Plasma Proteomics in Healthy Subjects with Differences in Tissue Glucocorticoid Sensitivity Identifies a Novel Proteomic Signature

: Significant inter-individual variation in terms of susceptibility to several stress-related disorders, such as myocardial infarction and Alzheimer’s disease, and therapeutic response has been observed among healthy subjects. The molecular features responsible for this phenomenon have not been fully elucidated. Proteomics, in association with bioinformatics analysis, offer a comprehensive description of molecular phenotypes with clear links to human disease pathophysiology. The aim of this study was to conduct a comparative plasma proteomics analysis of glucocorticoid resistant and glucocorticoid sensitive healthy subjects and provide clues of the underlying physiological differences. For this purpose, 101 healthy volunteers were given a very low dose (0.25 mg) of dexamethasone at midnight, and were stratified into the 10% most glucocorticoid sensitive (S) (n = 11) and 10% most glucocorticoid resistant (R) (n = 11) according to the 08:00 h serum cortisol concentrations determined the following morning. One month following the very-low dose dexamethasone suppression test, DNA and plasma samples were collected from the 22 selected individuals. Sequencing analysis did not reveal any genetic defects in the human glucocorticoid receptor (NR3C1) gene. To investigate the proteomic profile of plasma samples, we used Liquid Chromatography–Mass Spectrometry (LC-MS/MS) and found 110 up-regulated and 66 down-regulated proteins in the S compared to the R group. The majority of the up-regulated proteins in the S group were implicated in platelet activation. To predict response to cortisol prior to administration, a random forest classifier was developed by using the proteomics data in order to distinguish S from R individuals. Apolipoprotein A4 (APOA4) and gelsolin (GSN) were the most important variables in the classification, and warrant further investigation. Our results indicate that a proteomics signature may differentiate the S from the R healthy subjects, and may be useful in clinical practice. In addition, it may provide clues of the underlying molecular mechanisms of the chronic stress-related diseases, including myocardial infarction and Alzheimer’s disease.

Contactless Measurement of Vital Signs Using Thermal and RGB Cameras: A Study of COVID 19-Related Health Monitoring

In this study, a contactless vital signs monitoring system was proposed, which can measure body temperature (BT), heart rate (HR) and respiration rate (RR) for people with and without face masks using a thermal and an RGB camera. The convolution neural network (CNN) based face detector was applied and three regions of interest (ROIs) were located based on facial landmarks for vital sign estimation. Ten healthy subjects from a variety of ethnic backgrounds with skin colors from pale white to darker brown participated in several different experiments. The absolute error (AE) between the estimated HR using the proposed method and the reference HR from all experiments is 2.70±2.28 beats/min (mean ± std), and the AE between the estimated RR and the reference RR from all experiments is 1.47±1.33 breaths/min (mean ± std) at a distance of 0.6–1.2 m.

Longitudinal Changes and Recovery in Heart Rate Variability of Young Healthy Subjects When Exposure to a Hypobaric Hypoxic Environment

Background: The autonomic nervous system (ANS) is crucial for acclimatization. Investigating the responses of acute exposure to a hypoxic environment may provide some knowledge of the cardiopulmonary system’s adjustment mechanism.Objective: The present study investigates the longitudinal changes and recovery in heart rate variability (HRV) in a young healthy population when exposed to a simulated plateau environment.Methods: The study followed a strict experimental paradigm in which physiological signals were collected from 33 healthy college students (26 ± 2 years, 171 cm ± 7 cm, 64 ± 11 kg) using a medical-grade wearable device. The subjects were asked to sit in normoxic (approximately 101 kPa) and hypoxic (4,000 m above sea level, about 62 kPa) environments. The whole experimental process was divided into four stable resting measurement segments in chronological order to analyze the longitudinal changes of physical stress and recovery phases. Seventy-six time-domain, frequency-domain, and non-linear indicators characterizing rhythm variability were analyzed in the four groups.Results: Compared to normobaric normoxia, participants in hypobaric hypoxia had significantly lower HRV time-domain metrics, such as RMSSD, MeanNN, and MedianNN (p < 0.01), substantially higher frequency domain metrics such as LF/HF ratio (p < 0.05), significantly lower Poincaré plot parameters such as SD1/SD2 ratio and other Poincaré plot parameters are reduced considerably (p < 0.01), and Refined Composite Multi-Scale Entropy (RCMSE) curves are reduced significantly (p < 0.01).Conclusion: The present study shows that elevated heart rates, sympathetic activation, and reduced overall complexity were observed in healthy subjects exposed to a hypobaric and hypoxic environment. Moreover, the results indicated that Multiscale Entropy (MSE) analysis of RR interval series could characterize the degree of minor physiological changes. This novel index of HRV can better explain changes in the human ANS.

Reference Interval for Serum Concentration of Small Dense LDL Cholesterol in the Healthy Japanese Population

Background: Small dense low-density lipoprotein (sdLDL), a smaller and denser subfraction among whole LDL particles, is known to be highly atherogenic. The reference interval (RI) is not strictly defined for serum concentration of sdLDL-cholesterol (sdLDL-C) in Japan. The purpose of this study is to set the RI for sdLDL-C in healthy subjects. Methods: The population of this cross-sectional study were consisted of 40,862 individuals who had annual health checkups, and healthy subjects were extracted based on exclusion criteria such as medical history, social history, and blood sampling test results. Their serum sdLDL-C values were statistically analyzed and the RIs were set in men, premenopausal women, and postmenopausal women separately. Results: The mean values of serum sdLDL-C in healthy subjects were 23.9 mg/dL in men, 20.0 mg/dL in premenopausal women and 23.7 mg/dL in postmenopausal women, and the RIs were 12.6-45.3 mg/dL in men, 11.4-35.1 mg/dL in premenopausal women and 14.6-38.6 mg/dL in postmenopausal women. Serum sdLDL-C values were significantly higher in men than in women. Besides, sdLDL-C values were significantly higher in postmenopausal women than in premenopausal women. In both genders, sdLDL-C values tended to increase with age. Conclusion: These results suggest that the RIs for sdLDL-C are recommended as follows: 13-45 mg/dL in men, 11-35 mg/dL in premenopausal women, and 15-39 mg/dL in postmenopausal women, respectively. Aside from these RIs, it is also necessary to define clinical cutoff values graded according to individual risk levels for atherosclerotic cardiovascular diseases.

