Healthy Human Subjects Research Articles

Comparison of tet(X4)-containing contigs assembled from metagenomic sequencing data with plasmid sequences of isolates from a cohort of healthy subjects.

Recently discovered tet(X) gene variants have provided new insights into microbial antibiotic resistance mechanisms and their potential consequences for public health. This study focused on detection, analysis, and characterization of Tet(X4)-positive Enterobacterales from the gut microbiota of a healthy cohort of individuals in Singapore using cultivation-dependent and cultivation-independent approaches. Twelve Tet(X4)-positive Enterobacterales strains that were previously obtained from the cohort were fully genome-sequenced and comparatively analyzed. A metagenomic sequencing (MS) data set of the same samples was mined for contigs that harbored the tet(X4) resistance gene. The sequences of tet(X4)-containing contigs and plasmids sequences were compared. The presence of the resistance genes floR and estT (previously annotated as catD) was detected in the same cassette in 10 and 12 out of the 12 tet(X4)-carrying plasmids, respectively. MS detected tet(X4)-containing contigs in 2 out of the 109 subjects, while cultivation-dependent analysis previously reported a prevalence of 10.1%. The tet(X4)-containing sequences assembled from MS data are relatively short (~14 to 33 kb) but show high similarity to the respective plasmid sequences of the isolates. Our findings show that MS can complement efforts in the surveillance of antibiotic resistance genes for clinical samples, while it has a lower sensitivity than a cultivation-based method when the target organism has a low abundance. Further optimization is required if MS is to be utilized in antibiotic resistance surveillance.IMPORTANCEThe global rise in antibiotic resistance makes it necessary to develop and apply new approaches to detect and monitor the prevalence of antibiotic resistance genes in human populations. In this regard, of particular interest are resistances against last-resort antibiotics, such as tigecycline. In this study, we show that metagenomic sequencing can help to detect high abundance of the tigecycline resistance gene tet(X4) in fecal samples from a cohort of healthy human subjects. However, cultivation-based approaches currently remain the most reliable and cost-effective method for detection of antibiotic-resistant bacteria.

Efficacy and Safety of Skin Radiance Collagen on Skin and Hair Matrix: A Placebo-Controlled Clinical Trial in Healthy Human Subjects.

Collagen supplements are rising in the market as collagen has been demonstrated to be an important protein in the human aging process. Also, it is safe and easily absorbed in the body. Hence the aim of this study was to examine the effectiveness and safety of a collagen and antioxidant-rich treatment compared to a placebo in relation to various skin and hair indicators in healthy adult human subjects. Forty healthy adult non-pregnant/non-lactating women (aged 38-50 years) provided their informed consent in writing before their participation. Skin Radiance Collagen (SRC) treatment and a placebo were assessed for efficacy before application on Day 1, and post-application on Days 28 and 56, to measure changes in skin elasticity, hydration, brightness, pigmentation; texture, wrinkles, dryness, smoothness, fine lines, changes in the crow's feet region; as well as hair strength and hair fall. It was observed after 56 days that therapy with SRC, compared to placebo, produced a substantial effect on reduction of wrinkle depth and fine lines by 48.11% and 39%, respectively, with p-value <0.01 in the test group. There was a 15.69% improvement in skin hydration observed and 28% reduction in hair fall with p-value <0.01. SRC, a combination of collagen with hyaluronic acid (HA), biotin, and vitamins C and E, showed a significant improvement in skin and hair health, including improvements in skin elasticity, skin hydration, reduction in crow's feet area wrinkles and fine lines, hair fall, and decrease in roughness, leading to improved skin texture. Vitamin C in the formulation also acts as a collagen builder for the body and helps in preventing oxidative stress in the body. The test treatment SRC was found to be efficacious and safe in healthy human adult subjects.

Spectral Slope and Lempel-Ziv Complexity as Robust Markers of Brain States during Sleep and Wakefulness.

