Adult-Onset Type 1 Diabetes Development Following COVID-19 mRNA Vaccination.

During the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 vaccination-induced hyperglycemia and related complications have been reported. However, there have been few reports of type 1 diabetes triggered by COVID-19 vaccines in subjects without diabetes. Here, we report the case of a 56-year-old female patient who developed hyperglycemia after the second dose of COVID-19 mRNA-based vaccination without a prior history of diabetes. She visited our hospital with uncontrolled hyperglycemia despite administration of oral hyperglycemic agents. Her initial glycated hemoglobin level was high (11.0%), and fasting serum C-peptide level was normal. The fasting serum C-peptide level decreased to 0.269 ng/mL 5 days after admission, and the anti-glutamic acid decarboxylase antibody was positive. The patient was discharged in stable condition with insulin treatment. To our knowledge, this is the first case of the development of type 1 diabetes without diabetic ketoacidosis after mRNA-based COVID-19 vaccination, and is the oldest case of type 1 diabetes development under such circumstances.

Multicompartment Vesicles Formation by Emulsification-Induced Assembly of Poly(ethylene oxide)-block-poly(ε-caprolactone) and Their Dual-Loading Capability.

Emulsification-induced assembly is employed to allow structural diversity in nanoaggregates of a biocompatible amphiphilic polymer, poly(ethylene oxide)-block-poly(ε-caprolactone). Onion-like vesicles are efficiently produced by tuning the interfacial instability of the oil-in-water emulsion. The increase in the polymer concentration and use of the organic solvents with a low interfacial tension between water and the oil phase lead to a strong tendency of emulsion droplets to generate the onion-like vesicles. The vesicular networks and fibers are also obtained by controlling the concentration and type of the surfactant, respectively. Interestingly, the onion-like vesicles composed of alternating walls and water channels and the vesicular networks originated from a string of vesicles show dual-loading ability for hydrophobic and hydrophilic dyes but slightly different loading capacities. This result indicates that the development of a methodology to fabricate well-defined, unique nanostructures, such as multivesicular and multilamellar nanostructures, and subsequent elucidation of their structure-property relationships can provide useful guidance in the design of novel biomedical materials.

Experimental demonstration of highly sensitive optical sensor based on grating-assisted light coupling between strip and slot waveguides.

An optical sensor based on grating-assisted light coupling between a strip waveguide and a slot waveguide is demonstrated (the sensor was proposed and analyzed in [Opt. Express21, 5897-5909 (2013)]. The wavelength at which the light is strongly coupled between two waveguides is used to the measure the external medium's refractive index. The sensor was fabricated with silicon nitride waveguides and obvious grating induced band-rejection and band-pass characteristics were observed. The measured sensitivity of the fabricated sensor was -756.1 nm/RIU. Furthermore, by covering the strip waveguide with the silicon dioxide cladding, the sensitivity was measured to be as large as -1970 nm/RIU, which was 2.6 times enhanced. The experimental results agreed well with the calculated sensitivity values.

Precise control of quantum dot location within the P3HT-b-P2VP/QD nanowires formed by crystallization-driven 1D growth of hybrid dimeric seeds.

Herein, we report a simple fabrication of hybrid nanowires (NWs) composed of a p-type conjugated polymer (CP) and n-type inorganic quantum dots (QDs) by exploiting the crystallization-driven solution assembly of poly(3-hexylthiophene)-b-poly(2-vinylpyridine) (P3HT-b-P2VP) rod-coil amphiphiles. The visualization of the crystallization-driven growth evolution of hybrid NWs through systematic transmission electron microscopy experiments showed that discrete dimeric CdSe QDs bridged by P3HT-b-P2VP polymers were generated during the initial state of crystallization. These, in turn, assemble into elongated fibrils, forming the coaxial P3HT-b-P2VP/QDs hybrid NWs. In particular, the location of the QD arrays within the single strand of P3HT-b-P2VP can be controlled precisely by manipulating the regioregularity (RR) values of P3HT block and the relative lengths of P2VP block. The degree of coaxiality of the QD arrays was shown to depend on the coplanarity of the thiophene rings of P3HT block, which can be controlled by the RR value of P3HT block. In addition, the location of QDs could be regulated at the specific-local site of P3HT-b-P2VP NW according to the surface characteristics of QDs. As an example, the comparison of two different QDs coated with hydrophobic alkyl-terminated and hydroxyl-terminated molecules, respectively, is used to elucidate the effect of the surface properties of QDs on their nanolocation in the NW.

