Anti-Inflammatory Effects of an Extract from Pseudomonas aeruginosa and Its Purified Product 1-Hydroxyphenazine on RAW264.7 Cells.

The purpose of this study was to discuss the effects of an extract from the culture medium of Pseudomonas aeruginosa (P. aeruginosa) 2016NX1 (chloroform extract of P. aeruginosa, CEPA) and its purified product 1-hydroxyphenazine on RAW264.7 cell inflammation. Cell viability was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method. TNF-α production was determined by an ELISA method. The effects of CEPA and its purified product 1-hydroxyphenazine on cell morphology were investigated using an inverted microscope. Quantitative real-time PCR was performed to determine mRNA expression levels. CEPA and 1-hydroxyphenazine had no obvious toxicity to cells when their concentrations were no more than 20 µg ml-1 and 5 µg ml-1, respectively. Both CEPA and 1-hydroxyphenazine suppressed the secretion of TNF-α and significantly reduced the mRNA expression levels of TNF-α, IL-1ß, and IL-6. Both CEPA and 1-hydroxyphenazine inhibited M1 cell polarization after lipopolysaccharide (LPS) stimulation. The results in this article lay a good foundation for the biopharmaceutical applications of CEPA and 1-hydroxyphenazine in the future. CEPA and 1-hydroxyphenazine had certain anti-inflammatory activity, and inhibited LPS-induced RAW264.7 cell inflammation. Our findings suggest that CEPA and 1-hydroxyphenazine are potential chemicals with anti-inflammatory activity.

Effect of temporal misalignment on understanding Mandarin sentences in simulated combined electric-and-acoustic stimulation.

The present work assessed Mandarin sentence understanding when the electric and acoustic portions are not temporally aligned in simulated combined electric-and-acoustic stimulation (EAS). A relative time shift was added between the electric and acoustic portions, simulating the temporal misalignment effect in EAS processing. The processed stimuli were played to normal-hearing listeners to recognize. Experimental results showed a significant decrease of the intelligibility score caused by the temporal misalignment in the two portions of EAS processing, suggesting the need to avoid temporal misalignment in EAS. The preceding acoustic-portion more significantly decreased the understanding of EAS-processed Mandarin stimuli than the preceding electric-portion.

Quantification of three-dimensional computed tomography angiography for evaluating coronary luminal stenosis using digital subtraction angiography as the standard of reference.

OBJECTIVE: We sought to evaluate the accuracy of quantitative three-dimensional (3D) CT angiography (CTA) for the assessment of coronary luminal stenosis using digital subtraction angiography (DSA) as the standard of reference. METHOD: Twenty-three patients with 54 lesions were referred for CTA followed by DSA. The CTA scans were performed with 256-slice spiral CT. 3D CTA were reconstructed from two-dimensional CTA imaging sequences in order to extract the following quantitative indices: minimal lumen diameter, percent diameter stenosis (%DS), minimal lumen area, and percent area stenosis (%AS). Correlation and limits of agreement were calculated using Pearson correlation and Bland-Altman analysis, respectively. The diagnostic performance and the diagnostic concordance of 3D CTA-derived anatomic parameters (%DS, %AS) for the detection of severe coronary arterial stenosis (as assessed by DSA) were presented as sensitivity, specificity, diagnostic accuracy, and Kappa statistics. Of which vessels with %DS >50% or with %AS >75% were identified as severe coronary arterial lesions. RESULT: The correlations of the anatomic parameters between 3D CTA and DSA were significant (r = 0.51-0.74, P < 0.001). Bland-Altman analysis confirmed that the mean differences were small (from -1.11 to 27.39%), whereas the limits of agreement were relatively wide (from ±28.07 to ±138.64%). Otherwise, the diagnostic accuracy (74.1% with 58.3% sensitivity and 86.7% specificity for DS%; 74.1% with 45.8% sensitivity and 96.7% specificity for %AS) and the diagnostic concordance (k = 0.46 for DS%; 0.45 for %AS) of 3D CTA-derived anatomic parameters for the detection of severe stenosis were moderate. CONCLUSION: 3D advanced imaging reconstruction technique is a helpful tool to promote the use of CTA as an alternative to assess luminal stenosis in clinical practice.

