Subacute Development of Polymyalgia Rheumatica (PMR) In Diabetic Patient with Clinical Efficacy of Tocilizumab and Xultophy

The patient is 76-year-old men with previous history of type 2 diabetes mellitus (T2DM) in 2012, acute myocardial infarct (AMI) in 2015 and dyslipidemia in 2017. He had no health or medical problems of rheumatism and joints. As his social and sports history, he was an excellent long-distance runner with the similar level to Olympian Kenji Kimihara during 14-30 years old. He worked hard from 38 years as city assembly member. In 2019, he continued low carbohydrate diet (LCD) with decreased HbA1c from 9.0% to 6.3% for half year. In autumn 2021, he developed subacute generalized arthralgia and muscle weakness with elevated HbA1c 10.6%. He was diagnosed as polymyalgia rheumatica (PMR). For treatment, prednisolone was not effective, and then he was provided Tocilizumab (Actemra). It showed remarkable efficacy for symptom improvement and normalized C-reactive protein (CRP) 8.3 to <0.1 mg/dL, matrix metalloproteinase-3 (MMP-3) 610 to 79 ng/mL. For glucose control, he was initiated insulin human 4-4-4 to 14-14-14 units, followed by Xultophy 18 to 5 doses with satisfactory glucose variability. HbA1c was remarkably decreased from 10.6% to 6.4 % about 2 months. Various discussion perspective was described, and this article will be hopefully useful for future practice and research

The Membrane-Associated Adaptor Protein DOK5 Is Upregulated in Systemic Sclerosis and Associated with IGFBP-5-Induced Fibrosis

Systemic sclerosis (SSc) is characterized by excessive fibrosis of the skin and internal organs due to fibroblast proliferation and excessive production of extracellular matrix (ECM). We have shown that insulin-like growth factor binding protein (IGFBP)-5 plays an important role in the development of fibrosis in vitro, ex vivo, and in vivo. We identified a membrane-associated adaptor protein, downstream of tyrosine kinase/docking protein (DOK)5, as an IGFBP-5-regulated target gene using gene expression profiling of primary fibroblasts expressing IGFBP-5. DOK5 is a tyrosine kinase substrate associated with intracellular signaling. Our objective was to determine the role of DOK5 in the pathogenesis of SSc and specifically in IGFBP-5-induced fibrosis. DOK5 mRNA and protein levels were increased in vitro by endogenous and exogenous IGFBP-5 in primary human fibroblasts. DOK5 upregulation required activation of the mitogen-activated protein kinase (MAPK) signaling cascade. Further, IGFBP-5 triggered nuclear translocation of DOK5. DOK5 protein levels were also increased in vivo in mouse skin and lung by IGFBP-5. To determine the effect of DOK5 on fibrosis, DOK5 was expressed ex vivo in human skin in organ culture. Expression of DOK5 in human skin resulted in a significant increase in dermal thickness. Lastly, levels of DOK5 were compared in primary fibroblasts and lung tissues of patients with SSc and healthy donors. Both DOK5 mRNA and protein levels were significantly increased in fibroblasts and skin tissues of patients with SSc compared with those of healthy controls, as well as in lung tissues of SSc patients. Our findings suggest that IGFBP-5 induces its pro-fibrotic effects, at least in part, via DOK5. Furthermore, IGFBP-5 and DOK5 are both increased in SSc fibroblasts and tissues and may thus be acting in concert to promote fibrosis

Spin susceptibility and fluctuation corrections in the BCS-BEC crossover regime of an ultracold Fermi gas

We investigate magnetic properties and effects of pairing fluctuations in the BCS (Bardeen-Cooper-Schrieffer)-BEC (Bose-Einstein condensation) crossover regime of an ultracold Fermi gas. Recently, Liu and Hu, and Parish, pointed out that the strong-coupling theory developed by Nozi\`eres and Schmitt-Rink (NSR), which has been extensively used to successfully clarify various physical properties of cold Fermi gases, unphysically gives negative spin susceptibility in the BCS-BEC crossover region. The same problem is found to also exist in the ordinary non-self-consistent T-matrix approximation. In this paper, we clarify that this serious problem comes from incomplete treatment in term of pseudogap phenomena originating from strong pairing fluctuations, as well as effects of spin fluctuations on the spin susceptibility. Including these two key issues, we construct an extended T-matrix theory which can overcome this problem. The resulting positive spin susceptibility agrees well with the recent experiment on a 6Li Fermi gas done by Sanner and co-workers. We also apply our theory to a polarized Fermi gas to examine the superfluid phase transition temperature Tc, as a function of the polarization rate. Since the spin susceptibility is an important physical quantity, especially in singlet Fermi superfluids, our results would be useful in considering how singlet pairs appear above and below Tc in the BCS-BEC crossover regime of cold Fermi gases.Comment: 21 pages, 9 figure

