Hypertension Medication and Medicare Beneficiaries: Prescription Drug Coverage Satisfaction and Medication Non-Adherence among Older Adults.

Hypertension is so prevalent and requires strict adherence to medications to prevent further disease or death, but there is no study examining factors related to prescription drug non-adherence among 65 years old and older. This study aims to assess the likelihood of medication nonadherence among patients based on factors such as age, race, and socioeconomic status, with the goal of identifying strategies to enhance medication adherence and mitigate associated health risks. Using the 2020 Medicare Current Beneficiary Survey Public Use File to represent nationwide Medicare beneficiaries (unweighted n = 3917, weighted n = 27,134,782), medication non-adherence was related to multiple independent variables (i.e., age, sex, race/ethnicity, socioeconomic status, comorbidities, insurance coverage, and satisfaction with insurance). Cross-tabulations and Wald chi-square tests were used to determine how much each variable was related to non-adherence. Multivariate logistic regression was used to examine the association between medication non-adherence and factors such as prescription drug coverage satisfaction and cost-reducing behavior. Specific trends in medication non-adherence emerged among beneficiaries. Non-adherence was higher in older adults aged 65- to 74-year-olds and those with more chronic conditions (OR = 2.24; 95% CI = 1.74-2.89). If patients were dissatisfied with the medications on the insurance formulary or struggled to find a pharmacy that accepted their medication coverage, they had worse adherence (OR = 2.63; 95% CI = 1.80-3.84). Formulary and coverage must be expanded to improve adherence to antihypertensive medications in Medicare beneficiaries. Older adults aged 65 to 74 years may be less adherent to their medications because they do not see the seriousness of the disease and could benefit from further counseling. Patients with limited activities of daily living and more comorbidities may struggle with complex treatment regimens and should use adherence assistance tools.

A Bee Trp-Arg Dense Peptide with Antiproliferation Efficacy against the Prostate Cancer Cell Line DU145.

Prostate cancer accounts for 14% of male cancer-related fatalities in the UK. Given the challenges associated with hormone-based therapies in the context of androgen-independent prostate cancer, there is an imperative need for research into anticancer drugs. N0821, a peptide belonging to the Trp-Arg dense region and derived from the homologous region of various bee species, shows substantial potential for an anticancer effect. Both MTT assays and 3D spheroid assays were conducted to substantiate its antiproliferation potential and strongly indicated the antiproliferation effect of N0820 (WWWWRWWRKI) and N0821 (YWWWWRWWRKI). Notably, the mechanism underlying this effect is related to the downregulation of CCNA2 and the upregulation of CCNE1. Cell cycle arrest results from the reduction of CCNA2 in the S/G2 phase, leading to the accumulation of CCNE1. Our peptides were predicted to make an α-helix structure. This can act as an ion channel in the cell membrane. Therefore, we analyzed genes implicated in the influx of calcium ions into the mitochondria. Trp-Arg dense-region peptides are known for their antibacterial properties in targeting cell membranes, making the development of resistance less likely. Hence, further research in this area is essential and promising.

Association between albuminuria and retinal microvascular parameters measured with swept-source optical coherence tomography angiography in patients with diabetic retinopathy.

PURPOSE: To evaluate the relationship between urine albumin excretion (UAE) and retinal microvascular parameters assessed using swept-source optical coherence tomography angiography (SS-OCTA) in patients with diabetic retinopathy (DR). METHODS: This retrospective cross-sectional study included 180 patients with diabetes and 50 age-matched controls. Patients with diabetes were grouped according to the five-stage DR severity, combined with the presence of albuminuria. All subjects underwent 12×12mm2 field SS-OCTA. The foveal avascular zone metrics, vessel density, and capillary nonperfusion area (NPA) were quantified using a semi-automatic software algorithm on three different rectangular fields (3×3 mm2, 6×6 mm2, and 10×10 mm2). The correlations between albuminuria and the four OCTA parameters were analyzed. RESULTS: A total of 105 subjects had normal UAE, and 75 subjects had albuminuria. Of the 102 subjects whose DR severity was higher than mild non-proliferative DR (NPDR), capillary NPA on the 3×3 mm2, 6×6 mm2, and 10×10 mm2 fields was significantly larger in the albuminuria group. None of the OCTA parameters were significantly different between the two groups in subjects with mild NPDR or without DR. Multiple logistic regression analysis showed that an increase in NPA in the 6×6 mm2 and 10×10 mm2 fields was a significant risk factor for the presence of albuminuria (odds ratio = 1.92 and 1.35). CONCLUSION: An increase in capillary NPA was independently associated with albuminuria in patients with clinically significant DR levels. SS-OCTA imaging can be a useful marker for the early detection of diabetic nephropathy.

