LONGITUDINAL CHANGE OF RETINAL LAYER THICKNESS IN COGNITIVELY NORMAL ELDERLY SUBJECTS: Population-Based Cohort Study.

PURPOSE: To identify longitudinal retinal layer thickness changes in normal eyes of cognitively healthy elderly people. METHODS: Post hoc analysis was performed on 57 cognitively healthy elderly participants from the population-based Korean Longitudinal Study on Health and Aging and Korean Longitudinal Study on Cognitive Aging and Dementia cohort studies who underwent baseline and final optical coherence tomography scans. The peripapillary retinal nerve fiber layer, subfoveal choroid, and average retinal layer thickness at four quadrant (nasal, temporal, superior, and inferior) points 1 mm, 2 mm, and 3 mm from the center of the fovea were measured. RESULTS: The mean age of subjects was 75.1 years and the mean follow-up period was 55.9 months. Among the analyzed retinal layers, both the ganglion cell-inner plexiform layer and the outer nuclear layer at all 1 mm, 2 mm, and 3 mm points showed a statistically significant decrease in thickness at the final visit compared with baseline. The annual decrease rates were -1.2 µm/year at 1 mm (total -6.6%), -1.3 µm/year at 2 mm (total -8.4%), and -1.1 µm/year at 3 mm (total -9.7%) for ganglion cell-inner plexiform layer and -0.6 µm/year at 1 mm (total -4.2%), -0.5 µm/year at 2 mm (total -3.9%), and -0.4 µm/year at 3 mm (total -4.1%) for outer nuclear layer. CONCLUSION: Aging plays a significant role in the reduction of ganglion cell-inner plexiform layer and outer nuclear layer thicknesses in cognitively healthy elderly individuals.

Feasibility of Simultaneous Anodal Transcranial Direct Current Stimulation During Gait Training in Chronic Stroke Patients: A Randomized Double-Blind Pilot Clinical Trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a therapeutic tool for improving post-stroke gait disturbances, with ongoing research focusing on specific protocols for its application. We evaluated the feasibility of a rehabilitation protocol that combines tDCS with conventional gait training. METHODS: This was a randomized, double-blind, single-center pilot clinical trial. Patients with unilateral hemiplegia due to ischemic stroke were randomly assigned to either the tDCS with gait training group or the sham stimulation group. The anodal tDCS electrode was placed on the tibialis anterior area of the precentral gyrus while gait training proceeded. Interventions were administered 3 times weekly for 4 weeks. Outcome assessments, using the 10-meter walk test, Timed Up and Go test, Berg Balance Scale, Functional Ambulatory Scale, Modified Barthel Index, and European Quality of Life 5 Dimensions 3 Level Version, were conducted before and after the intervention and again at the 8-week mark following its completion. Repeated-measures analysis of variance (ANOVA) was used for comparisons between and within groups. RESULTS: Twenty-six patients were assessed for eligibility, and 20 were enrolled and randomized. No significant differences were observed between the tDCS with gait training group and the sham stimulation group in gait speed after the intervention. However, the tDCS with gait training group showed significant improvement in balance performance in both within-group and between-group comparisons. In the subgroup analysis of patients with elicited motor-evoked potentials, comfortable pace gait speed improved in the tDCS with gait training group. No serious adverse events occurred throughout the study. CONCLUSIONS: Simultaneous anodal tDCS during gait training is a feasible rehabilitation protocol for chronic stroke patients with gait disturbances. CLINICAL TRIAL REGISTRATION: URL: https://cris.nih.go.kr; Registration number: KCT0007601; Date of registration: 11 July 2022.

Immunogenicity and Potential for Intraocular Inflammation of Intravitreal Anti-VEGF Drugs.

Background: Concerns of intraocular inflammation associated with intravitreal administration of anti-VEGF drugs have been risen and the exact mechanism is not yet elucidated. Objective: To explore the relationship between immunogenicity and intraocular inflammation in intravitreal anti-VEGF drugs. Methods: This review examines the immunogenicity of individual intravitreal anti-VEGF drugs and their potential link to intraocular inflammation. Results: We suggest that the main cause of intraocular inflammation is the presence of pre-existing and treatment-induced antidrug antibodies, along with considerations related to the molecular structure, which includes the drug's format and size. Conclusions: Researchers and clinicians involved in the advancement of new anti-VEGF drugs should take into consideration the factors related to intraocular inflammation that have been discussed.