Transport, magnetic and superconducting properties of RuSr2RCu2O8 (R= Eu, Gd) doped with Sn

Ru{1-x}Sn{x}Sr2EuCu2O8 and Ru{1-x}Sn{x}Sr2GdCu2O8 have been comprehensively studied by microwave and dc resistivity and magnetoresistivity and by the dc Hall measurements. The magnetic ordering temperature T_m is considerably reduced with increasing Sn content. However, doping with Sn leads to only slight reduction of the superconducting critical temperature T_c accompanied with the increase of the upper critical field B_c2, indicating an increased disorder in the system and a reduced scattering length of the conducting holes in CuO2 layers. In spite of the increased scattering rate, the normal state resistivity and the Hall resistivity are reduced with respect to the pure compound, due to the increased number of itinerant holes in CuO2 layers, which represent the main conductivity channel. Most of the electrons in RuO2 layers are presumably localized, but the observed negative magnetoresistance and the extraordinary Hall effect lead to the conclusion that there exists a small number of itinerant electrons in RuO$_2$ layers that exhibit colossal magnetoresistance.Comment: 10 pages, 9 figure

Effects of carbon incorporation on doping state of YBa2Cu3Oy

Effects of carbon incorporation on the doping state of YBa2Cu3Oy (Y-123) were investigated. Quantitative carbon analysis revealed that carbon could be introduced into Y-123 from both the precursor and the sintering gas. Nearly carbon-free (< 200 ppm) samples were prepared from a vacuum-treated precursor by sintered at 900 &#730;C and cooling with 20 &#730;C /min in flowing oxygen gas. The lower Tc (= 88 K) and higher oxygen content (y = 6.98) strongly suggested the overdoping state, which was supported by the temperature dependence of resisitivity and thermoelectric power. The nuclear quadrapole resonance spectra and the Raman scattering spectra indicated that there was almost no oxygen defect in the Cu-O chain in these samples. On the other hand, in the same cooling condition, the samples sintered in air stayed at optimal doping level with Tc = 93 K, and the intentionally carbon-doped sample was in the underdoping state. It is revealed that about 60% of incorporated carbon was substituted for Cu at the chain site in the form of CO32+, and the rest remains at the grain boundary as carbonate impurities. Such incorporation affected the oxygen absorption process in Y-123. It turned out that the oxygen content in Y-123 cannot be controlled only by the annealing temperature and the oxygen partial pressure but also by the incorporated carbon concentration.Comment: 16pages, 9figure

Anisotropic Ru3+ 4d5 magnetism in the alpha-RuCl3 honeycomb system: susceptibility, specific heat and Zero field NMR

Hexagonal alpha-Ru trichloride single crystals exhibit a strong magnetic anisotropy and we show that upon applying fields up to 14 T in the honeycomb plane the successive magnetic order at T1 = 14 K and T2 = 8 K could be completely suppressed whereas in the perpendicular direction the magnetic order is robust. Furthermore the field dependence of chi(T) implies coexisting ferro- and antiferromagnetic exchange between in-plane components of Ru^3+-spins, whereas for out-of-plane components a strong antiferromagnetic exchange becomes evident. 101^Ru zero-field nuclear magnetic resonance in the ordered state evidence a complex (probably non coplanar chiral) long-range magnetic structure. The large orbital moment on Ru^3+ is found in density-functional calculations.Comment: 5 pages and 4 figure