Evaluation of the Drug-Induced Liver Injury Potential of Saxagliptin through Reactive Metabolite Identification in Rats.

A liver injury was recently reported for saxagliptin, which is a dipeptidyl peptidase-4 (DPP-4) inhibitor. However, the underlying mechanisms of saxagliptin-induced liver injury remain unknown. This study aimed to evaluate whether saxagliptin, a potent and selective DPP-4 inhibitor that is globally used for treating type 2 diabetes mellitus, binds to the nucleophiles in vitro. Four DPP-4 inhibitors, including vildagliptin, were evaluated for comparison. Only saxagliptin and vildagliptin, which both contain a cyanopyrrolidine group, quickly reacted with L-cysteine to enzyme-independently produce thiazolinic acid metabolites. This saxagliptin-cysteine adduct was also found in saxagliptin-administered male Sprague-Dawley rats. In addition, this study newly identified cysteinyl glycine conjugates of saxagliptin and 5-hydroxysaxagliptin. The observed metabolic pathways were hydroxylation and conjugation with cysteine, glutathione, sulfate, and glucuronide. In summary, we determined four new thiazoline-containing thiol metabolites (cysteine and cysteinylglycine conjugates of saxagliptin and 5-hydroxysaxagliptin) in saxagliptin-administered male rats. Our results reveal that saxagliptin can covalently bind to the thiol groups of cysteine residues of endogenous proteins in vivo, indicating the potential for saxagliptin to cause drug-induced liver injury.

Seven-year outcomes of combined treatment of anti-vascular endothelial growth factor with photodynamic therapy for polypoidal choroidal vasculopathy; according to polypoidal lesion regression.

PURPOSE: To evaluate the long-term prognosis of polypoidal choroidal vasculopathy (PCV) treated with anti-vascular endothelial growth factor (anti-VEGF) combined with verteporfin photodynamic therapy (PDT), according to polypoidal lesion regression. METHODS: This study retrospectively reviewed the data of 33 naïve eyes with PCV treated with anti-VEGF combined with verteporfin PDT and followed-up for at least 7 years. The collected data included demographic profile, best-corrected visual acuity (BCVA), central foveal thickness (CFT), PED volume, and presence of submacular hemorrhage. Regression of polypoidal lesion was determined using indocyanine green angiography and optical coherence tomography. All eyes were divided into regression or persistent groups, based on the polypoidal lesion regression one year after the initial combined treatment. RESULTS: BCVA improvement was maintained for 3 years in the regression (p = 0.001) and 1 year in the persistent (p = 0.006) groups, respectively. The mean BCVA of the regression group was better than that of the persistent group over 7 years, but the difference was significant only at 1 year (p = 0.037). The number of eyes which maintained BCVA less than or equal to 0.3 logMAR at 7 years was 11 eyes (64.7%) in regression group and 4 eyes (25.0%) in persistent group (p = 0.022). CONCLUSIONS: Regression of the polypoidal lesion at 1 year after the initial combination treatment was associated with favorable long-term visual prognosis, particularly in terms of maintaining good visual acuity.

Diagnosing Polypoidal Choroidal Vasculopathy Using Color Fundus Photography, Optical Coherence Tomography, and Optical Coherence Tomography Angiography.