Laser and anti-vascular endothelial growth factor treatment for drusenoid pigment epithelial detachment in age-related macular degeneration: 24-month outcomes.

PURPOSE: After the 12-month interim safety analysis, we investigated the 24-month primary endpoint outcomes of drusenoid pigment epithelial detachment (dPED) after laser and intravitreal anti-VEGF treatment. METHODS: Twenty-one patients with treatment-naïve bilateral intermediate AMD with dPED and visual acuity ≤ 83 letters (Snellen 20/23) were enrolled. The subject eye received low-energy PASCAL® laser (532 nm) treatment, and the fellow eye was used as the control. Intravitreal injections were administered at 3-month intervals from baseline to 12 months. Treatment outcomes, safety and development of advanced AMD lesions were analyzed. RESULTS: The mean drusen area and dPED height were significantly reduced (17.3 ± 2.7% vs. 112.8 ± 3.1%, P < 0.001 and 11.8 ± 4.7% vs. 119.1 ± 4.6%, P < 0.001, respectively) and the mean BCVA improved (5.11 ± 1.35 vs. 0.83 ± 1.03 letters, P = 0.014) in the study eyes compared to those in the control eyes. Development of parafoveal iRORA (nGA) (67%, 12 of 18 eyes) and cRORA (GA) (22%, 4 of 18 eyes) was observed in the study eyes, whereas three cases of iRORA and cRORA in the control eyes (17%, 3 of 18 eyes; P = 0.010 and P = 0.791, respectively). CONCLUSIONS: Laser and anti-VEGF treatment may be a potential treatment option for intermediate AMD with dPED. However, considering the relatively high rate of secondary iRORA and cRORA development, long-term follow-up is mandatory to clarify the safety and efficacy of this treatment.

Normal to supernormal 30-Hz flicker ERGs predict visual function and prognosis in central retinal artery occlusion.

PURPOSE: To determine whether normal to supernormal 30-Hz flicker ERGs are associated with visual function and prognosis in patients with central retinal artery occlusion (CRAO). METHODS: A total of 133 patients diagnosed with unilateral acute non-arteritic CRAO by examination with electroretinography (ERG) were examined. Thirty-hertz flicker ERG amplitudes were analyzed according to the severity of CRAO, and their correlation with visual function and prognosis was assessed. All patients were categorized into one of three groups according to the flicker ERG amplitude ratios between affected and fellow eyes: ≥ 110%, supernormal; 90-110%, normal; and < 90%, subnormal. RESULTS: Thirty-hertz flicker ERG parameters differed significantly according to the severity of retinal ischemia, i.e., between incomplete versus complete CRAO: mean amplitude (55.89 ± 24.38 > 45.41 ± 23.47 µV, P = 0.029), amplitude ratio (76.1 ± 23.1% > 58.7 ± 25.7%, P < 0.001), and proportion of normal to supernormal flicker ERGs (30.5% > 12.4%, P < .001). One-month and final follow-up visual function and prognosis were better in the normal to supernormal flicker ERGs: 1 month BCVA (1.55 ± 0.65 > 2.05 ± 0.61 logMAR, P < .001), final BCVA (1.32 ± 0.79 > 1.97 ± 0.68 logMAR, P < .001), 1-month VA improvement (- 0.50 ± 0.47 > - 0.10 ± 0.29 logMAR, P < .001), and final VA improvement (- 0.74 ± 0.61 > - 0.18 ± 0.37 logMAR, P < .001). CONCLUSIONS: Normal to supernormal 30-Hz flicker ERG changes in eyes with CRAO are associated with the milder severity of retinal ischemia and showed better visual function and outcome than the subnormal ERG group.

A Prediction Model for the Intraocular Pharmacokinetics of Intravitreally Injected Drugs Based on Molecular Physicochemical Properties.