Nonoscillatory measures of brain activity such as the spectral slope and Lempel-Ziv complexity are affected by many neurological disorders and modulated by sleep. A multitude of frequency ranges, particularly a broadband (encompassing the full spectrum) and a narrowband approach, have been used especially for estimating the spectral slope. However, the effects of choosing different frequency ranges have not yet been explored in detail. Here, we evaluated the impact of sleep stage and task engagement (resting, attention, and memory) on slope and complexity in a narrowband (30-45 Hz) and broadband (1-45 Hz) frequency range in 28 healthy male human subjects (21.54 ± 1.90 years) using a within-subject design over 2 weeks with three recording nights and days per subject. We strived to determine how different brain states and frequency ranges affect slope and complexity and how the two measures perform in comparison. In the broadband range, the slope steepened, and complexity decreased continuously from wakefulness to N3 sleep. REM sleep, however, was best discriminated by the narrowband slope. Importantly, slope and complexity also differed between tasks during wakefulness. While narrowband complexity decreased with task engagement, the slope flattened in both frequency ranges. Interestingly, only the narrowband slope was positively correlated with task performance. Our results show that slope and complexity are sensitive indices of brain state variations during wakefulness and sleep. However, the spectral slope yields more information and could be used for a greater variety of research questions than Lempel-Ziv complexity, especially when a narrowband frequency range is used.

Insights on Using Time-of-Flight Camera for Recovering Cardiac Pulse From Chest Motion in Depth Videos.

In this article, we introduce a novel use of depth camera to extract cardiac pulse signal from human chest area, in which the depth information is obtained from a near infrared sensor using time-of-flight technology. We successfully isolate weak chest motion due to heartbeat by processing a sequence of depth images without raising privacy concern. We discuss motion sensitivity in depth video with examples from actuator simulation and human chest motion. Compared to other imaging modalities, the depth image intensity can be directly used for micromotion reconstruction. To deal with the challenges of recovering heartbeat from the chest area, we develop a set of coherent processing techniques to suppress the unwanted motion interference from breathing motion and involuntary body motion and eventually obtain clean cardiac pulse signal. We, thus, derive inter-beat-interval, showing high consistency to the contact photoplethysmography. Additionally, we develop a graphical interpretation of the most and the less pulsatile principal components in eigen space. For validation, we test our method on ten healthy human subjects with different resting heart rates. More importantly, we conduct a set of experiments to study the robustness and weakness of our methods, including extended range, multi-subject, thickness of clothes and generation to other measurement site.

Skin temperature influence on transcutaneous carbon dioxide (CO2) conductivity and skin blood flow in healthy human subjects at the arm and wrist.

Objective: present transcutaneous carbon dioxide (CO2)-tcpCO2-monitors suffer from limitations which hamper their widespread use, and call for a new tcpCO2 measurement technique. However, the progress in this area is hindered by the lack of knowledge in transcutaneous CO2 diffusion. To address this knowledge gap, this study focuses on investigating the influence of skin temperature on two key skin properties: CO2 permeability and skin blood flow. Methods: a monocentric prospective exploratory study including 40 healthy adults was undertaken. Each subject experienced a 90 min visit split into five 18 min sessions at different skin temperatures-Non-Heated (NH), 35, 38, 41, and 44°C. At each temperature, custom sensors measured transcutaneous CO2 conductivity and exhalation rate at the arm and wrist, while Laser Doppler Flowmetry (LDF) assessed skin blood flow at the arm. Results: the three studied metrics sharply increased with rising skin temperature. Mean values increased from the NH situation up to 44°C from 4.03 up to 8.88 and from 2.94 up to 8.11 m·s-1 for skin conductivity, and from 80.4 up to 177.5 and from 58.7 up to 162.3 cm3·m-2·h-1 for exhalation rate at the arm and wrist, respectively. Likewise, skin blood flow increased elevenfold for the same temperature increase. Of note, all metrics already augmented significantly in the 35-38°C skin temperature range, which may be reached without active heating-i.e. only using a warm clothing. Conclusion: these results are extremely encouraging for the development of next-generation tcpCO2 sensors. Indeed, the moderate increase (× 2) in skin conductivity from NH to 44°C tends to indicate that heating the skin is not critical from a response time point of view, i.e. little to no skin heating would only result in a doubled sensor response time in the worst case, compared to a maximal heating at 44°C. Crucially, a skin temperature within the 35-38°C range already sharply increases the skin blood flow, suggesting that tcpCO2 correlates well with the arterial paCO2 even at such low skin temperatures. These two conclusions further strengthen the viability of non-heated tcpCO2 sensors, thereby paving the way for the development of wearable transcutaneous capnometers.