Silicon waveguide filter based on cladding modulated anti-symmetric long-period grating.

In this paper, we demonstrate an optical filter using cladding modulated anti-symmetric long-period grating in a two-mode silicon waveguide. The filter consists of a two-mode waveguide connected with an input and output single-mode waveguide through two linear tapers. The anti-symmetric grating is formed by placing two periodic arrays of silicon squares offset by half of a grating pitch along the two-mode waveguide. Light coupling occurs between two co-propagating modes at the coupling wavelength through the grating and results in a rejection band at the output. The grating pitch, coupling coefficient, transmission spectrum and 3-dB bandwidth of the grating are investigated with the coupled-mode theory. By using a cladding modulated grating, the grating coupling strength can be controlled over a wide range by the two-mode waveguide width or separation distance between the grating and waveguide. Band-rejection filters are experimentally demonstrated in 1-µm, 0.8-µm and 0.7-µm wide two-mode silicon waveguides and rejection bands with different bandwidths and maximal attenuation contrasts larger than 15 dB (~97% coupling efficiency) have been achieved.

Thermal characterization of electrical tracing-assisted dual-microring optical sensors.

In this paper, we study the temperature sensitivity of an electrical tracing-assisted dual-microring optical sensor, which consists of a sensing ring to detect the refractive index change on its surface and a tracing ring to trace the resonance wavelength shift of the sensing ring by the thermo-optic effect with a heating electrode on it. The wavelength shift measurement is therefore changed to electrical power variation measurement. Thanks to the real-time compensation effect of the tracing ring, the temperature dependence of the sensor is found to be intrinsically low. The resonance wavelength temperature sensitivity difference between the two rings is measured to be as low as 10.1 pm/°C, showing that the temperature dependence of the sensor in terms of wavelength per degree is reduced by ~6 times compared to that of a single ring sensor. The temperature sensitivity of the sensor in terms of electrical power per degree is measured to be -0.077 mW/°C. By using tracing ring with enhanced tuning efficiency, this value can be further decreased to -0.0057 W/°C. The experimental results agree well with the expectation. This type of sensors with low temperature dependence has great potential to be deployed in various practical point-of-care diagnostic applications.

Single-channel Mach-Zehnder interferometric biochemical sensor based on two-lateral-mode spiral waveguide.

We propose and demonstrate a single-channel Mach-Zehnder interferometric (MZI) biochemical sensor consisting of two single-mode waveguides connected by a two-lateral-mode spiral sensing waveguide through two discontinuous junctions. The use of a two-lateral-mode waveguide offers the advantage of simple fabrication using single-step lithography and etching process. Meanwhile, the two-mode waveguide folded in a spiral layout can achieve high sensitivity of a long sensing waveguide while providing a compact sensing area compatible with commercial spotting machine and requiring small volume of sample. The sensor is demonstrated in silicon waveguides and the effect of the discontinuity offset distance on the interference visibility is studied. The bulk and surface sensitivity of a fabricated sensor with a 4582-µm-long two-mode spiral waveguide folded within a 185 µm diameter spot are characterized to be 461.6 π/RIU (refractive index unit) and 1.135 π/ng mm(-2), respectively. The biosensing capability of the sensor is verified by the measurement of biotin-streptavidin interaction of different concentrations.

Biotin-streptavidin binding interactions of dielectric filled silicon bulk acoustic resonators for smart label-free biochemical sensor applications.

Sensor performance of a dielectric filled silicon bulk acoustic resonator type label-free biosensor is verified with biotin-streptavidin binding interactions as a model system. The mass sensor is a micromachined silicon square plate with a dielectric filled capacitive excitation mechanism. The resonance frequency of the biotin modified resonator decreased 315 ppm when exposed to streptavidin solution for 15 min with a concentration of 10(-7) M, corresponding to an added mass of 3.43 ng on the resonator surface. An additional control is added by exposing a bovine serum albumin (BSA)-covered device to streptavidin in the absence of the attached biotin. No resonance frequency shift was observed in the control experiment, which confirms the specificity of the detection. The sensor-to-sensor variability is also measured to be 4.3%. Consequently, the developed sensor can be used to observe in biotin-streptavidin interaction without the use of labelling or molecular tags. In addition, biosensor can be used in a variety of different immunoassay tests.

