Use of the reliable change index to evaluate the effect of a multicomponent exercise program on physical functions.

AIMS: Using the reliable change index (RCI), we aimed to examine the effect of a multicomponent exercise program on the individual level. METHODS: Overall, 270 adults (mean age, 78 years) completed a multicomponent physical exercise program (strength, aerobic, gait, and balance) for 40 min, 1-2 times per week, continued up to 1 year at a daycare center. Effectiveness was assessed using grip, ankle, knee, and hip strength; Timed Up & Go (TUG); Berg Balance Scale (BBS); gait speed; and 6-min walking distance. These were measured at baseline and every 3 months thereafter. We calculated the RCI using the data between two-time points (baseline and at 3, 6, 9, or 12 months) in each participant and then calculated the mean RCI value across the participants. A paired t-test was also employed to evaluate the effect of the intervention as an average-based statistics. RESULTS: The highest mean RCI values were on ankle plantar-flexion strength, followed by gait speed, hip abduction strength, BBS, knee extensor strength, 6-min walk distance, grip strength, and finally TUG. Paired t-test also revealed significant improvement with moderate effect sizes for ankle plantar-flexion strength (0.504), gait speed (0.413), hip abduction strength (0.374), BBS (0.334), knee extensor strength (0.264), and 6-min walk distance (0.248). Significant but small effect size was seen on TUG (0.183). CONCLUSION: The RCI is a convenient method of comparing the effect between different assessments, especially at an individual level. This index can be applied to the use of personal feedback.

Effects of emixustat hydrochloride in patients with proliferative diabetic retinopathy: a randomized, placebo-controlled phase 2 study.

PURPOSE: To 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). METHODS: Twenty-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-1ß, IL-6, IL-8, TGFß-1, and VEGF in the aqueous humor. RESULTS: Seven 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). CONCLUSION: Although 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 REGISTRATION: ClinicalTrials.gov identifier: NCT02753400 (April 2016).

Visual Performance as a Function of Clear Central Aperture Diameter with a Defocused Myopic Periphery.

SIGNIFICANCE: Visual performance is affected least by a 15° radial aperture surrounded by peripheral myopic defocus. This finding has important applications for spectacle and contact lens designs and myopia control optimization. PURPOSE: The purpose of this study was to assess the effect of clear central apertures of different diameters with a defocused retinal periphery, using a range of visual performance tasks. METHODS: Thirty visually normal subjects (mean age, 24.4 ± 3.3 years; 20 females; mean spherical equivalent of -1.28 D) were enrolled. Subjects wore five different spectacles during testing, all corrected for distance refraction, in random order: three single-vision spectacles with clear central apertures of 10, 12.5, and 15° radii with the periphery defocused using Fresnel "press-on" lenses (+3.5 D sphere), progressive addition lens (PAL) spectacles with a +3.5 D addition, and single-vision lens (SVL) spectacles with no peripheral defocus. Static and kinetic visual field sensitivities, reading rate and comprehension, head movements, global saccadic tracking, and saccadic visual search were evaluated. RESULTS: Reading rate and comprehension did not differ across the five test conditions; however, increased head movement was found with the smallest aperture compared with the PAL condition with adjusted P < .05. Static visual field sensitivity was reduced for all three apertures in eccentric regions when compared with the SVL and PAL conditions with adjusted P < .05, whereas kinetic sensitivity did not differ for any lens condition. The 15° aperture was superior to the 10 and 12.5° apertures based on its similarity to the SVL and PAL spectacle conditions in head movement during reading, the Michigan Tracking Test, and the vertical results of the Developmental Eye Movement Test. CONCLUSIONS: Visual performance is least affected adversely by a 15° aperture surrounded by a peripheral myopic defocus. This finding has important applications for spectacle and contact lens designs to optimize myopia treatment with minimal impact on visual performance.

Comparison of Inhibitor and Substrate Selectivity between Rodent and Human Vascular Adhesion Protein-1.