Involvement of neutrophil extracellular traps in the pathogenesis of glomerulonephritis in a case of systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis overlap syndrome

Systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are autoimmune diseases that often cause rapidly progressive glomerulonephritis, with neutrophil extracellular traps (NETs) involved in their pathogenesis. However, the involvement of NETs in the renal damage caused by SLE/AAV overlap syndrome has not been clarified yet. In this study, we detected renal deposition of NETs in a patient with SLE/AAV overlap syndrome. In addition, a significantly increased level of NET-inducing activity was observed in the patient’s serum, which improved with treatment. On the other hand, a markedly lower level of NET degradation was observed in the patient’s serum as compared to healthy subjects’ sera, without any posttreatment changes. These findings suggest that NETs may play a role in the pathogenesis of renal injury associated with SLE/AAV overlap syndrome.

Detection of COVID-19 in smartphone-based breathing recordings: A pre-screening deep learning tool

This study was sought to investigate the feasibility of using smartphone-based breathing sounds within a deep learning framework to discriminate between COVID-19, including asymptomatic, and healthy subjects. A total of 480 breathing sounds (240 shallow and 240 deep) were obtained from a publicly available database named Coswara. These sounds were recorded by 120 COVID-19 and 120 healthy subjects via a smartphone microphone through a website application. A deep learning framework was proposed herein that relies on hand-crafted features extracted from the original recordings and from the mel-frequency cepstral coefficients (MFCC) as well as deep-activated features learned by a combination of convolutional neural network and bi-directional long short-term memory units (CNN-BiLSTM). The statistical analysis of patient profiles has shown a significant difference (p-value: 0.041) for ischemic heart disease between COVID-19 and healthy subjects. The Analysis of the normal distribution of the combined MFCC values showed that COVID-19 subjects tended to have a distribution that is skewed more towards the right side of the zero mean (shallow: 0.59±1.74, deep: 0.65±4.35, p-value: <0.001). In addition, the proposed deep learning approach had an overall discrimination accuracy of 94.58% and 92.08% using shallow and deep recordings, respectively. Furthermore, it detected COVID-19 subjects successfully with a maximum sensitivity of 94.21%, specificity of 94.96%, and area under the receiver operating characteristic (AUROC) curves of 0.90. Among the 120 COVID-19 participants, asymptomatic subjects (18 subjects) were successfully detected with 100.00% accuracy using shallow recordings and 88.89% using deep recordings. This study paves the way towards utilizing smartphone-based breathing sounds for the purpose of COVID-19 detection. The observations found in this study were promising to suggest deep learning and smartphone-based breathing sounds as an effective pre-screening tool for COVID-19 alongside the current reverse-transcription polymerase chain reaction (RT-PCR) assay. It can be considered as an early, rapid, easily distributed, time-efficient, and almost no-cost diagnosis technique complying with social distancing restrictions during COVID-19 pandemic.

Characterization of stroke-related upper limb motor impairments across various upper limb activities by use of kinematic core set measures

Background Upper limb kinematic assessments provide quantifiable information on qualitative movement behavior and limitations after stroke. A comprehensive characterization of spatiotemporal kinematics of stroke subjects during upper limb daily living activities is lacking. Herein, kinematic expressions were investigated with respect to different movement types and impairment levels for the entire task as well as for motion subphases. Method Chronic stroke subjects with upper limb movement impairments and healthy subjects performed a set of daily living activities including gesture and grasp movements. Kinematic measures of trunk displacement, shoulder flexion/extension, shoulder abduction/adduction, elbow flexion/extension, forearm pronation/supination, wrist flexion/extension, movement time, hand peak velocity, number of velocity peaks (NVP), and spectral arc length (SPARC) were extracted for the whole movement as well as the subphases of reaching distally and proximally. The effects of the factors gesture versus grasp movements, and the impairment level on the kinematics of the whole task were tested. Similarities considering the metrics expressions and relations were investigated for the subphases of reaching proximally and distally between tasks and subgroups. Results Data of 26 stroke and 5 healthy subjects were included. Gesture and grasp movements were differently expressed across subjects. Gestures were performed with larger shoulder motions besides higher peak velocity. Grasp movements were expressed by larger trunk, forearm, and wrist motions. Trunk displacement, movement time, and NVP increased and shoulder flexion/extension decreased significantly with increased impairment level. Across tasks, phases of reaching distally were comparable in terms of trunk displacement, shoulder motions and peak velocity, while reaching proximally showed comparable expressions in trunk motions. Consistent metric relations during reaching distally were found between shoulder flexion/extension, elbow flexion/extension, peak velocity, and between movement time, NVP, and SPARC. Reaching proximally revealed reproducible correlations between forearm pronation/supination and wrist flexion/extension, movement time and NVP. Conclusion Spatiotemporal differences between gestures versus grasp movements and between different impairment levels were confirmed. The consistencies of metric expressions during movement subphases across tasks can be useful for linking kinematic assessment standards and daily living measures in future research and performing task and study comparisons. Trial registration: ClinicalTrials.gov Identifier NCT03135093. Registered 26 April 2017, https://clinicaltrials.gov/ct2/show/NCT03135093.