Distinctive Roles of Medial Prefrontal Cortex Subregions in Strategic Conformity to Social Hierarchy.

People often align their behaviors and decisions with others' expectations, especially those of higher social positions, when they are being observed. However, little attention has been paid to the neural mechanisms underlying increased conformity to the social hierarchy under social observation. Using a preference rating task, we investigated whether and how individual preferences for novel stimuli were influenced by others' preferences by manipulating others' social hierarchy and observational context. The behavioral results showed that human participants of both sexes were more likely to change their preferences to match those of a superior partner in a public than in a private context. fMRI data revealed distinct contributions of the subregions of the medial prefrontal cortex (mPFC) to increased conformity to social hierarchy under observation. Specifically, the ventral mPFC showed increased activity when participants' preferences aligned with those of superior partners, regardless of behavioral manifestation. The rostral mPFC showed increased activity when conforming to a superior partner and nonconforming to an inferior one, indicating goal-dependent valuation. The dorsal mPFC showed increased activity in private conditions with a superior partner but only in those with a higher tendency to conform. These findings support the hierarchical allostatic regulation model of the mPFC function for social valuation and suggest strategic conformity as a way to minimize metabolic costs.SIGNIFICANCE STATEMENT This study revealed distinct roles of subregions of the mPFC in increased conformity to individuals of different social ranks under observation. Specifically, the ventral mPFC showed increased activity when participants' preferences aligned with those of higher-ranking partners, whereas the rostral mPFC showed increased activity when conforming to a superior partner and nonconforming to an inferior partner, indicating goal-dependent valuation. The dorsal mPFC was more active in private conditions with a superior partner but only in those with a higher tendency to conform. These findings support the hierarchical allostatic regulation model of the mPFC function for social valuation and suggest strategic conformity as a way to minimize metabolic costs.

Host genetic effects in pneumonia.

Given the coronavirus disease 2019 (COVID-19) pandemic, investigations into host susceptibility to infectious diseases and downstream sequelae have never been more relevant. Pneumonia is a lung disease that can cause respiratory failure and hypoxia and is a common complication of infectious diseases, including COVID-19. Few genome-wide association studies (GWASs) of host susceptibility and severity of pneumonia have been conducted. We performed GWASs of pneumonia susceptibility and severity in the Vanderbilt University biobank (BioVU) with linked electronic health records (EHRs), including Illumina Expanded Multi-Ethnic Global Array (MEGAEX)-genotyped European ancestry (EA, n= 69,819) and African ancestry (AA, n = 15,603) individuals. Two regions of large effect were identified: the CFTR locus in EA (rs113827944; OR = 1.84, p value = 1.2 × 10-36) and HBB in AA (rs334 [p.Glu7Val]; OR = 1.63, p value = 3.5 × 10-13). Mutations in these genes cause cystic fibrosis (CF) and sickle cell disease (SCD), respectively. After removing individuals diagnosed with CF and SCD, we assessed heterozygosity effects at our lead variants. Further GWASs after removing individuals with CF uncovered an additional association in R3HCC1L (rs10786398; OR = 1.22, p value = 3.5 × 10-8), which was replicated in two independent datasets: UK Biobank (n = 459,741) and 7,985 non-overlapping BioVU subjects, who are genotyped on arrays other than MEGAEX. This variant was also validated in GWASs of COVID-19 hospitalization and lung function. Our results highlight the importance of the host genome in infectious disease susceptibility and severity and offer crucial insight into genetic effects that could potentially influence severity of COVID-19 sequelae.

Sex-specific associations between adipokine profiles and carotid-intima media thickness in the Cameron County Hispanic Cohort (CCHC).

