A comparative analysis of chronic inducible urticaria in 423 patients: Clinical and laboratory features and comorbid conditions.

BACKGROUND: Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU) which require specific physical or non-physical triggers to occur. They may be isolated or may coexist with chronic spontaneous urticaria (CSU). Despite their frequent appearance in dermatology clinics, there is scarce information on the distinguishing features among the most common subtypes of CIndU as well as isolated CIndU versus CSU plus CIndU. OBJECTIVES: To compare clinical and laboratory characteristics, and comorbid conditions among the most common CIndU types and isolated CIndU versus CSU plus CIndU. METHODS: We retrospectively analysed CIndU patients and compared patients' demographic, clinical and laboratory characteristics across isolated CIndU, CSU plus CIndU, symptomatic dermographism (SD), cold urticaria (ColdU) and cholinergic urticaria (ChoU). RESULTS: A total of 423 patients (~70% isolated CIndU, ~30% CSU plus CIndU, ~5% mixed CIndU subtypes) were included in the study. The most frequent CIndU subtypes were SD (68.6%; 290/423), ColdU (11.4%; 48/423) and ChoU (10.9%; 46/423). Isolated CIndU patients were younger than CSU plus CIndU (33.74 ± 12.72 vs. 37.06 ± 11.84, p = 0.010). Angioedema, emergency referrals, need for systemic steroids, comorbid systemic disorders were more frequent and baseline urticaria control test scores were lower in CSU plus CIndU patients (vs. CIndU, p < 0.001, p = 0.008, p < 0.001, p = 0.031, p = 0.036, respectively). Among CIndU subtypes, ChoU patients were younger (24.9 ± 12.2 vs. 34.47 ± 12.12 vs. 31.38 ± 14.95; p < 0.001) and had male predominance (p < 0.001) while SD patients had no angioedema (p < 0.001) and had higher frequency of increased total IgE levels (p = 0.006). CONCLUSIONS: Isolated CIndU and CSU plus CIndU seems to be different endotypes of CU where CSU plus CIndU presents a more severe and refractory course. There are distinctive features of each CIndU subtype. These suggest involvement of different pathomechanistic pathways in these subtypes that need to be clarified in future studies.

Long-term changes of Th17 and regulatory T cells in peripheral blood of dogs with spinal cord injury after intervertebral disc herniation.

BACKGROUND: Intervertebral disc herniation (IVDH) is one of the most common causes of spinal cord injury (SCI) in dogs. As a result of acute SCI, a complex inflammatory response occurs in the spinal cord. Th17 cells (Th17) produce pro-inflammatory cytokines, while regulatory T cells (Treg) have opposite effects producing anti-inflammatory cytokines. Therefore, the aim of this study was to determine whether Th17- and Treg cells are involved in the pathogenesis of SCI or whether cellular changes occur due to coexisting inflammatory diseases. We hypothesized that chronic alterations in the Th17/Treg ratio are associated with a worse outcome after SCI. METHODS: Twenty-six paretic or plegic dogs with IVDH with and without coexisting inflammatory disease were investigated in the acute stage of the disease and after recovery of SCI. In addition, a healthy control group was included (n = 14). Quantification of Th17 and Treg cells, from peripheral blood samples, was performed by multicolor flow cytometry and IL17 was measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: After recovery significantly higher levels of Th17 (p = 0.0265) and Treg cells (p = 0.00025) were detected compared to acute IVDH but Th17/Treg ratio did not differ significantly. Recovered dogs and the control group did not differ significantly from each other. No association between an imbalance in the ratio and neurologic severity or underlying inflammatory diseases was found. CONCLUSION: This study demonstrated that altered Th17 and Treg levels in peripheral blood are altered in the acute stage of IVDH, preexisting inflammatory diseases seem not to influence these cell populations. Th17 and Treg cells could be considered when evaluating new treatment strategies for SCI.

Multimodal Structure Solution with 19F NMR Crystallography of Spin Singlet Molybdenum Oxyfluorides.