PURPOSE: To compare the diagnostic accuracy of differentiating polypoidal choroidal vasculopathy (PCV) from exudative age-related macular degeneration (AMD), using color fundus photography (CFP), optical coherence tomography (OCT), and swept-source OCT angiography (SS-OCTA) without using indocyanine green angiography (ICGA). METHODS: Treatment-naive eyes with exudative AMD that underwent CFP, OCT, SS-OCTA, and ICGA imaging before treatment were identified. Images of each patient were categorized into two sets (set A, CFP + OCT; set B, CFP + SS-OCTA). In set B, both the en face and cross-sectional B scans were analyzed. Each set was reviewed by two graders, and it was determined whether the presumed diagnosis was PCV. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for the diagnosis of PCV were assessed for each set by comparing diagnoses that included ICGA. The number of polypoidal lesions in each set was calculated and compared to ICGA. RESULTS: A total of 94 eyes from 94 patients with AMD were included in the study, of which 66.0% were male, and the mean age was 71.8 ± 9.0 years. The PCV diagnosis rate using ICGA was 45.7%. The sensitivity was 0.88 for set A and 0.93 for set B, while the specificity was 0.94 for set A and 0.96 for set B. The AUC was 0.90 (95% confidence interval [CI], 0.83-0.97) for set A and 0.96 (95% CI, 0.90-1.00) for set B. Set A detected 1.28 ± 0.91 polypoidal lesions, while set B detected 1.47 ± 1.01; ICGA showed 1.51 ± 0.86. CONCLUSIONS: This study highlights that, without using ICGA, both CFP combined with OCT and CFP combined with SS-OCTA demonstrate high sensitivity, specificity, and AUC in diagnosing PCV. It is evident that SS-OCTA contributes to enhancing sensitivity, specificity, and AUC for PCV diagnosis.

Perifoveal Microvascular Changes following Internal Limiting Membrane Peeling Surgery for Epiretinal Membrane and Macular Hole.

INTRODUCTION: The aim of the study was to evaluate perifoveal microvasculature changes following pars plana vitrectomy with internal limiting membrane peeling for the epiretinal membrane (ERM) and macular hole (MH). METHODS: This retrospective study included 59 eyes from 59 patients. Subjects were divided into two groups: an ERM group (n = 43) and an MH group (n = 16) based on the initial diagnosis. Swept-source optical coherence tomography angiography (SS-OCTA) was performed in the macular area, pre- and postoperatively. Perifoveal microvascular changes were calculated using MATLAB from the 6 × 6 mm SS-OCTA images, excluding the foveal avascular zone. Pre- and postoperative perifoveal vessel densities (pfVDs) were separately analyzed in six sectors (superior, superotemporal, inferotemporal, inferior, inferonasal, and superonasal) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The baseline characteristics and other clinical factors were compared between the ERM and MH groups. RESULTS: The postoperative best-corrected visual acuity significantly improved in both groups (p < 0.05). One year after surgery, the pfVD in the SCP of the ERM group significantly decreased in the inferotemporal sector (p = 0.049). The postoperative pfVD in the DCP of the MH group significantly decreased in temporal sectors (p < 0.05). The postoperative mean pfVD in the SCP in the MH group was significantly lower than that in the ERM group (p = 0.003). The presence of a dissociated optic nerve fiber layer (DONFL) was 75% in the MH group and 22% in the ERM group (p = 0.018). The correlation between the pfVD and DONFL was not statistically significant. CONCLUSION: Postoperative pfVD reduction in the temporal sector, a corresponding area in which DONFL is present after MH surgery, was significantly observed. After vitreoretinal surgery in MH patients, OCTA may serve as a useful tool for monitoring perifoveal microvascular changes, especially in temporal sectors.

Filipendula glaberrima Nakai extract inhibits the bacterial infection by induction of HBD2 and HBD3 expression, and reduction of the inflammatory activity.

Defensins and inflammation are innate immune barriers of the body against infectious pathogens. Searching for a compound that can inhibit infectious diseases by affecting human ß-defensin (HBD) and proinflammatory cytokines is the new trend in research to control bacterial infection. The aim of this study is to provide a natural compound, Filipendula glaberrima Nakai extract (FGE), which is able to induce the expression of an antimicrobial defensin as well as reduce inflammation. FGE induced the expression of HBD2 and HBD3 through activating both p38 and NF-κB signaling pathways. Furthermore, FGE inhibited the expression of TNF-α and IL-6 via p38 and NF-κB pathways in Staphylococcus aureus-stimulated THP1 cells. Injection of FGE alleviated cutaneous erythema and swelling caused by S. aureus injection in mice ears. Taken together, FGE could reduce bacterial infection by inducing the expression of defensin and anti-inflammatory activity.

