Effect of ipragliflozin on carotid intima-media thickness in type 2 diabetes patients

Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes

Semiconducting Electronic Structure of the Ferromagnetic Spinel HgCr2Se4\mathbf{Hg}\mathbf{Cr}_2\mathbf{Se}_4 Revealed by Soft-X-Ray Angle-Resolved Photoemission Spectroscopy

We study the electronic structure of the ferromagnetic spinel $\mathrm{Hg}\mathrm{Cr}_2\mathrm{Se}_4$ by soft-x-ray angle-resolved photoemission spectroscopy (SX-ARPES) and first-principles calculations. While a theoretical study has predicted that this material is a magnetic Weyl semimetal, SX-ARPES measurements give direct evidence for a semiconducting state in the ferromagnetic phase. Band calculations based on the density functional theory with hybrid functionals reproduce the experimentally determined band gap value, and the calculated band dispersion matches well with ARPES experiments. We conclude that the theoretical prediction of a Weyl semimetal state in $\mathrm{Hg}\mathrm{Cr}_2\mathrm{Se}_4$ underestimates the band gap, and this material is a ferromagnetic semiconductor.Comment: 6+13 pages, 4+13 figure

Three-Dimensional Imaging of Plant Organs Using a Simple and Rapid Transparency Technique

Clearing techniques eliminate factors that interfere with microscopic observation, including light scattering and absorption by pigments and cytoplasmic components. The techniques allow fluorescence-based detailed analyses of materials and characterization of the three-dimensional structure of organs. We describe a simple and rapid clearing and imaging method, termed ‘TOMEI’ (Transparent plant Organ MEthod for Imaging), which enables microscopic observation of intact plant organs. This method involves a clearing reagent containing 2,2′-thiodiethanol. Conveniently, transparent plant organs were prepared within only 3-6 h. We detected fluorescent stains at a depth of approximately 200 µm using confocal laser scanning microscopy and analyzed fluorescent proteins in internal tissues of transparent organs cleared using TOMEI. We adapted TOMEI for various plant organs of Arabidopsis thaliana and Oryza sativa, including leaves, flower buds, flower stalks, root and nematode-infected root-knots. We visualized whole leaves of A. thaliana from the adaxial epidermis to the abaxial epidermis as well as protoxylem and metaxylem vessels of vascular bundles embedded in spongy mesophyll cells. Inner floral organs were observed in flower buds cleared using TOMEI without the need to prepare sections or remove sepals. Multicolor imaging of fluorescent proteins and dyes, and analyses of the three-dimensional structure of plant organs based on optical sections are possible using TOMEI. We analyzed root-knots cleared using TOMEI and revealed that nematodes induce giant cell expansion in a DNA content-dependent manner. The TOMEI method is applicable to analysis of fluorescent proteins and dyes quantitatively with cell morphological characteristics in whole plant organs

Immunology and Microbiology Development and Efficacy of a Drug-Releasing Soft Contact Lens

PURPOSE. The purpose of this study was to investigate the uptake and the release of antibiotics from a newly synthesized drug delivery hydrogel soft contact lens (SCL) using an ion ligand mechanism. METHODS. The antibiotics used were Gatifloxacin (GFLX) and Moxifloxacin (MFLX). The uptake amount and the sustained-release kinetics of antibiotics were investigated in vitro, and were also compared with newly synthesized SCLs, etafilcon A and polymacon. The antibiotic concentrations in the cornea, aqueous humor, and crystalline lens, and the effect against bacterial proliferation were investigated in vivo using rabbit subjects. Additionally the drug release efficacy of the new SCL was compared with that of eye drop administrations. RESULTS. In vitro, antibiotic uptake was increased with the weight percent (wt%) of the anionic group, and the released amount of antibiotics was highest during the initial 1 hour period, which then decreased over the next 72 hours. The released antibiotics volume of the new SCLs was significantly higher throughout 72 hours than that of the other two materials, etafilcon A and polymacon (P < 0.01). Whereas in vivo, the concentrations found in the cornea and aqueous humor were higher than those for the eye drop groups (P < 0.05 or P < 0.01). Antibiotic release at those sites decreased over 72 hours. No bacterial populations were detectable in the group treated with the new SCL presoaked in antibiotics throughout the experimental periods. CONCLUSIONS. The new SCLs released the antibiotics over several days, and showed improved penetration into the eye, along with prevention of bacterial proliferation

Predictors of silent hypoxia in hospitalized patients with COVID-19 in Japan

INTRODUCTION: Silent hypoxia (SH) is common in patients with coronavirus disease (COVID-19) in Japan and other countries. Early identification of SH is important as more treatment options for COVID-19 have become available. This study aimed to identify predictors of SH using a nationwide COVID-19 registry of hospitalized patients. METHODS: Adult patients who were admitted to hospital with COVID-19 between January 2020 and June 2021 and who were hypoxic on admission (SpO(2): 70–93%), not transferred from another facility, and who did not have disturbance of consciousness, confusion, or dementia, were included. SH was defined as hypoxia in the absence of shortness of breath/dyspnea upon admission. Predictors of SH were identified using univariable and multivariable logistic regression. RESULTS: The study included 1904 patients, of whom 990 (52%) satisfied the criteria for SH. Compared to patients without SH, patients with SH were older, more likely to be female, and had a slightly higher SpO(2) on admission. Compared to patients without SH, patients with SH had a lower prevalence of chronic lung disease (CLD) other than chronic obstructive pulmonary disease (COPD), asthma, and obesity. Multivariable analysis revealed that the independent predictors of SH were older age, a shorter interval from symptom onset to admission, higher SpO(2), and an absence of CLD or COPD. CONCLUSIONS: The absence of underlying lung disease and older age were important predictors of SH. The results of this study, which is the largest such study reported to date in Japan, may help clarify the mechanism of SH