Cuffless and Continuous Blood Pressure Estimation from the Heart Sound Signals.

Cardiovascular disease, like hypertension, is one of the top killers of human life and early detection of cardiovascular disease is of great importance. However, traditional medical devices are often bulky and expensive, and unsuitable for home healthcare. In this paper, we proposed an easy and inexpensive technique to estimate continuous blood pressure from the heart sound signals acquired by the microphone of a smartphone. A cold-pressor experiment was performed in 32 healthy subjects, with a smartphone to acquire heart sound signals and with a commercial device to measure continuous blood pressure. The Fourier spectrum of the second heart sound and the blood pressure were regressed using a support vector machine, and the accuracy of the regression was evaluated using 10-fold cross-validation. Statistical analysis showed that the mean correlation coefficients between the predicted values from the regression model and the measured values from the commercial device were 0.707, 0.712, and 0.748 for systolic, diastolic, and mean blood pressure, respectively, and that the mean errors were less than 5 mmHg, with standard deviations less than 8 mmHg. These results suggest that this technique is of potential use for cuffless and continuous blood pressure monitoring and it has promising application in home healthcare services.

A stochastic filtering approach to recover strain images from quasi-static ultrasound elastography.

BACKGROUND: Model-based reconstruction algorithms have shown potentials over conventional strain-based methods in quasi-static elastographic image by using realistic finite element (FE) or bio-mechanical model constraints. However, it is still difficult to properly handle the discrepancies between the model constraint and ultrasound data, and the measurement noise. METHODS: In this paper, we explore the usage of Kalman filtering algorithm for the estimation of strain imaging in quasi-static ultrasound elastography. The proposed strategy formulates the displacement distribution through biomechanical models, and the ultrasound-derived measurements through observation equations. Through this filtering strategy, the discrepancies are quantitatively modelled as one Gaussian white noise, and the measurement noise of ultrasound data is modelled as another independent Gaussian white noise. The optimal estimation of kinematic functions, i.e. the full displacement and velocity field, are computed through this Kalman filter. Then the strain images can be easily calculated from the estimated displacement field. RESULTS: The accuracy and robustness of our proposed framework is first evaluated in synthetic data in controlled conditions, and the performance of this framework is then evaluated in the real data collected from elastography phantoms and patients with favourable results. CONCLUSIONS: The potential of our algorithm is to provide the distribution of mechanically meaningful strain under a proper biomechanical model constraint. We address the model-data discrepancy and measurement noise by introducing process noise and measurement noise in our framework, and then the mechanically meaningful strain is estimated through the Kalman filter in the minimum mean square error (MMSE) sense.

Bioreductive prodrugs as cancer therapeutics: targeting tumor hypoxia.

Hypoxia, a state of low oxygen, is a common feature of solid tumors and is associated with disease progression as well as resistance to radiotherapy and certain chemotherapeutic drugs. Hypoxic regions in tumors, therefore, represent attractive targets for cancer therapy. To date, five distinct classes of bioreactive prodrugs have been developed to target hypoxic cells in solid tumors. These hypoxia-activated prodrugs, including nitro compounds, N-oxides, quinones, and metal complexes, generally share a common mechanism of activation whereby they are reduced by intracellular oxidoreductases in an oxygen-sensitive manner to form cytotoxins. Several examples including PR-104, TH-302, and EO9 are currently undergoing phase II and phase III clinical evaluation. In this review, we discuss the nature of tumor hypoxia as a therapeutic target, focusing on the development of bioreductive prodrugs. We also describe the current knowledge of how each prodrug class is activated and detail the clinical progress of leading examples.