A Novel Interaction between MFN2/Marf and MARK4/PAR-1 Is Implicated in Synaptic Defects and Mitochondrial Dysfunction.

As cellular energy powerhouses, mitochondria undergo constant fission and fusion to maintain functional homeostasis. The conserved dynamin-like GTPase, Mitofusin2 (MFN2)/mitochondrial assembly regulatory factor (Marf), plays a role in mitochondrial fusion, mutations of which are implicated in age-related human diseases, including several neurodegenerative disorders. However, the regulation of MFN2/Marf-mediated mitochondrial fusion, as well as the pathologic mechanism of neurodegeneration, is not clearly understood. Here, we identified a novel interaction between MFN2/Marf and microtubule affinity-regulating kinase 4 (MARK4)/PAR-1. In the Drosophila larval neuromuscular junction, muscle-specific overexpression of MFN2/Marf decreased the number of synaptic boutons, and the loss of MARK4/PAR-1 alleviated the synaptic defects of MFN2/Marf overexpression. Downregulation of MARK4/PAR-1 rescued the mitochondrial hyperfusion phenotype caused by MFN2/Marf overexpression in the Drosophila muscles as well as in the cultured cells. In addition, knockdown of MARK4/PAR-1 rescued the respiratory dysfunction of mitochondria induced by MFN2/Marf overexpression in mammalian cells. Together, our results indicate that the interaction between MFN2/Marf and MARK4/PAR-1 is fine-tuned to maintain synaptic integrity and mitochondrial homeostasis, and its dysregulation may be implicated in neurologic pathogenesis.

Wound healing effects of Asparagus lucidus Lindl extract through the phosphorylation of ERK1/2.

BACKGROUND: Skin is the outermost part of the human body and is essential in maintaining body homeostasis. In the event of skin injury, rapid wound repair is crucial to protect the body. In this study, we investigated the wound-healing properties of Asparagus lucidus Lindl extract by promoting keratinocyte proliferation. METHODS: To evaluate the effect of Asparagus lucidus Lindl extract on skin regeneration, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to measure keratinocyte proliferation, while an in vitro wound-healing assay was performed to evaluate wound closure through keratinocyte re-epithelialization. The intracellular mechanisms of the extract were studied using Western blot analysis to measure the phosphorylated forms of mitogen-activated protein kinases and protein kinase B. The mRNA expression of cell cycle-related genes was analyzed using quantitative real time-PCR analysis. A murine in vivo wound-healing assay was also conducted to observe the effect of the extract on wound closure. RESULTS: Asparagus lucidus Lindl extract induced 131.15% keratinocyte proliferation compared to the control in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The in vitro wound-healing assay showed that the extract improved wound closure by 216.94% through keratinocyte re-epithelialization. Western blot analysis revealed that the phosphorylated form of extracellular signal-regulated kinase 1/2 was increased by extract treatment. Quantitative real time-PCR analysis showed a dose-dependent increase in the mRNA expression of c-fos, c-jun, and VEGF. The in vivo wound-healing assay showed a significant increase (22.13%) of wound closure compared to the control on day 5. CONCLUSION: Asparagus lucidus Lindl extract promotes keratinocyte proliferation by activating the extracellular signal-regulated kinase 1/2 pathway and up-regulating the mRNA expression of c-fos, c-jun, and vascular endothelial growth factor.

Identification of a Novel ERK5 (MAPK7) Inhibitor, MHJ-627, and Verification of Its Potent Anticancer Efficacy in Cervical Cancer HeLa Cells.

Extracellular signal-regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinase (MAPK) family, is involved in key cellular processes. However, overexpression and upregulation of ERK5 have been reported in various cancers, and ERK5 is associated with almost every biological characteristic of cancer cells. Accordingly, ERK5 has become a novel target for the development of anticancer drugs as inhibition of ERK5 shows suppressive effects of the deleterious properties of cancer cells. Herein, we report the synthesis and identification of a novel ERK5 inhibitor, MHJ-627, and verify its potent anticancer efficacy in a yeast model and the cervical cancer HeLa cell line. MHJ-627 successfully inhibited the kinase activity of ERK5 (IC50: 0.91 µM) and promoted the mRNA expression of tumor suppressors and anti-metastatic genes. Moreover, we observed significant cancer cell death, accompanied by a reduction in mRNA levels of the cell proliferation marker, proliferating cell nuclear antigen (PCNA), following ERK5 inhibition due to MHJ-627 treatment. We expect this finding to serve as a lead compound for further identification of inhibitors for ERK5-directed novel approaches for oncotherapy with increased specificity.

