Age-Related Characteristics of Resting-State Electroencephalographic Signals and the Corresponding Analytic Approaches: A Review.

The study of the effects of aging on neural activity in the human brain has attracted considerable attention in neurophysiological, neuropsychiatric, and neurocognitive research, as it is directly linked to an understanding of the neural mechanisms underlying the disruption of the brain structures and functions that lead to age-related pathological disorders. Electroencephalographic (EEG) signals recorded during resting-state conditions have been widely used because of the significant advantage of non-invasive signal acquisition with higher temporal resolution. These advantages include the capability of a variety of linear and nonlinear signal analyses and state-of-the-art machine-learning and deep-learning techniques. Advances in artificial intelligence (AI) can not only reveal the neural mechanisms underlying aging but also enable the assessment of brain age reliably by means of the age-related characteristics of EEG signals. This paper reviews the literature on the age-related features, available analytic methods, large-scale resting-state EEG databases, interpretations of the resulting findings, and recent advances in age-related AI models.

Risk factors for stroke among anthropometric indices and lipid profiles in the Korean population: a large-scale cross-sectional study.

Stroke is strongly associated with death and disability. However, the associations between stroke and lipid profiles such as total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), and red blood cells (RBCs) and anthropometric indices such as waist circumference and waist-to-height ratio (WHtR) remain unclear. The objective of this study was to investigate these relationships in a Korean population. This large-scale cross-sectional study included data from 38,190 subjects collected from 2010 to 2018 by the Korea National Health and Nutrition Examination Survey (KNHANES). Simple logistic regression models and multiple logistic regression models were used to evaluate the association of stroke with lipid profiles and anthropometric indices in the crude model, adjusted Model 1, and fully adjusted Model 2. In men, stroke was negatively associated with height, weight, and hematocrit level. Total cholesterol and triglycerides were strongly negatively associated with stroke in Model 2. Creatinine level and stroke were weakly associated. Additionally, height, weight, total cholesterol, triglycerides, and hematocrit and creatinine levels were associated with stroke both before and after adjustment. In women, in Model 2, stroke was positively associated with height, weight, and creatinine level. A strong negative association was found between total cholesterol and stroke. Stroke was negatively associated with hemoglobin level, hematocrit level, and RBCs. Additionally, total cholesterol, hemoglobin level, hematocrit level, creatinine level, and RBCs were associated with stroke both before and after adjustment. Weight and height were more closely associated with stroke than waist circumference and WHtR in Korean men. Our results suggested that the association of stroke with triglycerides, height, and weight differed according to sex and that HDL-C was not associated with stroke in people of either sex.

Pulse sharpness as a quantitative index of vascular aging.

The aim of this study was to develop a robust algorithm to quantify pulse sharpness that can complement the limitations of radial augmentation index (rAIx) and explore the role of this quantitative sharpness index in reflecting vascular aging or arterial stiffness. The pulse sharpness index (PSI) was developed by combining the end point angle and virtual height, and 528 radial pulses were analyzed. The PSI could be uniformly applied to various waveform morphologies, even those with no or vague tidal waves, unlike the rAIx. Significant sex differences were identified in the rAIx and PSI (P < 0.01 for both), and significant age-dependent decreases in the PSI were observed (P < 0.01). In addition, the PSI and age were correlated (r = - 0.550) at least as strong as the rAIx and age (r = 0.532), and the PSI had a significant negative correlation with arterial stiffness (r = - 0.700). Furthermore, the multiple linear regression model for arterial stiffness using the PSI, age, sex and heart rate showed the excellent performance (cross-validated R2 = 0.701), and the PSI was found to have the greatest influence on arterial stiffness. This study confirmed that the PSI could be a quantitative index of vascular aging and has potential for use in inferring arterial stiffness with an advantage over the rAIx.

Radial Pulse and Electrocardiography Modulation by Mild Thermal Stresses Applied to Feet: An Exploratory Study with Randomized, Crossover Design.