Planar CuO_2 hole density estimation in multilayered high-T_c cuprates

We report that planar CuO_2 hole densities in high-T_c cuprates are consistently determined by the Cu-NMR Knight shift. In single- and bi-layered cuprates, it is demonstrated that the spin part of the Knight shift K_s(300 K) at room temperature monotonically increases with the hole density $p$ from underdoped to overdoped regions, suggesting that the relationship of K_s(300 K) vs. p is a reliable measure to determine p. The validity of this K_s(300 K)-p relationship is confirmed by the investigation of the p-dependencies of hyperfine magnetic fields and of spin susceptibility for single- and bi-layered cuprates with tetragonal symmetry. Moreover, the analyses are compared with the NMR data on three-layered Ba_2Ca_2Cu_3O_6(F,O)_2, HgBa_2Ca_2Cu_3O_{8+delta}, and five-layered HgBa_2Ca_4Cu_5O_{12+delta}, which suggests the general applicability of the K_s(300 K)-p relationship to multilayered compounds with more than three CuO_2 planes. We remark that the measurement of K_s(300 K) enables us to separately estimate p for each CuO_2 plane in multilayered compounds, where doped hole carriers are inequivalent between outer CuO_2 planes and inner CuO_2 planes.Comment: 7 pages, 5 figures, 2 Tables, to be published in Physical Review

Opening of a pseudogap in a quasi-two dimensional superconductor due to critical thermal fluctuations

We examine the role of the anisotropy of superconducting critical thermal fluctuations in the opening of a pseudogap in a quasi-two dimensional superconductor such as a cuprate-oxide high-temperature superconductor. When the anisotropy between planes and their perpendicular axis is large enough and its superconducting critical temperature T_c is high enough, the fluctuations are much developed in its critical region so that lifetime widths of quasiparticles are large and the energy dependence of the selfenergy deviates from that of Landau's normal Fermi liquids. A pseudogap opens in such a critical region because quasiparticle spectra around the chemical potential are swept away due to the large lifetime widths. The pseudogap never smoothly evolves into a superconducting gap; it starts to open at a temperature higher than T_c while the superconducting gap starts to open just at T_c. When T_c is rather low but the ratio of varepsilon_G(0)/k_BT_c, with varepsilon_G(0) the superconducting gap at T=0K and k_B the Boltzmann constant, is much larger than a value about 4 according to the mean-field theory, the pseudogap must be closing as temperature T approaches to the low T_c because thermal fluctuations become less developed as T decreases. Critical thermal fluctuations cannot cause the opening of a prominent pseudogap in an almost isotropic three dimensional superconductor, even if its T_c is high.Comment: 25 pages, 5 figures (14 subfigures

Human Skin Culture as an Ex Vivo Model for Assessing the Fibrotic Effects of Insulin-Like Growth Factor Binding Proteins

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology. A hallmark of SSc is fibrosis of the skin and internal organs. We recently demonstrated increased expression of IGFBP-3 and IGFBP-5 in primary cultures of fibroblasts from the skin of patients with SSc. In vitro, IGFBP-3 and IGFBP-5 induced a fibrotic phenotype and IGFBP-5 triggered dermal fibrosis in mice. To assess the ability of IGFBPs to trigger fibrosis, we used an ex vivo human skin organ culture model. Our findings demonstrate that IGFBP-3 and IGFBP-5, but not IGFBP-4, increase dermal and collagen bundle thickness in human skin explants, resulting in substantial dermal fibrosis and thickening. These fibrotic effects were sustained for at least two weeks. Our findings demonstrate that human skin ex vivo is an appropriate model to assess the effects of fibrosis-inducing factors such as IGFBPs, and for evaluating the efficacy of inhibitors/therapies to halt the progression of fibrosis and potentially reverse it

Nuclear spin-spin coupling in La_{2-x}Sr_{x}CuO_{4} studied by stimulated echo decay

We have performed copper NQR experiments in high temperature superconductors YBa_{2}Cu_{4}O_{8}, YBa_{2}Cu_{3}O_{7}, and La_{2-x}Sr_{x}CuO_{4} (x=0.12 and 0.15), using the stimulated echo technique. The stimulated echo intensity is analyzed by a model that includes the spin-lattice relaxation process (T_ {1 }-process) and the fluctuating local field due to nuclear spin-spin coupling. The model gives quantitative account of the experimental results in Y-based compounds using the known values of 1/T_{1} and 1/T_{2G}, the gaussian decay rate of the spin echo intensity. The same model applied to LSCO enables us to extract the value of T_{2G}. Our results indicate that T_{1}T/T_{2G} is independent of temperature, implying that the dynamic exponent is one in La_{2-x}Sr_{x}CuO_{4}.Comment: 14 pages, 11 fugures, The bibliography field is correcte