Alignment, calibration, and validation of an adaptive optics scanning laser ophthalmoscope for high-resolution human foveal imaging.

In prior art, advances in adaptive optics scanning laser ophthalmoscope (AOSLO) technology have enabled cones in the human fovea to be resolved in healthy eyes with normal vision and low to moderate refractive errors, providing new insight into human foveal anatomy, visual perception, and retinal degenerative diseases. These high-resolution ophthalmoscopes require careful alignment of each optical subsystem to ensure diffraction-limited imaging performance, which is necessary for resolving the smallest foveal cones. This paper presents a systematic and rigorous methodology for building, aligning, calibrating, and testing an AOSLO designed for imaging the cone mosaic of the central fovea in humans with cellular resolution. This methodology uses a two-stage alignment procedure and thorough system testing to achieve diffraction-limited performance. Results from retinal imaging of healthy human subjects under 30 years of age with refractive errors of less than 3.5 diopters using either 680 nm or 840 nm light show that the system can resolve cones at the very center of the fovea, the region where the cones are smallest and most densely packed.

Changes to the shape, orientation and packing of red cells as a function of retinal capillary size.

The free diameter of a red blood cell exceeds the lumen diameter of capillaries in the central nervous system, requiring significant deformation of cells. However the deformations undertaken in vivo are not well established due to the difficulty in observing cellular capillary flow in living human tissue. Here, we used high resolution adaptive optics imaging to non-invasively track 17,842 red blood cells in transit through 121 unique capillary segments of diameter 8 µm or less in the retina of 3 healthy human subjects. Within each vessel, a 2D en face profile was generated for the "average cell", whose shape was then inferred in 3D based on the key assumption of a circular capillary cross-section. From this we estimated the average volume, surface area, orientation, and separation between red cells within each capillary tube. Our results showed a network filtration effect, whereby narrower vessels were more likely to contain smaller cells (defined by surface area, which is thought not to vary during a cell's passage through the vascular system). A bivariate linear model showed that for larger cells in narrower vessels: cells re-orient themselves to align with the flow axis, their shape becomes more elongated, there are longer gaps between successive cells, and remarkably, that cell volume is less which implies the ejection of water from cells to facilitate capillary transit. Taken together, these findings suggest that red cells pass through retinal capillaries with some reluctance. A biphasic distribution for cell orientation and separation was evident, indicating a "tipping point" for vessels narrower than approx. 5 µm. This corresponds closely to the typical capillary lumen diameter, and may maximize sensitivity of cellular flow to small changes in diameter. We suggest that the minimization of unnecessary oxygen exchange, and hence of damage via reactive oxygen pathways, may have provided evolutionary pressure to ensure that capillary lumens are generally narrower than red blood cells.

Exercise and Protection from Age-Related Cognitive Decline.

In this chapter, we review the cross-sectional evidence in healthy human subjects for physical activity and cardiorespiratory fitness to offer neuroprotection and moderate cognitive decline in older age. The role of exercise training on cognition in healthy older adults and those diagnosed with mild cognitive impairment (MCI) is also discussed, including the evidence from neuroimaging studies that document changes to brain structure and function after a period of exercise training and improved fitness. Finally, in reference to animal models, the potential neurophysiological mechanisms for physical activity and exercise to impact human brain health are highlighted.