OBJECTIVE: To investigate the changes in radial pulse induced by thermal stresses (TSs). METHODS: Sixty subjects were enrolled. Using an open-label, 2×2 crossover randomization design, both feet of each subject were immersed in 15 °C water for cold stress (CS) and in 40 °C water for heat stress (HS) for 5 min each. Radial pulse, respiration and electrocardiogram (ECG) signals were recorded before, during and immediately after the TSs. RESULTS: The analysis of heart rate variability revealed that CS increased the low-frequency (LF) and high-frequency (HF) components (P <0.05) and that HS reduced the LF and HF components (P <0.01). Both TSs reduced the normalized LF, increased the normalized HF, and reduced the LF/HF ratio. The differences in the ECG signals were more dominant during the TS sessions, but those in the radial pulse signals became more dominant immediately after the TS sessions. CS decreased the pulse depth (P <0.01) and increased the radial augmentation index (P <0.1), and HS increased the pulse pressure (P <0.1) and subendocardial viability ratio (P <0.01). There were no significant differences in pulse rate during the three time sequences of each TS. The respiration rate was increased (P <0.1), and the pulse rate per respiration (P/R ratio) was significantly decreased (P <0.05) with CS. The HF region (10-30 Hz) of the pulse spectral density was suppressed during both TSs. CONCLUSIONS: CS induced vasoconstriction and sympathetic reactions, and HS induced vasodilation and parasympathetic reactions. Based on definitions used in pulse diagnosis, we made the novel discoveries that the pulse became slower (decreased P/R ratio), more floating and tenser under CS and that the HF region of the spectral power decreased significantly under both TSs.

A comparative study of the radial pulse between primary dysmenorrhea patients and healthy subjects during the menstrual phase.

The aim of this study was to compare radial pulse characteristics between primary dysmenorrhea (PD) patients and healthy subjects throughout the menstrual cycle. A total of 48 females aged 20 to 29 years participated, and all subjects were assigned to two groups according to their visual analogue scale scores. The radial pulse of each subject was obtained using a pulse tonometric device during menstrual, follicular, and luteal phases. In addition, various pulse analysis indices were used to estimate the pulse characteristics. The pulse tension index (PTI) and pulse depth index (PDI) in the patient group were significantly lower than those in the healthy group during the menstrual phase (P < 0.01 and <0.001, respectively). According to univariate logistic regression results, the PTI, PDI and optimal applied pressure (OAP) were significantly correlated with PD, and the model based on the PTI and OAP performed best (AUC = 0.828). This study is the first to analyze pulse tension inferred from the PTI and to apply this parameter to clinical practice. The results of this study confirmed the possibility of quantitatively measuring pulse tension and suggest that the PTI and OAP can serve as potential clinical indicators for pain disorders.

Pulse wave response characteristics for thickness and hardness of the cover layer in pulse sensors to measure radial artery pulse.

BACKGROUND: Piezo-resistive pressure sensors are widely used for measuring pulse waves of the radial artery. Pulse sensors are generally fabricated with a cover layer because pressure sensors without a cover layer are fragile when they come into direct contact with the skin near the radial artery. However, no study has evaluated the dynamic pulse wave response of pulse sensors depending on the thickness and hardness of the cover layer. This study analyzed the dynamic pulse wave response according to the thickness and hardness of the cover layer and suggests an appropriate thickness and hardness for the design of pulse sensors with semiconductor device-based pressure sensors. METHODS: Pulse sensors with 6 different cover layers with various thicknesses (0.8 mm, 1 mm, 2 mm) and hardnesses (Shore type A; 30, 43, 49, 71) were fabricated. Experiments for evaluating the dynamic pulse responses of the fabricated sensors were performed using a pulse simulator to transmit the same pulse wave to each of the sensors. To evaluate the dynamic responses of the fabricated pulse sensors, experiments with the pulse sensors were conducted using a simulator that artificially generated a constant pulse wave. The pulse wave simulator consisted of a motorized cam device that generated the artificial radial pulse waveform by adjusting the stroke of the cylindrical air pump and an air tube that conveyed the pulse to the artificial wrist. RESULTS: The amplitude of the measured pulse pressure decreased with increasing thickness and hardness of the cover layer. Normalized waveform analysis showed that the thickness rather than the hardness of the cover layer contributed more to waveform distortion. Analysis of the channel distribution of the pulse sensor with respect to the applied constant dynamic pressure showed that the material of the cover layer had a large effect. CONCLUSIONS: In this study, in-line array pulse sensors with various cover layers were fabricated, the dynamic pulse wave responses according to the thickness and the hardness of the cover layer were analyzed, and an appropriate thickness and hardness for the cover layer were suggested. The dynamic pulse wave responses of pulse sensors revealed in this study will contribute to the fabrication of improved pulse sensors and pulse wave analyses.