Vascular adhesion protein-1 (VAP-1) is an ectoenzyme that functions as a copper-containing amine oxidase and is involved in leukocyte adhesion at sites of inflammation. Inhibition of VAP-1 oxidative deamination has become an attractive target for anti-inflammatory therapy with demonstrated efficacy in rodent models of inflammation. A previous comparison of purified recombinant VAP-1 from mouse, rat, monkey, and human gene sequences predicted that rodent VAP-1 would have higher affinity for smaller hydrophilic substrates/inhibitors because of its narrower and more hydrophilic active site channel. An optimized in vitro oxidative deamination fluorescence assay with benzylamine (BA) was used to compare inhibition of five known inhibitors in recombinant mouse, rat, and human VAP-1. Human VAP-1 was more sensitive compared to rat or mouse VAP-1 (lowest IC50 concentration) to semicarbazide but was least sensitive to hydralazine and LJP-1207. Hydralazine had a lower IC50 in rats compared to humans, although not significant. However, the IC50 of hydralazine was significantly higher in the rat compared to mouse VAP-1. The larger hydrophobic compounds from Astellas (compound 35c) and Boehringer Ingelheim (PXS-4728A) were hypothesized to have higher binding affinity for human VAP-1 compared to rodent VAP-1 since the channel in human VAP-1 is larger and more hydrophobic than that in rodent VAP-1. Although the sensitivity of these two inhibitors was the lowest in the mouse enzyme, we found no significant differences between mouse, rat, and human VAP-1. Michaelis-Menten kinetics of the small primary amines phenylethylamine and tyramine were also compared to the common marker substrate BA demonstrating that BA had the highest affinity among the substrates. Rat VAP-1 had the highest affinity for all three substrates and mouse VAP-1 had intermediate affinity for BA and phenylethylamine, but tyramine was not a substrate for mouse VAP-1 under these assay conditions. These results suggest that comparing oxidative deamination in mouse and rat VAP-1 may be important if using these species for preclinical efficacy models.

Emixustat Hydrochloride for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Clinical Trial.

PURPOSE: To determine whether emixustat hydrochloride (emixustat) reduces the rate of enlargement of geographic atrophy (GA) compared with placebo in subjects with age-related macular degeneration (AMD) and to evaluate the safety and tolerability of emixustat over 24 months of treatment. DESIGN: Multicenter, randomized, double-masked, placebo-controlled, phase 2b/3 clinical trial. PARTICIPANTS: Patients with GA secondary to AMD, a visual acuity score of at least 35 letters, and GA with a total area of 1.25 to 18 mm2 were enrolled. METHODS: Subjects were randomized (1:1:1:1) to emixustat 2.5 mg, 5 mg, 10 mg, or placebo, administered orally once daily for 24 months. Visits included screening, baseline, and months 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, and 25. MAIN OUTCOME MEASURES: The primary efficacy end point was the mean annual growth rate of total GA area in the study eye, as measured by a central reading center using fundus autofluorescence (FAF) images. The change from baseline in normal luminance best-corrected visual acuity (NL-BCVA) was a secondary efficacy end point. RESULTS: Of 508 randomized subjects, 320 completed the study. Demographics and baseline characteristics were comparable between treatment groups. On average, GA lesions in the study eye grew at a similar rate in each group (emixustat: 1.69 to 1.84 mm2/year; placebo: 1.69 mm2/year; P ≥ 0.81). Changes in NL-BCVA were also comparable between groups. Subjects with a larger low luminance deficit (LLD) at baseline (≥20 letters) demonstrated a more rapid growth of GA over 24 months. No relationship was observed between the risk-allele status of the AMD-associated single-nucleotide polymorphisms tested and the growth rate of GA. The most common adverse events in emixustat-treated subjects were delayed dark adaptation (55%), chromatopsia (18%), visual impairment (15%), and erythropsia (15%). CONCLUSIONS: Emixustat did not reduce the growth rate of GA in AMD. The most common adverse events were ocular in nature and likely related to the drug's mechanism of action. Data gained from this study over a 2-year period add to the understanding of the natural history of GA and the baseline characteristics affecting the growth rate of GA.

