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Kae Sunagawa,1,2 Keiji Hirai,3 Sumito Sunagawa,1,2 Norifumi Kamiya,1 Isao Komesu,1 Yusako Sunagawa,1 Hiroshi Sunagawa,1 Ken Nakachi,4 Aizan Hirai,5 Susumu Ookawara,3 Yoshiyuki Morishita3 1Sunagawa Medical Clinic, Okinawa, Japan; 2Division of Endocrinology, Diabetes and Metabolism, Hematology, and Rheumatology, University of the Ryukyus, Okinawa, Japan; 3Division of Nephrology, Saitama Medical Center, Jichi Medical University, Saitama, Japan; 4Department of Internal Medicine, Shonan Hospital, Okinawa, Japan; 5Department of Internal Medicine, Chiba Cerebral and Cardiovascular Center, Chiba, JapanCorrespondence: Keiji Hirai, Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Saitama-shi, Saitama-ken, 330-8503, Japan, Tel +81 48 647 2111, Fax +81 48 647 6831, Email keijihirai@kfy.biglobe.ne.jpPurpose: The aim of this study was to investigate the additional effects of empagliflozin on liraglutide in patients with advanced-stage type 2 diabetic kidney disease.Patients and Methods: Forty-one patients were randomly assigned (1:1) to treatment with liraglutide alone during the first 6 months and subsequent treatment with liraglutide plus empagliflozin during the next 6 months (liraglutide plus empagliflozin group) (n = 20) or treatment with liraglutide alone for 12 months (liraglutide group) (n = 21). Liraglutide was administered subcutaneously once daily at a starting dose of 0.3 mg/day and up-titrated weekly by 0.3 mg to a maximum dose of 0.9 mg/day. Empagliflozin was administered orally at a dose of 10 mg once daily. The primary outcome was the change in renal function (estimated glomerular filtration rate) during the latter 6 months. Secondary outcomes were changes in body weight, systolic blood pressure, hemoglobin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio during the latter 6 months.Results: Empagliflozin significantly increased the hemoglobin concentration (from 12.9 ± 1.9 to 13.7 ± 1.9 g/dL; p< 0.05) and decreased body weight (from 66.1 ± 12.9 to 64.5 ± 12.6 kg; p< 0.05). No significant differences were observed between the groups for estimated glomerular filtration rate, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, uric acid, blood glucose, hemoglobin A1c, and urine protein creatinine ratio.Conclusion: Empagliflozin increased hemoglobin concentration and decreased body weight in patients with advanced-stage type 2 diabetic kidney disease who received liraglutide. However, empagliflozin did not provide short-term benefits with regard to renal function decline, urinary protein excretion, or glycemic control in these patients.Keywords: empagliflozin, sodium-glucose co-transporter 2 inhibitor, liraglutide, glucagon-like peptide-1 receptor agonist, diabetic kidney disease, diabetic nephropathy

