Deeper insight into ferroptosis: association with Alzheimer's, Parkinson's disease, and brain tumors and their possible treatment by nanomaterials induced ferroptosis.

Ferroptosis is an emerging and novel type of iron-dependent programmed cell death which is mainly caused by the excessive deposition of free intracellular iron in the brain cells. This deposited free iron exerts a ferroptosis pathway, resulting in lipid peroxidation (LiPr). There are mainly three ferroptosis pathways viz. iron metabolism-mediated cysteine/glutamate, and LiPr-mediated. Iron is required by the brain as a redox metal for several physiological activities. Due to the iron homeostasis balance disruption, the brain gets adversely affected which further causes neurodegenerative diseases (NDDs) like Parkinson's and Alzheimer's disease, strokes, and brain tumors like glioblastoma (GBS), and glioma. Nanotechnology has played an important role in the prevention and treatment of these NDDs. A synergistic effect of nanomaterials and ferroptosis could prove to be an effective and efficient approach in the field of nanomedicine. In the current review, the authors have highlighted all the latest research in the field of ferroptosis, specifically emphasizing on the role of major molecular key players and various mechanisms involved in the ferroptosis pathway. Moreover, here the authors have also addressed the correlation of ferroptosis with the pathophysiology of NDDs and theragnostic effect of ferroptosis and nanomaterials for the prevention and treatment of NDDs.

A Review of Approaches to the Metallic and Non-Metallic Synthesis of Benzimidazole (BnZ) and Their Derivatives for Biological Efficacy.

Heterocyclic compounds are significant lead drug candidates based on their various structure-activity relationships (SAR), and their use in pharmaceutics is constantly developing. Benzimidazole (BnZ) is synthesized by a condensation reaction between benzene and imidazole. The BnZ structure consists of two nitrogen atoms embedded in a five-membered imide ring which is fused with a benzene ring. This review examines the conventional and green synthesis of metallic and non-metallic BnZ and their derivatives, which have several potential SARs, along with a wide range of pharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, anti-tubercular, and anti-protozoal properties. These compounds have been proven by pharmacological investigations to be efficient against different strains of microbes. Therefore, in this review, the structural variations of BnZ are listed along with various applications, predominantly related to their biological activities.

Two-stage learning-based prediction of bronchopulmonary dysplasia in very low birth weight infants: a nationwide cohort study.

Introduction: The aim of this study is to develop an enhanced machine learning-based prediction models for bronchopulmonary dysplasia (BPD) and its severity through a two-stage approach integrated with the duration of respiratory support (RSd) using prenatal and early postnatal variables from a nationwide very low birth weight (VLBW) infant cohort. Methods: We included 16,384 VLBW infants admitted to the neonatal intensive care unit (NICU) of the Korean Neonatal Network (KNN), a nationwide VLBW infant registry (2013-2020). Overall, 45 prenatal and early perinatal clinical variables were selected. A multilayer perceptron (MLP)-based network analysis, which was recently introduced to predict diseases in preterm infants, was used for modeling and a stepwise approach. Additionally, we applied a complementary MLP network and established new BPD prediction models (PMbpd). The performances of the models were compared using the area under the receiver operating characteristic curve (AUROC) values. The Shapley method was used to determine the contribution of each variable. Results: We included 11,177 VLBW infants (3,724 without BPD (BPD 0), 3,383 with mild BPD (BPD 1), 1,375 with moderate BPD (BPD 2), and 2,695 with severe BPD (BPD 3) cases). Compared to conventional machine learning (ML) models, our PMbpd and two-stage PMbpd with RSd (TS-PMbpd) model outperformed both binary (0 vs. 1,2,3; 0,1 vs. 2,3; 0,1,2 vs. 3) and each severity (0 vs. 1 vs. 2 vs. 3) prediction (AUROC = 0.895 and 0.897, 0.824 and 0.825, 0.828 and 0.823, 0.783, and 0.786, respectively). GA, birth weight, and patent ductus arteriosus (PDA) treatment were significant variables for the occurrence of BPD. Birth weight, low blood pressure, and intraventricular hemorrhage were significant for BPD ≥2, birth weight, low blood pressure, and PDA ligation for BPD ≥3. GA, birth weight, and pulmonary hypertension were the principal variables that predicted BPD severity in VLBW infants. Conclusions: We developed a new two-stage ML model reflecting crucial BPD indicators (RSd) and found significant clinical variables for the early prediction of BPD and its severity with high predictive accuracy. Our model can be used as an adjunctive predictive model in the practical NICU field.