Admittance swarm-based adaptive controller for lower limb exoskeleton with gait trajectory shaping

The motivation for developing a rehabilitation lower-limb exoskeleton robot was to provide functional robot-assisted therapy for assisting physiotherapists in improving hemiplegic patients’ walking recovery. Rehabilitation tasks required robust and precise trajectory-tracking performance, mainly achieved with exoskeleton robots. This paper presents a study on the gait trajectory cycles of a rehabilitation lower-limb exoskeleton robot controlled by an Admittance Swarm Initialized Adaptive (ASIA). The aim of this paper was to develop a robust adaptive controller integrated with admittance model to overcome human–robot interaction forces generated by the wearer. The parameters of the ASIA controller were efficiently initialized using swarm beetle antenna searching. An experiment was conducted on a prototype lower limb exoskeleton with four degrees of freedom, involving a healthy human subject for gait trajectory analysis. The results demonstrated the effectiveness of the proposed method in terms of control performance, steady-state error reduction, and robustness. The statistical analysis revealed that the ASIA performed 63 %, 53 % and 48 % less in average error compared to adaptive conventional controllers used in the same exoskeleton platform. The findings ascertained the potential of the ASIA controller in improving human mobility through lower limb exoskeleton applications.

Clinical evaluation of three different anterior reference points on protrusive condylar guidance angle using a semi adjustable articulator and lateral cephalogram

Background: Studies had shown that different anterior reference points can mount the maxillary cast in variable position in the articulator which may affect the protrusive condylar guidance angle on setting the semi adjustable articulator. So there is a need for search of reliable anterior reference point in orienting the maxillary cast on the articulation for accurate prosthesis fabrication. Aim: The aim of this study was to determine the effect of 3 different anterior reference points Orbitale, Orbitale minus 7mm, 36mm from the incisal edge of maxillary central or lateral incisor on the protrusive condylar guidance values registered on Hanau wide vue articulator and compare it to the protrusive condylar guidance angle obtained from lateral Cephalometric tracings. Materials and methods: A total of 30 healthy human subjects were randomly selected for this study from volunteer dental students. Orbitale, Orbitale minus 7mm, 36mm from the maxillary incisal edge of the subjects were the three anterior reference points used for facebow transfer using Hanau springbow. With the help of protrusive records, articulation was done in Hanau wide vue articulator using this record and condylar inclination values were noted on right side and left side.Three sets of lateral cephalometric radiographs were taken in maximum intercuspation and protrusive position, traced manually and values tabulated for all 30 subjects. Results: Mean value of orbitale is highest and mean value of 36mm from the maxillary incisal edge is lowest. Conclusion: Orbitale can be used as a reliable anterior reference point in facebow transfer using hanau wide vue articulator.

Heterogeneity in Neutrophil Extracellular Traps from Healthy Human Subjects.

Neutrophil extracellular traps (NETs), a key component of early defense against microbial infection, are also associated with tissue injury. NET composition has been reported to vary with some disease states, but the composition and variability of NETs across many healthy subjects provide a critical comparison that has not been well investigated. We evaluated NETs from twelve healthy subjects of varying ages isolated from multiple blood draws over a three-and-one-half-year period to delineate the variability in extracellular DNA, protein, enzymatic activities, and susceptibility to protease inhibitors. We calculated correlations for NET constituents and loss of human bronchial epithelial barrier integrity, measured by transepithelial electrical resistance, after NET exposure. We found that although there was some variability within the same subject over time, the mean NET total DNA, dsDNA, protein, LDH, neutrophil elastase (NE), and proteinase 3 (PR3) in isolated NETs were consistent across subjects. NET serine protease activity varied considerably within the same donor from day to day. The mean NET cathepsin G and MPO were significantly different across donors. IL-8 > IL-1RA > G-CSF were the most abundant cytokines in NETs. There was no significant difference in the mean concentration or variability of IL-8, IL-1RA, G-CSF, IL-1α, IL-1β, or TNF-α in different subjects' NETs. NET DNA concentration was correlated with increased NET neutrophil elastase activity and higher NET IL-1RA concentrations. The mean reduction in protease activity by protease inhibitors was significantly different across donors. NET DNA concentration correlated best with reductions in the barrier integrity of human bronchial epithelia. Defining NET concentration by DNA content correlates with other NET components and reductions in NET-driven epithelial barrier dysfunction, suggesting DNA is a reasonable surrogate measurement for these complex structures in healthy subjects.