The Unknown Abnormal Condition Monitoring Method for Pumped-Storage Hydroelectricity.

Pumped-storage hydroelectricity (PSH) is a facility that stores energy in the form of the gravitational potential energy of water by pumping water from a lower to a higher elevation reservoir in a hydroelectric power plant. The operation of PSH can be divided into two states: the turbine state, during which electric energy is generated, and the pump state, during which this generated electric energy is stored as potential energy. Additionally, the condition monitoring of PSH is generally challenging because the hydropower turbine, which is one of the primary components of PSH, is immersed in water and continuously rotates. This study presents a method that automatically detects new abnormal conditions in target structures without the intervention of experts. The proposed method automatically updates and optimizes existing abnormal condition classification models to accommodate new abnormal conditions. The performance of the proposed method was evaluated with sensor data obtained from on-site PSH. The test results show that the proposed method detects new abnormal PSH conditions with an 85.89% accuracy using fewer than three datapoints and classifies each condition with a 99.73% accuracy on average.

Optical coherence tomography angiography biomarkers in a bi-monthly maintenance dosing aflibercept in patients with neovascular age-related macular degeneration.

PURPOSE: To evaluate the correlations between swept-source optical coherence tomography angiography (SS-OCTA) parameters and clinical outcomes in eyes with neovascular age-related macular degeneration (nAMD) administered a bimonthly intravitreal aflibercept regimen. METHODS: This prospective, single-arm, interventional study enrolled 33 patients with treatment-naïve nAMD. The eyes received three monthly aflibercept injections followed by five bi-monthly regimens (total 50 weeks). The structural parameters including central subfield thickness (CST) and 5 mm pigment epithelial detachment (PED) volume and microvascular parameters including macular neovascularization (MNV) area, vessel density (VD), and vessel length density (VLD) were recorded every before and 1 week after treatment. RESULTS: Patients who gained > 5 letters of best-corrected visual acuity (BCVA) from the baseline showed greater decreases in VD and VLD during the loading phase. Patients without recurrent or persistent fluid during the maintenance phase showed greater decreases in CST and 5 mm PED volume after the first injection. The decrease in mean VD during the loading phase was significantly correlated with the final BCVA (r = -0.820, p = 0.004). Moreover, the decrease in mean VLD during the loading phase was significantly correlated with the improvement in the final BCVA (r = -0.726, p = 0.017). CONCLUSIONS: The decrease in mean VD during the loading phase was significantly negatively correlated with the final BCVA at the last visit. The decrease in mean VLD during the loading phase, mean CST during the loading phase, and the improvement in final BCVA showed significant correlations. Therefore, early changes in OCTA microvascular and OCT structural parameters could help predict clinical outcomes in nAMD. TRIAL REGISTRATION: The trial was registered with the Clinical Research Information Service (CRIS), which joined the WHO International Clinical Trials Registry Platform (ICTRP) (Registration number: KCT0007375, Date of first trial registration: 10/06/2022).

Primary and additional treatment preference in aggressive retinopathy of prematurity and type 1 retinopathy of prematurity.

OBJECTIVE: This study aimed to evaluate the preference for antivascular endothelial growth factor (anti-VEGF) versus laser ablation therapy as primary and additional treatment in aggressive retinopathy of prematurity (ROP) and type 1 ROP. METHODS: This multicentre retrospective study was conducted at nine medical centres across South Korea. A total of 94 preterm infants with ROP who underwent primary treatment between January 2020 and December 2021 were enrolled. All eyes were classified as having type 1 ROP or aggressive ROP. Data on the zone, primary treatment chosen, injection dose, presence of reactivation and additional treatment were collected and analysed. RESULTS: Seventy infants (131 eyes) with type 1 ROP and 24 infants (45 eyes) with aggressive ROP were included. Anti-VEGF injection was selected as the primary treatment in 74.05% of the infants with type 1 ROP and 88.89% with aggressive ROP. Anti-VEGF injection was selected as the ROP was located in zone I or posterior zone II, and laser ablation was selected when it was located in zone II. The anti-VEGF injection doses varied and tended to be higher in the aggressive ROP group. Infants with aggressive ROP were 2.08 times more likely to require additional treatment than those with type 1 ROP. When ROP reactivation occurred, laser therapy was preferred as an additional treatment. CONCLUSION: In Korea, the preference for anti-VEGF therapy or laser therapy differed according to ROP subtype, zone and primary or secondary treatment. These findings suggest that ROP treatment are considered according to ROP subtype, location and reactivation.