Cystic Periventricular Leukomalacia Worsens Developmental Outcomes of Very-Low-Birth Weight Infants with Intraventricular Hemorrhage-A Nationwide Cohort Study.

Cystic periventricular leukomalacia (cPVL) is a major brain injury involving periventricular white matter that leads to neurodevelopmental impairment in very-low-birth weight (VLBW) infants. We investigated the neurodevelopmental outcomes (motor, cognition, visual, and hearing) of 5734 VLBW infants born between 2013 and 2019 and enrolled in the Korean Neonatal Network. Cranial ultrasound results were stratified by the presence of cPVL and severity of intraventricular hemorrhage (IVH) (no, low-grade [I/II], high-grade [III]). Neurodevelopmental impairment was evaluated using cerebral palsy for motor and Bayley Scales of Infant Development for cognition. cPVL was associated with motor, cognitive, and visual impairments in those without IVH and with low-grade IVH in pairwise comparisons (Cochran−Mantel−Haenszel p < 0.001). Conversely, cPVL was non-significantly correlated with cognitive impairment in high-grade IVH. In regression models adjusted for neonatal variables, isolated cPVL was strongly associated with motor (22.04; 11.39−42.63) and cognitive (3.10; 1.54−6.22) impairments. This study underlines the overall considerable significance of cPVL on NDI with divergent impacts depending on the severity of IVH and developmental indices.

Early screening tool for developmental delay in infancy: Quantified assessment of movement asymmetry using IR-UWB radar.

In the untact COVID-19 era, the feasibility of a noncontact, impulse-radio ultrawideband (IR-UWB) radar sensor has important medical implications. Premature birth is a major risk factor for brain injury and developmental delay; therefore, early intervention is crucial for potentially achieving better developmental outcomes. Early detection and screening tests in infancy are limited to the quantification of differences between normal and spastic movements. This study investigated the quantified asymmetry in the general movements of an infant with hydrocephalus and proposes IR-UWB radar as a novel, early screening tool for developmental delay. To support this state-of-the-art technology, data from actigraphy and video camcorder recordings were adopted simultaneously to compare relevant time series as the infant grew. The data from the three different methods were highly concordant; specifically, the ρz values comparing radar and actigraphy, which served as the reference for measuring movements, showed excellent agreement, with values of 0.66 on the left and 0.56 on the right. The total amount of movement measured by radar over time increased overall; movements were almost dominant on the left at first (75.2% of total movements), but following shunt surgery, the frequency of movement on both sides was similar (54.8% of total movements). As the hydrocephalus improved, the lateralization of movement on radar began to coincide with the clinical features. These results support the important complementary role of this radar system in predicting motor disorders very early in life.

Effects of Ponderal Index on Neonatal Mortality and Morbidities in Extremely Premature Infants.

BACKGROUND: To evaluate how intrauterine stress affects extremely premature infants in terms of intrauterine growth restriction. We hypothesized that extremely premature infants with mildly-low ponderal index (MPI) would have better neonatal outcomes. METHODS: We selected 2,721 subjects of 23 to 28 weeks of gestation between 2013 and 2015 from Korean Neonatal Network database. They were divided into 4 groups based on ponderal index (PI) percentile; PI ≤ 3rd as severely-low PI (SPI, n = 82), 3rd < PI ≤ 10th as MPI (n = 190), 10th < PI ≤ 90th as adequate PI (API, n = 2,179), and PI > 90th as high PI (HPI, n = 270). RESULTS: The mortality in MPI and API groups was comparable (16.3% vs. 16.9%). It was significantly lower than that in the SPI and HPI groups (30.5% and 24.9%, respectively; P = 0.001). The MPI and API groups had better neonatal morbidities compared with the SPI and/or HPI groups, while the MPI group (8.2%) showed a lower incidence of severe intraventricular hemorrhage (IVH) than the other groups (SPI, 21.3%; API, 15.0%; HPI, 19.7%, respectively; P = 0.004). The MPI group had a trend of a bottom in neonatal mortality and morbidities in extremely premature infants. CONCLUSION: The MPI and API groups had lower mortality, massive pulmonary hemorrhage, severe bronchopulmonary dysplasia or death, pulmonary hypertension and neonatal seizure rates than the SPI and/or HPI groups, while the MPI group showed a lower incidence of severe IVH than the other groups. We speculate that the lower incidence of neonatal morbidities and mortality in the MPI group indicating mild intrauterine stress might accelerate fetal maturation resulting in better outcomes in extremely premature infants.