PURPOSE: This study was aimed at determining the intraocular pharmacokinetics based on molecular physicochemical properties in a rabbit model. METHODS: The entire dataset was obtained from previous literature, and research articles regarding 70 molecular compounds were investigated. The intravitreal half-lives in rabbit eyeballs of 22 macromolecules and 48 micromolecules were analyzed. Multiple linear regression analysis was carried out with non-collinear independent variables (molecular weight [MW] and lipophilicity) influencing intravitreal half-lives. The best-fit equations were selected based on the correlation coefficients and goodness-of-fit statistics. RESULTS: The best-fit models obtained from the entire dataset, macromolecules, and micromolecules suggest the correlation between molecular physicochemical properties (MW and lipophilicity) and intravitreal half-life. Exclusion of outlier molecules (amphotericin B and foscarnet) leads to a better-fit correlation. MW is the definite single factor affecting intravitreal half-lives of macromolecules (Log t1/2 = 0.148 + 0.370 Log MW, R2 = 0.769), while both MW and lipophilicity influence the intraocular pharmacokinetics of micromolecules (Log t1/2 = -1.213 + 0.762 Log MW - 0.115 Log p, R2 = 0.554). CONCLUSION: The present study indicates that intravitreal half-life could be predicted based on molecular physicochemical properties (MW and lipophilicity). Also, increasing MW while reducing lipophilicity would be a reliable method for prolonging the intravitreal half-life of small chemical drugs, while MW is the single major determinant for large biologic drugs.

Prevalence and incidence of sarcoidosis in Korea: a nationwide population-based study.

BACKGROUND: The prevalence and incidence of sarcoidosis varies worldwide. We estimated the prevalence and incidence of sarcoidosis in Korea using nationwide claims data from the Korean Health Insurance Review and Assessment Service. METHODS: Cases of sarcoidosis were identified for any visit between 2007 to 2016 that listed the Korean Classification of Disease, 7th edition code of sarcoidosis and rare incurable disease exempted calculation code. A narrow case definition was used as follows: 1) ≥ two sarcoidosis-coded visits within 1 year of the first claim, 2) no claims for other diseases that could form granuloma. RESULTS: A total of 4791 patients (narrow, n = 2388) visited medical institutions for sarcoidosis during the study period; 2999 patients (narrow, n = 1696) were newly identified between 2009 and 2015. The sarcoidosis prevalence was 9.37 per 105 people (narrow, 4.69) and was highest between ages 60-69 years. The incidence rate was 0.85 per 105 population at risk (narrow, 0.48), with the highest incidence rate between ages 50-59 years. For incident cases (mean age: 48.5 year), the age distribution in whole population and females showed monophasic patterns peaking at aged 50-59 years, while males had biphasic incidence peak at aged 30-39 years and 60-69 years. The annual incidence rates showed increasing trends from 0.85 per 105 population at risk in 2009 to 0.97 per 105 population at risk in 2015. CONCLUSIONS: In comparison with previous reports, the prevalence and incidence of sarcoidosis in Korea have increased and middle-aged women showed the highest risk.

Clinical characteristics of recurrent non-arteritic retinal artery occlusion.

OBJECTIVES: To investigate the recurrent non-arteritic retinal artery occlusion (RAO) in the same or opposite eye. METHODS: We searched the RAO registry at Seoul National University Bundang Hospital and included patients with recurrent RAO in the present study. Ophthalmic and systemic features were analysed to identify risk factors and visual outcomes. RESULTS: Of the 850 patients in the non-arteritic RAO cohort, 11 (1.3%) experienced a second RAO recurrence, either in the same (5 patients; 0.6%) or opposite (6 patients; 0.7%) eye. The same eye group experienced an earlier recurrence (1-2 months, median 1 month) than the opposite eye group, where the time to recurrence was notably longer (8-66 months, median 22 months). Best corrected visual acuity (BCVA) in the same eye group decreased after the recurrence of RAO. In the same eye group, initial BCVA ranged from 20/200 to counting fingers (CF), while BCVA during RAO recurrence ranged from CF to hand motion. When RAO recurred in the opposite eye, the reduction in visual acuity was less severe than the reduction of the initial episode: initial episode ranged from 20/400 to light perception and recurrent episode ranged from 20/25 to 20/400. Patients exhibited varying degrees of carotid (81.8%) and cerebral (9.1%) artery occlusions. Additionally, one patient in each group (total 2 patients, 18.2%) experienced a stroke 6 months after RAO recurrence. CONCLUSIONS: Since the RAO recurrences could lead to devastating visual impairment, it is essential to emphasise the importance of risk factor screening to patients while collaborating with neurologists and cardiologists.

