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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.

Background: Despite the effectiveness of cardiac rehabilitation (CR), the actual participation rate in CR is low. While home-based CR offers a viable alternative, it faces challenges in participation due to factors such as a lack of self-motivation and fear of exercising without supervision. Utilizing a mobile healthcare application (app) during counseling may be an effective strategy for patients. Therefore, the aim of this study was to assess whether 6 weeks of home-based CR with exercise readjustment using a mobile app is an effective therapy for patients with acute myocardial infarction (AMI). Methods: Post-AMI patients eligible for home-based CR were randomized into the intervention group (CR-Mobile) and the control group, which followed the usual home-based CR protocol (CR-Usual). Both groups participated in a 6-week home-based CR program, with exercise readjustment and encouragement carried out every 2 weeks. The CR-Mobile group was supervised using data recorded in the mobile app, while the CR-Usual group was supervised via phone consultations. The primary outcome measured was maximal oxygen consumption (VO2max). Results: Within-group comparisons showed significant improvements in VO2max (PCR-Mobile = 0.011 vs. PCR-Usual = 0.020) and METs (PCR-Mobile = 0.011 vs. PCR-Usual = 0.011) for both groups. Conclusions: These findings suggest that a 6-week home-based CR program with exercise readjustment using a mobile app can potentially enhance exercise capacity as effectively as verbal supervision.

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.

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.

Abstract 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.

Abstract A simple optical fiber sensor based on localized surface plasmon resonance was constructed for direct and rapid measurement of thyroglobulin (Tg). Specific tests for Tg in patients that have undergone thyroidectomy are limited because of insufficient sensitivity, complicated procedures, and in some cases, a long time to yield a result. A sensitive, fast, and simple method is necessary to relieve the psychological and physical burden of the patient. Various concentrations of Tg were measured in a microfluidic channel using an optical fiber sensor with gold nanoparticles. The sensor chip has a detection limit of 93.11 fg/mL with no specificity for other antigens. The potential applicability of the Tg sensing system was evaluated using arbitrary samples containing specific concentrations of Tg. Finally, the sensor can be employed to detect Tg in the patient’s serum, with a good correlation when compared with the commercial kit.

Abstract Fiber optic based localized surface plasmon resonance (FO-LSPR) sensor is one of the biosensors that detects specific biomolecules and can detect the onset of disease. In this paper, we propose two methods to improve the signal to noise ratio (SNR) of the sensor, which is one of the main characteristics of the FO-LSPR sensor. The first method is to increase the intensity of the sensor by increasing the size of gold nanoparticle (Au NP) formed on the optical fiber surface by Au capping method. The second method is to form a structure that reduces the reflection by increasing the roughness of the surface by etching the surface of the optical fiber using the Au NP formed on the surface of the optical fiber as a mask. Increasing the roughness of the optical fiber surface can reduce the background signal of the sensor. The two methods mentioned above can increase the SNR of the sensor. When the SNR of the sensor is increased, the efficiency of the sensor is improved.

Abstract We propose a novel localized surface plasmon resonance (LSPR) sensor system based on polymer material. The proposed LSPR system consists of the incident medium with low-loss polymer waveguide and the chemically immobilized plasmonic nanoparticles for on-chip LSPR sensing. Because of low coupling efficiency of conventional methods, usually intricate test equipment such as dark field microscopes equipped with cooled charge-coupled device detectors is required to perform nanoparticles LSPR sensing. Using a polymer optical waveguide instead of conventional free-space excitation techniques (e.g., using an objective lens) in the LSPR sensing system offers miniaturization, low cost, and potable sensing capability. The integration of this hybrid plasmonic-photonic sensor with optical system based on fiber optic is measured to refractive index with a sensitivity of 3.10/RIU.

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.

