In the last decade, cuffless blood pressure measurement technology has been widely studied because it could be applied to a wearable apparatus. Electrocardiography (ECG), photo-plethysmography (PPG), and phonocardiography are always used to detect the pulse transit time (PTT) because the changed tendencies of the PTT and blood pressure have a negative relationship. In this study, the PPG signal was replaced by the impedance plethysmography (IPG) signal and was used to detect the PTT. The placement and direction of the electrode array for the IPG measurement were discussed. Then, we designed an IPG ring that could measure an accurate IPG signal. Twenty healthy subjects participated in this study. The changes in blood pressure after exercise were evaluated through the changes of the PTT. The results showed that the change of the systolic pressure had a better relationship with the change of the PTT_IPG than that of the PTT_PPG (r = 0.700 vs. r = 0.450). Moreover, the IPG ring with spot electrodes would be more suitable to develop with the wearable cuffless blood pressure monitor than the PPG sensor.

As photoplethysmographic (PPG) signals are comprised of numerous pieces of important physiological information, they have been widely employed to measure many physiological parameters. However, only a high-quality PPG signal can provide a reliable physiological assessment. Unfortunately, PPG signals are easily corrupted by motion artifacts and baseline drift during recording. Although several rule-based algorithms have been developed for evaluating the quality of PPG signals, few artificial intelligence-based algorithms have been presented. Thus, this study aims to classify the quality of PPG signals by using two two-dimensional deep convolution neural networks (DCNN) when the PPG pulse is used to measure cardiac stroke volume (SV) by impedance cardiography. An image derived from a PPG pulse and its differential pulse is used as the input to the two DCNN models. To quantify the quality of individual PPG pulses, the error percentage of the beat-to-beat SV measured by our device and medis^® CS 2000 synchronously is used to determine whether the pulse quality is high, middle, or low. Fourteen subjects were recruited, and a total of 3135 PPG pulses (1342 high quality, 73 middle quality, and 1720 low quality) were obtained. We used a traditional DCNN, VGG-19, and a residual DCNN, ResNet-50, to determine the quality levels of the PPG pulses. Their results were all better than the previous rule-based methods. The accuracies of VGG-19 and ResNet-50 were 0.895 and 0.925, respectively. Thus, the proposed DCNN may be applied for the classification of PPG quality and be helpful for improving the SV measurement in impedance cardiography.

Cigarette smoking is a well-established risk factor for various diseases, such as cardiovascular diseases, neurodegeneration, and cancer. Cadmium nitrate (Cd(NO₃)₂) is one of the major products from the cigarette smoke. Up to now, no supporting evidence on Cd(NO₃)₂-induced apoptosis and its related working mechanism in neurons has been found. In present study, the mode of cell death, caspase activities, reactive oxygen species (ROS) generation, and mitochondrial dysfunction in N2a cells, which are neuron-like cells, were assessed by Annexin V-FITC and PI assays, caspase fluorometric assay, DCFH-DA fluorescence assay, and JC-1 fluorescence assay respectively. The results showed that not only Cd(NO₃)₂ induced apoptosis and necrosis but also the activities of caspase-3 and -9 expressed in a concentration-dependent manner. In addition, Cd(NO₃)₂ also induced both mitochondrial dysfunction and ROS generation in a concentration-dependent manner. All these indicated that in N2a cells parallel trends could be observed in apoptosis, caspase-3 and -9 activities, mitochondrial dysfunction, and ROS generation when induced by Cd(NO₃)₂. Furthermore, Cd(NO₃)₂-induced apoptosis, caspases activities, mitochondrial dysfunction, and ROS generation were reduced by N-acetyl-l-cysteine (NAC). These results indicated that Cd(NO₃)₂-induced neuronal apoptosis was reduced by NAC via intrinsic apoptotic caspase cascade activities and their up-stream factors, including mitochondrial dysfunction and ROS generation.