Non-contact Sleep/Wake Monitoring Using Impulse-Radio Ultrawideband Radar in Neonates.

Background: The gold standard for sleep monitoring, polysomnography (PSG), is too obtrusive and limited for practical use with tiny infants or in neonatal intensive care unit (NICU) settings. The ability of impulse-radio ultrawideband (IR-UWB) radar, a non-contact sensing technology, to assess vital signs and fine movement asymmetry in neonates was recently demonstrated. The purpose of this study was to investigate the possibility of quantitatively distinguishing and measuring sleep/wake states in neonates using IR-UWB radar and to compare its accuracy with behavioral observation-based sleep/wake analyses using video recordings. Methods: One preterm and three term neonates in the NICU were enrolled, and voluntary movements and vital signs were measured by radar at ages ranging from 2 to 27 days. Data from a video camcorder, amplitude-integrated electroencephalography (aEEG), and actigraphy were simultaneously recorded for reference. Radar signals were processed using a sleep/wake decision algorithm integrated with breathing signals and movement features. Results: The average recording time for the analysis was 13.0 (7.0-20.5) h across neonates. Compared with video analyses, the sleep/wake decision algorithm for neonates correctly classified 72.2% of sleep epochs and 80.6% of wake epochs and achieved a final Cohen's kappa coefficient of 0.49 (0.41-0.59) and an overall accuracy of 75.2%. Conclusions: IR-UWB radar can provide considerable accuracy regarding sleep/wake decisions in neonates, and although current performance is not yet sufficient, this study demonstrated the feasibility of its possible use in the NICU for the first time. This unobtrusive, non-contact radar technology is a promising method for monitoring sleep/wake states with vital signs in neonates.

Feasibility of non-contact cardiorespiratory monitoring using impulse-radio ultra-wideband radar in the neonatal intensive care unit.

BACKGROUND: Current cardiorespiratory monitoring equipment can cause injuries and infections in neonates with fragile skin. Impulse-radio ultra-wideband (IR-UWB) radar was recently demonstrated to be an effective contactless vital sign monitor in adults. The purpose of this study was to assess heart rates (HRs) and respiratory rates (RRs) in the neonatal intensive care unit (NICU) using IR-UWB radar and to evaluate its accuracy and reliability compared to conventional electrocardiography (ECG)/impedance pneumography (IPG). METHODS: The HR and RR were recorded in 34 neonates between 3 and 72 days of age during minimal movement (51 measurements in total) using IR-UWB radar (HRRd, RRRd) and ECG/IPG (HRECG, RRIPG) simultaneously. The radar signals were processed in real time using algorithms for neonates. Radar and ECG/IPG measurements were compared using concordance correlation coefficients (CCCs) and Bland-Altman plots. RESULTS: From the 34 neonates, 12,530 HR samples and 3,504 RR samples were measured. Both the HR and RR measured using the two methods were highly concordant when the neonates had minimal movements (CCC = 0.95 between the RRRd and RRIPG, CCC = 0.97 between the HRRd and HRECG). In the Bland-Altman plot, the mean biases were 0.17 breaths/min (95% limit of agreement [LOA] -7.0-7.3) between the RRRd and RRIPG and -0.23 bpm (95% LOA -5.3-4.8) between the HRRd and HRECG. Moreover, the agreement for the HR and RR measurements between the two modalities was consistently high regardless of neonate weight. CONCLUSIONS: A cardiorespiratory monitor using IR-UWB radar may provide accurate non-contact HR and RR estimates without wires and electrodes for neonates in the NICU.