Cellulose Acetate Membrane Electrophoresis Based Urinary Proteomics for the Identification of Characteristic Proteins.

BACKGROUND: Analysis of urinary proteins using cellulose acetate membrane electrophoresis (CAME) is a useful and challenging method for the recognition of damaged sites in the kidney. However, protein content of each CAME fraction is still not completely understood. METHODS: In this study, an effective method of protein extraction from each band fractionated by CAME was established, which enabled us to examine the extracted proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry. RESULTS: Proteins were extracted from the gel and analyzed by mass spectrometry. In all, 31 proteins were identified, including 20 urinary proteins that were newly identified in the CAME-based analysis. CONCLUSION: This methodology was useful for identifying the proteins responsible for creating unique bands on CAME in a urine sample of a patient with drug-induced interstitial nephritis. These findings provide in-depth characterization of urinary protein contents in each CAME fraction.

Phase ii, randomized, placebo-controlled, 90-day study of emixustat hydrochloride in geographic atrophy associated with dry age-related macular degeneration.

PURPOSE: This study assessed the safety, tolerability, and pharmacodynamics of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in subjects with geographic atrophy associated with dry age-related macular degeneration. METHODS: Subjects were randomly assigned to oral emixustat (2, 5, 7, or 10 mg once daily) or placebo (3:1 ratio) for 90 days. Recovery of rod photoreceptor sensitivity after a photobleach was measured by electroretinography. Safety evaluations included analysis of adverse events and ophthalmic examinations. RESULTS: Seventy-two subjects (54 emixustat and 18 placebo) were evaluated. Emixustat suppressed rod photoreceptor sensitivity in a dose-dependent manner. Suppression plateaued by Day 14 and was reversible within 7 days to 14 days after drug cessation. Most systemic adverse events were not considered treatment related. Dose-related ocular adverse events (chromatopsia, 57% emixustat vs. 17% placebo and delayed dark adaptation, 48% emixustat vs. 6% placebo) were mild to moderate in severity, and the majority resolved on study or within 7 days to 14 days after study drug cessation. Reversibility of these adverse events with long-term administration, however, is undetermined. CONCLUSION: In this Phase II study, emixustat produced a dose-dependent reversible effect on rod function that is consistent with the proposed mechanism of action. These results support further testing of emixustat for the treatment of geographic atrophy associated with dry age-related macular degeneration.

Real-time duplex applications of loop-mediated AMPlification (LAMP) by assimilating probes.

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.

Phase 1, dose-ranging study of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in healthy volunteers.

BACKGROUND: Emixustat hydrochloride (formerly ACU-4429) is a nonretinoid compound with a unique mode of action in the retinal pigment epithelium, where it modulates the biosynthesis of visual chromophore through its effect on retinal pigment epithelium-specific 65 kDa protein isomerase. This study provides clinicians with a background for understanding the pharmacokinetics and safety profile of orally administered emixustat. METHODS: This randomized, double-masked, placebo-controlled Phase 1b study evaluated the pharmacokinetics, tolerability, and safety of a 14-day course of oral emixustat (5, 10, 20, 30, or 40 mg) or placebo (3:1 ratio) once daily in healthy volunteers. RESULTS: A total of 40 subjects were enrolled (mean age, 38 years; 75% male). Emixustat (n = 30) was rapidly absorbed (median T(max), 3.0-5 hours) and readily eliminated (mean t(1/2), 4.6-7.9 hours), and mean C(max) and AUC(0-24) generally increased in proportion to dose. No significant accumulation of emixustat was observed with multiple-dose administration. Ocular adverse events occurred in 67% of the subjects who received emixustat; all were considered mild and resolved after study completion. Systemic adverse events were minimal. CONCLUSION: Oral emixustat was safe and well tolerated when administered once daily for 14 days with minimal systemic adverse events reported. These data support evaluation of emixustat in subjects with geographic atrophy associated with dry age-related macular degeneration.