Age-Related Changes in Blood Volume Pulse Wave at Fingers and Ears.

OBJECTIVE: The decline in vascular elasticity with aging can be manifested in the shape of pulse wave. The study investigated the pulse wave features that are sensitive to age and the pattern of these features change with increasing age were examined. METHODS: Five features were proposed and extracted from the photoplethysmography (PPG)-based pulse wave or its first derivative wave. The correlation between these PPG features and ages was studied in 100 healthy subjects with a wide range of ages (20-71 years). Piecewise regression coefficients were calculated to examine the rates of change of the PPG features with age at different age stages. RESULTS: The proposed PPG features obtained from the finger showed a strong and significant correlation with age (with r = 0.76 - 0.77, p < 0.01), indicating higher sensitivity to age changes compared to the PPG features reported in previous studies (with r = 0.66 - 0.75). The correlation remained significant even after correcting for other clinical variables. The rate of change of the PPG feature values was found to be significantly faster in subjects aged ≥40 years compared to those aged < 40 years in the healthy population. This rate of change was similar to the age-related progression of arterial stiffness evaluated by pulse wave velocity (PWV), which is considered a gold standard for evaluating vascular stiffness. CONCLUSIONS: The proposed PPG features showed a high correlation with chronological age in healthy subjects and exhibited a similar age-related change trend as PWV. SIGNIFICANCE: With the convenience of PPG measures, the proposed age-related features have the potential to be used as biomarkers for vascular aging and estimating the risk of cardiovascular disease.

Filtering-induced changes of pulse transmit time across different ages: a neglected concern in photoplethysmography-based cuffless blood pressure measurement.

Background: Pulse transit time (PTT) is a key parameter in cuffless blood pressure measurement based on photoplethysmography (PPG) signals. In wearable PPG sensors, raw PPG signals are filtered, which can change the timing of PPG waveform feature points, leading to inaccurate PTT estimation. There is a lack of comprehensive investigation of filtering-induced PTT changes in subjects with different ages. Objective: This study aimed to quantitatively investigate the effects of aging and PTT definition on the infinite impulse response (IIR) filtering-induced PTT changes. Methods: One hundred healthy subjects in five different ranges of age (i.e., 20-29, 30-39, 40-49, 50-59, and over 60 years old, 20 subjects in each) were recruited. Electrocardiogram (ECG) and PPG signals were recorded simultaneously for 120 s. PTT was calculated from the R wave of ECG and PPG waveform features. Eight PTT definitions were developed from different PPG waveform feature points. The raw PPG signals were preprocessed then further low-pass filtered. The difference between PTTs derived from preprocessed and filtered PPG signals, and the relative difference, were calculated and compared among five age groups and eight PTT definitions using the analysis of variance (ANOVA) or Scheirer-Ray-Hare test with post hoc analysis. Linear regression analysis was used to investigate the relationship between age and filtering-induced PTT changes. Results: Filtering-induced PTT difference and the relative difference were significantly influenced by age and PTT definition (p < 0.001 for both). Aging effect on filtering-induced PTT changes was consecutive with a monotonous trend under all PTT definitions. The age groups with maximum and minimum filtering-induced PTT changes depended on the definition. In all subjects, the PTT defined by maximum peak of PPG had the minimum filtering-induced PTT changes (mean: 16.16 ms and 5.65% for PTT difference and relative difference). The changes of PTT defined by maximum first PPG derivative had the strongest linear relationship with age (R-squared: 0.47 and 0.46 for PTT difference relative difference). Conclusion: The filtering-induced PTT changes are significantly influenced by age and PTT definition. These factors deserve further consideration to improve the accuracy of PPG-based cuffless blood pressure measurement using wearable sensors.

The Changes of Cardiovascular Neurotransmitter Levels under Low-Intensity Focused Ultrasound Stimulation of the Vagus Nerve.

