Development of a broadband superluminescent diode based on self-assembled InAs quantum dots and demonstration of high-axial-resolution optical coherence tomography imaging

We developed a near-infrared (NIR) superluminescent diode (SLD) based on self-assembled InAs quantum dots (QDs) and demonstrated high-axial-resolution optical coherence tomography (OCT) imaging using this QD-based SLD (QD-SLD). The QD-SLD utilized InAs QDs with controlled emission wavelengths as a NIR broadband light emitter, and a tilted waveguide with segmented electrodes was prepared for edge-emitting broadband electroluminescence (EL) spanning approximately 1–1.3 μm. The bandwidth of the EL spectrum was increased up to 144 nm at a temperature of 25 °C controlled using a thermoelectric cooler. The inverse Fourier transform of the EL spectrum predicted a minimum resolution of 3.6 μm in air. The QD-SLD was subsequently introduced into a spectral-domain (SD)-OCT setup, and SD-OCT imaging was performed for industrial and biological test samples. The OCT images obtained using the QD-SLD showed an axial resolution of ~4 μm, which was almost the same as that predicted from the spectrum. This axial resolution is less than the typical size of a single biological cell (~5 μm), and the practical demonstration of high-axial-resolution OCT imaging shows the application of QD-SLDs as a compact OCT light source, which enables the development of a portable OCT system

High-Throughput Cryopreservation of Plant Cell Cultures for Functional Genomics

Suspension-cultured cell lines from plant species are useful for genetic engineering. However, maintenance of these lines is laborious, involves routine subculturing and hampers wider use of transgenic lines, especially when many lines are required for a high-throughput functional genomics application. Cryopreservation of these lines may reduce the need for subculturing. Here, we established a simple protocol for cryopreservation of cell lines from five commonly used plant species, Arabidopsis thaliana, Daucus carota, Lotus japonicus, Nicotiana tabacum and Oryza sativa. The LSP solution (2 M glycerol, 0.4 M sucrose and 86.9 mM proline) protected cells from damage during freezing and was only mildly toxic to cells kept at room temperature for at least 2 h. More than 100 samples were processed for freezing simultaneously. Initially, we determined the conditions for cryopreservation using a programmable freezer; we then developed a modified simple protocol that did not require a programmable freezer. In the simple protocol, a thick expanded polystyrene (EPS) container containing the vials with the cell–LSP solution mixtures was kept at −30°C for 6 h to cool the cells slowly (pre-freezing); samples from the EPS containers were then plunged into liquid nitrogen before long-term storage. Transgenic Arabidopsis cells were subjected to cryopreservation, thawed and then re-grown in culture; transcriptome and metabolome analyses indicated that there was no significant difference in gene expression or metabolism between cryopreserved cells and control cells. The simplicity of the protocol will accelerate the pace of research in functional plant genomics

Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM

Improved Monitoring of the Hyperglycemic State in Type 1 Diabetes Patients by Use of the Glycoalbumin/HbA1c Ratio

AIM: Generally, the level of glycoalbumin (GA) is approximately 3 times higher than that of HbA1c. However, in type 1 diabetic patients, we often find an even higher GA/HbA1c ratio of nearly 3.5. Therefore, this study was performed to examine the significance of a higher GA/HbA1c ratio. METHODS: 17 type 1 diabetic patients were enrolled in part 1 of the study and divided into two groups, one with a higher and the other with a lower GA/HbA1c ratio. In both groups, the correlation between GA or HbA1c level and each "4-point" capillary glucose level was analyzed. 80 type 1 diabetic patients were enrolled in part 2 of the study and the relationship between mean GA/HbA1c ratio in the past year and degree of diabetic retinopathy was analyzed. RESULTS: In part 1 of the study, we found positive correlations between GA and bedtime capillary glucose levels and between HbA1c and bedtime capillary glucose levels in the higher GA/HbA1c group (r = 0.86, p = 0.023; r = 0.95, p = 0.012, respectively), but not in the lower GA/HbA1c group. In part 2 of the study, a significant positive correlation between GA/HbA1c ratio and severity of retinopathy could be observed (r = 0.269, p = 0.017). CONCLUSIONS: A higher GA/HbA1c ratio may reflect a postprandial hyperglycemic state and simultaneous monitoring of GA and HbA1c may improve the management of diabetic patients