Effect of Glycyrrhizic Acid on Scopolamine-Induced Cognitive Impairment in Mice.

PURPOSE: Cognitive impairment is one of the main symptoms of Alzheimer disease and other dementias. Glycyrrhiza uralensis is a natural product that has a protective effect against cognitive impairment. In this study, we investigated whether glycyrrhizic acid, among the main bioactive components of Glycyrrhiza uralensis, has a neuroprotective effect on scopolamine-induced cognitive impairment. METHODS: Twenty-week-old male Institute of Cancer Research mice were used in this study. The scopolamine-induced cognitive impairment mice model was used. Glycyrrhizic acid was orally administered to mice once daily for 21 days, while scopolamine (1 mg/kg) treatment was delivered 30 minutes before behavioral tests. Donepezil (2 mg/kg) was used as a positive drug control. To evaluate the effect of glycyrrhizic acid, the following assessments were performed on hippocampal tissue: Y-maze test, acetylcholinesterase activity, antioxidant enzymes' activity (superoxide dismutase, catalase). Western blotting for phosphor-extracellular signal-regulated kinase, P38, and c-Jun NH2-terminal kinase was conducted. RESULTS: We found that glycyrrhizic acid administration significantly improved scopolamine-induced cognitive impairment in the Y-maze test. The acetylcholinesterase activity, superoxide dismutase, and catalase activity in the glycyrrhizic acid-treated group showed a significant reversal of cognitive impairment compared with the scopolamine-treated group. CONCLUSION: Our results suggest that glycyrrhizic acid has a neuroprotective effect on cognitive function in scopolamine-induced cognitive impairment.

Surgical ligation of patent ductus arteriosus in preterm neonates weighing less than 1500g: a 9-year single center experience.

BACKGROUND: The aim of this study was to determine the feasibility and outcomes of early surgical ligation in preterm neonates with hemodynamically significant patent ductus arteriosus (HSPDA) and to investigate predictors for surgical treatment after unsuccessful medical management. METHODS: Medical records from the neonatal intensive care unit of Hanyang University Seoul Hospital from January 2010 to December 2018 were retrospectively reviewed. 233 preterm neonates weighing less than 1500g with HSPDA were enrolled in our study. Of these preterm neonates, 134 underwent surgical ligation and were subdivided into the early ligation group (n = 49; within 10 days of age) and the late ligation group (n = 85; after 10 days of age). RESULTS: The mean gestational age and birth weight were significantly lower in the patent ductus arteriosus (PDA) ligation group than in the Non-ligation group (p <  0.001). PDA ductal diameter > 2.0 mm (p <  0.001), low Apgar score at 5 min (p = 0.033), and chorioamnionitis (p = 0.037) were the predictors for receiving surgical treatment for PDA. Early ligation was significantly associated with a low incidence of culture-proven sepsis (p = 0.004), mechanical ventilator time > 4 weeks (p = 0.007), necrotizing enterocolitis stage (NEC) ≥ III (p = 0.022), and intraventricular hemorrhage (IVH) grade ≥ III (p = 0.035). CONCLUSIONS: Early surgical ligation minimizes the adverse effects of HSPDA in predicted preterm neonates who subsequently require surgical treatment for PDA. This result suggests that in preterm neonates weighing less than 1500g with HSPDA that is unresponsive to medical treatment, delayed ductal closure should be avoided to reduce severe NEC, severe IVH, culture-proven sepsis, and facilitate earlier endotracheal extubation.

Combination of Arsenic Trioxide and Valproic Acid Efficiently Inhibits Growth of Lung Cancer Cells via G2/M-Phase Arrest and Apoptotic Cell Death.

