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Abstract Cerebral hyperperfusion syndrome (CHS) is a serious complication after bypass surgery in Moyamoya disease (MMD), with autoregulatory dysfunction being a major pathogenesis. This study investigated the change of perioperative autoregulation and preoperative prognostic potentials in MMD with postoperative CHS. Among 26 hemispheres in 24 patients with adult MMD undergoing combined bypass, 13 hemispheres experienced postoperative CHS. Arterial blood pressure and cerebral blood flow velocity were perioperatively measured with transcranial Doppler ultrasound during resting and the Valsalva maneuver (VM). Autoregulation profiles were discovered in both the CHS and non-CHS groups using mean flow index (Mxa), VM Autoregulatory Index (VMAI), and a new metric termed VM Overshooting Index (VMOI). The CHS group had inferior autoregulation than the non-CHS group as indicated by VMOI on preoperative day 1 and postoperative 3rd day. Deteriorated autoregulation was observed via Mxa in the CHS group than in the non-CHS group on the postoperative 3rd and discharge days. Postoperative longitudinal autoregulation recovery in the CHS group was found in a logistic regression model with diminished group differences over the time course. This work represents a step forward in utilizing autoregulation indices derived from physiological signals, to predict the postoperative CHS in adult MMD.

Abstract Background and objectives This study aimed to analyze and present updated trends in atrial fibrillation (AF) epidemiology within the Korean population, providing a foundation for planning and implementing appropriate management and treatment strategies for patients with AF. Patients and methods We used the Korean National Health Insurance Service database to evaluate the prevalence, incidence, comorbidities, and clinical adverse outcomes of patients with AF in Korea between 2013 and 2022. Results AF prevalence in Korean adults aged ≥ 20 years doubled (1.1 to 2.2%) between 2013 and 2022, with significant increases observed across various sex and age groups. Similarly, the number of newly diagnosed patients with AF per year increased steadily, with the incidence rising from 184 to 275 per 100,000 person-years, particularly among older populations. Over this period, the mean age of patients with AF increased from 67.7 to 70.3 years, and comorbidities prevalence and CHA2DS2-VASc score rose significantly, indicating a higher stroke risk. Compared with patients without AF, AF was associated with an increased risk of mortality (hazard ratio [HR]: 1.78), ischemic stroke (HR: 2.39), major bleeding (HR: 2.10), myocardial infarction (HR: 1.44), and heart failure admission (HR: 2.42). Conclusion AF prevalence and incidence have steadily increased between 2013 and 2022, with a more pronounced increase in older patients. Patients with AF are increasingly becoming a high-risk population and are at increased risk of clinical adverse outcomes compared to non-AF patients. Therefore, a sustained national effort to improve AF awareness and comprehensive care quality for patients with AF is required.

Background We hypothesized that analysis of serial ECGs could predict new‐onset atrial fibrillation (AF) more accurately than analysis of a single ECG by detecting the subtle cardiac remodeling that occurs immediately before AF occurrence. Our aim in this study was to compare the performance of 2 types of machine learning (ML) algorithms. Methods and Results Standard 12‐lead ECGs of patients selected by cardiologists between January 2010 and May 2021 were used for ML model development. Two ML models (single ECG and serial ECG) were developed using a light gradient boosting machine‐learning algorithm. Model performance was evaluated based on the area under the receiver operating characteristic curve, sensitivity, specificity, accuracy, and F1 score. We trained the ML models on 415 964 ECGs from 176 090 patients. When testing the 2 ML models using external validation data sets, the performance of the serial‐ML model was significantly better than that of the single‐ML model for predicting new‐onset AF (single‐ versus serial‐ML model: sensitivity 0.744 versus 0.810; specificity 0.742 versus 0.822; accuracy 0.743 versus 0.816; F1 score 0.743 versus 0.815; area under the receiver operating characteristic curve 0.812 versus 0.880; P