Evaluating numerous techniques for the effects of electromagnetic waves on the Electro Cardio Gram (ECG)

&lt;p&gt;Nowadays, due to the widespread use of mobile phones and the proliferation of mobile towers the human body parts especially the heart are getting affected. Furthermore, these waves are ubiquitous in our modern society, with various sources emitting these waves in our environment. As medical devices become more prevalent and wireless technologies continue to advance, concerns have been raised regarding the potential impact of electromagnetic waves on human health. It is important to monitor the condition of your heart. With the increase in the number of mobile phones, there is also an increase in electromagnetic radiation, which can affect the human heart. The heart is an important component of the human body and an electrocardiogram (ECG) can provide valuable information about its condition. ECG parameters can show how well the heart is working. In this paper, the author proposes how ECG parameters change under the influence of mobile phones in three different situations. A comprehensive experimental setup was devised. A group of healthy human subjects volunteered to participate in the study, with each subject undergoing ECG recording under controlled conditions. The subjects were exposed to varying intensities and frequencies of electromagnetic waves generated by a standardized source. Statistical analysis was performed to compare the ECG measurements obtained during exposure to electromagnetic waves with those obtained in a controlled environment without electromagnetic wave exposure. This study contributes to the growing body of research on the potential health effects of electromagnetic waves. By specifically focusing on the ECG signal, which is vital for cardiovascular diagnostics, this research provides valuable insights into the safety and reliability of using ECG in environments with electromagnetic wave exposure. The findings will help inform healthcare professionals, engineers, and policymakers to establish appropriate guidelines and safety measures concerning the use of medical devices and wireless technologies in proximity to patients or individuals with cardiac conditions.&lt;/p&gt;

A clinical investigation on the safety and effectiveness of an ayurvedic hair oil in controlling hair fall (khalitya) in healthy adult human subjects: a study on hair fall management

Background: Hair loss, commonly associated with genetics, hormones, or health conditions, is prevalent. Dandruff, resulting in flaky scalp skin, is also widespread. Ayurvedic herbal remedies show potential for addressing these hair issues. This clinical trial assesses the efficacy and safety of an ayurvedic hair oil in healthy adults with hair loss (alopecia). The aim is to evaluate its purported benefits in reducing hair fall, stimulating hair growth and alleviating scalp dandruff. Methods: This 8-week study involved 30 subjects with hair fall. After obtaining subject consent, a test hair oil was applied topically. Assessments included evaluating hair-fall, scalp dandruff, hair-growth rate, density, and thickness. Ayurvedic assessment determined hair type. Phototrichogram, pluck-test measured growth, with endpoints including pull-test, combing-test, dermatological evaluation, and subjective questionnaires. Statistical analysis used R software (Version: 4.1.2). Results: The study revealed significant therapeutic efficacy. The mean hair-growth rate increased significantly by 227µm/day (79.92±69.31%) over 8 weeks (p&lt;0.01). Hair-fall decreased by 63.49±21.44%, from 97 to 31 hairs. Hair-thickness and density improved by 34.26±16.36% (p&lt;0.01) and 39.82±34.3% (p&lt;0.01) respectively. Scalp dandruff showed a reduction of 76.33±15.95% (p&lt;0.01). The A:T ratio shifted positively from 3:1 to 5:1, indicating an increase in hairs in the anagen phase. No adverse effects were observed. Conclusions: Consistent use of 'moha: 5-in-1' hair oil over 8 weeks was well-tolerated and found effective. It significantly decreased hair fall, promoted hair growth, and improved scalp health by reducing dandruff. This confirms its safety and efficacy among study participants, establishing it as suitable choice for holistic daily hair care.

