Use of near-infrared systems for investigations of hemodynamics in human in vivo bone tissue: a systematic review

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.A range of technologies using near infrared (NIR) light have shown promise at providing real time measurements of hemodynamic markers in bone tissue in vivo, an exciting prospect given existing difficulties in measuring hemodynamics in bone tissue. This systematic review aimed to evaluate the evidence for this potential use of NIR systems, establishing their potential as a research tool in this field. Major electronic databases including MEDLINE and EMBASE were searched using pre‐planned search strategies with broad scope for any in vivo use of NIR technologies in human bone tissue. Following identification of studies by title and abstract screening, full text inclusion was determined by double blind assessment using predefined criteria. Full text studies for inclusion were data extracted using a predesigned proforma and quality assessed. Narrative synthesis was appropriate given the wide heterogeneity of included studies. Eighty‐eight full text studies fulfilled the inclusion criteria, 57 addressing laser Doppler flowmetry (56 intra‐operatively), 21 near infrared spectroscopy, and 10 photoplethysmography. The heterogeneity of the methodologies included differing hemodynamic markers, measurement protocols, anatomical locations, and research applications, making meaningful direct comparisons impossible. Further, studies were often limited by small sample sizes with potential selection biases, detection biases, and wide variability in results between participants. Despite promising potential in the use of NIR light to interrogate bone circulation, the application of NIR systems in bone requires rigorous assessment of the reproducibility of potential hemodynamic markers and further validation of these markers against alternative physiologically relevant reference standards.This systematic review was supported by the College of Radiographers Industry Partnership Scheme (CORIPS) Doctoral Fellowship Grant (Applicant 003). The CORIPS are providing financial support but have no input into the design, performance or analysis of this systematic review. WDS, FC and CT would like to acknowledge the NIHR Exeter Clinical Research Facility and the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR Exeter Clinical Research Facility, the NHS, the NIHR or the Department of Health in England

Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts

BACKGROUND: Astronauts participating in long duration space missions are at an increased risk of physiological disruptions. The development of visual impairment and intracranial pressure (VIIP) syndrome is one of the leading health concerns for crew members on long-duration space missions; microgravity-induced fluid shifts and chronic elevated cabin CO2 may be contributing factors. By studying physiological and molecular changes in one identical twin during his 1-year ISS mission and his ground-based co-twin, this work extends a current NASA-funded investigation to assess space flight induced "Fluid Shifts" in association with the development of VIIP. This twin study uniquely integrates physiological and -omic signatures to further our understanding of the molecular mechanisms underlying space flight-induced VIIP. We are: (i) conducting longitudinal proteomic assessments of plasma to identify fluid regulation-related molecular pathways altered by long-term space flight; and (ii) integrating physiological and proteomic data with genomic data to understand the genomic mechanism by which these proteomic signatures are regulated. PURPOSE: We are exploring proteomic signatures and genomic mechanisms underlying space flight-induced VIIP symptoms with the future goal of developing early biomarkers to detect and monitor the progression of VIIP. This study is first to employ a male monozygous twin pair to systematically determine the impact of fluid distribution in microgravity, integrating a comprehensive set of structural and functional measures with proteomic, metabolomic and genomic data. This project has a broader impact on Earth-based clinical areas, such as traumatic brain injury-induced elevations of intracranial pressure, hydrocephalus, and glaucoma. HYPOTHESIS: We predict that the space-flown twin will experience a space flight-induced alteration in proteins and peptides related to fluid balance, fluid control and brain injury as compared to his pre-flight protein/peptide signatures. Conversely, the trajectory of these protein signatures will remain relatively constant in his ground based co-twin. METHODS: We are using proteomic and standard immunoelectrophoresis techniques to delineate the change in protein signatures throughout the course of a long duration space flight in relation to the development of VIIP. We are also applying a novel cell-based metaboloic organ system assay ("Organs on a Plate") to address how these circulating biomarkers affect physiological processes at the cellular and organ level which could result in VIIP symptoms. These molecular data will be correlated with physiological measures (eg. extra and intracellular fluid volume, vascular filling/flow patterns, MRI, and Optic Coherence Tomography. DISCUSSION: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Biosamples will be batch processed when received from ISS after the conclusion of the 1-year mission. Omic and Physiological measures from the twin astronauts will be compared to similar data being collected on twin subjects who participated in simulated microgravity study. bed rest study

Chick Embryo Partial Ischemia Model: A New Approach to Study Ischemia Ex Vivo

Background: Ischemia is a pathophysiological condition due to blockade in blood supply to a specific tissue thus damaging the physiological activity of the tissue. Different in vivo models are presently available to study ischemia in heart and other tissues. However, no ex vivo ischemia model has been available to date for routine ischemia research and for faster screening of anti-ischemia drugs. In the present study, we took the opportunity to develop an ex vivo model of partial ischemia using the vascular bed of 4th day incubated chick embryo. Methodology/Principal Findings: Ischemia was created in chick embryo by ligating the right vitelline artery using sterile surgical suture. Hypoxia inducible factor- 1 alpha (HIF-1a), creatine phospho kinase-MB and reactive oxygen species in animal tissues and cells were measured to confirm ischemia in chick embryo. Additionally, ranolazine, N-acetyl cysteine and trimetazidine were administered as an anti-ischemic drug to validate the present model. Results from the present study depicted that blocking blood flow elevates HIF-1a, lipid peroxidation, peroxynitrite level in ischemic vessels while ranolazine administration partially attenuates ischemia driven HIF-1a expression. Endothelial cell incubated on ischemic blood vessels elucidated a higher level of HIF-1a expression with time while ranolazine treatment reduced HIF-1a in ischemic cells. Incubation of caprine heart strip on chick embryo ischemia model depicted an elevated creatine phospho kinase-MB activity under ischemic condition while histology of the treated heart sections evoked edema and disruption of myofibril structures. Conclusions/Significance: The present study concluded that chick embryo partial ischemia model can be used as a novel ex vivo model of ischemia. Therefore, the present model can be used parallel with the known in vivo ischemia models in understanding the mechanistic insight of ischemia development and in evaluating the activity of anti-ischemic drug.status: publishe