Effectiveness of insulin degludec/liraglutide versus insulin degludec/insulin aspart in Japanese patients with type 2 diabetes.

Aims: To evaluate and compare the effectiveness of once-daily insulin degludec/liraglutide (IDegLira) to that of once-daily insulin degludec/insulin aspart (IDegAsp) after switching from basal insulin therapy at 6 months by assessing changes in hemoglobin A1c (HbA1c), body weight, and insulin doses in patients with type 2 diabetes (T2D). Materials and methods: A total of 91 patients with T2D with HbA1c levels exceeding 7.0% were included in this study. Adjusted least square mean changes in HbA1c, body weight, and total insulin doses were compared between the IDegLira group and IDegAsp group. Subgroup analyses were performed, stratified by median values of HbA1c (< 8.5 and ≥ 8.5%), obesity (body mass index < 25 and ≥ 25 kg/m2), and basal insulin doses (< 14 and ≥ 14 units) at baseline to assess treatment interaction by subgroup. Results: The IDegLira group showed a greater reduction in HbA1c levels than the IDegAsp group (- 0.17 vs - 0.79%, p = 0.003) with comparable body weight changes. The analyses of adjusted mean changes of total insulin doses showed that the IDegAsp group had a larger increase than the IDegLira group (3.64 vs 1.30 unis, p = 0.016). The effect of IDegLira on HbA1c levels was superior to that of IDegAsp in patients with high HbA1c. There were no inter-group differences in the rate of hypoglycemic episodes. Conclusions: Once-daily IDegLira had greater effects on HbA1c and a lesser increase in insulin doses than IDegAsp when patients are switched from basal insulin therapy. Moreover, the effect on HbA1c was enhanced in patients with high HbA1c levels at baseline.

Loop-mediated amplification of the Clavibacter michiganensis subsp. michiganensis micA gene is highly specific.

Loop-mediated amplification (LAMP) was used to specifically identify Clavibacter michiganensis subsp. michiganensis, causal agent of bacterial canker of tomato. LAMP primers were developed to detect micA, a chromosomally stable gene that encodes a type II lantibiotic, michiganin A, which inhibits growth of other C. michiganensis subspecies. In all, 409 bacterial strains (351 C. michiganensis subsp. michiganensis and 58 non-C. michiganensis subsp. michiganensis) from a worldwide collection were tested with LAMP to determine its specificity. LAMP results were compared with genetic profiles established using polymerase chain reaction (PCR) amplification of seven genes (dnaA, ppaJ, pat-1, chpC, tomA, ppaA, and ppaC). C. michiganensis subsp. michiganensis strains produced eight distinct profiles. The LAMP reaction identified all C. michiganensis subsp. michiganensis strains and discriminated them from other C. michiganensis subspecies and non-Clavibacter bacteria. LAMP has advantages over immunodiagnostic and other molecular detection methods because of its specificity and isothermal nature, which allows for easy field application. The LAMP reaction is also not affected by as many inhibitors as PCR. This diagnostic tool has potential to provide an easy, one-step test for rapid identification of C. michiganensis subsp. michiganensis.

Molecular diagnostics in a teacup: Non-Instrumented Nucleic Acid Amplification (NINA) for rapid, low cost detection of Salmonella enterica.