Naoko Kamiya,1 Yukiko Ishikawa,1 Kazuhiko Kotani,2 Shuji Hatakeyama,1,3 Masami Matsumura1 1Division of General Internal Medicine, Jichi Medical University Hospital, Shimotsuke-shi, Tochigi, Japan; 2Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Shimotsuke-shi, Tochigi, Japan; 3Division of Infectious Diseases, Jichi Medical University Hospital, Shimotsuke-shi, Tochigi, JapanCorrespondence: Naoko Kamiya, Division of General Internal Medicine, Jichi Medical University Hospital, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan, Tel +81-285-58-7498, Fax +81-285-40-5160, Email m01015no@jichi.ac.jpBackground: Lymphomas, including Hodgkin lymphoma and non-Hodgkin lymphoma, are one of the differentials for peripheral lymphadenopathy and are difficult to diagnose clinically. Biopsy is essential for diagnosing lymphoma, although it is invasive. Non-invasive methods are required to identify patients with suspected lymphoma who should undergo a biopsy. The relevance of the monocyte-to-lymphocyte ratio has recently been reported to be a useful diagnostic marker in children with lymphoma and a prognostic marker of various other diseases. This study aimed to determine the relevance of the monocyte-to-lymphocyte ratio in the diagnosis of lymphoma in adults.Methods: The study included 246 adult outpatients (median age of 49.0 years) presenting with peripheral lymphadenopathy. The final diagnosis was determined by reviewing the medical records. We categorized all patients into either the lymphoma group or the non-lymphoma group. The lymphoma group included patients who underwent biopsy and were diagnosed with lymphoma by histopathology, while the non-lymphoma group included those diagnosed with disease excluding lymphoma. The monocyte-to-lymphocyte ratios were compared between the two groups.Results: Of the participants, 33 (13.4%) were assigned to the lymphoma group. The median age of the lymphoma and non-lymphoma groups were 67.0 years (interquartile range [IQR] 55.5– 75.5 years) and 46.0 years (IQR 36.0– 61.0 years), respectively. The lymphocyte and monocyte levels showed no significant differences between the two groups individually. Nonetheless, the monocyte-to-lymphocyte ratio was significantly higher in the lymphoma group (median, 0.36; IQR, 0.24– 0.73) than in the non-lymphoma group (median, 0.29; IQR, 0.21– 0.43; P = 0.022), independent of lymph node diameter ≥ 1 cm and C-reactive protein levels.Conclusion: This study suggests that the monocyte-to-lymphocyte ratio can be a helpful diagnostic marker for lymphoma in adults with peripheral lymphadenopathy when the etiology is unclear even after a medical interview and physical examination.Keywords: lymphadenopathy, lymphoma, monocyte-to-lymphocyte ratio, diagnostic marker

This paper presents a new scheme for the first- and second-order design sensitivity analysis of the two-dimensional elastic problem by using Trefftz method. In the Trefftz method, the physical quantities are approximated by superposition of regular T-complete functions. Therefore, direct differentiation of the approximate expressions with respect to design parameters leads to the regular expressions of the sensitivities. The present schemes are applied to some examples in order to confirm the validity.

Transcutaneous drug delivery is a promising method in terms of drug repositioning and reformulation because of its non-invasive and easy-to-use features. To overcome the skin barrier, which is the biggest challenge in transcutaneous drug delivery, a number of techniques, such as microemulsion, solid-in-oil dispersions and liposomes, have been studied extensively. However, the low viscosity of these formulations limits drug retention on the skin and reduces patient acceptability. Although viscosity can be increased by adding a thickening reagent, such an addition often alters formulation nanostructures and drug solubility, and importantly, decreases skin permeability. In this study, a gel-like lyotropic liquid crystal (LLC) was used as a tool to enhance skin permeability. In particular, we prepared 1-monolinolein (ML)-based LLCs with different water contents. All LLCs significantly enhanced skin permeation of a peptide drug, an epitope peptide of melanoma, despite their high viscoelasticity. Fourier transform infra-red spectroscopic analysis of the skin surface treated with the LLCs revealed that the gyroid geometry more strongly interacted with the lamellar structure inside the stratum corneum (SC) than the diamond geometry. Finally, as the result of the in vivo tumor challenge experiment using B16F10 melanoma-bearing mice, the LLC with the gyroid geometry showed stronger vaccine effect against tumor than a subcutaneous injection. Collectively, ML-based LLCs, especially with the gyroid geometry, are a promising strategy to deliver biomacromolecules into skin. Transcutaneous drug delivery is a promising method for drug repositioning and reformulation because of its non-invasive and easy-to-use features. To overcome the skin barrier, which is the biggest challenge in transcutaneous drug delivery, we used a gel-like lyotropic liquid crystal (LLC) as a novel tool to enhance skin permeability. In this paper, we demonstrated that an LLC with a specific liquid crystalline structure has the highest skin permeation enhancement effect for a peptide antigen as a model drug. Moreover, the peptide antigen-loaded LLC showed a vaccine effect that was comparable to a subcutaneous injection in vivo. This study provides a basis for designing a transcutaneous delivery system of peptide drugs with LLC. [Display omitted] [ABSTRACT FROM AUTHOR]

Research was conducted to study the structure of segregated networks in SiC/Si3n4 particulate composites. The SiC powders that were utilized as starting powders were mixed with Si3n4 powders in an ethanol solution to form green composite solids while the average of SiC particles were measured by scanning electron microscopy. Results indicated that composites with segregated distribution of conductive particles in an insulator matrix becomes electrically conductive at much smaller amount of conducting particle to form percolating networks.