BACKGROUND: Adipokines are hormones secreted from adipose tissue and are associated with cardiometabolic diseases (CMD). Functional differences between adipokines (leptin, adiponectin, and resistin) are known, but inconsistently reported associations with CMD and lack of studies in Hispanic populations are research gaps. We investigated the relationship between subclinical atherosclerosis and multiple adipokine measures. METHODS: Cross-sectional data from the Cameron County Hispanic Cohort (N = 624; mean age = 50; Female = 70.8%) were utilized to assess associations between adipokines [continuous measures of adiponectin, leptin, resistin, leptin-to-adiponectin ratio (LAR), and adiponectin-resistin index (ARI)] and early atherosclerosis [carotid-intima media thickness (cIMT)]. We adjusted for sex, age, body mass index (BMI), smoking status, cytokines, fasting blood glucose levels, blood pressure, lipid levels, and medication usage in the fully adjusted linear regression model. We conducted sexes-combined and sex-stratified analyses to account for sex-specificity and additionally tested whether stratification of participants by their metabolic status (metabolically elevated risk for CMD as defined by having two or more of the following conditions: hypertension, dyslipidemia, insulin resistance, and inflammation vs. not) influenced the relationship between adipokines and cIMT. RESULTS: In the fully adjusted analyses, adiponectin, leptin, and LAR displayed significant interaction by sex (p < 0.1). Male-specific associations were between cIMT and LAR [ß(SE) = 0.060 (0.016), p = 2.52 × 10-4], and female-specific associations were between cIMT and adiponectin [ß(SE) = 0.010 (0.005), p = 0.043] and ARI [ß(SE) = - 0.011 (0.005), p = 0.036]. When stratified by metabolic health status, the male-specific positive association between LAR and cIMT was more evident among the metabolically healthy group [ß(SE) = 0.127 (0.015), p = 4.70 × 10-10] (p for interaction by metabolic health < 0.1). However, the female-specific associations between adiponectin and cIMT and ARI and cIMT were observed only among the metabolically elevated risk group [ß(SE) = 0.014 (0.005), p = 0.012 for adiponectin; ß(SE) = - 0.015 (0.006), p = 0.013 for ARI; p for interaction by metabolic health < 0.1]. CONCLUSION: Associations between adipokines and cIMT were sex-specific, and metabolic health status influenced the relationships between adipokines and cIMT. These heterogeneities by sex and metabolic health affirm the complex relationships between adipokines and atherosclerosis.

Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents.

BACKGROUND: Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors. METHODS: We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling. RESULTS: We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels. CONCLUSIONS: The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers. IMPACT: This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.

Dynamic relationships between body fat and circulating adipokine levels from adolescence to young adulthood: The Santiago Longitudinal Study.

BACKGROUND AND AIMS: Adipose tissue secretes adipokines such as adiponectin and leptin, playing important roles in energy metabolism. The longitudinal associations between such adipokines and body fat accumulation have not been established, especially during adolescence and young adulthood and in diverse populations. The study aims to assess the longitudinal association between body fat measured with dual X-ray absorptiometry and plasma adipokines from adolescence to young adulthood. METHODS AND RESULTS: Among Hispanic/Latino participants (N = 537) aged 16.8 (SD: 0.3) years of the Santiago Longitudinal Study, we implemented structural equation modeling to estimate the sex-specific associations between adiposity (body fat percent (BF%) and proportion of trunk fat (PTF)) and adipokines (adiponectin and leptin levels) during adolescence (16 y) and these values after 6 years of follow-up (22 y). In addition, we further investigated whether the associations differed by baseline insulin resistance (IR) status. We found evidence for associations between 16 y BF% and 22 y leptin levels (ß (SE): 0.58 (0.06) for females; 0.53 (0.05) for males), between 16 y PTF and 22 y adiponectin levels (ß (SE): -0.31 (0.06) for females; -0.18 (0.06) for males) and between 16 y adiponectin levels and 22 y BF% (ß (SE): 0.12 (0.04) for both females and males). CONCLUSION: We observed dynamic relationships between adiposity and adipokines levels from late adolescence to young adulthood in a Hispanic/Latino population further demonstrating the importance of this period of the life course in the development of obesity.

Moving Object Tracking Based on Sparse Optical Flow with Moving Window and Target Estimator.