BACKGROUND: Our previous study has shown that stimulation of the vagus nerve with low-intensity focused ultrasound could modulate blood pressure (BP), but the underlying mechanisms remain unclear. This study investigated the changes of cardiovascular neurotransmitter levels to indirectly evaluate the responses of the autonomic nervous system and renin-angiotensin system under low-intensity focused ultrasound stimulation (FUS) of the vagus nerve. METHODS: Cardiovascular neurotransmitter levels of epinephrine (EPI), norepinephrine (NE), and angiotensin II (ANGII) were measured and compared before and after the FUS in seven spontaneously hypertensive rats; and were also measured and compared between a target stimulation group (FUS, n = 6) and non-target stimulation group (Control, n = 5) after stimulation to exclude the influence of potential confounding factors. RESULTS: The t-test results showed that the levels of EPI, NE, and ANGII were significantly decreased (P < 0.05) after stimulation compared to before stimulation. Additionally, the levels of NE and EPI were significantly lower (P < 0.05) in the FUS group than in the Control group after stimulation, indicating that the activities of the sympathetic nervous system and renin-angiotensin system of the vagus nerve might be inhibited by FUS of the vagus nerve. CONCLUSION: These findings reveal the mechanism of BP lowing in response to FUS of the vagus nerve.Clinical Relevance-This study revealed the mechanism of BP lowering in response to focused ultrasound stimulation of the vagus nerve through analyzing the changes of cardiovascular neurotransmitter levels.

Autonomic modulation by low-intensity focused ultrasound stimulation of the vagus nerve.

Objective.Our previous study has shown that low-intensity focused ultrasound stimulation (FUS) of the vagus nerve could modulate blood pressure (BP), but its underlying mechanisms remain unclear. We hypothesized that low-intensity FUS of the vagus nerve would regulate autonomic function and thus BP.Approach.17 anesthetized spontaneously hypertensive rats were treated with low-intensity FUS of the left vagus nerve for 15 min each trial. Continuous BP, heart rate, respiration rate (RR), and core body temperature were simultaneously recorded to evaluate the effects on BP and other physiological parameters. Heart rate variability (HRV), systolic BP variability, and baroreflex sensitivity were computed to evaluate the autonomic modulation function. A Control-sham group without stimulation and another Control-FUS group with non-target stimulation were also examined to exclude the influence of potential confounding factors on autonomic modulation.Main results.A prolonged significant decrease in BP, pulse pressure, RR, the normalized low-frequency power of HRV, and the low-to-high frequency power ratio of HRV were found after the low-intensity FUS of the left vagus nerve in comparison with the baseline and those of the control groups, demonstrating that activities of the sympathetic nervous system were inhibited. The prolonged significant increase of the normalized high-frequency power of HRV suggested the activation of parasympathetic activity.Significance.Low-intensity FUS of the left vagus nerve effectively improved the autonomic function by activating parasympathetic efferent and inhibiting sympathetic efferent, which contributes to BP reduction. The findings shed light on the hypotensive mechanism underlying FUS.

Discovery of JND003 as a New Selective Estrogen-Related Receptor α Agonist Alleviating Nonalcoholic Fatty Liver Disease and Insulin Resistance.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of chronic liver diseases and is causally linked to hepatic insulin resistance and reduced fatty acid oxidation. Therapeutic treatments targeting both hepatic insulin resistance and lipid oxidative metabolism are considered as feasible strategies to alleviate this disease. Emerging evidence suggests Estrogen-Related Receptor alpha (ERRα), the first orphan nuclear receptor identified, as a master regulator in energy homeostasis by controlling glucose and lipid metabolism. Small molecules improving the functions of ERRα may provide a new option for management of NAFLD. In the present study, by using liver-specific Errα knockout mouse (Errα-LKO), we showed that liver-specific deletion of ERRα exacerbated diet-evoked fatty liver, hepatic and systemic insulin resistance in mice. A potent and selective ERRα agonist JND003 (7) was also discovered. In vitro and in vivo investigation demonstrated that the compound enhanced the transactivation of ERRα downstream target genes, which was accompanied by improved insulin sensitivity and fatty liver symptoms. Furthermore, the therapeutic effects were completely abolished in Errα-LKO mice, indicative of its on-target efficacy. Our study thus suggests that hepatic ERRα is a viable target for NAFLD and that ERRα agonist may serve as an intriguing pharmacological option for management of metabolic diseases.

New aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein.

a-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5 g bound to a-FABP with an apparent K(i) value below 1.0 nM, while did not inhibit h-FABP at 50 µM and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5 g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases.

A Pilot Study of Thermal Effect of Low-intensity Focused Ultrasound on Blood Pressure Modulation.

Our recent study showed that low-intensity focused ultrasound stimulation (FUS) of the vagus nerve is capable of lowering blood pressure (BP). However, it remains unknown that what is the underlying mechanisms of BP modulation with FUS. In our preliminary experiments, we noticed that there was temperature elevation accompanied the FUS. Thus, to verify whether the thermal effect of ultrasound contributes in the BP-lowering effect, this study compared the BP response under the FUS (with thermal effect and mechanical effect) and the alternative heating source treatment (AHST) (with thermal effect only) of left vagus nerve. Six Sprague Dawley rats were randomly divided into two groups (FUS, n=3 and AHST, n=3). In vivo temperature measurements were conducted to evaluate the heating performance of the FUS and the AHST. Blood pressure (BP) waveform was continuously recorded from the right common artery and was used for analyzing systolic BP (SBP), diastolic BP (DBP), mean BP (MBP), and heart rate (HR). The results showed that the SBP, DBP, MBP and HR decreased during the 15-min FUS. However, most of the SBP, DBP, MBP and HR increased during the 15-min AHST, which had the approximate temperature elevation of the FUS. Thus, the thermal effect of ultrasound probably does not contribute in the BP-lowering effect induced by low-intensity FUS of the vagus nerve.

Blood Pressure Modulation With Low-Intensity Focused Ultrasound Stimulation to the Vagus Nerve: A Pilot Animal Study.

OBJECTIVE: For hypertensive individuals, their blood pressure (BP) is often managed by taking medications. However, antihypertensive drugs might cause adverse effects such as congestive heart failure and are ineffective in significant numbers of the hypertensive population. As an alternative method for hypertension management, non-drug devices-based neuromodulation approaches such as functional electrical stimulation (FES) have been proposed. The FES approach requires the implantation of a stimulator into the body. One recently emerging technique, called low-intensity focused ultrasound stimulation (FUS), has been proposed to non-invasively modulate neural activities. In this pilot study, the feasibility of adopting low-intensity FUS neuromodulation for BP regulation was investigated using animal models. METHODS: A FUS system was developed for BP modulation in rabbits. For each rabbit, the low-intensity FUS with different acoustic intensities was used to stimulate its exposed left vagus nerve, and the BP waveform was synchronously recorded in its right common carotid artery. The effects of the different FUS intensities on systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MAP), and heart rate (HR) were extensively examined from the BP recordings. RESULTS: The results demonstrated that the proposed FUS method could successfully induce changes in SBP, DBP, MAP, and HR values. When increasing acoustic intensities, the values of SBP, DBP, and MAP would tend to decrease more substantially. CONCLUSION: The findings of this study suggested that BP could be modulated through the FUS, which might provide a new way for non-invasive and non-drug management of hypertension.

Investigating the physiological mechanisms of the photoplethysmogram features for blood pressure estimation.