Complex crystal structures with subtle atomic-scale details are now routinely solved using complementary tools such as X-ray and/or neutron scattering combined with electron diffraction and imaging. Identifying unambiguous atomic models for oxyfluorides, needed for materials design and structure-property control, is often still a considerable challenge despite their advantageous optical responses and applications in energy storage systems. In this work, NMR crystallography and single-crystal X-ray diffraction are combined for the complete structure solution of three new compounds featuring a rare triangular early transition metal oxyfluoride cluster, [Mo3O4F9]5-. After framework identification by single-crystal X-ray diffraction, 1D and 2D solid-state 19F NMR spectroscopy supported by ab initio calculations are used to solve the structures of K5[Mo3O4F9]·3H2O (1), K5[Mo3O4F9]·2H2O (2), and K16[Mo3O4F9]2[TiF6]3·2H2O (3) and to assign the nine distinct fluorine sites in the oxyfluoride clusters. Furthermore, 19F NMR identifies selective fluorine dynamics in K16[Mo3O4F9]2[TiF6]3·2H2O. These dual scattering and spectroscopy methods are used to demonstrate the generality and sensitivity of 19F shielding to small changes in bond length, on the order of 0.01 Å or less, even in the presence of hydrogen bonding, metal-metal bonding, and electrostatic interactions. Starting from the structure models, the nature of chemical bonding in the molybdates is explained by molecular orbital theory and electronic structure calculations. The average Mo-Mo distance of 2.505 Å and diamagnetism in 1, 2, and 3 are attributed to a metal-metal bond order of unity along with a 1a21e4 electronic ground state configuration for the [Mo3O4F9]5- cluster, leading to a rare trimeric spin singlet involving d2 Mo4+ ions. The approach to structure solution and bonding analysis is a powerful strategy for understanding the structures and chemical properties of complex fluorides and oxyfluorides.

Lithium Diffusion in Niobium Tungsten Oxide Shear Structures.

Niobium tungsten oxides with crystallographic shear structures form a promising class of high-rate Li-ion anode materials. Lithium diffusion within these materials is studied in this work using density functional theory calculations, specifically nudged elastic band calculations and ab initio molecular dynamics simulations. Lithium diffusion is found to occur through jumps between 4-fold coordinated window sites with low activation barriers (80-300 meV) and is constrained to be effectively one-dimensional by the crystallographic shear planes of the structures. We identify a number of other processes, including rattling motions with barriers on the order of the thermal energy at room temperature, and intermediate barrier hops between 4-fold and 5-fold coordinated lithium sites. We demonstrate differences regarding diffusion pathways between different cavity types; within the ReO3-like block units of the structures, cavities at the corners and edges host more isolated diffusion tunnels than those in the interior. Diffusion coefficients are found to be in the range of 10-12 to 10-11 m2 s-1 for lithium concentrations of 0.5 Li/TM. Overall, the results provide a complete picture of the diffusion mechanism in niobium tungsten oxide shear structures, and the structure-property relationships identified in this work can be generalized to the entire family of crystallographic shear phases.

Ionic and Electronic Conduction in TiNb2O7.