Short-Term Efficacy of Pulsed Radiofrequency Thermal Stimulation on Acupoints for Chronic Low Back Pain: A Preliminary Study of a Randomized, Single-Blinded, Placebo-Controlled Trial.

BACKGROUND: The objective of this study was to evaluate the pain-relief efficacy of thermal stimulation induced by a pulsed radiofrequency (PRF) thermal stimulation applied to acupoints (APs) in patients with low back pain (LBP). The study was designed as a randomized, single-blinded, placebo-controlled trial. Methods. Fifty-six LBP patients whose minimum pain intensity score on a visual analogue scale (VAS, 0-100 mm) was more than 30 mm were randomly allocated to either the placebo-controlled or the treatment group at a 1:1 ratio. The treatment and placebo-controlled groups received PRF thermal stimulation plus cupping therapy and cupping therapy only, respectively. Each patient was scheduled to receive a total of three treatment sessions over one week with allowing a window up to 4 days. Six of the 13 predefined APs were selected differently for each session depending on the change in patient's symptoms and intensity of pain. The primary outcome was the mean difference between the placebo-controlled and treatment group of VAS changes from the baseline to the end of the follow-up period. RESULTS: The patients' reported VAS scores from baseline to the end of follow-up (average: 9.8 days) were significantly decreased by 8.036 points (two-sided 95% CI, -11.841 to -4.231) and 13.393 points (two-sided 95% CI: 17.198 to -9.588) in the treatment and the placebo-controlled groups, respectively. However, the change in VAS scores between the treatment group and the placebo-controlled group was not significantly different (2.015 mm, two-sided 95% CI: -5.288 to 9.317). CONCLUSION: The trial results indicated that treatment with either PRF thermal stimulation with cupping therapy or cupping therapy alone effectively relieved LBP. The efficacy of PRF thermal stimulation combined with cupping therapy was not superior to that of cupping therapy alone. Trial registration number: Clinical Research Information Service (KCT0002137). The trial was registered retrospectively on 10 November, 2016.

Development of a Tonometric Sensor with a Decoupled Circular Array for Precisely Measuring Radial Artery Pulse.

The radial artery pulse is one of the major diagnostic indices used clinically in both Eastern and Western medicine. One of the prominent methods for measuring the radial artery pulse is the piezoresistive sensor array. Independence among channels and an appropriate sensor arrangement are important for effectively assessing the spatial-temporal information of the pulse. This study developed a circular-type seven-channel piezoresistive sensor array using face-down bonding (FDB) as one of the sensor combination methods. The three-layered housing structure that included independent pressure sensor units using the FDB method not only enabled elimination of the crosstalk among channels, but also allowed various array patterns to be created for effective pulse measurement. The sensors were arranged in a circular-type arrangement such that they could estimate the direction of the radial artery and precisely measure the pulse wave. The performance of the fabricated sensor array was validated by evaluating the sensor sensitivity per channel, and the possibility of estimating the blood vessel direction was demonstrated through a radial artery pulse simulator. We expect the proposed sensor to allow accurate extraction of the pulse indices for pulse diagnosis.

Genetic Inhibition Of The Ubiquitin Ligase Rnf5 Attenuates Phenotypes Associated To F508del Cystic Fibrosis Mutation.

Cystic fibrosis (CF) is caused by mutations in the CFTR chloride channel. Deletion of phenylalanine 508 (F508del), the most frequent CF mutation, impairs CFTR trafficking and gating. F508del-CFTR mistrafficking may be corrected by acting directly on mutant CFTR itself or by modulating expression/activity of CFTR-interacting proteins, that may thus represent potential drug targets. To evaluate possible candidates for F508del-CFTR rescue, we screened a siRNA library targeting known CFTR interactors. Our analysis identified RNF5 as a protein whose inhibition promoted significant F508del-CFTR rescue and displayed an additive effect with the investigational drug VX-809. Significantly, RNF5 loss in F508del-CFTR transgenic animals ameliorated intestinal malabsorption and concomitantly led to an increase in CFTR activity in intestinal epithelial cells. In addition, we found that RNF5 is differentially expressed in human bronchial epithelia from CF vs. control patients. Our results identify RNF5 as a target for therapeutic modalities to antagonize mutant CFTR proteins.