We report on the use of a novel non-instrumented platform to enable a Loop Mediated isothermal Amplification (LAMP) based assay for Salmonella enterica. Heat energy is provided by addition of a small amount (<150 g) of boiling water, and the reaction temperature is regulated by storing latent energy at the melting temperature of a lipid-based engineered phase change material. Endpoint classification of the reaction is achieved without opening the reaction tube by observing the fluorescence of sequence-specific FRET-based assimilating probes with a simple handheld fluorometer. At or above 22°C ambient temperature the non-instrumented devices could maintain reactions above a threshold temperature of 61°C for over 90 min-significantly longer than the 60 min reaction time. Using the simple format, detection limits were less than 20 genome copies for reactions run at ambient temperatures ranging from 8 to 36°C. When used with a pre-enrichment step and non-instrumented DNA extraction device, trace contaminations of Salmonella in milk close to 1 CFU/mL could be reliably detected. These findings illustrate that the non- instrumented amplification approach is a simple, viable, low-cost alternative for field-based food and agricultural diagnostics or clinical applications in developing countries.

[Molecular heterogeneity of alpha 1-antitrypsin in the urine of the urolithiasis].

Randall's plaque theory is regarded as the most plausible mechanism of urinary stone formation; however, we speculated that urine proteins are necessarily involved in the process of stone formation. We focused on alpha 1-antitrypsin (alpha1-AT), a protein verified to be present in urinary calculi, and which is considered as a protein of inflammation, comparing its presence in healthy subjects and patients with urolithiasis. Quantitative analysis of alpha1-AT was performed with ELISA, whereas qualitative analysis was performed with SDS PAGE, two-dimensional electrophoresis, and western blotting. The results revealed a molecular heterogeneity in alpha1-AT, which can be classified into four patterns, a concentration-independent difference in alpha1-AT molecules found in the urine of patients and healthy subjects. A wider distribution of protein isoelectric points was found in urolithiasis (3.0-8.0) than in healthy subjects (4.0-5.0). We suggest that this new finding with molecular heterogeneity was due to the urolithiasis.

Safety and effect on rod function of ACU-4429, a novel small-molecule visual cycle modulator.

BACKGROUND: ACU-4429 is a first in class small-molecule visual cycle modulator that inhibits the isomerase complex and, in mouse models of retinal degeneration, prevents the accumulation of A2E. The purpose of this study was to assess the tolerability, pharmacokinetics, pharmacodynamics, and safety of a single, orally administered dose of ACU-4429 in healthy subjects. METHODS: Sequential cohorts were administered single doses ranging from 2 mg to 75 mg. Full-field electroretinograms were recorded before and after exposure to full-field bleaching light. Pharmacokinetics samples were taken at predetermined times. Safety assessments included adverse events, vital signs, clinical laboratory assays, electrocardiograms, and ophthalmologic examination. RESULTS: After 45-minute dark adaptation, electroretinographic findings demonstrated a dose-related slowing of the rate of recovery that reached its maximum on Day 2 and returned to baseline by Day 7. Mean area under the concentration curve and peak plasma concentration increased proportionally with increasing doses. Median time to peak concentration was 4 hours postdose. Mean elimination mean half-life was 4 hours to 6 hours. Adverse events were mild and visual in nature (dyschromatopsia and alteration in dark adaptation), transient, and resolved within a few days. Adverse event frequency was dose dependent. CONCLUSION: Oral administration of ACU-4429 produced a dose-dependent inhibition of the b-wave of the electroretinograms, was well tolerated up to 75 mg, and demonstrated linear pharmacokinetics across doses.

Randomised study evaluating the pharmacodynamics of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease.