OBJECTIVE: Photoplethysmogram (PPG) signals have been widely used to estimate blood pressure (BP) cufflessly and continuously. A number of different PPG features have been proposed and extracted from PPG signals with the aim of accurately estimating BP. However, the underlying physiological mechanisms of PPG-based BP estimation still remain unclear, particularly those corresponding to various PPG features. In this study, the physiological mechanisms of PPG features for BP estimation were investigated, which may provide further insight. APPROACH: Experiments with cold stimuli and an exercise trial were designed to change the total peripheral vascular resistance (TPR) and cardiac output (CO), respectively. Instantaneous BP and continuous PPG signals from 12 healthy subjects were recorded throughout the experiments. A total of 65 PPG features were extracted from the original, the first derivative, and the second derivative waves of PPG. The significance of the change of PPG features in the cold stimuli phase and in the early exercise recovery period was compared with that in the baseline phase. MAIN RESULTS: Intensity-specific PPG features changed significantly (p < 0.05) in the cold stimuli phase compared with the baseline phase, demonstrating that they were TPR-correlated. Time-specific PPG features changed significantly (p < 0.05) in the early exercise recovery period compared with the baseline phase, suggesting they were CO-correlated. Most of the PPG features associated with slope and area changed obviously both in the cold stimuli phase and in the early exercise recovery period, indicating that they should be TPR-correlated and CO-correlated. SIGNIFICANCE: The findings of this study explained the intrinsic physiological mechanisms underlying PPG features used for BP estimation, and provided insights for exploring more diagnostic applications of the PPG features.

A Characteristic Filtering Method for Pulse Wave Signal Quality Assessment.

Pulse wave is an important physiological signal widely used in clinic. In practical applications, the pulse wave recordings are easily corrupted by different interferences. Sometimes, it is very difficult to eliminate the noise by commonly used filtering methods. In this study, we proposed a filtering method based on the characteristics of pulse wave recordings to remove the noisy outliers. Firstly, five characteristics, short-term energy (SE), ascending intensity difference (AID), descending intensity difference (DID), ascending time difference (ATD), and descending time difference (DTD), were chosen as metrics and calculated from cardiac pulse wave. Then the median lines of the five metrics were obtained using a median filter, respectively. An acceptable value range around the median line of each metric was set based on histogram distribution analysis and was used to examine pulse wave recordings cardiac-cycle-by-cycle. For each cardiac cycle, when one or more of its five characteristic values exceed(s) the acceptable range, the pulse wave recording segment was discarded from further analysis. With this proposed method, the noisy outliers could be efficiently identified from the pulse wave recordings. This suggests that the proposed preprocessing method would be useful in improving the assessment performance of pulse-wave-based clinical applications. Additionally, the method might also be extended used in other physiological signals pre-processing, such as ECG, blood pressure wave, etc.

Reply to Comment on 'New photoplethysmogram indicators for improving cuffless and continuous blood pressure estimation accuracy'.

OBJECTIVE: This article was written by the invitation of the editorial board of Physiological Measurement. It is a Reply to the Comment regarding our recently published paper entitled 'New photoplethysmogram indicators for improving cuffless and continuous blood pressure estimation accuracy' (Lin et al 2018 Physiol. Meas. 29 025005). APPROACH: We appreciate van Helmond and Joseph's (2018 Physiol. Meas. 098001) interests and comments on our previous paper. In the Comment, they discussed in detail the physiology underlying the pulse arrive time (PAT)-based methods for blood pressure (BP) measurement, and concluded that there are inherent physiological reasons precluding the development of an accurate continuous cuffless BP measurement using PAT-based methods. We could agree with the comments of van Helmond and Joseph about the physiology underlying PAT-based methods for BP measurement. It may be difficult to minimize the confounding effects of physiological factors such as pre-ejection period and smooth muscle tone, etc. However, in this Reply, we discuss some potential solutions to deal with these problems from an engineering point of view. MAIN RESULTS: When heart rate, more photoplethysmogram (PPG) features, PAT, robust machine learning models, and other techniques were adopted for BP estimation, it is promising for improving the accuracy of BP estimation to an acceptable range that can meet professional standards (e.g. Advancement of Medical Instrumentation (AAMI) standard, British Hypertension Society (BHS) protocol). SIGNIFICANCE: PAT- and/or PPG-based methods may be a promising technique for continuous and unobtrusive blood pressure measurement.