Arsenic trioxide (ATO; As2O3) has anti-cancer effects in various solid tumors as well as hematological malignancy. Valproic acid (VPA), which is known to be a histone deacetylase inhibitor, has also anti-cancer properties in several cancer cells including lung cancer cells. Combined treatment of ATO and VPA (ATO/VPA) could synergistically enhance anti-cancer effects and reduce ATO toxicity ATO. In this study, the combined anti-cancer effects of ATO and VPA (ATO/VPA) was investigated in NCI-H460 and NCI-H1299 lung cancer cells in vitro and in vivo. A combination of 3 µM ATO and 3 mM VPA (ATO/VPA) strongly inhibited the growths of both lung cancer cell types. DNA flow cytometry indicated that ATO/VPA significantly induced G2/M-phase arrest in both cell lines. In addition, ATO/VPA strongly increased the percentages of sub-G1 cells and annexin V-FITC positive cells in both cells. However, lactate dehydrogenase (LDH) release from cells was not increased in ATO/VPA-treated cells. In addition, ATO/VPA increased apoptosis in both cell types, accompanied by loss of mitochondrial membrane potential (MMP, ∆Ψm), activation of caspases, and cleavage of anti-poly ADP ribose polymerase-1. Moreover, a pan-caspase inhibitor, Z-VAD, significantly reduced apoptotic cell death induced by ATO/VPA. In the xenograft model, ATO/VPA synergistically inhibited growth of NCI-H460-derived xenograft tumors. In conclusion, the combination of ATO/VPA effectively inhibited the growth of lung cancer cells through G2/M-phase arrest and apoptotic cell death, and had a synergistic antitumor effect in vivo.

Altered structural brain networks at term-equivalent age in preterm infants with grade 1 intraventricular hemorrhage.

BACKGROUND: Preterm infants are at risk for structural disruption of brain connectivity due to perinatal complications encountered during the fetal and neonatal periods. This study aimed to investigate the development of connectivity using diffusion tensor imaging at near-term age and the effect of grade 1 intraventricular hemorrhage on it. METHODS: A total of 86 infants (55 preterm infants, 24 full-term infants) without apparent brain injury underwent diffusion magnetic resonance imaging (MRI) between 36 and 41 weeks post-menstrual age. The diffusion-MRI based connectomics were constructed from 64-segmented regions by using the Johns Hopkins University neonate atlas and were weighted with fractional anisotropy. The connectomes were quantified in the structural networks and investigated using network metrics, such as the clustering coefficient, local efficiency, characteristic path length, global efficiency, and small-worldness. We compared the differences in the brain networks of preterm infants with or without grade 1 intraventricular hemorrhage in binary and fractional anisotropy-weighted (wFA) connectomes. RESULTS: The 55 preterm infants had a mean gestational age at birth of 29.3 ± 4.1 weeks and the 24 term-born infants, 38.1 ± 1.1 weeks. A total of 13 of the 55 preterm infants (23.6%) were diagnosed with grade 1 intraventricular hemorrhage. The development of connectivity of the brain network in preterm infants without intraventricular hemorrhage was comparable at near-term age to that in term infants. The preterm infants with germinal matrix hemorrhage exhibited higher clustering (0.093 ± 0.015 vs. 0.088 ± 0.007, p = 0.027) and local efficiency (0.151 ± 0.022 vs. 0.141 ± 0.010, p = 0.025), implying the potential for segregation. However, the preterm infants with intraventricular hemorrhage revealed a longer path length (0.291 ± 0.035 vs. 0.275 ± 0.019, p = 0.020) and lower global efficiency (3.998 ± 0.473 vs. 4.212 ± 0.281, p = 0.048), indicating a decreased integration in the wFA connectivity matrix than those without germinal matrix hemorrhage, after correcting for gestational age, sex, bronchopulmonary dysplasia, and age at scan. CONCLUSION: Grade 1 intraventricular hemorrhage in preterm infants may enhance the capacity for local information transfer and the relative reinforcement of the segregation of networks at the expense of global integration capacity.

Non-contact diagnosis of obstructive sleep apnea using impulse-radio ultra-wideband radar.