Moving object detection and tracking are technologies applied to wide research fields including traffic monitoring and recognition of workers in surrounding heavy equipment environments. However, the conventional moving object detection methods have faced many problems such as much computing time, image noises, and disappearance of targets due to obstacles. In this paper, we introduce a new moving object detection and tracking algorithm based on the sparse optical flow for reducing computing time, removing noises and estimating the target efficiently. The developed algorithm maintains a variety of corner features with refreshed corner features, and the moving window detector is proposed to determine the feature points for tracking, based on the location history of the points. The performance of detecting moving objects is greatly improved through the moving window detector and the continuous target estimation. The memory-based estimator provides the capability to recall the location of corner features for a period of time, and it has an effect of tracking targets obscured by obstacles. The suggested approach was applied to real environments including various illumination (indoor and outdoor) conditions, a number of moving objects and obstacles, and the performance was evaluated on an embedded board (Raspberry pi4). The experimental results show that the proposed method maintains a high FPS (frame per seconds) and improves the accuracy performance, compared with the conventional optical flow methods and vision approaches such as Haar-like and Hog methods.

The effect of pelvic movements of a gait training system for stroke patients: a single blind, randomized, parallel study.

BACKGROUND: Aging societies lead to higher demand for gait rehabilitation as age-related neurological disorders such as stroke and spinal cord injury increase. Since conventional methods for gait rehabilitation are physically and economically burdensome, robotic gait training systems have been studied and commercialized, many of which provided movements confined in the sagittal plane. For better outcomes of gait rehabilitation with more natural gait patterns, however, it is desirable to provide pelvic movements in the transverse plane. In this study, a robotic gait training system capable of pelvic motions in the transverse plane was used to evaluate the effect of the pelvic motions on stroke patients. METHOD: Healbot T, which is a robotic gait training system and capable of providing pelvic movements in the transverse plane as well as flexion/extension of the hip and knee joints and adduction/abduction of the hip joints, is introduced and used to evaluate the effect of the pelvic movement on gait training of stroke patients. Gait trainings in Healbot T with and without pelvic movements are carried out with stroke patients having hemiparesis. EXPERIMENT: Twenty-four stroke patients with hemiparesis were randomly assigned into two groups and 23 of them successfully completed the experiment except one subject who had dropped out due to personal reasons. Pelvis-on group was provided with pelvic motions whereas no pelvic movement was allowed for pelvis-off group during 10 sessions of gait trainings in Healbot T. Electromyography (EMG) signals and interaction forces as well as the joint angles of the robot were measured. Gait parameters such as stride length, cadence, and walking speed were measured while walking on the ground without assistance of Healbot T after gait training on 1st, 5th, and 10th day. RESULT: Stride length significantly increased in both groups. Furthermore, cadence and walking speed of the pelvis-on group were increased by 10.6% and 11.8%. Although interaction forces of both groups except the thighs showed no differences, EMG signals from gluteus medius of the pelvis-on group increased by 88.6% during stance phase. In addition, EMG signals of biceps femoris, gastrocnemius medial, and gastrocnemius lateral of the pelvis-on group increased whereas EMG signals of the pelvis-off group except gastrocnemius lateral showed no difference after gait trainings. CONCLUSION: Gait training using a robotic gait training system with pelvic movements was conducted to investigate the effects of lateral and rotational pelvic movements in gait training of stroke patients. The pelvic movements affected to increase voluntary muscle activation during the stance phase as well as cadence and walking speed. CLINICAL TRIAL REGISTRATION: KCT0003762, 2018-1254, Registered 28 October 2018, https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=14310<ype=&rtype=.

Effects of aerobic and resistance exercises on circulating apelin-12 and apelin-36 concentrations in obese middle-aged women: a randomized controlled trial.