Association of hypertension with physical factors of wrist pulse waves using a computational approach: a pilot study.

BACKGROUND: The objectives of this pilot study were to examine the association between hypertension and physical factors of wrist pulse waves to avoid subjective diagnoses in Traditional Chinese Medicine (TCM) and Traditional Korean Medicine (TKM). An additional objective was to assess the predictive power of individual and combined physical factors in order to identify the degree of agreement between diagnosis accuracies using physical factors and using a sphygmomanometer in the prediction of hypertension. METHODS: In total, 393 women aged 46 to 73 years participated in this study. Logistic regression (LR) and a naïve Bayes algorithm (NB) were used to assess statistically significant differences and the predictive power of hypertension, and a wrapper-based machine learning method was used to evaluate the predictive power of combinations of physical factors. RESULTS: In both wrists, L-PPI and R-PPI (maximum pulse amplitudes in the left Gwan and right Gwan) were the factors most strongly associated with hypertension after adjusting for age and body mass index (p = <0.001, odds ratio (OR) = 2.006 on the left and p = <0.001, OR = 2.504 on the right), and the best predictors (NB-AUC = 0.692, LR-AUC = 0.7 on the left and NB-AUC = 0.759, LR-AUC = 0.763 on the right). Analyses of both individual and combined physical factors revealed that the predictive power of the physical factors in the right wrist was higher than for the left wrist. The predictive powers of the combined physical factors were higher than those of the best single predictors in both the left and right wrists. CONCLUSION: We suggested new physical factors related to the sum of the area on the particular region of pulse waves in both wrists. L-PPI and R-PPI among all variables used in this study were good indicators of hypertension. Our findings support the quantification and objectification of pulse patterns and disease in TCM and TKM for complementary and alternative medicine.

Color distribution differences in the tongue in sleep disorder.

Introduction. According to traditional East Asian medicine (TEAM) theory, the tongue represents conditions of qi and blood. In the present study, the relationship between the tongue and the qi and blood in conditions with no apparent disease was investigated. Methods. A total of 454 elderly people with no apparent disease were recruited. Two Korean oriental medicine doctors classified subjects into a normal group (n = 402) and a sleep disorder group (n = 52). Three to five weeks after the experiment, 153 subjects were rerecruited for a second experiment. Two-dimensional color histograms, whose seven variables represent the color distribution in Commission Internationale de l'Éclairage 1976 (L∗, a∗, b∗) color space, were produced from tongue images. Results. The color of the tongue body in the sleep disorder group appeared paler than that in the normal group, and the tongue coating in the normal group was less widely distributed compared with that in the sleep disorder group. The differences in tongue color between the normal at first experiment and sleep disorder at second experiment conditions were similar to the differences between the normal and the sleep disorder groups. Conclusions. The tongue states in the sleep disorder group indicate a qi and blood deficiency according to TEAM theory.

Constitution-specific features of perspiration and skin visco-elasticity in SCM.

BACKGROUND: Human skin properties have been used as an important diagnostic component in traditional medicine as they change with health conditions. Sasang constitutional medicine (SCM) puts emphasis on the recognition of the constitution-specific skin features prior to the diagnostic decision of health. In this work, in search of skin-characteristics effectively reflecting SCM features, we compared several skin properties such as perspiration, visco-elasticity, elasticity, and elasticity hysteresis, in several candidate body parts. METHODS: We conducted a clinical study in which a total of 111 healthy females aged 50 - 70 years participated with their Sasang constitution (SC) types determined objectively by the Sasang constitutional analytic tool. Perspiration on the skin surface was estimated by using a capacitance sensor to measure the amount of moisture on the palm, forehead, and philtrum before and after a heating stimulus. We acquired the visco-elasticity, elasticity, and elasticity hysteresis at the forearm by Dermalab's elasticity sensing device. An analysis of covariance (ANCOVA) was conducted to evaluate the effect of SC on the nine skin features acquired. RESULTS: The visco-elasticity of the forearm of the Soeum-in (SE) group was significantly lower than that of the Taeeum-in (TE) group (F = 68.867, p < 0.001), whereas the elasticity hysteresis of the SE group was higher than that of the TE group (F = 10.364, p < 0.01). The TE group had more perspiration on the forehead than the SE group (F = 9.050, p < 0.01). The SE group had a large perspiration difference between the philtrum and the forehead compared with the TE group (F = 7.892, p < 0.01). CONCLUSIONS: We found four significant skin features that reflect the inherent constitutional attributes of the TE and SE groups in accordance with SCM literature; the visco-elasticity, elasticity hysteresis, perspiration on the forehead and philtrum. Our findings are based on a novel interpretation of the SCM literature and will contribute to developing the constitutional health status evaluation system in SCM.