While full-night polysomnography is the gold standard for the diagnosis of obstructive sleep apnea, its limitations include a high cost and first-night effects. This study developed an algorithm for the detection of respiratory events based on impulse-radio ultra-wideband radar and verified its feasibility for the diagnosis of obstructive sleep apnea. A total of 94 subjects were enrolled in this study (23 controls and 24, 14, and 33 with mild, moderate, and severe obstructive sleep apnea, respectively). Abnormal breathing detected by impulse-radio ultra-wideband radar was defined as a drop in the peak radar signal by ≥30% from that in the pre-event baseline. We compared the abnormal breathing index obtained from impulse-radio ultra-wideband radar and apnea-hypopnea index (AHI) measured from polysomnography. There was an excellent agreement between the Abnormal Breathing Index and AHI (intraclass correlation coefficient = 0.927). The overall agreements of the impulse-radio ultra-wideband radar were 0.93 for Model 1 (AHI ≥ 5), 0.91 for Model 2 (AHI ≥ 15), and 1 for Model 3 (AHI ≥ 30). Impulse-radio ultra-wideband radar accurately detected respiratory events (apneas and hypopneas) during sleep without subject contact. Therefore, impulse-radio ultra-wideband radar may be used as a screening tool for obstructive sleep apnea.

Cognitive Outcomes of Children with Very Low Birth Weight at 3 to 5 Years of Age.

BACKGROUND: The cognitive consequences and risk factors based long-term outcome of very-low-birth-weight (VLBW; < 1,500 g) infants in Korea has not been studied. The aim of this study was to determine the influence of perinatal and neonatal risk factors on the cognitive performance of VLBW children at 3 to 5 years of age. METHODS: We enrolled 88 VLBW infants without cystic periventricular leukomalacia for the assessment of their demographic data, cognitive performance, and development of cerebral palsy (CP) at 3 to 5 years of age. Cognitive performance was assessed using the Korean version of the Wechsler Preschool and Primary Scale of Intelligence IV. Growth data were assessed with measurements of weight, height, and head circumference (HC) at the corrected ages of 6, 12, and 18 months, and 3 to 5 years of age. RESULTS: In the VLBW group, the full-scale intelligence quotient (FSIQ) was 96.1 ± 15.2 at the mean age of 4.5 years. The incidence rate of CP was 3.4%. Overall, 17% (15/88) of the VLBW children had a below-average FSIQ (< 85). We divided the VLBW children into the abnormal FSIQ group (< 85, n = 15) and the normal FSIQ group (≥ 85, n = 73). VLBW children with intrauterine growth retardation (IUGR) was associated with a below-average FSIQ at the mean age of 4.5 years (< 85, 8/15, 53.3% vs. ≥ 85, 5/73, 6.8%; P < 0.001). After controlling for associated clinical factors, IUGR in the VLBW children was found to be associated with an abnormal FSIQ at the mean age of 4.5 years (P = 0.025). The weight, height, and HC obtained for both groups showed that normal growth was maintained at the mean age of 4.5 years with no significant difference between abnormal and normal FSIQ groups. CONCLUSION: Fifteen of 88 (17%) of the VLBW children had a below-average FSIQ (< 85). VLBW with IUGR is associated with poor cognitive outcomes at the mean age of 4.5 years.

Validation of noncontact cardiorespiratory monitoring using impulse-radio ultra-wideband radar against nocturnal polysomnography.

PURPOSE: Polysomnography (PSG) is a standard diagnostic test for obstructive sleep apnea (OSA). However, PSG requires many skin-contacted sensors to monitor vital signs of patients, which may also hamper patients' sleep. Because impulse-radio ultra-wideband (IR-UWB) radar can detect the movements of heart and lungs without contact, it may be utilized for vital sign monitoring during sleep. Therefore, we aimed to verify the accuracy and reliability of the breathing rate (BR) and the heart rate (HR) measured by IR-UWB radar. METHOD: Data acquisition with PSG and IR-UWB radar was performed simultaneously in 6 healthy volunteers and in 15 patients with suspected OSA. Subjects were divided into 4 groups (normal, mild OSA, moderate OSA, and severe OSA) according to the apnea-hypopnea index (AHI). BRs and HRs obtained from the radar using a software algorithm were compared with the BRs (chest belt) and the HRs (electrocardiography) obtained from the PSG. RESULTS: In normal and in mild OSA, BRs (intraclass correlation coefficients R [ICCR] 0.959 [0.956-0.961] and 0.957 [0.955-0.960], respectively) and HRs ([ICCR] 0.927 [0.922-0.931] and 0.926 [0.922-0.931], respectively) measured in the radar showed excellent agreement with those measured in PSG. In moderate and severe OSA, BRs ([ICCR] 0.957 [0.956-0.959] and 0.873 [0.864-0.882], respectively) and HRs ([ICCR] 0.907 [0.904-0.910] and 0.799 [0.784-0.812], respectively) from the two methods also agreed well. CONCLUSIONS: The IR-UWB radar could accurately measure BRs and HRs in sleeping patients with OSA. Therefore, IR-UWB radar may be utilized as a cardiopulmonary monitor during sleep.