BACKGROUND/AIMS: Stargardt disease is a rare, inherited, degenerative disease of the retina that is the most common type of hereditary macular dystrophy. Currently, no approved treatments for the disease exist. The purpose of this study was to characterise the pharmacodynamics of emixustat, an orally available small molecule that targets the retinal pigment epithelium-specific 65 kDa protein (RPE65), in subjects with macular atrophy secondary to Stargardt disease. METHODS: In this multicentre study conducted at six study sites in the USA, 23 subjects with macular atrophy secondary to Stargardt disease were randomised to one of three doses of daily emixustat (2.5 mg, 5 mg or 10 mg) and treated for 1 month. The primary outcome was the suppression of the rod b-wave recovery rate on electroretinography after photobleaching, which is an indirect measure of RPE65 inhibition. RESULTS: Subjects who received 10 mg emixustat showed near-complete suppression of the rod b-wave amplitude recovery rate postphotobleaching (mean=91.86%, median=96.69%), whereas those who received 5 mg showed moderate suppression (mean=52.2%, median=68.0%). No effect was observed for subjects who received 2.5 mg emixustat (mean=-3.31%, median=-12.23%). The adverse event profile was consistent with prior studies in other patient populations and consisted primarily of ocular adverse events likely related to RPE65 inhibition. CONCLUSION: This study demonstrated dose-dependent suppression of rod b-wave amplitude recovery postphotobleaching, confirming emixustat's biological activity in patients with Stargardt disease. These findings informed dose selection for a 24-month phase 3 trial (SeaSTAR Study) that is now comparing emixustat to placebo in the treatment of Stargardt disease-associated macular atrophy.

Longitudinal effects of physical exercise on health-related outcomes based on frailty status in community-dwelling older adults.

AIM: To clarify the difference in the longitudinal effects of physical exercise on health-related outcomes according to the baseline frailty status (frail or non-frail) in community-dwelling older adults. METHODS: Participants included 177 adults aged ≥65 years who carried out multicomponent physical exercises (strength, aerobic, gait and balance) for 40 min, one to three times per week, for 1 year at a day-care center. Bodyweight, comfortable walking speed, 6-min walking distance and Mini-Mental State Examination were measured at baseline and every 3 months. For longitudinal trend, we analyzed the change in scores from baseline for each outcome using the linear mixed effects model. Fixed effects included "group" (frail or non-frail), "time" (4 time points every 3 months, from 3 to 12 months) and "interaction between group and time." RESULTS: The effect sizes from baseline showed almost all positive values for each outcome. The linear mixed effects model showed significant effects on "interaction between group and time" in changes in bodyweight (P = 0.033), "group" in changes in walking speed (P = 0.013) and "time" in changes in the Mini-Mental State Examination (P < 0.001). Bodyweight showed a decreasing trend in the non-frail group after 3 months, unlike in the frail group. For walking speed, moderate effect sizes (d = 0.67-0.74) were sustained over time in the frail group, as did lesser effect sizes (d = 0.26-0.40) in the non-frail group. CONCLUSIONS: Exercise-based multicomponent interventions were effective for both groups. The longitudinal effects on walking speed and bodyweight were greater in the frail group. Geriatr Gerontol Int 2022; 22: 213-218.

Biometric and refractive changes following the monocular application of peripheral myopic defocus using a novel augmented-reality optical system in adults.

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.

A Cross-Sectional Study on the Association between Body Mass Index and Frailty According to Sex in Elderly Patients with Disabilities from an Elderly Day-Care Center.

The association between body mass index (BMI) and frailty in elderly patients with disabilities is unclear. We aimed to investigate the association between BMI and frailty in the elderly with disabilities according to sex. This cross-sectional study included 280 elderly patients with disabilities from an elderly daycare center. BMI classification for the Asian population was used to categorize the patients into four groups: underweight, normal, overweight, and obese. Frailty score was based on the phenotypic definition of frailty and consisted of five criteria derived from the revised Japanese version of the Cardiovascular Health Study. Those who had three or more criteria were considered frail. Logistic regression models were constructed to investigate the associations between frailty and BMI in each group (males and females). In females, being underweight was significantly associated with frailty after adjusting for confounders (age and Mini-Mental State Examination score); after adding medical history as a confounder, the aforementioned association was not significant. In males, BMI was not significantly associated with frailty. The association between BMI and frailty differed according to sex among the elderly with disabilities. This finding provides important information regarding frailty risk to workers in daycare facilities.

The correlation of salivary telomere length and single nucleotide polymorphisms of the ADIPOQ, SIRT1 and FOXO3A genes with lifestyle-related diseases in a Japanese population.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Effect of short-term peripheral myopic defocus on ocular biometrics using Fresnel "press-on" lenses in humans.

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.