAIDs in mastocytosis patients and the associated clinical and laboratory features of the disease. Methods: Medical records from 418 adults to 223 pediatric mastocytosis patients were retrospectively reviewed. Patients were classified according to tolerance patterns to NSAIDs and other COX inhibitors (COXi) and compared for epidemiological, clinical and laboratory findings. Results: Overall, 87% of adults and 91% of pediatric patients tolerated NSAIDs and other COXi. Among adult and pediatric patients presenting DHRs, 5% and 0% reacted to multiple NSAIDs, 4% and 0.7% were single reactors, and 3% and 8% were single reactors with known tolerance to paracetamol but unknown tolerance to other COXi, respectively. Among adults, hypersensitivity to ≥2 drugs was more frequent among females (p = 0.009), patients with prior history of anaphylaxis to triggers other than NSAIDs or other COXi and Hymenoptera venom (p = 0.009), presence of baseline flushing (p = 0.02), baseline serum tryptase ≥48 ng/ml (p = 0.005) and multilineage KIT mutation (p = 0.02). In contrast, tolerance to NSAIDs and other COXi was more frequent among males (p = 0.02), in patients with anaphylaxis caused by Hymenoptera venom (p = 0.02), among individuals who had skin lesions due to mastocytosis (p = 0.01), and in cases that had no baseline pruritus (p = 0.006). Based on these parameters, a score model was designed to stratify mastocytosis patients who have never received NSAIDs or other COXi apart from paracetamol, according to their risk of DHR. Conclusions: Our results suggest that despite the frequency of MC mediator related symptoms elicited by NSAIDs and other COXi apart from paracetamol is increased among mastocytosis patients versus the general population, it is lower than previously estimated and associated with unique disease features. Patients that tolerated NSAIDs and other COXi following disease onset should keep using them. In turn, adults with unknown tolerance to such drugs and a positive score should be challenged with a preferential/selective COX-2 inhibitor, while the remaining may be challenged with ibuprofen. © 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.Funding text 1: This work was supported by grants from the Carlos III Health Institute co‐financed by the European Regional Development Fund (PI19/01166) and CIBERONC CB16/12/00400, Ministerio de Ciencia e Innovación (Madrid, Spain), Asociación Española de Mastocitosis y Enfermedades Relacionadas (AEDM 2019), Fondos de Investigación para Enfermedades Raras del Ministerio de Sanidad, Servicios Sociales e Igualdad (Madrid, Spain). ; Funding text 2: This work was supported by grants from the Carlos III Health Institute co-financed by the European Regional Development Fund (PI19/01166) and CIBERONC CB16/12/00400, Ministerio de Ciencia e Innovación (Madrid, Spain), Asociación Española de Mastocitosis y Enfermedades Relacionadas (AEDM 2019), Fondos de Investigación para Enfermedades Raras del Ministerio de Sanidad, Servicios Sociales e Igualdad (Madrid, Spain)

Sr_14Cu_24O_41Sr\_{14}Cu\_{24}O\_{41} : a complete model for the chain sub-system

A second neighbor $t-J+V$ model for the chain subsystem of the $Sr\_{14}Cu\_{24}O\_{41}$ has been extracted from ab-initio calculations. This model does not use periodic approximation but describes the entire chain through the use of the four-dimensional crystallographic description. Second neighbors interactions are found to be of same order than the first neighbors ones. The computed values of the second neighbors magnetic interaction are coherent with experimental estimations of the intra-dimer magnetic interactions, even if slightly smaller. The reasons of this underestimation are detailed. The computed model allowed us to understand the origin of the chain dimerisation and predicts correctly the relative occurrence of dimers and free spins. The orbitals respectively supporting the magnetic electrons and the holes have been found to be essentially supported by the copper 3d orbitals (spins) and the surrounding oxygen $2p$ orbitals (holes), thus giving a strong footing to the existence of Zhang-Rice singlets

The role of dynamical polarization of the ligand to metal charge transfer excitations in {\em ab initio} determination of effective exchange parameters

The role of the bridging ligand on the effective Heisenberg coupling parameters is analyzed in detail. This analysis strongly suggests that the ligand-to-metal charge transfer excitations are responsible for a large part of the final value of the magnetic coupling constant. This permits to suggest a new variant of the Difference Dedicated Configuration Interaction (DDCI) method, presently one of the most accurate and reliable for the evaluation of magnetic effective interactions. This new method treats the bridging ligand orbitals mediating the interaction at the same level than the magnetic orbitals and preserves the high quality of the DDCI results while being much less computationally demanding. The numerical accuracy of the new approach is illustrated on various systems with one or two magnetic electrons per magnetic center. The fact that accurate results can be obtained using a rather reduced configuration interaction space opens the possibility to study more complex systems with many magnetic centers and/or many electrons per center.Comment: 7 pages, 4 figure