Intraocular Concentration of Stem Cell Factor/c-KIT and Galectin-1 in Retinal Diseases.

Purpose: To investigate the intraocular concentration profiles of stem cell factor (SCF)/c-KIT, galectin-1 (GAL-1), and vascular endothelial growth factor (VEGF)-A with regard to retinal disease and treatment response. Methods: The study group included 13 patients with dry age-related macular degeneration (AMD), 196 with neovascular AMD (nAMD), 21 with diabetic macular edema (DME), 10 with retinal vein occlusion (RVO), and 34 normal subjects with cataracts. Aqueous humor levels of SCF, c-KIT, GAL-1, and VEGF-A were analyzed by immunoassay according to disease group and treatment response. Results: Increased aqueous levels of SCF, c-KIT, and GAL-1 were observed in eyes with nAMD (2.67 ± 3.66, 296.84 ± 359.56, and 3945.61 ± 5976.2 pg/mL, respectively), DME (1.64 ± 0.89, 238.80 ± 265.54, and 3701.23 ± 4340.54 pg/mL, respectively), and RVO (4.62 ± 8.76, 509.63 ± 647.58, and 9079.60 ± 11909.20 pg/mL, respectively) compared with controls (1.13 ± 0.24, 60.00 ± 0.00, and 613.27 ± 1595.12 pg/mL, respectively). In the eyes of nAMD, the levels of all three cytokines correlated positively with VEGF-A levels. After intravitreal injections of anti-VEGF agents, the levels of GAL-1 and VEGF-A decreased significantly, whereas those of SCF and c-Kit showed no significant change. Eyes of nAMD patients with improved vision after treatment had significantly lower levels of c-KIT, GAL-1, and VEGF-A at baseline. Conclusions: The intraocular levels of cytokines were significantly elevated in eyes with nAMD, DME, and RVO compared to the controls and they showed different response to anti-VEGF treatment. With this result and their known association with angiogenesis, these cytokines may be potential therapeutic targets for future research.

Joubert syndrome presenting bilateral peroneal neuropathies: A case report.

RATIONALE: Joubert syndrome (JS) is a rare genetic disorder that presents with various neurological symptoms, primarily involving central nervous system dysfunction. Considering the etiology of JS, peripheral nervous system abnormalities cannot be excluded; however, cases of JS accompanied by peripheral nervous system abnormalities have not yet been reported. Distinct radiological findings on brain magnetic resonance imaging were considered essential for the diagnosis of JS. However, recently, cases of JS with normal or nearly normal brain morphology have been reported. To date, there is no consensus on the most appropriate diagnostic method for JS when imaging-based diagnostic approach is challenging. This report describes the case of an adult patient who exhibited bilateral peroneal neuropathies and was finally diagnosed with JS through genetic testing. PATIENT CONCERNS AND DIAGNOSIS: A 27-year-old man visited our outpatient clinic due to a gait disturbance that started at a very young age. The patient exhibited difficulty maintaining balance, especially when walking slowly. Oculomotor apraxia was observed on ophthalmic evaluation. During diagnostic workups, including brain imaging and direct DNA sequencing, no conclusive findings were detected. Only nerve conduction studies revealed profound bilateral peroneal neuropathies. We performed whole genome sequencing to obtain a proper diagnosis and identify the gene mutation responsible for JS. LESSONS: This case represents the first instance of peripheral nerve dysfunction in JS. Further research is needed to explore the association between JS and peripheral nervous system abnormalities. Detailed genetic testing may serve as a valuable tool for diagnosing JS when no prominent abnormalities are detected in brain imaging studies.

Low Molecular Weight Collagen Peptide (LMWCP) Promotes Hair Growth by Activating the Wnt/GSK-3ß/ß-Catenin Signaling Pathway.