Continuous Structural Displacement Monitoring Using Accelerometer, Vision, and Infrared (IR) Cameras.

With the rapid development of computer vision, vision cameras have been used as noncontact sensors for structural displacement measurements. However, vision-based techniques are limited to short-term displacement measurements because of their degraded performance under varying illumination and inability to operate at night. To overcome these limitations, this study developed a continuous structural displacement estimation technique by combining measurements from an accelerometer with vision and infrared (IR) cameras collocated at the displacement estimation point of a target structure. The proposed technique enables continuous displacement estimation for both day and night, automatic optimization of the temperature range of an infrared camera to ensure a region of interest (ROI) with good matching features, and adaptive updating of the reference frame to achieve robust illumination-displacement estimation from vision/IR measurements. The performance of the proposed method was verified through lab-scale tests on a single-story building model. The displacements were estimated with a root-mean-square error of less than 2 mm compared with the laser-based ground truth. In addition, the applicability of the IR camera for displacement estimation under field conditions was validated using a pedestrian bridge test. The proposed technique eliminates the need for a stationary sensor installation location by the on-site installation of sensors and is therefore attractive for long-term continuous monitoring. However, it only estimates displacement at the sensor installation location, and cannot simultaneously estimate multi-point displacements which can be achieved by installing cameras off-site.

Alpinia japonica extract induces apoptosis of hepatocellular carcinoma cells through G0/G1 cell cycle arrest and activation of JNK.

Hepatic cancer was the third most prevalent cause of cancer-related death worldwide in 2018, and its incidence is increasing. While therapeutic agents for hepatic cancer have improved, these agents can cause serious side effects, including damage to healthy tissues. To overcome this limitation, more than 3,000 plants have been used globally as common alternatives for cancer treatment. The anti-cancer activity of Alpinia japonica, one of the traditional herbal medicines (Korean name: Kkot-yang-ha), was investigated. Water extract of A. japonica (AJ) decreased the cell viability of hepatic cancer cells. AJ extract showed greater than 70% loss of mitochondrial potential in HepG2 cells as demonstrated by JC-1 staining. Apoptosis was induced by treatment with AJ extract as shown through FACS analysis, and G0/G1 phase arrest of 76.66% HepG2 cells was confirmed through cell cycle analysis and quantitative RT-PCR. Improper regulation of ERK1/2 might contribute to cell death, and JNK activation is necessary for apoptosis induced by stress stimuli. AJ extract stimulated the phosphorylation of JNK and ERK1/2, mitogen-activated protein kinases (MAPKs), in HepG2 cells. AJ extract has anticancer activity by inhibiting cell cycle progression, leading to apoptosis of hepatic cancer cells. This extract could potentially be used as a therapeutic agent for hepatic cancer.

PREDICTION OF DIABETIC RETINOPATHY SEVERITY USING A COMBINATION OF RETINAL NEURODEGENERATION AND CAPILLARY NONPERFUSION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To generate a prediction model of diabetic retinopathy (DR) severity stages based on retinal neurodegeneration and capillary nonperfusion area (NPA) detected using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: A total of 155 treatment-naïve eyes were retrospectively included. Macular ganglion cell/inner plexiform layer (mGCIPL) thickness in six macular regions was measured. A custom algorithm was used to calculate capillary NPA from 3 × 3 mm 2 and 12 × 12 mm 2 field OCTA images. The region of interest was selected as circular areas of 3 mm and 12 mm diameter and divided into six subsections. Classification and regression tree analysis identified the best predictors to discriminate between the five DR stages. RESULTS: Inferotemporal sector showed the largest mean NPA, and the inferior hemispheric NPA was significantly larger compared with the superior hemisphere. The mean mGCIPL thickness was significantly correlated with NPA of 12 × 12 mm 2 field in participants with early stage DR. Inferior hemispheric NPA of 12 × 12 mm 2 field and mean mGCIPL thickness were the two best variables to discriminate no DR versus mild nonproliferative DR (NPDR) and mild versus moderate NPDR (accuracy: 88.8% and 93.5%). Meanwhile, a combination of NPA of 12 × 12 mm 2 and 3 × 3 mm 2 fields was the best prediction model to discriminate moderate versus severe NPDR and severe NPDR versus PDR (accuracy: 91.8% and 94.1%). CONCLUSION: A combination model of capillary NPA and mGCIPL thickness may be a novel biomarker for predicting DR severity. Capillary nonperfusion seems to initially occur in the midperipheral retina with macular neurodegeneration and progress posteriorly.

