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Aims/Introduction This study aimed to evaluate and compare the effectiveness of oral semaglutide after adding to or switching from incretin‐related drugs by assessing the changes in HbA1c and body weight (BW) in participants with type 2 diabetes in clinical settings. Materials and Methods A total of 368 participants were divided into groups according to antidiabetic medications before oral semaglutide treatment; incretin‐related drug‐naïve (naïve), switching from dipeptidyl peptide‐4 inhibitors (DPP‐4i) or glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) groups. Adjusted mean changes in HbA1c and BW at 6 months after oral semaglutide administration were compared among the three groups. Similar analyses were performed in the GLP‐1 RAs group between GLP‐1RAs before switching. Results Mean change of HbA1c in DPP‐4i and GLP‐1 RA groups was −0.67% (95% confidence interval [CI]: −0.79 to −0.54) and −0.13% (95% CI: −0.40 to 0.15), respectively, which were significantly smaller than incretin‐related drug‐naïve group; −0.85% (95% CI: −1.08 to −0.62). Mean change in BW between the naïve and DPP‐4i groups had no differences; however, these changes were lower in the GLP‐1 RA group than in the naïve group. Mean change in HbA1c between pretreatment with GLP‐1 RAs had no differences; however, the mean change in BW in the dulaglutide group was significantly higher than that in the injectable semaglutide group. Conclusion Oral semaglutide reduced HbA1c levels and BW after adding or switching from other incretin‐related drugs in Japanese participants with type 2 diabetes. Oral semaglutide reduced HbA1c levels and BW after adding or switching from other incretin‐related drugs in Japanese participants with type 2 diabetes. Oral semaglutide had effects on HbA1c and BW similar to that of injectable GLP‐1 RAs.

This study assessed axial length and choroidal thickness changes following short-term peripheral myopic defocus in normal adult subjects. Twenty subjects underwent defocus sessions by viewing a full-field projected movie 4 m away for 4 h in the morning, while wearing spectacle lenses, corrected for distance vision in both eyes. The right eye, serving as the test eye, was peripherally defocused using a Fresnel lens overlay of + 3.50 D with a central clear aperture of 11.5 mm (correlating to a clear central visual field of approximately 23°), while the left eye served as the control (with no Fresnel lens overlay). A subset of 10 subjects from the same cohort also underwent additional defocus sessions with + 5.00 D of peripheral defocus. Axial length was measured and radial sub-foveal choroidal scans were obtained before and after the defocus sessions. The increase in axial length of the test eyes were significantly less than the control eyes under both peripheral defocus conditions (p < 0.05). The difference in mean change for choroidal thickness between test and control eyes was not significant for either dioptric condition. Our results demonstrated that short-term peripheral myopic defocus significantly inhibited axial elongation in adult humans, without significant changes in choroidal thickness.

Isothermal nucleic-acid amplification methods such as Loop-Mediated isothermal AMPlification (LAMP) are increasingly appealing alternatives to PCR for use in portable diagnostic system due to the low cost, weight, and power requirements of the instrumentation. As such, interest in developing new probes and other functionality based on the LAMP reaction has been intense. Here, we report on the development of duplexed LAMP assays for pathogen detection using spectrally unique Assimilating Probes. As proof of principle, we used a reaction for Salmonella enterica as a model coupled with a reaction for λ-phage DNA as an internal control, as well as a duplexed assay to sub-type specific quarantine strains of the bacterial wilt pathogen Ralstonia solanacearum. Detection limits for bacterial DNA analyzed in individual reactions was less than 100 genomic equivalents in all cases, and increased by one to two orders of magnitude when reactions were coupled in duplexed formats. Even so, due to the more robust activity of newly available strand-displacing polymerases, the duplexed assays reported here were more powerful than analogous individual reactions reported only a few years ago, and represent a significant advance for incorporation of internal controls to validate assay results in the field.

Purpose We investigated whether patients who have been issued a do-not-attempt-resuscitation order (DNAR) preoperatively (hereafter, DNAR patients) are informed of the DNAR code change when they undergo anesthesia. We also conducted a survey of the awareness of medical staff regarding perioperative DNARs, and investigated the current situation at a single-center in Japan. Methods For DNAR patients managed by anesthesiologists from January 2019 to September 2022, we retrospectively investigated whether the patient was informed of the DNAR code change or the DNAR was automatically suspended without explanation. Next, in July 2023, a questionnaire survey on perioperative DNARs was conducted among all medical staff at our center. Results Among the 4,164 cases managed by anesthesiologists during the study period, 100 DNAR patients (2.4%) were identified. Of these, 27 patients received an explanation about the DNAR code change before surgery. Multivariate analysis showed that female patients (odds ratio [OR] 5.3, 95% confidence interval [CI] 3.8–6.7; p  = 0.023) and patients with low Barthel Index (OR 0.98, 95% CI 0.96–0.99; p  = 0.010) tended to receive explanations about DNAR code changes. In the questionnaire survey, 25% of the 1,051 respondents answered that DNAR code changes should be explained to patients before surgery. Conclusion In clinical practice, 27% of DNAR patients were informed of DNARs code change before surgery. Perioperative advance care planning should be further promoted in clinical practice by creating guidelines and training programs regarding perioperative DNARs.