Taking the Power Back: Designing a Replicable Neighborhood Grid

Transitioning to alternative energy can help the environment and lower energy bills, but the process can be complicated, and the up-front costs can be high for individual homeowners. In collaboration with the Australian Energy Foundation, our team worked with residents of Halpin Street in Brunswick West, VIC, investigating the path they might take and the options they might consider in setting up a neighborhood microgrid. Through the literature review, interviews with local companies and residents, and solar mapping software, we identified the best options for energy generation, storage, monitoring systems, and AC/DC inverters, sharing our recommendations with residents and outlining our process so other neighborhoods might work together to pursue this path

Thirty days of spaceflight does not alter murine calvariae structure despite increased Sost expression

Previously our laboratory documented increases in calvaria bone volume and thickness in mice exposed to 15 days of spaceflight aboard the NASA Shuttle mission STS-131. However, the tissues were not processed for gene expression studies to determine what bone formation pathways might contribute to these structural adaptations. Therefore, this study was designed to investigate both the structural and molecular changes in mice calvariae after a longer duration of spaceflight. The primary purpose was to determine the calvaria bone volume and thickness of mice exposed to 30 days of spaceflight using micro-computed tomography for comparison with our previous findings. Because sclerostin, the secreted glycoprotein of the Sost gene, is a potent inhibitor of bone formation, our second aim was to quantify Sost mRNA expression using quantitative PCR. Calvariae were obtained from six mice aboard the Russian 30-day Bion-M1 biosatellite and seven ground controls. In mice exposed to 30 days of spaceflight, calvaria bone structure was not significantly different from that of their controls (bone volume was about 5% lower in spaceflight mice, p = 0.534). However, Sost mRNA expression was 16-fold (16.4 ± 0.4, p < 0.001) greater in the spaceflight group than that in the ground control group. Therefore, bone formation may have been suppressed in mice exposed to 30 days of spaceflight. Genetic responsiveness (e.g. sex or strain of animals) or in-flight environmental conditions other than microgravity (e.g. pCO2 levels) may have elicited different bone adaptations in STS-131 and Bion-M1 mice. Although structural results were not significant, this study provides biochemical evidence that calvaria mechanotransduction pathways may be altered during spaceflight, which could reflect vascular and interstitial fluid adaptations in non-weight bearing bones. Future studies are warranted to elucidate the processes that mediate these effects and the factors responsible for discordant calvaria bone adaptations between STS-131 and Bion-M1 mice

Shear stress promotes nitric oxide production in endothelial cells by sub-cellular delocalization of eNOS: A basis for shear stress mediated angiogenesis

This study aims to investigate the role of shear stress in cellular remodeling and angiogenesis with relation to nitric oxide (NO). We observed a 2-fold increase in endothelial cell (EC) migration in relation to actin re-arrangements under 15 dyne/cm2 shear stress. Blocking NO production inhibited the migration and ring formation of ECs by 6-fold and 5-fold, respectively under shear stress. eNOS-siRNA knockdown technique also ascertained a 3-fold reduction in shear stress mediated ring formation. In ovo artery ligation model with a half and complete flow block for 30 min showed a reduction of angiogenesis by 50% and 70%, respectively. External stimulation with NO donor showed a 2-fold recovery in angiogenesis under both half and complete flow block conditions. NO intensity clustering studies by using Diaminofluorescein diacetate (DAF-2DA) probed endothelial monolayer depicted pattern-changes in NO distribution and cluster formation of ECs under shear stress. Immunofluorescence and live cell studies revealed an altered sub-cellular localization pattern of eNOS and phospho-eNOS under shear stress. In conclusion, shear-induced angiogenesis is mediated by nitric oxide dependent EC migration

Aging Decreases Hand Volume Expansion with Water Immersion

Hands may show early signs of aging with altered skin texture, skin permeability and vascular properties. In clinics, a hand volumeter is used to measure swelling of hands due to edema, carpal tunnel syndrome or drug interventions. The hand volume measurements are generally taken without taking age into consideration. We hypothesized that age affects hand volumeter measurements and that the younger age group (≤40 years) records a greater change in hand volume as compared to the older group (&gt;40 years). Four volumetric measurements were taken at 5 min intervals during 20 min of water immersion using a clinically-approved hand volumeter. After 20 min of immersion, the hand volume changes of the younger age group were significantly higher than the older age group (p &lt; 0.001). Specifically, the right-hand volume of the younger age group (≤40 years, n = 30) increased by 4.3 ± 2%, and the left hand increased by 3.4 ± 2.1%. Conversely, the right-hand volume of the older age group (&gt;40 years, n = 10) increased by 2.2 ± 2.0%, and the left hand decreased by 0.6 ± 2.4% after 20 min of water immersion. The data are presented as Mean ± SD. Hand volume changes were not correlated with body mass index (BMI) or gender, and furthermore, neither of these two variables affected the relationship between age and hand volume changes with water immersion. We conclude that the younger age group has a higher increase in hand volume with water immersion as compared to the older age group