TiNb2O7 is a Wadsley-Roth phase with a crystallographic shear structure and is a promising candidate for high-rate lithium ion energy storage. The fundamental aspects of the lithium insertion mechanism and conduction in TiNb2O7, however, are not well-characterized. Herein, experimental and computational insights are combined to understand the inherent properties of bulk TiNb2O7. The results show an increase in electronic conductivity of seven orders of magnitude upon lithiation and indicate that electrons exhibit both localized and delocalized character, with a maximum Curie constant and Li NMR paramagnetic shift near a composition of Li0.60TiNb2O7. Square-planar or distorted-five-coordinate lithium sites are calculated to invert between thermodynamic minima or transition states. Lithium diffusion in the single-redox region (i.e., x ≤ 3 in LixTiNb2O7) is rapid with low activation barriers from NMR and DLi = 10-11 m2 s-1 at the temperature of the observed T1 minima of 525-650 K for x ≥ 0.75. DFT calculations predict that ionic diffusion, like electronic conduction, is anisotropic with activation barriers for lithium hopping of 100-200 meV down the tunnels but ca. 700-1000 meV across the blocks. Lithium mobility is hindered in the multiredox region (i.e., x > 3 in LixTiNb2O7), related to a transition from interstitial-mediated to vacancy-mediated diffusion. Overall, lithium insertion leads to effective n-type self-doping of TiNb2O7 and high-rate conduction, while ionic motion is eventually hindered at high lithiation. Transition-state searching with beyond Li chemistries (Na+, K+, Mg2+) in TiNb2O7 reveals high diffusion barriers of 1-3 eV, indicating that this structure is specifically suited to Li+ mobility.

Cation Disorder and Lithium Insertion Mechanism of Wadsley-Roth Crystallographic Shear Phases from First Principles.

Wadsley-Roth crystallographic shear phases form a family of compounds that have attracted attention due to their excellent performance as lithium-ion battery electrodes. The complex crystallographic structure of these materials poses a challenge for first-principles computational modeling and hinders the understanding of their structural, electronic and dynamic properties. In this article, we study three different niobium-tungsten oxide crystallographic shear phases (Nb12WO33, Nb14W3O44, Nb16W5O55) using an enumeration-based approach and first-principles density-functional theory calculations. We report common principles governing the cation disorder, lithium insertion mechanism, and electronic structure of these materials. Tungsten preferentially occupies tetrahedral and block-central sites within the block-type crystal structures, and the local structure of the materials depends on the cation configuration. The lithium insertion proceeds via a three-step mechanism, associated with an anisotropic evolution of the host lattice. Our calculations reveal an important connection between long-range and local structural changes: in the second step of the mechanism, the removal of local structural distortions leads to the contraction of the lattice along specific crystallographic directions, buffering the volume expansion of the material. Niobium-tungsten oxide shear structures host small amounts of localized electrons during initial lithium insertion due to the confining effect of the blocks, but quickly become metallic upon further lithiation. We argue that the combination of local, long-range, and electronic structural evolution over the course of lithiation is beneficial to the performance of these materials as battery electrodes. The mechanistic principles we establish arise from the compound-independent crystallographic shear structure and are therefore likely to apply to niobium-titanium oxide or pure niobium oxide crystallographic shear phases.

An Unusual Presentation of 46,XY Pure Gonadal Dysgenesis: Spontaneous Breast Development and Menstruation.

46,XY pure gonadal dysgenesis (Swyer syndrome) is characterized by normal female genitalia at birth. It usually first becomes apparent in adolescence with delayed puberty and amenorrhea. Rarely, patients can present with spontaneous breast development and/or menstruation. A fifteen-year-old girl presented to our clinic with the complaint of primary amenorrhea. On physical examination, her external genitals were completely female. Breast development and pubic hair were compatible with Tanner stage V. Hormonal evaluation revealed a hypergonadotropic state despite a normal estrogen level. Chromosome analysis revealed a 46,XY karyotype. Pelvic ultrasonography showed small gonads and a normal sized uterus for age. SRY gene expression was confirmed by multiplex polymerase chain reaction. Direct sequencing on genomic DNA did not reveal a mutation in the SRY, SF1 and WT1 genes. After the diagnosis of Swyer syndrome was made, the patient started to have spontaneous menstrual cycles and therefore failed to attend her follow-up visits. After nine months, the patient underwent diagnostic laparoscopy. Frozen examination of multiple biopsies from gonad tissues revealed gonadoblastoma. With this report, we emphasize the importance of performing karyotype analysis, which is diagnostic for Swyer syndrome, in all cases with primary or secondary amenorrhea even in the presence of normal breast development. We also suggest that normal pubertal development in patients with Swyer syndrome may be associated with the presence of a hormonally active tumor.