Impact of sitagliptin on endometrial mesenchymal stem-like progenitor cells : a randomised, double-blind placebo-controlled feasibility trial

Background: Recurrent pregnancy loss (RPL) is associated with the loss of endometrial mesenchymal stem-like progenitor cells (eMSC). DPP4 inhibitors may increase homing and engraftment of bone marrow-derived cells to sites of tissue injury. Here, we evaluated the effect of the DPP4 inhibitor sitagliptin on eMSC in women with RPL, determined the impact on endometrial decidualization, and assessed the feasibility of a full-scale clinical trial. Methods: A double-blind, randomised, placebo-controlled feasibility trial on women aged 18 to 42 years with a history of 3 or more miscarriages, regular menstrual cycles, and no contraindications to sitagliptin. Thirty-eight subjects were randomised to either 100 mg sitagliptin daily for 3 consecutive cycles or identical placebo capsules. Computer generated, permuted block randomisation was used to allocate treatment packs. Colony forming unit (CFU) assays were used to quantify eMSC in midluteal endometrial biopsies. The primary outcome measure was CFU counts. Secondary outcome measures were endometrial thickness, study acceptability, and first pregnancy outcome within 12 months following the study. Tissue samples were subjected to explorative investigations. Findings: CFU counts following sitagliptin were higher compared to placebo only when adjusted for baseline CFU counts and age (RR: 1.52, 95% CI: 1.32–1.75, P<0.01). The change in CFU count was 1.68 in the sitagliptin group and 1.08 in the placebo group. Trial recruitment, acceptability, and drug compliance were high. There were no serious adverse events. Explorative investigations showed that sitagliptin inhibits the expression of DIO2, a marker gene of senescent decidual cells. Interpretation: Sitagliptin increases eMSCs and decreases decidual senescence. A large-scale clinical trial evaluating the impact of preconception sitagliptin treatment on pregnancy outcome in RPL is feasible and warranted. Funding: Tommy's Baby Charity. Clinical trial registration: EU Clinical Trials Register no. 2016-001120-54

Asymptotic analysis of the model for distribution of high-tax payers

The z-transform technique is used to investigate the model for distribution of high-tax payers, which is proposed by two of the authors (K. Y and S. M) and others. Our analysis shows an asymptotic power-law of this model with the exponent -5/2 when a total ``mass'' has a certain critical value. Below the critical value, the system exhibits an ordinary critical behavior, and scaling relations hold. Above the threshold, numerical simulations show that a power-law distribution coexists with a huge ``monopolized'' member. It is argued that these behaviors are observed universally in conserved aggregation processes, by analizing an extended model.Comment: 5pages, 3figure

(2,2′-Bipyridine-4,4′-dicarb­oxy­lic acid-κ2 N,N′)chlorido(2,2′:6′,2′′-terpyridyl-κ3 N,N′,N′′)ruthenium(II) perchlorate ethanol monosolvate monohydrate

In the title compound, [RuCl(C15H11N3)(C12H8N2O4)]ClO4·C2H5OH·H2O, the geometry of the ClN5 coordination set around the RuII atom is close to octa­hedral, but distorted on account of the limited bite angles of the polypyridyl ligands. The complexes are linked by O—H⋯O hydrogen bonds between the carboxyl groups and the crystal lattice water mol­ecules into chains along [110]. Face-to-face stacking inter­actions are formed between terpyridine ligands, with inter­planar separations of 3.66 (1) and 3.42 (1) Å, and between bipyridine-4,4′-dicarb­oxy­lic acid ligands, with inter­planar separations of 3.65 (1) and 3.72 (1) Å. Three O atoms of the perchlorate ion are each disordered equally over two positions. The hy­droxy group of the ethanol mol­ecule is also disordered over two sites with refined occupancies of 0.794 (9) and 0.206 (9)

The investigation of acute optic neuritis: a review and proposed protocol

Optic neuritis is an inflammatory optic neuropathy that affects many patients with multiple sclerosis (MS) at some point during their disease course. Differentiation of acute episodes of MS-associated optic neuritis from other autoimmune and inflammatory optic neuropathies is vital for treatment choice and further patient management, but is not always straightforward. Over the past decade, a number of new imaging, laboratory and electrophysiological techniques have entered the clinical arena. To date, however, no consensus guidelines have been devised to specify how and when these techniques can be most rationally applied for the diagnostic work-up of patients with acute optic neuritis. In this article, we review the literature and attempt to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials

Variational Monte Carlo Study of Spin-Gapped Normal State and BCS-BEC Crossover in Two-Dimensional Attractive Hubbard Model

We study properties of normal, superconducting (SC) and CDW states for an attractive Hubbard model on the square lattice, using a variational Monte Carlo method. In trial wave functions, we introduce an interspinon binding factor, indispensable to induce a spin-gap transition in the normal state, in addition to the onsite attractive and intersite repulsive factors. It is found that, in the normal state, as the interaction strength $|U|/t$ increases, a first-order spin-gap transition arises at $|U_{\rm c}|\sim W$ ($W$: band width) from a Fermi liquid to a spin-gapped state, which is conductive through hopping of doublons. In the SC state, we confirm by analysis of various quantities that the mechanism of superconductivity undergoes a smooth crossover at around |U_{\ma{co}}|\sim |U_{\rm c}| from a BCS type to a Bose-Einstein condensation (BEC) type, as $|U|/t$ increases. For |U|<|U_{\ma{co}}|, quantities such as the condensation energy, a SC correlation function and the condensate fraction of onsite pairs exhibit behavior of $\sim \exp(-t/|U|)$, as expected from the BCS theory. For |U|>|U_{\ma{co}}|, quantities such as the energy gain in the SC transition and superfluid stiffness, which is related to the cost of phase coherence, behave as $\sim t^2/|U|\propto T_{\rm c}$, as expected in a bosonic scheme. In this regime, the SC transition is induced by a gain in kinetic energy, in contrast with the BCS theory. We refer to the relevance to the pseudogap in cuprate superconductors.Comment: 14 pages, 22 figures, submitted to Journal of the Physical Society of Japa

Low temperature properties of the fermionic mixtures with mass imbalance in optical lattice

We study the attractive Hubbard model with mass imbalance to clarify low temperature properties of the fermionic mixtures in the optical lattice. By combining dynamical mean-field theory with the continuous-time quantum Monte Carlo simulation, we discuss the competition between the superfluid and density wave states at half filling. By calculating the energy and the order parameter for each state, we clarify that the coexisting (supersolid) state, where the density wave and superfluid states are degenerate, is realized in the system. We then determine the phase diagram at finite temperatures.Comment: 5 pages, 4 figures, accepted for publication in J. Phys. Soc. Jp

Disruption of the leptomeningeal blood barrier in neuromyelitis optica spectrum disorder

OBJECTIVE: To describe leptomeningeal blood-barrier impairment reflected by MRI gadolinium-enhanced lesions in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD). METHODS: A retrospective case series of 11 AQP4-IgG-positive NMOSD patients with leptomeningeal enhancement (LME) were collected from 5 centers. External neuroradiologists, blinded to the clinical details, evaluated MRIs. RESULTS: LME was demonstrated on postcontrast T1-weighted and fluid-attenuated inversion recovery images as a sign of leptomeningeal blood-barrier disruption and transient leakage of contrast agent into the subarachnoid space in 11 patients, 6 in the brain and 6 in the spinal cord. The patterns of LME were linear or extensive and were accompanied by periependymal enhancement in 5 cases and intraparenchymal enhancement in all cases. The location of LME in the spinal cord was adjacent to intraparenchymal contrast enhancement with involvement of a median number of 12 (range 5-17) vertebral segments. At the time of LME on MRI, all patients had a clinical attack such as encephalopathy (36%) and/or myelopathy (70%) with median interval between symptom onset and LME of 12 days (range 2-30). LME occurred in association with an initial area postrema attack (44%), signs of systemic infection (33%), or AQP4-IgG in CSF (22%) followed by clinical progression. LME was found at initial clinical presentation in 5 cases and at clinical relapses leading to a diagnosis of NMOSD in 6 cases. CONCLUSION: This study suggests that altered leptomeningeal blood barrier may be accompanied by intraparenchymal blood-brain barrier breakdown in patients with AQP4-IgG-positive NMOSD during relapses