New assessment model of pulse depth based on sensor displacement in pulse diagnostic devices.

An accurate assessment of the pulse depth in pulse diagnosis is vital to determine the floating and sunken pulse qualities (PQs), which are two of the four most basic PQs. In this work, we proposed a novel model of assessing the pulse depth based on sensor displacement (SD) normal to the skin surface and compared this model with two previous models which assessed the pulse depth using contact pressure (CP). In contrast to conventional stepwise CP variation tonometry, we applied a continuously evolving tonometric mechanism at a constant velocity and defined the pulse depth index as the optimal SD where the largest pulse amplitude was observed. By calculating the pulse depth index for 18 volunteers, we showed that the pulse was deepest at Cheok (significance level: P < 0.01), while no significant difference was found between Chon and Gwan. In contrast, the two CP-based models estimated that the pulse was shallowest at Gwan (P < 0.05). For the repeated measures, the new SD-based model showed a smaller coefficient of variation (CV ≈ 7.6%) than the two CP-based models (CV ≈ 13.5% and 12.3%, resp.). The SD-based pulse depth assessment is not sensitive to the complex geometry around the palpation locations and temperature variation of contact sensors, which allows cost-effective sensor technology.

The concept of sasang health index and constitution-based health assessment: an integrative model with computerized four diagnosis methods.

SASANG CONSTITUTIONAL MEDICINE (SCM) SHARES ITS PHILOSOPHY WITH THAT OF PERSONALIZED MEDICINE: it provides constitution-specific treatment and healthcare individualized for each patient. In this work, we propose the concept of the Sasang Health Index (SHI) as an attempt to assess the individualized health status in the framework of SCM. From the target population of females in their fifties and older, we recruited 298 subjects and collected their physiological data, including complexion, radial pulse, and voice, and their questionnaire responses. The health status of each subject was evaluated by two Korean medical doctors independently, and the SHI model was obtained by combining all the integrative features of the phenotype data using a regression technique. As a result, most subjects belonged to either the healthy, subhealthy, or slightly diseased group, and the intraclass correlation coefficient between the two doctors' health scoring reached 0.95. We obtained an SHI model for each constitution type with adjusted R-squares of 0.50, 0.56, and 0.30, for the TE, SE, and SY constitution types, respectively. In the proposed SHI model, the significant characteristics used in the health assessment consisted of constitution-specific features in accordance with the classic literature and features common to all the constitution types.

Novel diagnostic model for the deficient and excess pulse qualities.

The deficient and excess pulse qualities (DEPs) are the two representatives of the deficiency and excess syndromes, respectively. Despite its importance in the objectification of pulse diagnosis, a reliable classification model for the DEPs has not been reported to date. In this work, we propose a classification method for the DEPs based on a clinical study. First, through factor analysis and Fisher's discriminant analysis, we show that all the pulse amplitudes obtained at various applied pressures at Chon, Gwan, and Cheok contribute on equal orders of magnitude in the determination of the DEPs. Then, we discuss that the pulse pressure or the average pulse amplitude is appropriate for describing the collective behaviors of the pulse amplitudes and a simple and reliable classification can be constructed from either quantity. Finally, we propose an enhanced classification model that combines the two complementary variables sequentially.

Review on the current trends in tongue diagnosis systems.