Low molecular weight collagen peptide (LMWCP) is a collagen hydrolysate derived from fish. We investigated the effects of LMWCP on hair growth using human dermal papilla cells (hDPCs), human hair follicles (hHFs), patch assay, and telogenic C57BL/6 mice, while also examining the underlying mechanisms of its action. LMWCP promoted proliferation and mitochondrial potential, and the secretion of hair growth-related factors, such as EGF, HB-EGF, FGF-4, and FGF-6 in hDPCs. Patch assay showed that LMWCP increased the neogeneration of new HFs in a dose-dependent manner. This result correlated with an increase in the expression of dermal papilla (DP) signature genes such as, ALPL, SHH, FGF7, and BMP-2. LMWCP upregulated phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin, and nuclear translocation of ß-catenin, and it increased the expression of Wnt3a, LEF1, VEGF, ALP, and ß-catenin. LMWCP promoted the growth of hHFs and increased the expression of ß-catenin and VEGF. Oral administration of LMWCP to mice significantly stimulated hair growth. The expression of Wnt3a, ß-catenin, PCNA, Cyclin D1, and VEGF was also elevated in the back skin of the mice. Furthermore, LMWCP increased the expression of cytokeratin and Keratin Type I and II. Collectively, these findings demonstrate that LMWCP has the potential to increase hair growth via activating the Wnt/ß-catenin signaling pathway.

The Effect of Repetitive Transcranial Magnetic Stimulation on Cognition in Diffuse Axonal Injury in a Rat Model.

Diffuse axonal injury (DAI) following sudden acceleration and deceleration can lead to cognitive function decline. Various treatments have been proposed. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive stimulation technique, is a potential treatment for enhancing neuroplasticity in cases of brain injury. The therapeutic efficacy of rTMS on cognitive function remains unconfirmed. This study investigated the effects of rTMS and the underlying molecular biomechanisms using a rat model of DAI. Sprague-Dawley rats (n = 18) were randomly divided into two groups: one receiving rTMS after DAI and the other without brain stimulation. All rats were subjected to sudden acceleration and deceleration using a DAI modeling machine to induce damage. MRI was performed to confirm the DAI lesion. The experimental group received rTMS at a frequency of 1 Hz over the frontal cortex for 10 min daily for five days. To assess spatial memory, we conducted the Morris water maze (MWM) test one day post-brain damage and one day after the five-day intervention. A video tracking system recorded the escape latency. After post-MWM tests, all rats were euthanized, and their brain tissues, particularly from the hippocampus, were collected for immunohistochemistry and western blot analyses. The escape latency showed no difference on the MWM test after DAI, but a significant difference was observed after rTMS between the two groups. Immunohistochemistry and western blot analyses indicated increased expression of BDNF, VEGF, and MAP2 in the hippocampal brain tissue of the DAI-T group. In conclusion, rTMS improved cognitive function in the DAI rat model. The increased expression of BDNF, VEGF, and MAP2 in the DAI-T group supports the potential use of rTMS in treating cognitive impairments associated with DAI.

Effects of self-efficacy, self-esteem, and disability acceptance on the social participation of people with physical disabilities: Focusing on COVID-19 pandemic.

PURPOSE: The objective of this study was to understand the effects of self-efficacy, self-esteem, and the degree of disability acceptance of people with physical disabilities living in COVID-19 pandemic on their social participation. METHODS: Among the 4577 registered disabled people who participated in the 2nd wave of the Panel Survey of Employment for the Disabled (PSED), 1682 people with physical disabilities who faithfully answered all the survey items were selected as the final study subjects. This study used the variables of social participation, self-efficacy, self-esteem, and disability acceptance, which were validated by experts' review and consulting and research at the Korea Employment Agency for Persons with Disability. Pearson's correlation analysis and multiple linear regression analysis were performed to identify variables that could predict the social participation of the study subjects. RESULTS: The self-efficacy, self-esteem, and the degree of disability acceptance of people with physical disabilities were positively correlated with social participation. The results of this study showed that self-efficacy, self-esteem, the degree of disability acceptance, economic activity, and education level explained 22.4% of social participation. CONCLUSIONS: It was found that self-efficacy, self-esteem, and the degree of disability acceptance of people with physical disabilities were important variables affecting social participation. These psychoemotional variables shall be considered for intervention approaches to improve the social participation of people with physical disabilities in the future.

Impacts of Daily Life and Job Satisfaction on Social Participation of Persons with Visual Impairment.