Effects of Acute Beetroot Juice and Sodium Nitrate on Selected Blood Metabolites and Response to Transient Ischemia: A Crossover Randomized Clinical Trial

BackgroundModification of the nitrate (NO3)–nitrite (NO2)–nitric oxide (NO) pathway can be induced by oral intake of inorganic NO3 (NIT) or NO3-rich products, such as beetroot juice (BRJ). ObjectivesThe primary aim of this study was to evaluate the plasma changes in betaine, choline, trimethylamine (TMA), trimethylamine N-oxide (TMAO), and NO3/NO2 (NOx) concentrations over 4 h after single oral ingestion of NIT or BRJ. The flow-mediated skin fluorescence (FMSF) method was applied to measure the changes in nicotinamide adenine dinucleotide reduced form (NADH) in response to transient ischemia and reperfusion. We hypothesized that various sources of NO3 may differently affect endothelial and mitochondrial functions in healthy human subjects. MethodsIn a randomized crossover trial, 8 healthy young adults ingested 800 mg NO3 from either NIT or BRJ on 2 separate days with ≥3 d apart. Venous blood samples were collected every hour, and FMSF determination was applied bihourly. ResultsPlasma betaine and choline concentrations peaked at 1 h after BRJ ingestion, and remained significantly higher than baseline values at all time points (P < 0.001 and P < 0.001, compared to preingestion values). Over time, BRJ was more effective in increasing NOx compared with NIT (fixed-trial effect P < 0.001). Baseline fluorescence decreased after both NIT and BRJ consumption (fixed-time effect P = 0.005). Transient ischemia and reperfusion response increased because of NO3 consumption (fixed-time effect P = 0.003), with no differences between trials (P = 0.451; P = 0.912; P = 0.819 at 0, 2, and 4 h, respectively). ConclusionsAcute ingestion of BRJ elevated plasma betaine and choline, but not TMA and TMAO. Moreover, plasma NOx levels were higher in the BRJ trial than in the NIT trial. Various sources of NO3 positively affected endothelial and mitochondrial functions.This trial was registered at clinicaltrials.gov as NCT05004935.

Spatially-dependent model for rods and cones in the retina

We develop a mathematical model for photoreceptors in the retina. We focus on rod and cone outer segment dynamics and interactions with a nutrient source associated with the retinal pigment epithelium cells. Rod and cone densities (number per unit area of retinal surface) are known to have significant spatial dependence in the retina with cones located primarily near the fovea and the rods located primarily away from the fovea. Our model accounts for this spatial dependence of the rod and cone photoreceptor density as well as for the possibility of nutrient diffusion. We present equilibrium and dynamic solutions, discuss their relation to existing models, and estimate model parameters through comparisons with available experimental measurements of both spatial and temporal photoreceptor characteristics. Our model compares well with existing data on spatially-dependent regrowth of photoreceptor outer segments in the macular region of Rhesus Monkeys. Our predictions are also consistent with existing data on the spatial dependence of photoreceptor outer segment length near the fovea in healthy human subjects. We focus primarily on the healthy eye but our model could be the basis for future efforts designed to explore various retinal pathologies, eye-related injuries, and treatments of these conditions.

Simultaneous tensile and shear measurement of the human cornea in vivo using S0- and A0-wave optical coherence elastography

Understanding corneal stiffness is valuable for improving refractive surgery, detecting corneal abnormalities, and assessing intraocular pressure. However, accurately measuring the elastic properties, specifically the tensile and shear moduli that govern mechanical deformation, has been challenging. To tackle this issue, we have developed guided-wave optical coherence elastography that can simultaneously excite and analyze symmetric (S0) and anti-symmetric (A0) elastic waves in the cornea at around 10 kHz frequencies, enabling us to extract tensile and shear properties from measured wave dispersion curves. We verified the technique using elastomer phantoms and ex vivo porcine corneas and investigated the dependence on intraocular pressure using acoustoelastic theory that incorporates corneal tension and a nonlinear constitutive tissue model. In a pilot study involving six healthy human subjects aged 31 to 62, we measured shear moduli (Gzx) of 94±20 kPa (mean±standard deviation) and tensile moduli (Exx) of 4.0±1.1 MPa at central corneas. Our preliminary analysis of age-dependence revealed contrasting trends: -8.3±4.5 kPa/decade for shear and 0.30±0.21 MPa/decade for tensile modulus. This OCE technique has the potential to become a highly useful clinical tool for the quantitative biomechanical assessment of the cornea. Statement of SignificanceThis article reports an innovative elastography technique using two guided elastic waves, demonstrating the measurement of both tensile and shear moduli in human cornea in vivo with unprecedented precision. This technique paves the way for comprehensive investigations into corneal mechanics and holds clinical significance in various aspects of corneal health and disease management.