Abstract The necessity of bilateral bypass in adult moyamoya disease (MMD) remains unclear despite its recommendation for pediatric and hemorrhagic cases. We aimed to investigate the natural course of hemodynamically stable unoperated hemispheres after bypass surgery for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD. Among 288 patients, the mean age at the first operation of the unstable hemispheres was 40.8 ± 12.2 years. The mean follow-up period was 62.9 ± 46.5 months. 45 patients (15.6%) experienced stroke events in the unoperated hemisphere, consisting of hemorrhagic stroke in 8 (2.8%) and ischemic stroke in 37 (12.8%), including progressive transient ischemic attack in 25 (8.7%) and infarction in 12 (4.2%). Among them, 39 patients (13.5%) underwent bypass surgery. The annual risk of total stroke is 3.0%/patient-year, with 2.5% for ischemic stroke and 0.5% for hemorrhagic stroke. The 5- and 10-year cumulative risks of ischemic stroke were 13.4% and 18.3%, respectively, and those of hemorrhagic stroke were each 3.2%. The natural course of hemodynamically stable hemispheres contralateral to the operated ones appeared fairly good. Additional bypass surgery on the unoperated hemispheres should be considered for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD during the follow-up.

BackgroundData on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce.ObjectivesWe prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion.MethodsThe multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose.ResultsOf 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the “marginal zone,” defined as age 75–80 years, weight 60–65 kg, and creatinine levels 1.2–1.5 mg/dL.ConclusionsIn real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.

Background: The peptidyl-prolyl isomerase (PIN1) plays a vital role in cellular processes, including intracellular signaling and apoptosis. While oxidative stress is considered one of the primary mechanisms of pathogenesis in brain ischemic injury, the precise function of PIN1 in this disease remains to be elucidated. Objective: We constructed a cell-permeable PEP-1–PIN1 fusion protein and investigated PIN1’s function in HT-22 hippocampal cells as well as in a brain ischemic injury gerbil model. Methods: Transduction of PEP-1–PIN1 into HT-22 cells and signaling pathways were determined by Western blot analysis. Intracellular reactive oxygen species (ROS) production and DNA damage was confirmed by DCF-DA and TUNEL staining. Cell viability was determined by MTT assay. Protective effects of PEP-1-PIN1 against ischemic injury were examined using immunohistochemistry. Results: PEP-1–PIN1, when transduced into HT-22 hippocampal cells, inhibited cell death in H2O2-treated cells and markedly reduced DNA fragmentation and ROS production. This fusion protein also reduced phosphorylation of mitogen-activated protein kinase (MAPK) and modulated expression levels of apoptosis-signaling proteins in HT-22 cells. Furthermore, PEP-1–PIN1 was distributed in gerbil hippocampus neuronal cells after passing through the blood–brain barrier (BBB) and significantly protected against neuronal cell death and also decreased activation of microglia and astrocytes in an ischemic injury gerbil model. Conclusions: These results indicate that PEP-1–PIN1 can inhibit ischemic brain injury by reducing cellular ROS levels and regulating MAPK and apoptosis-signaling pathways, suggesting that PIN1 plays a protective role in H2O2-treated HT-22 cells and ischemic injury gerbil model.

Background The ECG is a simple, noninvasive screening method for cardiovascular disease and arrhythmia. The impact of ECG abnormality on mortality is not certain in low‐risk populations. To address this, we evaluated the association between ECG abnormality and mortality. Methods and Results We retrospectively assessed baseline ECG and all‐cause mortality and cardiovascular mortality in 660 383 patients presenting for medical check‐ups. Baseline ECG abnormalities were classified according to the Minnesota Code. Among the total 660 383 participants, 23 609 (3.6%) had major and 110 038 (16.7%) had minor ECG abnormalities. All‐cause mortality occurred in 7751 patients (1.1%) and cardiovascular mortality in 1180 (0.18%) over a median follow‐up period of 8.8 years. Major ECG abnormalities were associated with all‐cause mortality (hazard ratio [HR], 1.11 [95%, 1.03–1.2]) and cardiovascular mortality (HR, 1.92 [95% CI, 1.63–2.27]) compared with no ECG abnormalities. All‐cause mortality was associated with right atrial enlargement (HR, 2.11 [95% CI, 1.1–4.07]), left atrial enlargement (HR, 1.76 [95% CI, 1.1–2.84]), sinus tachycardia (HR, 1.52 [95% CI, 1.15–2.01]), complete atrioventricular block (HR, 2.1 [95% CI, 1.05–4.2]), atrial fibrillation (HR, 1.52 [95% CI, 1.26–1.84]), and left ventricular hypertrophy (HR, 1.15 [95% CI, 1.02–1.3]). Cardiovascular mortality was associated with left atrial enlargement (HR, 4.52 [95% CI, 2.15–9.5]), atrial fibrillation (HR, 3.22 [95% CI, 2.33–4.46]), left ventricular hypertrophy (HR, 1.72 [95% CI, 1.35–2.19]), major Q‐wave abnormality (HR, 1.6 [95% CI, 1.08–2.39]), and major ST‐T abnormality (HR, 1.76 [95% CI, 1.01–3.04]). Conclusions ECG abnormalities, including left atrial enlargement, left ventricular hypertrophy, atrial fibrillation, and major Q‐wave and ST‐T abnormalities, were associated with cardiovascular mortality in a low‐risk population.