Tongue diagnosis is an essential process to noninvasively assess the condition of a patient's internal organs in traditional medicine. To obtain quantitative and objective diagnostic results, image acquisition and analysis devices called tongue diagnosis systems (TDSs) are required. These systems consist of hardware including cameras, light sources, and a ColorChecker, and software for color correction, segmentation of tongue region, and tongue classification. To improve the performance of TDSs, various types TDSs have been developed. Hyperspectral imaging TDSs have been suggested to acquire more information than a two-dimensional (2D) image with visible light waves, as it allows collection of data from multiple bands. Three-dimensional (3D) imaging TDSs have been suggested to provide 3D geometry. In the near future, mobile devices like the smart phone will offer applications for assessment of health condition using tongue images. Various technologies for the TDS have respective unique advantages and specificities according to the application and diagnostic environment, but this variation may cause inconsistent diagnoses in practical clinical applications. In this manuscript, we reviewed the current trends in TDSs for the standardization of systems. In conclusion, the standardization of TDSs can supply the general public and oriental medical doctors with convenient, prompt, and accurate information with diagnostic results for assessing the health condition.

Novel diagnostic algorithm for the floating and sunken pulse qualities and its clinical test.

We propose a novel classification algorithm for the floating pulse and the sunken pulse using a newly defined coefficient (C(fs)). To examine the validity of the proposed algorithm, we carried out a clinical test in which 12 oriental medical doctors made pairwise diagnoses on the pulses of volunteering subjects. 169 subjects were simultaneously diagnosed by paired doctors, and the diagnoses in 121 subjects were concordant, yielding an accuracy of 72% and a Matthews correlation coefficient of 0.42, which indicates reasonable agreement between doctors. Two sample T-tests showed that subjects in the sunken pulse group had significantly higher BMI and C(fs) (P < .05) than those in the floating pulse group. The pulse classification by the algorithm converged with the diagnoses of paired doctors with an accuracy up to 69%. With these results, we confirm the validity of the novel classification algorithm for the floating and sunken pulses.

L-Ribose from L-arabinose by epimerization and its purification by 3-zone simulated moving bed chromatography.

L-Ribose has recently received attention as the starting material for nucleoside drugs. As it is not found in nature, it is being produced by enzymatic or epimerization reaction. We investigated an epimerization reaction by molybdenium oxide and examined the effects of temperature, solvent, and molybdenum oxide amount on epimerization. L-Ribose has a yield of 22% under the conditions of 100 kg/m3 L-arabinose, 20% methanol, 5 kg/m3 MoO3, and 90 degrees C. In addition, simulated moving bed (SMB) that was equipped with three NH2-HPLC columns was used to separate L-arabinose and L-ribose resulting from L-arabinose epimerization. A 3-zone SMB process was developed to eliminate the high pressure problem in the conventional 4-zone SMB. Aspen simulation was performed to determine the operating variables such as switching time, raffinate, and extract flow rates. Experimental purities of extract and raffinate were compared with the theoretical ones and they are found to be fairly well correlated.

Variations in non-invasive radial artery pulse waveform at different measuring positions.

Noninvasive radial artery pulse wave has been widely not only for the pulse wave analysis (PWA) itself but also for assessment of arterial stiffness with estimated aortic pulse wave from peripheral pulse wave. In this study, we tested the differences between the extracted parameters, including AIx, from radial artery pulse waves measured at three different positions preliminarily. A 30 years old female involved in this experiment and this subject has no evidence about cardiovascular diseases. Radial pulse waves were recorded at three different positions on left lower arm ten times for each position. These positions are widely used in pulse diagnosis of traditional medicine.As results of repeated measures ANOVA analysis, 9 parameters were found which had significantly differences in between measuring positions (P<0.05). These parameters wereP_AIx, PP_Amp, A_T1, A_Tr, AIx, AIx_@HR75, ESP, MP_Sysand MP_Dia. And, by Spearman correlation test at P2, it was observed that P_AIx (r =0.894), PP_Amp (r=-0.765),AIx_@HR75 (r=0.929), ESP (r=0.893) and MP_Dia (r=0.792)were highly correlated with AIx. Elaborately, the correlation coefficients between each parameter were high in similar degrees (r>0.70).Further studies on what make differences in these parameters between measuring positions are need. And, ultimately, we need to determine the best measuring process, including measuring position, hold-down pressure, signal quality validation and so on,so to achieve the optimal waveform which represents subject's health condition for both western medicine and traditional medicine.