BACKGROUND: The risk for obesity-related diseases increases with the prevalence of obesity. In obesity, adipokines secreted from adipose tissue induce inflammation, causing adverse effects. Recently, adipokines such as apelin, visfatin, and chemerin have been studied. Long-term resistance training improves health in middle-aged women by improving metabolic risk factors, body composition, and muscle strength. However, there is still a lack of evidence on the association of apelin concentration with different exercise types in middle-aged obese women This study aimed to investigate the effects of 8 weeks of aerobic and resistance exercises on apelin-12 and apelin-36 levels and thereby verify the effects of different exercise types in obese, middle-aged women. METHODS: Participants were middle-aged women aged 50-61 years, with no experience of systematic exercise in the last 6 months, and met the WHO obesity criteria for the Asia-Pacific region of waist circumference ≥ 80 cm and body fat percentage ≥ 30%. Subjects were selected and allocated to the aerobic exercise, resistance exercise, or no exercise group by block randomization. Body weight, body fat, and body mass index were measured by bioelectrical impedance analysis. Analysis of variance, the t-test, and Tukey's post-hoc test were performed. RESULTS: A total of 24 participants were selected with eight participants in each group. Both aerobic and resistance exercises were effective in altering the physical composition, showing significant decreases in weight, waist circumference, BMI, and body fat. The aerobic and resistance exercise group showed a significant, positive change in apelin-12 levels. CONCLUSIONS: In obese individuals, aerobic and resistance exercise were effective in improving obesity and reducing blood apelin-12 concentration, which is closely correlated with indicators of metabolic syndrome. Future research should focus on comparing the response of apelin to exercise in obese subjects treated with only dietary control and the response in the obese subjects of different ages and sex. TRIAL REGISTRATION: No. 1040917-201,506-BR-153-04 , Clinical Research Information Service (CRIS), Republic of Korea (05 October 2018, retrospectively registered).

The impact of differential cost sharing of prescription drugs on the use of primary care clinics among patients with hypertension or diabetes.

OBJECTIVES: Since 2011, the Korean government has implemented differential cost sharing to increase the utilization of primary care clinics for the management of chronic diseases. The objective of this study was to examine the impact of the prescription drug cost-sharing increase on outpatients' selection of the medical care institution. STUDY DESIGN: This was a pre-post comparison study. METHODS: Participants were 34,842 patients with hypertension and 13,886 patients with type 2 diabetes, who were all newly prescribed. Data were collected via national health insurance system claims. The change in the main medical care institution for disease management before and after the cost sharing policy was analyzed using logistic regression analysis. RESULTS: Nearly 18% of participants with hypertension and 22% of participants with diabetes used tertiary care or general hospital outpatient services before the policy was implemented. After the increased prescription drug coinsurance rate (by 10-20%), the likelihood of selecting primary care clinics or small hospitals was significantly higher among patients with hypertension within 1 year (odds ratio [95% confidence interval] = 1.29 [1.19-1.41]) than before. However, the policy effect was not significant among patients with diabetes. CONCLUSIONS: The cost sharing policy was effective in inducing patients with hypertension to manage their chronic disease in primary care institutions; however, this was not true for patients with diabetes. The assurance of high-quality disease management services and low out-of-pocket expenses may be needed to encourage patients with chronic diseases to use primary care clinics.

Microsphere-Based Nanoindentation for the Monitoring of Cellular Cortical Stiffness Regulated by MT1-MMP.

Biophysical properties are intimately connected to metastatic functions and aggressiveness in cancers. Especially, cellular stiffness is regarded as a biomarker for the understanding of metastatic potential and drug sensitivity. Here, protease-mediated changes of cortical stiffness are identified due to the deformation of cytoskeleton alignment at a cortex. For the past few decades, membrane type 1-matrix metalloproteinase (MT1-MMP) has been well known as a kernel protease enriched in podosomes during metastasis for extracellular matrix degradation. However, the biophysical significance of MT1-MMP expressing cancer cells is still unknown. Therefore, the nanomechanics of cancer cells is analyzed by a nanoindentation using a microsphere-attached cantilever of atomic force microscopy (AFM). In conclusion, the results suggest that MT1-MMP has contributed as a key regulator in cytoskeletal deformation related with cancer metastasis. Particularly, the AFM-based nanoindentation system for the monitoring of cortical nanomechanics will be crucial to understand molecular networks in cancers.

Individual Biometric Identification Using Multi-Cycle Electrocardiographic Waveform Patterns.