Preclinical Evaluation of a Noncontact Simultaneous Monitoring Method for Respiration and Carotid Pulsation Using Impulse-Radio Ultra-Wideband Radar.

There has been the possibility for respiration and carotid pulsation to be simultaneously monitored from a distance using impulse-radio ultra-wideband (IR-UWB) radar. Therefore, we investigated the validity of simultaneous respiratory rates (RR), pulse rates (PR) and R-R interval measurement using IR-UWB radar. We included 19 patients with a normal sinus rhythm (NSR) and 14 patients with persistent atrial fibrillation (PeAF). The RR, PR, R-R interval and rhythm were obtained simultaneously from the right carotid artery area in a supine position and under normal breathing conditions using IR-UWB radar. There was excellent agreement between the RR obtained by IR-UWB radar and that manually counted by a physician (intraclass correlation coefficient [ICC] 0.852). In the NSR group, there was excellent agreement between the PR (ICC 0.985), average R-R interval (ICC 0.999), and individual R-R interval (ICC 0.910) measured by IR-UWB radar and electrocardiography. In the PeAF group, PR (ICC 0.930), average R-R interval (ICC 0.957) and individual R-R interval (ICC 0.701) also agreed well between the two methods. These results demonstrate that IR-UWB radar can simultaneously monitor respiration, carotid pulse and heart rhythm with high precision and may thus be utilized as a noncontact continuous vital sign monitoring in clinical practice.

Non-contact respiration monitoring using impulse radio ultrawideband radar in neonates.

Vital sign monitoring in neonates requires adhesive electrodes, which often damage fragile newborn skin. Because impulse radio ultrawideband (IR-UWB) radar has been reported to recognize chest movement without contact in adult humans, IR-UWB may be used to measure respiratory rates (RRs) in a non-contact fashion. We investigated the feasibility of radar sensors for respiration monitoring in neonates without any respiratory support to compare the accuracy and reliability of radar measurements with those of conventional impedance pneumography measurements. In the neonatal intensive care unit, RRs were measured using radar (RRRd) and impedance pneumography (RRIP) simultaneously. The neonatal voluntary movements were measured using the radar sensor and categorized into three levels (low [M0], intermediate [M1] and high [M2]). RRRd highly agreed with RRIP (r = 0.90; intraclass correlation coefficient [ICC] = 0.846 [0.835-0.856]). For the M0 movement, there was good agreement between RRRd and RRIP (ICC = 0.893; mean bias -0.15 [limits of agreement (LOA) -9.6 to 10.0]). However, the agreement was slightly lower for the M1 (ICC = 0.833; mean bias = 0.95 [LOA -11.4 to 13.3]) and M2 (ICC = 0.749; mean bias = 3.04 [LOA -9.30 to 15.4]) movements than for the M0 movement. In conclusion, IR-UWB radar can provide accurate and reliable estimates of RR in neonates in a non-contact fashion. The performance of radar measurements could be affected by neonate movement.

Bronchopulmonary Dysplasia Is Associated with Altered Brain Volumes and White Matter Microstructure in Preterm Infants.