PurposeTo evaluate the effects of oral emixustat hydrochloride on pro-angiogenic and inflammatory cytokines in the aqueous humor, as well as other ophthalmic parameters, in subjects with proliferative diabetic retinopathy (PDR).MethodsTwenty-three patients with PDR, with or without diabetic macular edema (DME), were assigned to emixustat or placebo in daily oral doses ranging from 5 to 40 mg over a step-up titration period, for 84 days. The main outcome measures included levels of IL-1β, IL-6, IL-8, TGFβ-1, and VEGF in the aqueous humor.ResultsSeven of 12 subjects (58%) who were randomized to emixustat and 11 of 12 subjects (92%) who were randomized to placebo completed the study. No statistically significant differences between treatment groups were observed for changes in any of the aqueous humor cytokines tested. However, median VEGF levels were slightly reduced in the emixustat but not the placebo group (− 70.0 pg/mL versus + 42.7 pg/mL, or − 11.8% versus + 6.7%). In a post hoc analysis of all subjects (with or without DME), statistically significant differences between treatment arms in mean changes from baseline in central subfield thickness (CST; emixustat − 11.9 μm, placebo + 36.2 μm; P = 0.076) and total macular volume (TMV; emixustat − 0.13 mm3, placebo + 0.23 mm3; P = 0.026) were observed, both favoring emixustat. Emixustat’s safety profile was consistent with prior studies (i.e., the adverse events of delayed dark adaptation and visual impairment were more common in subjects treated with emixustat).ConclusionAlthough this pilot study did not demonstrate statistically significant differences in changes in aqueous humor cytokine levels between the emixustat and placebo groups, VEGF levels were slightly reduced in the emixustat but not in the placebo group. In addition, statistically significant differences favoring the emixustat group were observed in CST and TMV among all subjects. These data warrant further investigation of emixustat’s potential therapeutic effects in diabetic retinopathy.Trial registrationClinicalTrials.gov identifier: NCT02753400 (April 2016)

Aims/Introduction This study aimed to clarify the relationship between glucose metrics measured by continuous glucose monitoring (CGM) and diabetic retinopathy (DR) and albuminuria among Japanese individuals with type 1 diabetes mellitus. Materials and Methods The study included 294 individuals with type 1 diabetes (68.7% women) who underwent intermittent scanned CGM between March and April 2023. Multivariable logistic regression analysis was performed to examine the cross‐sectional association of each glucose metric (time in range [TIR], time above range [TAR], time below range, glucose management indicator [GMI], and coefficient of variation [CV]) with DR or albuminuria. Results The prevalence of DR and albuminuria was 27.6 and 13.6%, respectively. CGM metrics did not differ between individuals with DR and those without. However, individuals with albuminuria had significantly lower TIR and higher TAR than those without. The presence of DR was significantly associated with higher levels of TAR (odds ratio [OR] = 1.04, P < 0.001), GMI (OR = 2.13, P < 0.001), and HbA1c (OR = 2.07, P < 0.001), and with a lower level of TIR (OR = 0.97, P = 0.005). The presence of albuminuria was significantly associated with higher levels of TAR (OR = 1.05, P = 0.002), GMI (OR = 2.28, P = 0.005), and HbA1c (OR = 2.28, P < 0.001), and with a lower level of TIR (OR = 0.95, P = 0.007). Conclusion Decreased TIR and increased TAR and GMI were independently associated with a higher prevalence of DR and albuminuria in Japanese individuals with type 1 diabetes.

Aim The phase angle (PhA), assessed using bioelectrical impedance analysis (BIA), is becoming increasingly popular as an index of muscle quality associated with various health-related outcomes. This study aimed to clarify the relationship between PhA and sedentary behavior (SB), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA), which were objectively measured using accelerometers in older adults with disabilities requiring care. Methods We recruited 90 older adults (39 men and 51 women, mean age of 78.7 ± 6.7 years) with disabilities under the long-term care insurance system. Skeletal muscle mass index (SMI) and PhA of the lower limbs were measured using a multifrequency BIA instrument. Daily durations of SB, LPA, and MVPA per day were measured using a triaxial accelerometer. Nutritional status was assessed using the long form of the Mini Nutritional Assessment (MNA). Results The MVPA duration was significantly associated with lower limb PhA after adjusting for age, sex, SB and LPA durations, MNA score, and medical history ( p  = 0.037), whereas SB and LPA durations were not associated with lower limb PhA. The duration of SB, LPA, and MVPA were not significantly associated with lower limb SMI, whereas the MNA score was. Conclusions Lower limb PhA, but not lower limb SMI, was associated with MVPA duration, independent of nutritional status and medical history. Enhancing the duration of MVPA is needed to maintain the PhA and prevent further decline in physical function in older adults who require long-term care due to disabilities.