The electrocardiogram (ECG) waveform conveys information regarding the electrical property of the heart. The patterns vary depending on the individual heart characteristics. ECG features can be potentially used for biometric recognition. This study presents a new method using the entire ECG waveform pattern for matching and demonstrates that the approach can potentially be employed for individual biometric identification. Multi-cycle ECG signals were assessed using an ECG measuring circuit, and three electrodes can be patched on the wrists or fingers for considering various measurements. For biometric identification, our-fold cross validation was used in the experiments for assessing how the results of a statistical analysis will generalize to an independent data set. Four different pattern matching algorithms, i.e., cosine similarity, cross correlation, city block distance, and Euclidean distances, were tested to compare the individual identification performances with a single channel of ECG signal (3-wire ECG). To evaluate the pattern matching for biometric identification, the ECG recordings for each subject were partitioned into training and test set. The suggested method obtained a maximum performance of 89.9% accuracy with two heartbeats of ECG signals measured on the wrist and 93.3% accuracy with three heartbeats for 55 subjects. The performance rate with ECG signals measured on the fingers improved up to 99.3% with two heartbeats and 100% with three heartbeats of signals for 20 subjects.

Rough-Surface-Enabled Capacitive Pressure Sensors with 3D Touch Capability.

Fabrication strategies that pursue "simplicity" for the production process and "functionality" for a device, in general, are mutually exclusive. Therefore, strategies that are less expensive, less equipment-intensive, and consequently, more accessible to researchers for the realization of omnipresent electronics are required. Here, this study presents a conceptually different approach that utilizes the inartificial design of the surface roughness of paper to realize a capacitive pressure sensor with high performance compared with sensors produced using costly microfabrication processes. This study utilizes a writing activity with a pencil and paper, which enables the construction of a fundamental capacitor that can be used as a flexible capacitive pressure sensor with high pressure sensitivity and short response time and that it can be inexpensively fabricated over large areas. Furthermore, the paper-based pressure sensors are integrated into a fully functional 3D touch-pad device, which is a step toward the realization of omnipresent electronics.

Radial Distance Estimation with Tapered Whisker Sensors.

Rats use their whiskers as tactile sensors to sense their environment. Active whisking, moving whiskers back and forth continuously, is one of prominent features observed in rodents. They can discriminate different textures or extract features of a nearby object such as size, shape and distance through active whisking. There have been studies to localize objects with artificial whiskers inspired by rat whiskers. The linear whisker model based on beam theory has been used to estimate the radial distance, that is, the distance between the base of the whisker and a target object. In this paper, we investigate deflection angle measurements instead of forces or moments, based on a linear tapered whisker model to see the role of tapered whiskers found in real animals. We analyze how accurately this model estimates the radial distance, and quantify the estimation errors and noise sensitivity. We also compare the linear model simulation and nonlinear numerical solutions. It is shown that the radial distance can be estimated using deflection angles at two different positions on the tapered whisker. We argue that the tapered whisker has an advantage of estimating the radial distance better, as compared to an untapered whisker, and active sensing allows that estimation without the whisker's material property and thickness or the moment at base. In addition, we investigate the potential of passive sensing for tactile localization.

Local Homing Navigation Based on the Moment Model for Landmark Distribution and Features.

[-10]For local homing navigation, an agent is supposed to return home based on the surrounding environmental information. According to the snapshot model, the home snapshot and the current view are compared to determine the homing direction. In this paper, we propose a novel homing navigation method using the moment model. The suggested moment model also follows the snapshot theory to compare the home snapshot and the current view, but the moment model defines a moment of landmark inertia as the sum of the product of the feature of the landmark particle with the square of its distance. The method thus uses range values of landmarks in the surrounding view and the visual features. The center of the moment can be estimated as the reference point, which is the unique convergence point in the moment potential from any view. The homing vector can easily be extracted from the centers of the moment measured at the current position and the home location. The method effectively guides homing direction in real environments, as well as in the simulation environment. In this paper, we take a holistic approach to use all pixels in the panoramic image as landmarks and use the RGB color intensity for the visual features in the moment model in which a set of three moment functions is encoded to determine the homing vector. We also tested visual homing or the moment model with only visual features, but the suggested moment model with both the visual feature and the landmark distance shows superior performance. We demonstrate homing performance with various methods classified by the status of the feature, the distance and the coordinate alignment.