Absorbing-state phase transitions in fixed-energy sandpiles

We study sandpile models as closed systems, with conserved energy density $\zeta$ playing the role of an external parameter. The critical energy density, $\zeta_c$, marks a nonequilibrium phase transition between active and absorbing states. Several fixed-energy sandpiles are studied in extensive simulations of stationary and transient properties, as well as the dynamics of roughening in an interface-height representation. Our primary goal is to identify the universality classes of such models, in hopes of assessing the validity of two recently proposed approaches to sandpiles: a phenomenological continuum Langevin description with absorbing states, and a mapping to driven interface dynamics in random media. Our results strongly suggest that there are at least three distinct universality classes for sandpiles.Comment: 41 pages, 23 figure

New Circumspection of the Genus \u3ci\u3eGamochaeta\u3c/i\u3e (Asteraceae, Gnaphalieae) Inferred From Nuclear and Plastid DNA Sequences

Gamochaeta (tribe Gnaphalieae, Asteraceae) is composed of ca. 60 species primarily distributed in tropical and subtropical America. Within the tribe Gnaphalieae, the genus is characterized by capitula arranged in spikes or head-like clusters, few hermaphroditic central florets, truncate style branches with apical sweeping trichomes, pappus bristles connate at the base into a ring falling as a unit, and achenes with globose twin trichomes. Previous molecular phylogenetic studies have suggested the paraphyly of the genus, but have not provided a basis for redefining generic limits due to incomplete taxon sampling. To address this problem, DNA sequences from the plastid (trnL-F) and nuclear (ETS and ITS) genomes were analyzed from a broad taxon sample representing the full range of morphological variation known in the genus. Our results affirm that Gamochaeta is paraphyletic as presently circumscribed. Two clades can be recognized: one clade that includes the majority of the species currently assigned to Gamochaeta and a second clade that includes Gamochaetopsis, Stuckertiella and seven species of Gamochaeta. We present here a new circumscription of Gamochaeta, including two new combinations, Gamochaeta alpina and Gamochaeta peregrina, and the resurrection of Gamochaeta capitata. Our results also show Omalotheca supina, O. norvegica and O. sylvatica, which were placed by some authors in Gamochaeta or in Gnaphalium, form a monophyletic group distantly related to both genera

Raman and infrared spectroscopy of Sr2B′UO6 (B′ = Ni; Co) double perovskites

Temperature dependent normal modes and lattice thermal expansion of Sr 2B′UO6 (B′ = Ni, Co) double perovskites were investigated by Raman/infrared spectroscopies and synchrotron X-ray diffraction, respectively. Monoclinic crystal structures with space group P21/n were confirmed for both compounds, with no clear structural phase transition between 10 and 400 K. As predicted for this structure, the first-order Raman and infrared spectra show a plethora of active modes. In addition, the Raman spectra reveal an enhancement of the integrated area of an oxygen stretching mode, which is also observed in higher-order Raman modes, and an anomalous softening of ∼1 cm-1 upon cooling below T* ∼ 300 K. In contrast, the infrared spectra show conventional temperature dependence. The band profile phonon anomalies are possibly related to an unspecified electronic property of Sr2B′UO6 (B′ = Ni, Co).Centro de Química Inorgánic

Raman and infrared spectroscopy of Sr2B′UO6 (B′ = Ni; Co) double perovskites

Temperature dependent normal modes and lattice thermal expansion of Sr 2B′UO6 (B′ = Ni, Co) double perovskites were investigated by Raman/infrared spectroscopies and synchrotron X-ray diffraction, respectively. Monoclinic crystal structures with space group P21/n were confirmed for both compounds, with no clear structural phase transition between 10 and 400 K. As predicted for this structure, the first-order Raman and infrared spectra show a plethora of active modes. In addition, the Raman spectra reveal an enhancement of the integrated area of an oxygen stretching mode, which is also observed in higher-order Raman modes, and an anomalous softening of ∼1 cm-1 upon cooling below T* ∼ 300 K. In contrast, the infrared spectra show conventional temperature dependence. The band profile phonon anomalies are possibly related to an unspecified electronic property of Sr2B′UO6 (B′ = Ni, Co).Centro de Química Inorgánic

The First Millennium-Age Araucaria Araucana in Patagonia

This item is part of the Tree-Ring Research (formerly Tree-Ring Bulletin) archive. For more information about this peer-reviewed scholarly journal, please email the Editor of Tree-Ring Research at [email protected]