CKLF-like MARVEL transmembrane domain-containing 3 (CMTM3), a member of the CMTM family that is closely related to tumor occurrence and progression, plays crucial roles in the immune system, cardiovascular system, and male reproductive system. Recently, CMTM3 has emerged as a potential target for treating diseases related to bone formation. However, additional studies are needed to understand the mechanisms by which CMTM3 regulates the process of osteogenic differentiation. In this study, we observed a significant downregulation of Cmtm3 expression during the transdifferentiation of C2C12 myoblasts into osteoblasts induced by BMP4. Cmtm3 overexpression suppressed proliferation and osteogenic differentiation in BMP4-induced C2C12 cells, whereas its knockdown conversely facilitated the process. Mechanistically, Cmtm3 overexpression upregulated both the protein and mRNA levels of p53 and p21. Conversely, Cmtm3 knockdown exerted the opposite effects. Additionally, we found that Cmtm3 interacts with p53 and increases protein stability by inhibiting proteasome-mediated ubiquitination and degradation. Notably, Trp53 downregulation abrogated the inhibitory effect of Cmtm3 on BMP4-induced proliferation and osteogenic differentiation of C2C12 myoblasts. Collectively, our findings provide key insights into the role of CMTM3 in regulating myoblast proliferation and transdifferentiation into osteoblasts, highlighting its significance in osteogenesis research.

Peptide-based drug development is a promising direction due to its excellent biological activity, minimal immunogenicity, high in vivo stability, and efficient tissue penetrability. GV1001, an amphiphilic peptide, has proven effective as an anti-cancer vaccine, but its effect on osteoblast differentiation is unknown. To identify proteins interacting with GV1001, biotin-conjugated GV1001 was constructed and confirmed by mass spectrometry. Proteomic analyses were performed to determine GV1001’s interaction with osteogenic proteins. GV1001 was highly associated with peptidyl-prolyl isomerase A and co-immunoprecipitation assays revealed that GV1001 bound to peptidyl-prolyl cis-trans isomerase 1 (Pin1). GV1001 significantly increased alkaline phosphatase (ALP) activity, bone nodule formation, and the expression of osteogenic gene markers. GV1001-induced osteogenic activity was enhanced by Pin1 overexpression and abolished by Pin1 knockdown. GV1001 increased the protein stability and transcriptional activity of Runx2 and Osterix. Importantly, GV1001 administration enhanced bone mass density in the OVX mouse model, as verified by µCT analysis. GV1001 demonstrated protective effects against bone loss in OVX mice by upregulating osteogenic differentiation via the Pin1-mediated protein stabilization of Runx2 and Osterix. GV1001 could be a potential candidate with anabolic effects for the prevention and treatment of osteoporosis.

In recent years, the bakery industry has been exploring alternative fats to replace traditional solid fats. Shortening, a common baking ingredient, is produced through the hydrogenation of vegetable oils, resulting in high levels of saturated and trans fatty acids, despite its vegetable oil origin. The excessive consumption of these fats has been associated with negative health effects, including dyslipidemia and cardiovascular issues. Oleogels, incorporating hydroxypropyl methylcellulose (HPMC), xanthan gum (XG), and olive oil, were utilized to replace shortening in the production of white pan bread. The substitution of shortening with oleogel in the white pan bread preparation demonstrated potential reductions in saturated fat, trans fat, and the ratio of saturated fat to unsaturated fatty acids. Specifically, with the complete substitution of shortening with oleogel, saturated fatty acids decreased by 52.46% and trans fatty acids by 75.72%, with unsaturated fatty acids increasing by 57.18%. Our findings revealed no significant difference in volume between bread made with shortening and bread with up to 50% shortening substitution. Moreover, when compared to bread made with shortening and 50% oleogel substitution, no adverse effects on the quality characteristics of volume and expansion properties were observed, and the retrogradation rate was delayed. This study suggests that incorporating oleogels, formed with hydrocolloids such as HPMC and XG, to replace shortening in bread, in conjunction with traditional solid fats, provides positive effects on the quality and nutritional aspects of the bread compared to using oleogel alone. Through this study, we demonstrate the use of oleogels as a healthier alternative to shortening, without reducing the bread’s quality, thus offering a practical solution to reduce unhealthy fats in bakery products.