History-Based Response Threshold Model for Division of Labor in Multi-Agent Systems.

Dynamic task allocation is a necessity in a group of robots. Each member should decide its own task such that it is most commensurate with its current state in the overall system. In this work, the response threshold model is applied to a dynamic foraging task. Each robot employs a task switching function based on the local task demand obtained from the surrounding environment, and no communication occurs between the robots. Each individual member has a constant-sized task demand history that reflects the global demand. In addition, it has response threshold values for all of the tasks and manages the task switching process depending on the stimuli of the task demands. The robot then determines the task to be executed to regulate the overall division of labor. This task selection induces a specialized tendency for performing a specific task and regulates the division of labor. In particular, maintaining a history of the task demands is very effective for the dynamic foraging task. Various experiments are performed using a simulation with multiple robots, and the results show that the proposed algorithm is more effective as compared to the conventional model.

Autonomous Shepherding Behaviors of Multiple Target Steering Robots.

This paper presents a distributed coordination methodology for multi-robot systems, based on nearest-neighbor interactions. Among many interesting tasks that may be performed using swarm robots, we propose a biologically-inspired control law for a shepherding task, whereby a group of external agents drives another group of agents to a desired location. First, we generated sheep-like robots that act like a flock. We assume that each agent is capable of measuring the relative location and velocity to each of its neighbors within a limited sensing area. Then, we designed a control strategy for shepherd-like robots that have information regarding where to go and a steering ability to control the flock, according to the robots' position relative to the flock. We define several independent behavior rules; each agent calculates to what extent it will move by summarizing each rule. The flocking sheep agents detect the steering agents and try to avoid them; this tendency leads to movement of the flock. Each steering agent only needs to focus on guiding the nearest flocking agent to the desired location. Without centralized coordination, multiple steering agents produce an arc formation to control the flock effectively. In addition, we propose a new rule for collecting behavior, whereby a scattered flock or multiple flocks are consolidated. From simulation results with multiple robots, we show that each robot performs actions for the shepherding behavior, and only a few steering agents are needed to control the whole flock. The results are displayed in maps that trace the paths of the flock and steering robots. Performance is evaluated via time cost and path accuracy to demonstrate the effectiveness of this approach.

Landmark-Based Homing Navigation Using Omnidirectional Depth Information.

A number of landmark-based navigation algorithms have been studied using feature extraction over the visual information. In this paper, we apply the distance information of the surrounding environment in a landmark navigation model. We mount a depth sensor on a mobile robot, in order to obtain omnidirectional distance information. The surrounding environment is represented as a circular form of landmark vectors, which forms a snapshot. The depth snapshots at the current position and the target position are compared to determine the homing direction, inspired by the snapshot model. Here, we suggest a holistic view of panoramic depth information for homing navigation where each sample point is taken as a landmark. The results are shown in a vector map of homing vectors. The performance of the suggested method is evaluated based on the angular errors and the homing success rate. Omnidirectional depth information about the surrounding environment can be a promising source of landmark homing navigation. We demonstrate the results that a holistic approach with omnidirectional depth information shows effective homing navigation.

Source localization of intermittent rhythmic delta activity in a patient with acute confusional migraine: cross-spectral analysis using standardized low-resolution brain electromagnetic tomography (sLORETA).

Acute confusional migraine (ACM) shows typical electroencephalography (EEG) patterns of diffuse delta slowing and frontal intermittent rhythmic delta activity (FIRDA). The pathophysiology of ACM is still unclear but these patterns suggest neuronal dysfunction in specific brain areas. We performed source localization analysis of IRDA (in the frequency band of 1-3.5 Hz) to better understand the ACM mechanism. Typical IRDA EEG patterns were recorded in a patient with ACM during the acute stage. A second EEG was obtained after recovery from ACM. To identify source localization of IRDA, statistical non-parametric mapping using standardized low-resolution brain electromagnetic tomography was performed for the delta frequency band comparisons between ACM attack and non-attack periods. A difference in the current density maximum was found in the dorsal anterior cingulated cortex (ACC). The significant differences were widely distributed over the frontal, parietal, temporal and limbic lobe, paracentral lobule and insula and were predominant in the left hemisphere. Dorsal ACC dysfunction was demonstrated for the first time in a patient with ACM in this source localization analysis of IRDA. The ACC plays an important role in the frontal attentional control system and acute confusion. This dysfunction of the dorsal ACC might represent an important ACM pathophysiology.