Objective: This study is aimed at providing baseline data for improving the social participation of persons with visual impairment by verifying the impacts of daily life satisfaction and job satisfaction on their social participation. Methods: This study utilized data from the 5th survey of the 2nd wave of the Panel Survey of Employment for the Disabled (PSED) provided by the Korea Employment Agency for Persons with Disabilities (KEAD). Of the 511 persons with visual impairment who participated in the panel survey, 151 people who met the inclusion criteria were selected as the research subjects. This study compared social participation, job satisfaction, and daily life satisfaction, which were validated by experts' review, consulting, and research at the KEAD. Results: Daily life satisfaction and job satisfaction of persons with visual impairment had positive correlations with social participation. Job satisfaction had a statistically significant impact on social participation. Additionally, the stability of employment and monthly income were the variables affecting social participation. Conclusion: The result drawn in this study can be applied as basic data related to the social participation of people with visual impairment.

Atypical progress of frozen shoulder after COVID-19 vaccination: A case report.

BACKGROUND: After vaccination was mandated worldwide, various adverse effects associated with the coronavirus disease 2019 (COVID-19) vaccination, including shoulder pain, have been reported. Here, we report a case of new-onset shoulder pain after BNT162b2 (Comirnaty, Pfizer-BioNTech) mRNA vaccination. CASE SUMMARY: A 50-year-old man visited our rehabilitation center with left shoulder range of motion (ROM) limitation that had persisted for more than 5 mo. The history included no specific noteworthy events, except vaccination. The pain in the patient's left deltoid muscle appeared 1 day after the second BNT162b2 vaccination and intensified to severe pain. The patient self-administered aspirin, with which the pain subsided immediately, whereas ROM limitation persisted. At the first visit, the patient complained of dull pain and ROM restriction of the left shoulder (flexion 130°, abduction 110°, and external rotation 40°). Among the diagnostic studies conducted for the evaluation of the shoulder, magnetic resonance imaging showed a thickened coracohumeral ligament. Nerve conduction studies and needle electromyography showed no electrodiagnostic abnormalities. The patient received comprehensive rehabilitation for 7 mo and had an overall improvement in pain and ROM of the left shoulder. CONCLUSION: In this case of severe shoulder pain after COVID-19 vaccination that subsided immediately with aspirin treatment, the exact cause and mechanism of pain are unclear. However, the clinical symptoms and diagnostic workups in our report suggest the possibility that the COVID-19 vaccination triggered an immunochemical response that resulted in shoulder pathology.

Presence of Embolic Source and Outcome in Central Retinal Artery Occlusion.

OBJECTIVES: The etiology of central retinal artery occlusion (CRAO) is unclear in approximately 50% of patients, suggesting pathomechanical heterogeneity; moreover, little is known about outcomes according to etiology. This study investigated whether the presence of an embolic source affects outcome in CRAO. METHODS: CRAO patients within 7 days of symptom onset were retrospectively enrolled. Clinical parameters, including initial and 1-month visual acuity, CRAO subtype, and brain images, were reviewed. CRAO etiology was categorized as CRAO with or without an embolic source (CRAO-E+ and CRAO-E-). Visual improvement was defined as a decrease in logarithm of the minimum angle of resolution ≥0.3 at 1 month. RESULTS: A total of 114 patients with CRAO were included. Visual improvement was noted in 40.4% of patients. Embolic sources were identified in 55.3% of patients, and visual improvement group rather than no improvement group was more commonly associated with the presence of an embolic source. In multivariable logistic regression analysis, CRAO-E+ independently predicted visual improvement (odds ratio 3.00, 95% CI 1.15-7.81, p = 0.025). DISCUSSION: CRAO-E+ was found to be associated with a better outcome. CRAO-E+ may be more prone to recanalization than that CRAO-E-.

High-performance biosensor using a sandwich assay via antibody-conjugated gold nanoparticles and fiber-optic localized surface plasmon resonance.

For real-time and high-sensitivity analysis of low-concentration targets, a sandwich immunoassay using second antibody-second gold nanoparticle (2nd Ab-2nd AuNP) conjugates was combined with fiber-optic localized surface plasmon resonance (FO LSPR). An FO LSPR format was constructed by immobilizing AuNPs on a fiber-optic cross-section for compactness, portability, and ease of handling. In addition, it was combined with a microfluidic system to ensure reproducibility and reliability of measurements. A detection limit of 97.6 fg/mL (148 aM) was obtained for thyroglobulin (Tg) without a sandwich assay. The detection limit was enhanced by approximately 15 times (6.6 fg/mL, 10 aM) when a sandwich strategy was performed with a 2nd Ab-2nd AuNP signal amplifier to further improve the responsivity. Additionally, the good selectivity of the proposed method was confirmed against the unpaired antigen. To evaluate its practical applicability in the field, an FO LSPR biosensor boosted with a sandwich assay using antibody-functionalized AuNPs was applied to detect Tg contained in patient serum, and the results were compared and verified with those of a commercial radioimmunoassay kit. Based on the above results, the signal-enhancing immunoassay with FO LSPR will contribute to the development of optical biosensors for early diagnosis and preventive applications.