Introduction: Schinus terebinthifolia (ST) is a plant belonging to the cashew family Anacardiaceae, native to subtropical and tropical South America. ST is commonly called Brazil pepper and aroeira. Several reports have been made on the biological activities of ST, but studies on leaf extracts, especially lectins, have mainly been reported. Objectives: Our study analyzed the active compounds, antioxidant activities, xanthine oxidase inhibitory, elastase inhibitory, and tyrosinase inhibitory activities of S. terebinthifolia (ST) bark extract. Results: Hot water extracts showed the strongest electron donating ability (84.46%) and tyrosinase inhibitory activity (67.1%). Eighty percent ethanol extract showed the highest reducing power, total phenolic, xanthine oxidase (91.7%) and elastase inhibitory ability (85.44%). Catechin, α–amyrin, β–amyrone and 11-Oxo-.α-amyrin were identified through HPLC and GCMS analysis, while eighty percent extract contained the highest amount of catechin. Catechin, α–amyrin, and β–amyrone are considered to be the main xanthine oxidase inhibitors, while β–amyrone is considered to be the main inhibitor of xanthine oxidase and elastase. Conclusion: Through this study, we reported the basic information that S. terebinthifolia bark extract was used in folk medicine as an anti-inflammatory, anti-gout, and skin disease improvement material. S. terebinthifolia bark extract could be used as an anti-gout natural drug or cosmetic material. [ABSTRACT FROM AUTHOR]

Objective: Chronic subdural hematomas (cSDHs) are generally known to result from traumatic tears of bridging veins. However, the causes of repeat spontaneous cSDHs are still unclear. We investigated the changes in vasculature in the human dura mater and outer membrane (OM) of cSDHs to elucidate the cause of their spontaneous repetition. Methods: The dura mater was obtained from a normal control participant and a patient with repeat spontaneous cSDHs. The pathological samples from the patient included the dura mater and OM tightly adhered to the inner dura. The samples were analyzed with a particular focus on blood and lymphatic vessels by immunohistochemistry, 3-dimensional imaging using a transparent tissue clearing technique, and electron microscopy. Results: The dural border cell (DBC) layer of the dura mater and OM were histologically indistinguishable. There were 5.9 times more blood vessels per unit volume of tissue in the DBC layer and OM in the patient than in the normal control. The DBC layer and OM contained pathological sinusoidal capillaries not observed in the normal tissue; these capillaries were connected to the middle meningeal arteries via penetrating arteries. In addition, marked lymphangiogenesis in the periosteal and meningeal layers was observed in the patient with cSDHs. Conclusion: Neovascularization in the OM seemed to originate from the DBC layer; this is a potential cause of repeat spontaneous cSDHs. Embolization of the meningeal arteries to interrupt the blood supply to pathological capillaries via penetrating arteries may be an effective treatment option. [ABSTRACT FROM AUTHOR]

The striatum, known as the input nucleus of the basal ganglia, is extensively studied for its diverse behavioral roles. However, the relationship between its neuronal and vascular activity, vital for interpreting functional magnetic resonance imaging (fMRI) signals, has not received comprehensive examination within the striatum. Here, we demonstrate that optogenetic stimulation of dorsal striatal neurons or their afferents from various cortical and subcortical regions induces negative striatal fMRI responses in rats, manifesting as vasoconstriction. These responses occur even with heightened striatal neuronal activity, confirmed by electrophysiology and fiber-photometry. In parallel, midbrain dopaminergic neuron optogenetic modulation, coupled with electrochemical measurements, establishes a link between striatal vasodilation and dopamine release. Intriguingly, in vivo intra-striatal pharmacological manipulations during optogenetic stimulation highlight a critical role of opioidergic signaling in generating striatal vasoconstriction. This observation is substantiated by detecting striatal vasoconstriction in brain slices after synthetic opioid application. In humans, manipulations aimed at increasing striatal neuronal activity likewise elicit negative striatal fMRI responses. Our results emphasize the necessity of considering vasoactive neurotransmission alongside neuronal activity when interpreting fMRI signal. [ABSTRACT FROM AUTHOR]