NOHAS: A Novel Orthotic Hand Actuated by Servo Motors and Mobile App for Stroke Rehabilitation

The rehabilitation process after the onset of a stroke primarily deals with assisting in regaining mobility, communication skills, swallowing function, and activities of daily living (ADLs). This entirely depends on the specific regions of the brain that have been affected by the stroke. Patients can learn how to utilize adaptive equipment, regain movement, and reduce muscle spasticity through certain repetitive exercises and therapeutic interventions. These exercises can be performed by wearing soft robotic gloves on the impaired extremity. For post-stroke rehabilitation, we have designed and characterized an interactive hand orthosis with tendon-driven finger actuation mechanisms actuated by servo motors, which consists of a fabric glove and force-sensitive resistors (FSRs) at the tip. The robotic device moves the user’s hand when operated by mobile phone to replicate normal gripping behavior. In this paper, the characterization of finger movements in response to step input commands from a mobile app was carried out for each finger at the proximal interphalangeal (PIP), distal interphalangeal (DIP), and metacarpophalangeal (MCP) joints. In general, servo motor-based hand orthoses are energy-efficient; however, they generate noise during actuation. Here, we quantified the noise generated by servo motor actuation for each finger as well as when a group of fingers is simultaneously activated. To test ADL ability, we evaluated the device’s effectiveness in holding different objects from the Action Research Arm Test (ARAT) kit. Our device, novel hand orthosis actuated by servo motors (NOHAS), was tested on ten healthy human subjects and showed an average of 90% success rate in grasping tasks. Our orthotic hand shows promise for aiding post-stroke subjects recover because of its simplicity of use, lightweight construction, and carefully designed components.

Immunomodulation Sensitivity of Innate Immunity Cells in Healthy Human Subjects during 21-Day “Dry” Immersion

Immunomodulation Sensitivity of Innate Immunity Cells in Healthy Human Subjects during 21-Day “Dry” Immersion

Activated CTHRC1 promotes glycolysis in endothelial cells: Implications for metabolism and angiogenesis

CTHRC1 is transiently expressed by activated fibroblasts during tissue repair and in certain cancers, and CTHRC1 derived from osteocytes is detectable in circulation. Because its biological activity is poorly understood, we investigated whether the N terminus of CTHRC1 encodes a propeptide requiring cleavage to become activated. The effects of full-length versus cleaved recombinant CTHRC1 on endothelial cell metabolism and gene expression were examined in vitro. Respirometry was performed on Cthrc1 null and wildtype mice to obtain evidence for biological activity of CTHRC1 in vivo. Cleavage of the propeptide observed in vitro was attenuated in the presence of protease inhibitors, and cleaved CTHRC1 significantly promoted glycolysis whereas full-length CTHRC1 was less effective. The respiratory exchange ratio was significantly higher in wildtype mice compared to Cthrc1 null mice, supporting the findings of CTHRC1 promoting glycolysis in vivo. Key enzymes involved in glycolysis were significantly upregulated in endothelial cells in response to treatment with CTHRC1. In healthy human subjects, 58% of the cohort had detectable levels of circulating full-length CTHRC1, whereas all subjects with undetectable levels of full-length CTHRC1 (with one exception) had measurable levels of truncated CTHRC1 (88 pg/ml to >400 ng/ml). Our findings support a concept where CTHRC1 induction in activated fibroblasts at sites of ischemia such as tissue injury or cancer functions to increase glycolysis for ATP production under hypoxic conditions, thereby promoting cell survival and tissue repair. By promoting glycolysis under normoxic conditions, CTHRC1 may also be a contributor to the Warburg effect characteristically observed in many cancers.