Glutathionylation on RNA-binding proteins: a regulator of liquid‒liquid phase separation in the pathogenesis of amyotrophic lateral sclerosis.

RNA-binding proteins (RBPs) containing low-sequence complexity domains mediate the formation of cellular condensates and membrane-less organelles with biological functions via liquid‒liquid phase separation (LLPS). However, the abnormal phase transition of these proteins induces the formation of insoluble aggregates. Aggregates are pathological hallmarks of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). The molecular mechanisms underlying aggregate formation by ALS-associated RPBs remain largely unknown. This review highlights emerging studies on various posttranslational modifications (PTMs) related to protein aggregation. We begin with the introduction of several ALS-associated RBPs that form aggregates induced by phase separation. In addition, we highlight our recent discovery of a new PTM involved in the phase transition during the pathogenesis of fused-in-sarcoma (FUS)-associated ALS. We suggest a molecular mechanism through which LLPS mediates glutathionylation in FUS-linked ALS. This review aims to provide a detailed overview of the key molecular mechanisms of LLPS-mediated aggregate formation by PTMs, which will help further the understanding of the pathogenesis and development of ALS therapeutics.

Development of a Real-Time 6-DOF Motion-Tracking System for Robotic Computer-Assisted Implant Surgery.

In this paper, we investigate a motion-tracking system for robotic computer-assisted implant surgery. Failure of the accurate implant positioning may result in significant problems, thus an accurate real-time motion-tracking system is crucial for avoiding these issues in computer-assisted implant surgery. Essential features of the motion-tracking system are analyzed and classified into four categories: workspace, sampling rate, accuracy, and back-drivability. Based on this analysis, requirements for each category have been derived to ensure that the motion-tracking system meets the desired performance criteria. A novel 6-DOF motion-tracking system is proposed which demonstrates high accuracy and back-drivability, making it suitable for use in computer-assisted implant surgery. The results of the experiments confirm the effectiveness of the proposed system in achieving the essential features required for a motion-tracking system in robotic computer-assisted implant surgery.

MSF Enhances Human Antimicrobial Peptide ß-Defensin (HBD2 and HBD3) Expression and Attenuates Inflammation via the NF-κB and p38 Signaling Pathways.

Both defensin and inflammation are part of the human innate immune system that responds rapidly to pathogens. The combination of defensins with pro- or anti-inflammatory effects can be a potential research direction for the treatment of infection by pathogens. This study aimed to identify whether MSF (Miracle Synergy material made using Filipendula glaberrima), a probiotic lysate of Filipendula glaberrima extracts fermented with Lactiplantibacillus plantarum K8, activates the expression of human ß-defensin (HBD2 and HBD3) to protect the host against pathogens and inhibit inflammation caused by S. aureus, in vitro with Western blot analysis, qRT-PCR and in vivo studies with a mouse model were used to evaluate the effects of MSF. The MSF treatment induced HBD2 and HBD3 expression via the p38 and NF-κB pathways. Furthermore, MSF treatment significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-8), also through p38 and NF-κB in S. aureus-induced inflammatory condition. MSF treatment remarkably reduced erythema in mice ears caused by the injection of S. aureus, while K8 lysate treatment did not initiate a strong recovery. Taken together, MSF induced the expression of HBD2 and HDB3 and activated anti-inflammatory activity more than the probiotic lysates of L. plantarum K8. These findings show that MSF is a potential defensin inducer and anti-inflammatory agent.