While functional brain imaging studies in humans suggest that chronic cocaine use alters functional connectivity (FC) within and between key large-scale brain networks, including the default mode network (DMN), the salience network (SN), and the central executive network (CEN), cross-sectional studies in humans are challenging to obtain brain FC prior to cocaine use. Such information is critical to reveal the relationship between individual's brain FC and the subsequent development of cocaine dependence and brain changes during abstinence. Here, we performed a longitudinal study examining functional magnetic resonance imaging (fMRI) data in male rats (n = 7), acquired before cocaine self-administration (baseline), on 1 d of abstinence following 10 d of cocaine self-administration, and again after 30 d of experimenter-imposed abstinence. Using repeated-measures analysis of variance (ANOVA) with network-based statistics (NBS), significant connectivity changes were found between anterior insular cortex (AI) of the SN, retrosplenial cortex (RSC) of the DMN, somatosensory cortex, and caudate–putamen (CPu), with AI–RSC FC showing the most robust changes between baseline and 1 d of abstinence. Additionally, the level of escalated cocaine intake is associated with AI–RSC and AI– CPu FC changes between 1 d and 30 d of abstinence; further, the subjects’ AI–RSC FC prior to cocaine intake is a significant moderator for the AI–RSC changes during abstinence. These results provide novel insights into the roles of AI–RSC FC before and after cocaine intake and suggest this circuit to be a potential target to modulate large-scale network and associated behavioral changes in cocaine use disorders. [ABSTRACT FROM AUTHOR]

Background/purpose: Peri-implantitis is a representative etiology that affects the long-term survival of dental implants. It is known that decontamination of the implant surface is essential for the successful outcome of regenerative therapy for peri-implantitis. In the present study, the stability of a novel separable dental implant (SDI) was evaluated and compared with a conventional non-separable dental implant (NDI) using biomechanical and histomorphometric analyses. Materials and methods: In this animal study, 40 rabbits were implanted with two SDI fixtures in the left tibia and two NDI fixtures in the right tibia. The rabbits were sacrificed 3 and 6 weeks after implantation, and the implant samples were evaluated using resonance frequency analysis (RFA), micro-computed tomography (CT), removal torque testing, and histomorphometric analysis. Results: SDI exhibited comparable or better osseointegration and implant stability to NDI. In particular, SDI showed significantly higher implant stability quotient (ISQ) values immediately and 6 weeks after implantation, while removal torque values were significantly higher at both 3 and 6 weeks. In addition, microgaps on the histomorphometric images were not observed and abnormal signs or inflammation did not occur at the connection between the top and bottom parts of the SDI. Conclusion: The novel SDI fixture demonstrated sufficient osseointegration and biomechanical stability compared with NDI in this animal study. In addition, the changeable top part of SDI indicates that it may be effective in easily treating peri-implantitis in clinical practice. Additional future studies on the stability and clinical application after loading to the fixture are necessary.

While deep brain stimulation (DBS) is widely employed for managing motor symptoms in Parkinson's disease (PD), its exact circuit mechanisms remain controversial. To identify the neural targets affected by therapeutic DBS in PD, we analyzed DBS-evoked whole brain activity in female hemi-parkinsonian rats using functional magnetic resonance imaging (fMRI). We delivered subthalamic nucleus (STN) DBS at various stimulation pulse repetition rates using optogenetics, allowing unbiased examination of cell-type specific STN feedforward neural activity. Unilateral optogenetic STN DBS elicited pulse repetition rate-dependent alterations of blood-oxygenation-level-dependent (BOLD) signals in SNr (substantia nigra pars reticulata), GP (globus pallidus), and CPu (caudate putamen). Notably, this modulation effectively ameliorated pathological circling behavior in animals expressing the kinetically faster Chronos opsin, but not in animals expressing ChR2. Furthermore, mediation analysis revealed that the pulse repetition rate-dependent behavioral rescue was significantly mediated by optogenetic DBS induced activity changes in GP and CPu, but not in SNr. This suggests that the activation of GP and CPu are critically involved in the therapeutic mechanisms of STN DBS.