Mechanisms of Aging Vary with Developmental Stages in the Human Hematopoietic Trajectory

Background : Hematopoietic stem and progenitor cells (HSPCs) undergo functional changes with age. An unresolved issue is whether aging is induced by a shift in intrinsic state in which all HSPCs undergo coordinated changes in functional potential, or by clonal evolution of a senescent population.Identification of senescent cells in human hematopoiesis poses another challenge. In this study, we have identified lineage-specific, senescence-associated pathways at different developmental stages of HSPCs and have developed an “aging signature HSC” for non-primed human HSCs. Methods: HSPCs (CD34+ cells) were isolated from the bone marrow of healthy human subjects (old = &amp;gt;60 years; young = 21 to &amp;lt;35 years). Single-cell RNA-sequencing (scRNAseq) studies and downstream analysis were performed using different R packages for normalization, dimension reduction, clustering, classification, pseudotime ordering, and developmental trajectory analyses. Gene Set Enrichment Analysis, GSEA (version 4.3.2., Broad Institute, Inc) was applied to identify pathways and processes that were coordinately up- or down-regulated with aging. Results: HSPCs (CD34+ cells) were derived from 13 healthy human subjects (old subjects n = 6; young subjects n = 7). There were 26,076 genes identified. The HSPCs were ordered and classified along their developmental trajectory during differentiation processes from (1) hematopoietic stem cells (HSC) to (2) myeloid-lymphoid progenitors (MLP), (3) megakaryocyte-erythrocyte progenitors (MEP), (4) granulocytic-monocytic progenitors (GMP), (5) granulocyte- (G), and (6) monocyte- (Mono) progenitors, (7) dendritic cell (DC), (8) erythroid progenitors (E), as well as various subsets of lymphocytes (Ly1 to Ly4). The results are depicted in Figure 1A. Remarkable are the increases in HSCs (p &amp;lt; 0.05) and in Ly4 (p &amp;lt; 0.001) in old subjects. The Kolmogorov-Smirnov test showed a significant delay in the developmental “pseudotimes” of HSCs (p &amp;lt; 0.001) and of Ly4 (p &amp;lt; 0.05). We then compared the differences in GSEA between old and young subjects in each of the following clusters: (A) whole HSPCs; (B) HSPCs along myeloid pathway (mye-HSPC); (C) HSC-MLP-MEP; (D) HSC. The major findings relevant to aging are summarized in Fig. 1B. Pathways that are significantly increased in the old subjects and throughout all comparisons include: “Formation of senescence associated heterochromatin foci”, “Aging signature HSC”, “DNA damage telomere stress induced senescence”, and “TNFR1 induced NFKB signaling pathway”. “Hypoxia”, “P53 pathway”, “IL2 signaling”, “TNFA signaling via NFKB” were elevated upon enrichment of the primitive HSC population, while other pathways decreased: “Senescence associated secretory phenotype (SASP)”, “DNA methylation”. “Cell cycle” and “DNA repair” are consistently more abundant in young subjects. We analyzed the 512 cells in the HSC cluster with higher resolution and were able to identify a sub-cluster “MPP2A” that is significantly increased in old subjects (4.5% of all HSPCs and 28.5% of HSCs, versus 1.9% and 12.9% respectively in young subjects; p &amp;lt; 0.005). The results are depicted in the highlighted circles in Fig. 1A. This population is quiescent and is highly enriched in “aging signature HSC” in old subjects (p &amp;lt;0.0001). Prominent examples of these signature genes within this list are shown in Fig. 1C). Further along the trajectory, a unique population of B cells “Ly4” was found predominantly in old subjects. The transcriptome profile Ly4 is similar to immature and age-associated B cells (ABCs). This cluster of lymphoid cells may represent the precursors of ABCs described thus far only in peripheral blood, providing another evidence that the aging mechanisms at various differentiation stages are different. Conclusions: In this study, we have defined specific pathways that distinctly separate aging HSCPs from young ones, and shown that the definition of “aging signature” varies with developmental stages. The accumulation a small cluster in the non-primed HSC compartment, with “aging signature HSC” and cell cycle arrest in old subjects indicates that aging of human hematopoiesis is induced by clonal evolution. The abundance of a unique population among lymphoid precursors with expression profiles similar to ABCs demonstrates that lymphoid and myeloid progenitors age differently.