Real‐world risk of lower‐limb amputation associated with sodium–glucose cotransporter 2 inhibitors versus metformin: A propensity score‐matched model analysis in Japan

ABSTRACT Aims/Introduction We aimed to clarify the real‐world risk of lower‐limb amputation and identify factors related to increased risk in Japanese patients with type 2 diabetes using sodium–glucose cotransporter 2 inhibitors (SGLT2is). Materials and Methods We carried out a retrospective observational cohort study utilizing the Japanese Medical Data Vision, a diagnosis procedure combination database. We identified 107,296 patients with type 2 diabetes who were initiated on SGLT2is or metformin (control; n = 53,648 per group) using 1:1 propensity score matching from April 2014 to October 2019. The hazard ratio (HR) for the risk of lower‐limb amputation was analyzed using a Cox proportional hazards model adjusted for patients' baseline characteristics and use of concomitant medical agents. Results Of the 107,296 patients, 66 (0.06%); that is, 41 (0.08%) in the SGLT2is group and 25 (0.05%) in the metformin group, underwent amputation, with no significant difference in the proportions between the groups. There was no significant difference in the risk of amputation between the SGLT2is and metformin groups (HR 1.34, 95% confidence interval [CI] 0.80–2.24). However, female sex (HR 2.78, 95% CI 1.12–6.94) and use of strong statins (HR 2.68; 95% CI 1.18–8.20) were significantly associated with a higher risk of amputation in the SGLT2is group than in the metformin group. Conclusions SGLT2is might not be related to an increased risk of lower‐limb amputation in patients with type 2 diabetes in real‐world clinical practice. The possible increased risk of SGLT2is‐associated amputation in female patients with type 2 diabetes and patients with type 2 diabetes requiring strong statins is notable

The Role of the CXCL10/CXCR3 System in Type 1 Diabetes

Despite intervention with insulin, type 1 diabetes gradually deteriorates the patients' quality of life. The disease is characterized by an immune-mediated destruction of pancreatic beta-cells. Its etiology, however, remains controversial. Some studies argue that glutamic acid decarboxylase (GAD) antigen and GAD-reactive T cells are critical players in the development of diabetes by affecting the Th cell balance. A T-helper 1 (Th1)-dominant immune response is considered to be important in beta-cell failure in both human and animal models of type 1 diabetes. The Th1-type chemokine, CXCL10, and its receptor, CXCR3, are involved not only in the immune response, but also in the suppression of beta-cell proliferation. Thus, understanding the CXCL10/CXCR3 system may be important for finding a cure. In this short review, we discuss the role of the CXCL10/CXCR3 system in type 1 diabetes and propose relevant treatment options

Actual condition survey regarding mismatch of measurements between radioimmunoassay and enzyme‐linked immunosorbent assay tests for anti‐glutamic acid decarboxylase antibody in real‐world clinical practice

Abstract Anti‐glutamic acid decarboxylase antibody (GADA) is an important islet cell‐associated autoantibody for the diagnosis of autoimmune type 1 diabetes mellitus. In Japan, the GADA assay kit was recently changed from radioimmunoassay (RIA) to enzyme‐linked immunosorbent assay (ELISA). Thereafter, a mismatched measurement between the two tests became apparent in clinical situations. The present study aimed to clarify the actual extent of mismatch between the two measurements on a larger‐scale real‐world clinical practice. In this cross‐sectional non‐local/non‐hospital‐based study, we collected anonymized data on GADA levels of 598 participants, who were simultaneously measured with GADA‐RIA and GADA enzyme‐linked immunosorbent assay tests. We found that 34% of the GADA‐RIA‐positive participants showed negative results in the GADA enzyme‐linked immunosorbent assay test; the mismatch was predominantly observed in participants with relatively low GADA‐RIA levels (<32 U/mL). This considerable mismatch might lead to physicians’ confusion in diagnosing type 1 diabetes mellitus