Abstract The striatum, known as the input nucleus of the basal ganglia, is extensively studied for its diverse behavioral roles. However, the relationship between its neuronal and vascular activity, vital for interpreting functional magnetic resonance imaging (fMRI) signals, has not received comprehensive examination within the striatum. Here, we demonstrate that optogenetic stimulation of dorsal striatal neurons or their afferents from various cortical and subcortical regions induces negative striatal fMRI responses in rats, manifesting as vasoconstriction. These responses occur even with heightened striatal neuronal activity, confirmed by electrophysiology and fiber-photometry. In parallel, midbrain dopaminergic neuron optogenetic modulation, coupled with electrochemical measurements, establishes a link between striatal vasodilation and dopamine release. Intriguingly, in vivo intra-striatal pharmacological manipulations during optogenetic stimulation highlight a critical role of opioidergic signaling in generating striatal vasoconstriction. This observation is substantiated by detecting striatal vasoconstriction in brain slices after synthetic opioid application. In humans, manipulations aimed at increasing striatal neuronal activity likewise elicit negative striatal fMRI responses. Our results emphasize the necessity of considering vasoactive neurotransmission alongside neuronal activity when interpreting fMRI signal.

The demand for trade has led to unsustainable harvesting of medicinal plants, causing a decline in their population in natural habitats. This presents a notable problem, however, there is a lack of information regarding the severity of the threat to these resources. To address this, a study was conducted to identify high-value medicinal plants in the Annapurna Conservation Area in Nepal and evaluate their potential endangerment by using the Rapid Vulnerability Assessment method (RVA). The study also calculated the distribution of these plants in different habitats and their population size. Results showed that there were 19 threatened, high-value medicinal plants in the region frequently used by local communities and with high trade values. Rhizome/roots were the most commonly used plant parts (58%), followed by whole plants (37%). The wild population of these plants was found to be low, with varying abundance among different habitats. Overexploitation driven by high trade demand, low population density, and critical life forms were identified as the main threats to these plants. The study placed Dactylorhiza hatagirea and Neopicrorhiza scrophulariiflora in the highest threat category. Effective conservation and management measures, both in-situ and ex-situ, were suggested based on the population and threat status of these high-value medicinal plants.

In this paper, an electromagnetic analysis method is proposed to improve force characteristics by using spring permanent magnets (PMs) along the axial and circumferential directions of a linear oscillatory generator (LOG). For accurate electromagnetic analysis, a detailed analysis model of the LOG is developed, and the governing equations of each subdomain are derived based on Maxwell’s equations and electromagnetic theory. Analytical solutions of the magnetic vector potential in each subdomain are derived using boundary conditions. The reliability of the proposed method is verified through a comparison with the results of a two-dimensional finite element analysis (FEA). In particular, the force characteristics depending on the spring PM is effectively derived by considering the three-dimensional (3D) circumferential and axial end effects. The proposed analysis method is used to determine the thickness of spring PM that transforms the detent force of the LOG with the spring PM into restoring force. The reliability of the proposed analysis method is verified through comparison with the results of a 3D FEA.

The purpose of this study was to investigate the protective effects of 7S,15R-dihydroxy-16S,17S-epoxy-docosapentaenoic acid (diHEP-DPA) in retinal pigment epithelial (RPE) cell damage. ARPE-19 cells, a human RPE cell line, were cultured with diHEP-DPA and Bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E), followed by exposure to BL. Cell viability and cell death rates were determined. Western blotting was performed to determine changes in apoptotic factors, mitogen-activated protein kinase (MAPK) family proteins, inflammatory proteins, and oxidative and carbonyl stresses. The levels of pro-inflammatory cytokines in the culture medium supernatants were also measured. Exposure to A2E and BL increased the ARPE-19 cell death rate, which was alleviated by diHEP-DPA in a concentration-dependent manner. A2E and BL treatments induced apoptosis in ARPE-19 cells, which was also alleviated by diHEP-DPA. Analysis of the relationship with MAPK proteins revealed that the expression of p-JNK and p-P38 increased after A2E and BL treatments and decreased with exposure to diHEP-DPA in a concentration-dependent manner. DiHEP-DPA also affected the inflammatory response by suppressing the expression of inflammatory proteins and the production of pro-inflammatory cytokines. Furthermore, it was shown that diHEP-DPA regulated the proteins related to oxidative and carbonyl stresses. Taken together, our results provide evidence that diHEP-DPA can inhibit cell damage caused by A2E and BL exposure at the cellular level by controlling various pathways involved in apoptosis and inflammatory responses.