Since pluripotent embryonic stem cell (ESC) lines were first derived from the mouse, tremendous efforts have been made to establish ESC lines in several domestic species including the pig; however, authentic porcine ESCs have not yet been established. It has proven difficult to maintain an ESC-like state in pluripotent porcine cell lines due to the frequent occurrence of spontaneous differentiation into an epiblast stem cell (EpiSC)-like state during culture. We have been able to derive EpiSC-like porcine ESC (pESC) lines from blastocyst stage porcine embryos of various origins, including in vitro fertilized (IVF), in vivo derived, IVF aggregated, and parthenogenetic embryos. In addition, we have generated induced pluripotent stem cells (piPSCs) via plasmid transfection of reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) into porcine fibroblast cells. In this study, we analyzed characteristics such as marker expression, pluripotency and the X chromosome inactivation status in female of our EpiSC-like pESC lines along with our piPSC line. Our results show that these cell lines demonstrate the expression of genes associated with the Activin/Nodal and FGF2 pathways along with the expression of pluripotent markers Oct4, Sox2, Nanog, SSEA4, TRA 1-60 and TRA 1-81. Furthermore all of these cell lines showed in vitro differentiation potential, the X chromosome inactivation in female and a normal karyotype. Here we suggest that the porcine species undergoes reprogramming into a primed state during the establishment of pluripotent stem cell lines.

Abstract 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.

[This corrects the article DOI: 10.1371/journal.pone.0209118.].

In this study, Retina-RPE-Choroid-Sclera (RCS) and RPE-Choroid-Sclera (CS) were prepared by scraping them off neural retina, and using the Ussing chamber we measured the average time–concentration values in the acceptor chamber across five isolated rabbit tissues for each drug molecule. We determined the outward direction permeability of the RCS and CS and calculated the neural retina permeability. The permeability coefficients of RCS and CS were as follows: ganciclovir, 13.78 ± 5.82 and 23.22 ± 9.74; brimonidine, 15.34 ± 7.64 and 31.56 ± 12.46; bevacizumab, 0.0136 ± 0.0059 and 0.0612 ± 0.0264 (×10−6 cm/s). The calculated permeability coefficients of the neural retina were as follows: ganciclovir, 33.89 ± 12.64; brimonidine, 29.83 ± 11.58; bevacizumab, 0.0205 ± 0.0074 (×10−6 cm/s). Between brimonidine and ganciclovir, lipophilic brimonidine presented better RCS and CS permeability, whereas ganciclovir showed better calculated neural retinal permeability. The large molecular weight drug bevacizumab demonstrated a much lower permeability than brimonidine and ganciclovir. In conclusion, the ophthalmic drug permeability of RCS and CS is affected by the molecular weight and lipophilicity, and influences the intravitreal half-life.

Treatment options for retinal diseases, such as neovascular age-related macular degeneration, diabetic retinopathy, and retinal vascular disorders, have markedly expanded following the development of anti-vascular endothelial growth factor intravitreal injection methods. However, because intravitreal treatment requires monthly or bimonthly repeat injections to achieve optimal efficacy, recent investigations have focused on extended drug delivery systems to lengthen the treatment intervals in the long term. Dose escalation and increasing molecular weight of drugs, intravitreal implants and nanoparticles, hydrogels, combined systems, and port delivery systems are presently under preclinical and clinical investigations. In addition, less invasive techniques rather than intravitreal administration routes, such as topical, subconjunctival, suprachoroidal, subretinal, and trans-scleral, have been evaluated to reduce the treatment burden. Despite the latest advancements in the field of ophthalmic pharmacology, enhancing drug efficacy with high ocular bioavailability while avoiding systemic and local adverse effects is quite challenging. Consequently, despite the performance of numerous in vitro studies, only a few techniques have translated to clinical trials. This review discusses the recent developments in ocular drug delivery to the retina, the pharmacokinetics of intravitreal drugs, efforts to extend drug efficacy in the intraocular space, minimally invasive techniques for drug delivery to the retina, and future perspectives in this field.