Fiber Optic Plasmonic Sensors Based on Nanodome Arrays with Nanogaps.

In this study, a high-performance fiber optic surface plasmon resonance (FO-SPR) sensor using a dome array with nanogaps (DANG) is proposed for label-free real-time detection of biomolecules. A novel and simple method using polymer beads enables high sensitivity by allowing hotspots with nanometer spacing between the Au dome and the surrounding film. The nanodome structure, which comprises a polymer core and a Au shell, induces a localized surface plasmon, expands the sensing area, and extensively enhances the electromagnetic field. The refractive index sensitivity of the FO-SPR sensor with nanostructures, i.e., with nanogaps and nanodomes, was found to be 7.8 times higher than that of the FO-SPR sensor without nanostructures. The proposed sensor achieved a low detection limit of 38 fg/mL while quantifying thyroglobulin antibody-antigen interactions and exhibited excellent selectivity. In addition, it helped detect serum samples with a 103% recovery rate.

Colorimetric screening of elevated urinary mercury levels by a novel Hg2+-selective probe of resorufin phosphinothioate.

Urinary mercury levels are the most reliable indicators of mercury exposure but identifying them requires complex techniques and heavy instruments. In this research, we reported a simple and convenient urinary mercury analysis method using a readily available office scanner. Probe MP-1 synthesized by the reaction of resorufin and dimethylthiophosphinoyl chloride revealed Hg2+-selective chromogenic and fluorescent signaling behavior. Signaling was realized through Hg2+-induced deprotection of the phosphinothioate protecting group in the resorufin-based probe MP-1 to yield the parent fluorochrome. A pronounced colorimetric response of color change from light yellow to pink alongside a turn-on type fluorescence enhancement was perceived exclusively toward Hg2+ ions over other metal ions and anions. The colorimetry provided a more advantageous ratiometric approach than the simple fluorometric analysis exhibiting an off-on type response, with a detection limit of 12 nM (2.4 ppb). The Hg2+ signaling of the MP-1 probe was not disturbed by the presence of coexisting metal ions and anions. The sensitive and convenient diagnosis of clinically important neurological symptoms and fatal inorganic mercury levels in urine was successfully demonstrated using a standard office scanner.

Protective Effect of Ribes nigrum Extract against Blue Light-Induced Retinal Degeneration In Vitro and In Vivo.

Although blackcurrant has several health benefits, such as antioxidant and anti-inflammatory properties, its effects on the retina remain unclear. In this study, we investigated the efficacy of black currant extract (BCE) in an in vitro and in vivo model of dry age-related macular degeneration (AMD) induced by blue light. Dry macular degeneration is characterized by the abnormal accumulation of lipofuscin (e.g., N-retinylidene-N-retinylethanolamine, A2E) in the retina. Blue light (BL) significantly decreased the viability of A2E-laden human retinal pigment epithelial cells (ARPE-19). However, BCE treatment protected ARPE-19 cells from A2E and BL. A2E, which is oxidized by blue light, generates reactive oxygen species in RPE cells. Treatment with BCE significantly decreased (80.8%) reactive oxygen species levels induced by A2E and BL in a concentration-dependent manner. BCE inhibited A2E accumulation in ARPE-19 cells and significantly downregulated the expression of genes increased by A2E and BL in ARPE-19 cells. In vivo, oral administration of BCE (25-100 mg/kg) ameliorated ocular lesions of BL-induced retinal damage in a mouse model and rescued the thickness of the whole retina, photoreceptor segment layer, outer nuclear layer, and inner nuclear layer. The decrease in the number of nuclei in the outer nuclear layer induced by BL was also rescued by BCE. Additionally, BCE administration rescued (40.0%) the BL-induced reduction in the expression level of superoxide dismutase 1. Taken together, our results suggest that BCE may have preventive and therapeutic effects on dry AMD through its antioxidant activity and inhibition of lipofuscin accumulation in the retina.