A refractive index sensor design based on grating-assisted coupling between a strip waveguide and a slot waveguide.

In this paper, we present a design of a refractive index sensor based on grating-assisted light coupling between a strip waveguide and a slot waveguide. The slot waveguide serves as the sensing waveguide while the strip waveguide is used for light launching and detection. The wavelength at which the light is coupled from the strip waveguide to the slot waveguide serves as a measure of the refractive index of the external medium. The sensitivity of the sensor is ~1.46 × 10(3) nm/RIU (refractive index unit) and can be almost doubled by isolating the strip waveguide from the external medium. The effects of the slot-waveguide parameters on the sensitivity have also been investigated. In particular, it is found that the sensor can achieve extraordinarily high sensitivity (on the order of 10(5) nm/RIU) when the group indices of two waveguides are close. The temperature dependence of the sensor is also investigated and a sensor with very low temperature dependence can be achieved with a polymer isolation layer.

Silicon-based optoelectronic integrated circuit for label-free bio/chemical sensor.

We demonstrate a silicon-based optoelectronic integrated circuit (OEIC) for label-free bio/chemical sensing application. Such on-chip OEIC sensor system consists of optical grating couplers for vertical light coupling into silicon waveguides, a thermal-tunable microring as a tunable filter, an exposed microring as an optical label-free sensor, and a Ge photodetector for a direct electrical readout. Different from the conventional wavelength-scanning method, we adopt low-cost broadband ASE light source, together with the on-chip tunable filter to generate sliced light source. The effective refractive index change of the sensing microring induced by the sensing target is traced by scanning the supplied electrical power applied onto the tracing microring, and the detected electrical signal is read out by the Ge photodetector. For bulk refractive index sensing, we demonstrate using such OEIC sensing system with a sensitivity of ~15 mW/RIU and a detection limit of 3.9 µ-RIU, while for surface sensing of biotin-streptavidin, we obtain a surface mass sensitivity of S(m) = ~192 µW/ng·mm(-2) and a surface detection limit of 0.3 pg/mm(2). The presented OEIC sensing system is suitable for point-of-care applications.

Efficacy of Gemigliptin Add-on to Dapagliflozin and Metformin in Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Study (SOLUTION).

BACKGRUOUND: This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin. METHODS: In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks. RESULTS: The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was -0.66% (0.07) with a 95% confidence interval of -0.80% to -0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted. CONCLUSION: Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

Electrical tracing-assisted dual-microring label­free optical bio/chemical sensors.

We propose and demonstrate a novel electrical tracing-assisted dual-microring resonator-based optical sensor system in silicon-on-insulator substrate. The system comprises one microring resonator-based sensing element and another microring resonator-based tracing element integrated with electrical controller. The resonance wavelength shift of sensing microring induced by the refractive index change is traced and determined by direct voltage supply of the electrical tunable tracing microring. Such optical sensing system eliminates the traditional wavelength-scanning method thus provide a cost effective sensing scheme. Proof-of-principle demonstration by testing polyelectrolyte multilayer shows the sensitivity of ~4.0 mW/ng∙mm-2 and the detection limit of ~5.35 pg/mm2.

Thermal independent silicon-nitride slot waveguide biosensor with high sensitivity.

As the sensitivity and detection limit of photonic refractive index (RI) biosensor increases, the temperature dependence becomes a major challenge. In this paper, we present a Mach-Zehnder Interferometer (MZI) biosensor based on silicon nitride slot waveguides. The biosensor is designed for minimal temperature dependence without compromising the performance in terms of sensitivity and detection limit. With air cladding, the measured surface sensitivity and detection limit of MZI biosensor reach 7.16 nm/(ng mm(-2)) and 1.30 (pg mm(-2)), while achieving a low temperature dependence is 5.0 pm/° C. With water cladding, the measured bulk sensitivity and detection limit reach 1730(2π)/RIU and 1.29 × 10(-5) RIU respectively. By utilizing Vernier effect through cascaded MZI structures, the measured sensitivity enhancement factor is 8.38, which results in a surface detection limit of 0.155 (pg mm(-2)).

The hyperleptinemia and ObRb expression in hyperphagic obese rats.