Increased exposure to blue or visible light, fluctuations in oxygen tension, and the excessive accumulation of toxic retinoid byproducts places a tremendous amount of stress on the retina. Reduction of visual chromophore biosynthesis may be an effective method to reduce the impact of these stressors and preserve retinal integrity. A class of non-retinoid, small molecule compounds that target key proteins of the visual cycle have been developed. The first candidate in this class of compounds, referred to as visual cycle modulators, is emixustat hydrochloride (emixustat). Here, we describe the effects of emixustat, an inhibitor of the visual cycle isomerase (RPE65), on visual cycle function and preservation of retinal integrity in animal models. Emixustat potently inhibited isomerase activity in vitro (IC50 = 4.4 nM) and was found to reduce the production of visual chromophore (11-cis retinal) in wild-type mice following a single oral dose (ED50 = 0.18 mg/kg). Measure of drug effect on the retina by electroretinography revealed a dose-dependent slowing of rod photoreceptor recovery (ED50 = 0.21 mg/kg) that was consistent with the pattern of visual chromophore reduction. In albino mice, emixustat was shown to be effective in preventing photoreceptor cell death caused by intense light exposure. Pre-treatment with a single dose of emixustat (0.3 mg/kg) provided a ~50% protective effect against light-induced photoreceptor cell loss, while higher doses (1-3 mg/kg) were nearly 100% effective. In Abca4-/- mice, an animal model of excessive lipofuscin and retinoid toxin (A2E) accumulation, chronic (3 month) emixustat treatment markedly reduced lipofuscin autofluorescence and reduced A2E levels by ~60% (ED50 = 0.47 mg/kg). Finally, in the retinopathy of prematurity rodent model, treatment with emixustat during the period of ischemia and reperfusion injury produced a ~30% reduction in retinal neovascularization (ED50 = 0.46mg/kg). These data demonstrate the ability of emixustat to modulate visual cycle activity and reduce pathology associated with various biochemical and environmental stressors in animal models. Other attributes of emixustat, such as oral bioavailability and target specificity make it an attractive candidate for clinical development in the treatment of retinal disease.

The prevalence of myopia is growing at an alarming rate and is associated with axial elongation of the eye. The cause of this undesirable physiological change involves multiple factors. When the magnitude of myopia approaches high levels, this accompanying mechanical effect increases the risk of developing other clinical conditions associated with permanent vision loss. Prior work has investigated how we may halt or reverse this process of axial elongation associated with myopic progression when we expose the eye to a peripheral myopic defocus stimulus. Specifically, the known, short-term response to myopic defocus stimulation is promising and demonstrates the possibility of establishing more permanent effects by regulating the axial length of the eye with specific defocus stimulation. However, how to directly convert these known, short-term effects into more long-term, permanent changes to effectively prevent these unfavourable physiological and refractive changes over time is yet to be understood. Here, we show for the first time that we can produce sustained, long-term reductions in axial length and refractive endpoints with cumulative short-term exposure to specific myopic defocus stimuli using a novel optical design that incorporates an augmented reality optical system. We believe that this technology will have the potential to improve the quality of vision in mankind.

It has been reported that genetic factors are associated with risk factors and onset of lifestyle-related diseases, but this finding is still the subject of much debate. The aim of the present study was to investigate the correlation of genetic factors, including salivary telomere length and three single nucleotide polymorphisms (SNPs) that may influence lifestyle-related diseases, with lifestyle-related diseases themselves. In one year at a single facility, relative telomere length and SNPs were determined by using monochrome multiplex quantitative polymerase chain reaction and TaqMan SNP Genotyping Assays, respectively, and were compared with lifestyle-related diseases in 120 Japanese individuals near our university. In men and all participants, age was inversely correlated with relative telomere length with respective p values of 0.049 and 0.034. In men, the frequency of hypertension was significantly higher in the short relative telomere length group than in the long group with unadjusted p value of 0.039, and the difference in the frequency of hypertension between the two groups was of borderline statistical significance after adjustment for age (p = 0.057). Furthermore, in men and all participants, the sum of the number of affected lifestyle-related diseases, including hypertension, was significantly higher in the short relative telomere length group than in the long group, with p values of 0.004 and 0.029, respectively. For ADIPOQ rs1501299, men's ankle brachial index was higher in the T/T genotype than in the G/G and G/T genotypes, with p values of 0.001 and 0.000, respectively. For SIRT1 rs7895833, men's body mass index and waist circumference and all participants' brachial-ankle pulse wave velocity were higher in the A/G genotype than in the G/G genotype, with respective p values of 0.048, 0.032 and 0.035. For FOXO3A rs2802292, women's body temperature and all participants' saturation of peripheral oxygen were lower in the G/T genotype than in the T/T genotype, with respective p values of 0.039 and 0.032. However, relative telomere length was not associated with physiological or anthropometric measurements except for height in men (p = 0.016). ADIPOQ rs1501299 in men, but not the other two SNPs, was significantly associated with the sum of the number of affected lifestyle-related diseases (p = 0.013), by genotype. For each SNPs, there was no significant difference in the frequency of hypertension or relative telomere length by genotype. Relative telomere length and the three types of SNPs determined using saliva have been shown to be differentially associated with onset of and measured risk factors for lifestyle-related diseases consisting mainly of cardiovascular diseases and cancer.