The protective effect of hispidin against hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblast cells through Akt/GSK-3ß and ERK1/2 signaling pathway.

Hispidin, a phenolic compound from Phellinus linteus (a medicinal mushroom), has been shown to possess strong anti-oxidant, anti-cancer, anti-diabetic, and anti-dementia properties. However, the cardioprotective efficacy of hispidin has not yet been investigated. In the present study, we investigated the protective effect of hispidin against oxidative stress-induced apoptosis in H9c2 cardiomyoblast cells and neonatal rat ventricular myocytes. While the treatment of H9c2 cardiomyoblast cells with hydrogen peroxide caused a loss of cell viability and an increase in the number of apoptotic cells, hispidin significantly protected the cells against hydrogen peroxide-induced cell death without any cytotoxicity as determined by XTT assay, LDH release assay, Hoechst 33342 assay, and Western blotting of apoptosis proteins such as caspase-3, Bax, and Bcl-2. Our data also shows that hispidin significantly scavenged intracellular ROS, and markedly enhanced the expression of antioxidant enzymes such as heme oxygenase-1 and catalase, which was accompanied by the concomitant activation of Akt/GSK-3ß and ERK1/2 phosphorylation in H9c2 cardiomyoblast cells. The effects of hispidin on Akt and ERK phosphorylation were abrogated by LY294002 (a PI3K/Akt inhibitor) and U0126 (an ERK1/2 inhibitor). The effect of hispidin on GSK-3b activities was also blocked by LY294002. Furthermore, inhibiting the Akt/GSK-3ß and ERK1/2 pathway by these inhibitors significantly reversed the hispidin-induced Bax and Bcl-2 expression, apoptosis induction, and ROS production. These findings indicate that hispidin protects against apoptosis in H9c2 cardiomyoblast cells exposed to hydrogen peroxide through reducing intracellular ROS production, regulating apoptosis-related proteins, and the activation of the Akt/GSK-3ß and ERK1/2 signaling pathways.

The Protective Effect of INH2BP, a Novel PARP Inhibitor 5-Iodo-6-Amino-1,2-Benzopyrone, Against Hydrogen Peroxide-Induced Apoptosis Through ERK and p38 MAPK in H9c2 Cells.

INH2BP (5-iodo-6-amino-1,2-benzopyrone), a poly-ADP ribose polymerase inhibitor, has been shown to possess anti-cancer, anti-viral, and anti-inflammation properties. The aim of this study was to investigate the protective effect of INH2BP against oxidative stress-induced apoptosis in H9c2 cardiomyoblast cells. While the treatment of H9c2 cardiomyoblasts cells with hydrogen peroxide (H2O2) caused a loss of cell viability and an increase in the number of apoptotic cells, INH2BP significantly protected the cells against H2O2-induced cell death without any cytotoxicity. Our data also shows that INH2BP significantly scavenged intracellular reactive oxygen species (ROS), and markedly enhanced the expression of antioxidant enzymes such as Mn-SOD (superoxide) and Cu/Zn-SOD, and heme oxygenase-1, which was accompanied by the concomitant activation of extracellular regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) phosphorylation in H9c2 cells. The effects of INH2BP on ERK1/2 and p38 MAPK phosphorylation were abrogated by PD98059, an ERK1/2 inhibitor, and SB203580, a p38 inhibitor. In addition, inhibition of ERK1/2 and p38 MAPK by these inhibitors significantly attenuated INH2BP-mediated H9c2 viability as well as cleaved caspases-3, Bax, and Bcl-2 activation. Taken together, these results demonstrate that INH2BP prevents H2O2-induced apoptosis in H9c2 cells by reducing the production of intracellular ROS, regulating apoptotic-related proteins, and the activation of the ERK1/2 and p38 MAPK.