Leptin resistance associated with hyperleptinemia in high-fat-diet-induced obese rats and aged obese rats is well established, but it is not clear whether hyperphagia-induced obese rats also develop leptin resistance. We investigated whether Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are a strain of hyperphagia-induced obese rats, develop leptin resistance and whether caloric restriction reversed this leptin resistance-induced leptin receptor (ObRb) deficit. Twenty male OLETF rats, 20 male Long-Evans Tokushima Otsuka (LETO) rats, and 10 male Sprague Dawley (SD) rats were used. All rats were initially studied at 10 weeks of age and were freely fed with standard rat chow and water until they were 38 weeks of age. Daily food intake, body weight, and plasma leptin levels of OLETF rats were remarkably increased compared to LETO or SD rats from 10 to 38 weeks of age. When they were 38 weeks of age, all OLETF rats were randomly divided into two groups. One group was freely fed with standard rat chow (FD, or free diet group), and the other group (RD, or restricted diet group) was fed with only 70% of the amount consumed by the FD group. The LETO and SD rats were dismissed from further study. After 4 weeks of caloric restriction, the average body weight (636+/-33 g vs. 752+/-24 g, P<0.05) and abdominal adipose tissue weight (10.6+/-3.2g vs. 15.8+/-1.5 g, P<0.05) of the RD group were decreased compared with those of the FD group. Plasma leptin levels of the RD group were significantly decreased compared with those of the FD group (3.47+/-1.40 ng/mL vs. 11.55+/-1.16 ng/mL, P<0.05). The mRNA expression of ObRb and leptin-related suppressor of cytokine signaling 3 (SOCS3) in the hypothalamus, liver, and skeletal muscles of the RD group were significantly decreased compared with those of the FD group. Caloric restriction did not improve leptin receptor (ObRb) deficit or the downstream signaling of leptin in the liver, skeletal muscles, and hypothalamus. Thus, we demonstrated that OLETF rats, which are a strain of hyperphagia-induced obese rats, did not develop central or peripheral leptin resistance. We suggest that hyperleptinemia in OLETF rats is a compensatory mechanism to overcome obesity induced by hyperphagia.

Effect of Blood Pressure on Cardiovascular Diseases at 10-Year Follow-Up.

The American College of Cardiology/American Heart Association (ACC/AHA) recently published a Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. However, the data in other ethnic groups are not well known. We evaluated the prevalence and associated cardiovascular prognosis of Korean subjects with newly reclassified hypertension based on the 2017ACC/AHA guideline. We analyzed data from the Korean Health and Genome Study (n = 10,038). Supine blood pressure (BP) was measured thrice following a standardized protocol and averaged. There was a significant linear relation between BP profiles and cardiovascular disease (CVD)/mortality. Hazard ratio for CVD increased above a systolic BP of 120mm Hg. Systolic BP ≥130mm Hg was significantly associated with increased risk of CVD, coronary heart disease, stroke, CVD death, and total deaths. There was a similar significant linear relation with diastolic BP categories between CVD risk and death. BP is associated with an increased risk of CVD or all-cause mortalities. Moreover, the new BP categories of the 2017ACC/AHA guideline could be applicable for predicting CVD and death in Korean population.

Influence of Job-seeking Stress on Perimenstrual Symptoms of Female College Students in Health and Non-health related Majors: Mediating Effects of Stress Coping Styles.

PURPOSE: To determine effects of job-seeking stress on perimenstrual symptoms of female college students with health and non-health related majors and mediating effects of stress coping styles. METHODS: Data were collected from 189 female college students who were juniors or seniors. This study was conducted using questionnaires on job-seeking stress, perimenstrual symptoms, and stress coping styles. Data analysis included descriptive statistics, Pearson correlation analysis, and multiple regression analysis using SPSS, version 23.0. Mediation analysis was performed according to the Baron and Kenny method and Sobel test. RESULTS: Job-seeking stress was significantly and positively correlated with perimenstrual symptoms in non-health college students. Passive stress coping styles demonstrated a complete mediating effect on the relationship between job-seeking stress and perimenstrual symptoms of those with non-health related majors (ß=0.31, p=.002). Such effect was significant (Sobel test; Z=2.06, p=.039). CONCLUSION: Effects of job-seeking stress on perimenstrual symptoms were mediated by passive stress coping styles of non-health related major students. Based on findings of this study, effective stress cope strategies should be developed considering characteristics of majors to manage perimenstrual symptoms of female college students with high job-seeking stress.