Thalidomide has a significant effect in patients with thalassemia intermedia.

OBJECTIVE: To investigate the effect of thalidomide in patients with thalassemia intermedia. METHODS: We observed the effect of thalidomide in seven patients with thalassemia intermedia requiring blood transfusion. Four of the patients were transfusion-independent, and three patients were transfusion-dependent. RESULTS: For the four transfusion-independent patients, hemoglobin concentration increased significantly (≥2 g/dl) in three and moderately (1-2 g/dl) in one. After 3 months of treatment, hemoglobin concentration increased 3.2 ± 1.2 g/dl compared to pretreatment. Among the three transfusion-dependent patients, transfusion was terminated after one month of treatment in one patient and decreased >50% in the other two patients, accompanied by an increase in the average hemoglobin concentration. CONCLUSION: Thalidomide had a significant effect in patients with thalassemia intermedia. Further studies of a larger scale and more rigorous design are warranted.

New photoplethysmogram indicators for improving cuffless and continuous blood pressure estimation accuracy.

OBJECTIVE: The accuracy of cuffless and continuous blood pressure (BP) estimation has been improved, but it is still unsatisfactory for clinical uses. This study was designed to further increase BP estimation accuracy. APPROACH: In this study, a number of new indicators were extracted from photoplethysmogram (PPG) recordings and a linear regression method was used to construct BP estimation models based on the PPG indicators and pulse transit time (PTT). The performance of the BP estimation models was evaluated by the PPG recordings from 22 subjects when they performed mental arithmetic stress and Valsalva's manoeuvre tasks that could induce BP fluctuations. MAIN RESULTS: Our results showed that the best PPG-based BP estimation model could achieve a decrease of 0.31 ± 0.08 mmHg in systolic BP (SBP) and 0.33 ± 0.01 mmHg in diastolic BP (DBP) on estimation errors of grand absolute mean (GAM) and standard deviation (GSD) in comparison to the previously reported PPG-based methods. The best estimation model based on the combination of PPG and PPT could achieve a decrease (GAM & GSD) of 0.81 ± 0.95 mmHg in SBP and 0.75 ± 0.54 mmHg in DBP in comparison to the PPT-based methods. SIGNIFICANCE: The findings suggest that the newly proposed PPG indicators would be promising for improving the accuracy of continuous and cuffless BP estimation.

Using Muscle Synergy to Evaluate the Neck Muscular Activities during Normal Swallowing.

Swallowing is an extremely complex motion controlled by multiple muscles on the front neck region. Normal swallowing is dependent on orderly activation and co-coordination of the associated neck muscles, known as muscle synergy. However, evidence for muscle synergy during normal swallowing is rarely investigated. In this study, we studied the muscle synergy associated with swallowing saliva based on high-density (HD) surface electromyography (sEMG) signals acquired from four healthy subjects. The non-negative matrix factorization algorithm was applied to reconstruct the muscle activation patterns, and the values of variance accounted for (VAF) coefficients were computed to determine the number of muscle synergies. The results showed that the VAF values raised with the increase in the number of synergies on both the left and right sides of the neck. And the variation tendency of the VAF values was almost similar between the left and right area with a significant correlation ($\text{r}=0.9902 \pm 0.0046$, $\mathrm {p}<0.05)$. Furthermore, it was observed that an average of 5 muscle synergies was the minimum number required to sufficiently reconstruct the spatial characteristics of the synergism between both sides of the neck. These results suggest that the muscle synergy approach could serve as a promising candidate to evaluate the muscular co-contractions during swallowing, and it might be a useful method for dysphagia monitoring and diagnoses.