A silicon nitride (Si3N4) radial inflow turbine wheel was fabricated by injection molding at Toyota Central R&D Labs. The wheel was 142 mm in outer diameter and had 14 blades. The radial wheel was too bulky to manufacture as a homogeneous and defect-free body in one piece. It was divided into two pieces for injection molding and put together into one body by a cold isostatic pressing step after binder removal. Spin testing was executed at room temperature and the resulting photographs, taken from three directions, provided useful information about the fraction mode of the wheels. The maximum burst speed of the wheels at room temperature was 98,900 rpm, which corresponded to 145 percent of the design speed. In a hot rig test, one of the wheels survived 75,000 rpm for ten minutes at a turbine inlet temperature of 1050 degrees C.

Two types of silicon nitride ceramic rotor have been introduced into the Japanese market by Toyota Motor Corporation, named CT26 and CT12A, to improve engine acceleration response by the reduction in moment of inertia. In order to design a suitable blade shape for a ceramic rotor, the critical stress of the blade was determined by the results obtained experimentally from correlating the fracture origin over spin-tested rotors with centrifugal stress at fracture. A suitable blade shape has been determined for the CT26 turbocharger rotor type, which is identical to the metal rotor except for the disk diameter of hub back face and the blade thickness. The CT12A type is of similar design to the CT26 type; all dimensions could be reduced except for the inlet blade thickness, which is determined by foreign object damage (FOD) resistance.

Pore pressure plays a key role in the generation of earthquakes in subduction zones. However, quantitative constraints for its determination are quite limited. Here, we estimate the subsurface pore pressure by analyzing the transient upwelling flow of drilling mud from borehole C0023A of the International Ocean Discovery Program (IODP) Expedition 370, in the Nankai Trough off Cape Muroto. This upward flow provided the first direct evidence of an overpressured aquifer in the underthrust sediments off Cape Muroto. To estimate the pre‐drilling pore pressure in the overpressured aquifer around a depth of 950–1,050 m below sea floor, we examined the measured porosities of core samples retrieved from nearby IODP wells; we then proceeded to explain the observed time evolution of the flow rate of the upwelling flow by modeling various sized aquifers through solving a radial diffusion equation. It was observed that for a permeability of 10−13 m2, the aquifer possessed an initial excess pore pressure of ∼5–10 MPa above the hydrostatic pressure, with a lateral dimension of several hundred meters and thickness of several tens of meters. The overpressure estimates from the porosity‐depth profile at Site C0023 differ from those at other drill sites in the region, suggesting the possible existence of multiple overpressured aquifers with a patchy distribution in the underthrust sediments of the Nankai Trough. As pore pressure is relevant in maintaining fault stability, the overpressured aquifers may be the source of slow earthquakes that have been observed around the drilling site. Plain Language Summary: Fault zones often act as barriers to fluid flow, which can lead to the formation of aquifers of pressurized fluid in the vicinity of the fault. It is well known that pore fluid pressure plays a key role in the generation of subduction zone earthquakes, however quantification of pore fluid pressures around subduction zone faults has, up to now, been limited. The International Ocean Discovery Program (IODP) Expedition 370 drilled the Nankai Trough subduction zone off Cape Muroto (Japan), where slow earthquakes have been observed. While drilling, we observed a transient upwelling flow of drilling mud from the borehole. This flow provided the first direct evidence of an overpressured aquifer around the plate boundary fault. To constrain the properties of the aquifer we modeled aquifers with varying properties, and found that the upwelling mud at the drill‐site was likely generated by an aquifer with a lateral extent of hundreds of meters and with pore pressures considerably higher than the typical (hydrostatic) pore fluid pressure expected at this depth. Our results suggest that slow earthquakes that occur near Cape Muroto may be caused by relatively small, scattered, highly‐pressurized subsurface aquifers like the one we intersected during Expedition 370. Key Points: A transient borehole mud flow confirmed the existence of an overpressured aquifer beneath the Nankai Trough décollement off Cape MurotoThe aquifer of ∼5–10 MPa excess pore pressure was distributed over a lateral extent of hundreds of metersThe overpressured aquifer may have been the cause of slow earthquakes observed near the drilling site [ABSTRACT FROM AUTHOR]