BACKGROUND: Bronchopulmonary dysplasia (BPD), an inflammatory disease involving disrupted lung development, is associated with neurodevelopmental outcome in preterm infants. OBJECTIVE: This study examined the brain volume and white matter (WM) microstructure in preterm infants at term-equivalent age and explored the effects of BPD on brain development. METHOD: We studied 56 preterm infants (33 with BPD and 23 without BPD) with no evidence of focal abnormalities on conventional magnetic resonance imaging (MRI) at term-equivalent age. Regional brain volumes and diffusion tensor images were examined using advanced segmentation techniques to acquire quantitative volume measurements, and the JHU neonatal template was used for the atlas-based analysis. We compared these infants with 22 healthy term infants of a similar postmenstrual age. RESULTS: The preterm infants with BPD had smaller cerebral WM (p = 0.005) volumes than the preterm infants without BPD, independent of sex, gestational age, age at MRI scan, and total intracranial volume. Independent of sex, gestational age, and age at MRI scan, the preterm infants with BPD exhibited marked reductions in fractional anisotropy in the corpus callosum (p = 0.006), corticospinal tract (p = 0.003), and superior cerebellar peduncle (p = 0.002) compared with the infants with no BPD, with a significance level of p ≤ 0.008 as a Bonferroni correction for multiple comparisons. CONCLUSION: Our study highlights the potential impairing influence of BPD on WM and cerebellar development in preterm infants compared with those without BPD at term-equivalent age, suggesting its clinical significance for neurodevelopment in BPD infants.

A Novel Non-contact Heart Rate Monitor Using Impulse-Radio Ultra-Wideband (IR-UWB) Radar Technology.

We discovered that impulse-radio ultra-wideband (IR-UWB) radar could recognize cardiac motions in a non-contact fashion. Therefore, we measured the heart rate (HR) and rhythms using an IR-UWB radar sensor and evaluated the validity and reliability of the measurements in comparison to electrocardiography. The heart beats were measured in 6 healthy volunteers (18 samples) with normal sinus rhythm (NSR) and 16 patients (36 samples) with atrial fibrillation (AF) using both an IR-UWB radar sensor and electrocardiography simultaneously. The participants hold their breath for 20 seconds during the data acquisition. In subjects with NSR, there was excellent agreement of HR (intraclass correlation coefficient [ICC] 0.856), average R-R interval (ICC 0.997) and individual R-R intervals between the two methods (ICC 0.803). In subjects with AF, HR (ICC 0.871) and average R-R interval (ICC 0.925) from the radar sensor also agreed well with those from electrocardiography, though there was a small disagreement in the individual R-R intervals between the two methods (ICC 0.697). The rhythms computed by the signal-processing algorithm showed good agreement between the two methods (Cohen's Kappa 0.922). The IR-UWB radar sensor is precise and accurate for assessing HR and rhythms in a non-contact fashion.

Arsenic trioxide induces growth inhibition and death in human pulmonary artery smooth muscle cells accompanied by mitochondrial O2•- increase and GSH depletion.

Arsenic trioxide (ATO; As2 O3 ) induces cell death in various cells via oxidative stress. Expose to chronic arsenic is involved in the development of vascular diseases. However, little is known about the cytotoxic effects of ATO on human normal vascular smooth muscle cells (VSMCs). Thus, in this study, we investigated the effects of ATO on cell growth and death in human pulmonary artery smooth muscle (HPASM) cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. ATO treatment decreased the growth of HPASM cells with an IC50 of ∼30-50 µM at 24 h, and ATO induced HPASM cell death via apoptosis or necrosis dependent on the doses of it at this time. Treatment with 50 µM ATO did not increase ROS levels at the early time points, but it significantly increased mitochondrial O2•- levels at 24 h. ATO also induced GSH depletion in HPASM cells. N-acetyl cysteine (NAC; a well-known antioxidant) did not significantly affect apoptotic cell death, ROS levels, or GSH depletion in ATO-treated HPASM cells. However, l-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) intensified mitochondrial O2•- levels in ATO-treated HPASM cells, and significantly increased cell death and GSH depletion in these cells as well. In summary, we provided the first evidence that ATO inhibited the growth of HPASM cells, and induced apoptotic and/or necrotic cell death in these cells, accompanied by increases in mitochondrial O2•- level and GSH depletion.