Relationship between serum bilirubin levels and cardiovascular disease.

We tested the hypothesis that higher levels of bilirubin, a bile pigment with antioxidant properties, are associated with a decreased risk of cardiovascular disease (CVD). This study analyzed data from the Korean Health and Genome Study to examine the association between serum total bilirubin (TB) on CVD and CVD death. Serum TB was measured in a total of 8,844 subjects (4,196 males and 4,648 females) and evaluated for the development of new onset CVD from 2001 to 2012 (mean 8.1 years of follow-up). During the follow-up period, 689 cases of incident CVD (7.8%) were identified, and the prevalence of metabolic syndrome (MetS) at baseline was 26.1%. The prevalence of MetS decreased across bilirubin tertile categories. In addition to MetS itself, individual components of MetS significantly decreased with increased bilirubin tertiles. Moreover, the incidence of CVD decreased across bilirubin tertile categories. The hazard ratios (HRs) for developing coronary heart disease (CHD, HR 0.769, 95% CI 0.655-1.000) and CVD death (HR 0.513, 95% CI 0.267-0.985) was significantly lower in the highest tertile group (> 0.63 mg/dL) in comparison to the lowest tertile group (< 0.44 mg/dL) after adjusting for all confounding variables. In the present longitudinal study, a significant negative relationship was demonstrated between baseline bilirubin levels and incident CHD and CVD death.

Efficacy and tolerability of OROS methylphenidate in Korean children with attention-deficit/hyperactivity disorder.

This study evaluated the efficacy and tolerability in the initiation treatment of Concerta (OROS methylphenidate HCl) in Korean children with Attention-Deficit/Hyperactivity Disorder (AD/HD). One hundred and nineteen children with AD/HD were entered into a multi-center, open-label, four-week trial. The dosage of Concerta was adjusted by the investigators based on symptoms and safety assessments performed on a weekly basis. The safety of the drug and its efficacy for attention, behavior, and cognitive function were assessed. The primary outcome measures for efficacy were the Parent and Teacher IOWA Conners Rating Scales, Peer Interaction Items, and the Clinical Global Impression Scale. Cognitive tests (Continuous Performance Test, Matched Familiar Figure Test, Verbal Fluency Test, and Trail Making Test) were included as the secondary outcome measures. In most participants, OROS methylphenidate was well tolerated. There were significant improvements in attention, behavior, and function as measured by parents, teachers, and investigators. The benefit of the initiation of OROS methylphenidate in children with AD/HD was shown on the cognitive tests as well. These data provide support for the benefit of the once-daily methylphenidate preparation, Concerta in the treatment of Korean children with AD/HD. Children were initiated safely in this short-term trial, and its effectiveness was evident in the behavioral, as well as neuropsychological measurements.

Glucocorticoid-Induced Diabetes Mellitus: An Important but Overlooked Problem.

Glucocorticoids are widely used as potent anti-inflammatory and immunosuppressive drugs to treat a wide range of diseases. However, they are also associated with a number of side effects, including new-onset hyperglycemia in patients without a history of diabetes mellitus (DM) or severely uncontrolled hyperglycemia in patients with known DM. Glucocorticoid-induced diabetes mellitus (GIDM) is a common and potentially harmful problem in clinical practice, affecting almost all medical specialties, but is often difficult to detect in clinical settings. However, scientific evidence is lacking regarding the effects of GIDM, as well as strategies for prevention and treatment. Similarly to nonsteroid-related DM, the principles of early detection and risk factor modification apply. Screening for GIDM should be considered in all patients treated with medium to high doses of glucocorticoids. Challenges in the management of GIDM stem from wide fluctuations in postprandial hyperglycemia and the lack of clearly defined treatment protocols. Together with lifestyle measures, hypoglycemic drugs with insulin-sensitizing effects are indicated. However, insulin therapy is often unavoidable, to the point that insulin can be considered the drug of choice. The treatment of GIDM should take into account the degree and pattern of hyperglycemia, as well as the type, dose, and schedule of glucocorticoid used. Moreover, it is essential to instruct the patient and/or the patient's family about how to perform the necessary adjustments. Prospective studies are needed to answer the remaining questions regarding GIDM.