Photoplethysmography (PPG) has been extensively employed to acquire some physiological parameters such as heart rate, oxygen saturation, and blood pressure. However, PPG signals are frequently corrupted by motion artifacts and baseline wandering, especially for the reflective PPG sensor. Several different algorithms have been studied for determining the signal quality of PPG by the characteristic parameters of its waveform and the rule-based methods. The levels of signal quality usually were defined by the manual operations. Thus, whether the good PPG waveforms are enough to increase the accuracy of the measurement is still a subjective issue. The aim of this study is to use a fuzzy neural network to determine the signal quality indexes (SQI) of PPG pulses measured by the impedance cardiography. To test the algorithm performance, the beat-to-beat stroke volumes (SV) were measured with our device and the medis^® CS 2000, synchronously. A total of 1466 pulses from 10 subjects were used to validate our algorithm in which the SQIs of 1007 pulses were high, those of 71 pulses were in the middle, and those of 388 pulses were low. The total error of SV measurement was −18 ± 22.0 mL. The performances of the classification were that the sensitivity and specificity for the 1007 pulses with the high SQIs were 0.81 and 0.90, and the error of SV measurement was 6.4 ± 12.8 mL. The sensitivity and specificity for the 388 pulses with the low SQIs were 0.84 and 0.93, while the error of SV measurement was 30.4 ± 3.6 mL. The results show that the proposed algorithm could be helpful in choosing good-quality PPG pulses to increase the accuracy of SV measurement in the impedance plethysmography.

Genotoxic stress from environmental pollutants plays a critical role in cytotoxicity. The most abundant nitro-polycyclic aromatic hydrocarbon in environmental pollutants, 1-nitropyrene (1-NP), is generated during fossil fuel, diesel, and biomass combustion under sunlight. Macrophages, the key regulators of the innate immune system, provide the first line of defense against pathogens. The toxic effects of 1-NP on macrophages remain unclear. Through a lactate dehydrogenase assay, we measured the cytotoxicity induced by 1-NP. Our results revealed that 1-NP induced genotoxicity also named DNA damage, including micronucleus formation and DNA strand breaks, in a concentration-dependent manner. Furthermore, 1-NP induced p53 phosphorylation and nuclear accumulation; mitochondrial cytochrome c release; caspase-3 and -9 activation and cleavage; and poly (ADP-ribose) polymerase-1 (PARP-1) cleavage in a concentration-dependent manner. Pretreatment with the PARP inhibitor, 3-aminobenzamide, significantly reduced cytotoxicity, genotoxicity, and PARP-1 cleavage induced by 1-NP. Pretreatment with the caspase-3 inhibitor, z-DEVD-fmk, significantly reduced cytotoxicity, genotoxicity, PARP-1 cleavage, and caspase 3 activation induced by 1-NP. Pretreatment with the p53 inhibitor, pifithrin-α, significantly reduced cytotoxicity, genotoxicity, PARP-1 cleavage, caspase 3 activation, and p53 phosphorylation induced by 1-NP. We propose that cytotoxicity and genotoxicity induced by 1-NP by PARP-1 cleavage via caspase-3 and -9 activation through cytochrome c release from mitochondria and its upstream p53-dependent pathway in macrophages.

Objectives: Hydroxychloroquine (HCQ) is widely used to treat rheumatic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS). Cardiac arrhythmia has been concerned as important safety issue for HCQ. The aim of this study was to investigate whether hydroxychloroquine increases new-onset arrhythmia among patients with RA, SLE or SS. Methods: This was a retrospective cohort study that conducted from the longitudinal health insurance database of Taiwan. Patients with newly diagnosed RA, SLE or SS with age ≥20 years old were selected from 2000 to 2012. Patients who received HCQ and without HCQ treatment groups were matched by propensity score to minimize the effect of selection bias and confounders. The Cox proportional hazard model was used to analyze the risk of arrhythmia between the two groups after controlling for related variables. Results: A total of 15892 patients were selected to participate and finally 3575 patients were enrolled in each group after matching. There was no different risk of all arrhythmia in patients using HCQ than without HCQ (adjusted hazards ratio 0.81, 95% CI 0.61–1.07) and ventricular arrhythmia as well. The incidence of arrhythmia did not increase when HCQ co-administrated with macrolides. The arrhythmia risk was also not different regardless of daily HCQ dose 4 months. Conclusion: The administration of HCQ did not increase the risk of all cardiac arrhythmia and ventricular arrhythmia regardless of different duration of treatment (≦4 months or >4 months) or cumulative dose (<400mg or ≥400mg) in patients with common autoimmune diseases such as RA, SLE and SS.