Oxygen plays a key role in wound healing, and hypoxia is a major cause of wound healing impairment; therefore, treatments to improve hemodynamics and increase wound oxygenation are of particular ...interest for the treatment of chronic wounds. This article describes the roles of oxygen and angiogenesis in wound healing as well as the tools used to evaluate tissue oxygenation and perfusion and then presents a review of nanomedicines and gene therapies designed to improve perfusion and oxygenation and accelerate wound healing.
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Summary
Perineural dexamethasone has a ceiling dose of 4 mg for prolongation of analgesia duration after injection of long‐acting local anaesthetic for peripheral nerve block, but evidence for doses ...< 4 mg is lacking. This randomised controlled triple‐blind trial tested the hypothesis that increasing doses of perineural dexamethasone between 1 mg and 4 mg would prolong the duration of analgesia in a dose‐dependent manner. Eighty ASA physical status 1–2 patients scheduled for shoulder arthroscopy under general anaesthesia with ultrasound‐guided interscalene brachial plexus block were randomly allocated to receive saline (control), dexamethasone 1 mg, 2 mg, 3 mg and 4 mg, together with 20 ml ropivacaine 0.5%. Postoperative analgesia consisted of paracetamol, diclofenac and oxycodone on request, using a pre‐defined protocol. The primary outcome was the duration of analgesia, defined as the time between the block procedure and the first analgesic request. Secondary outcomes included rest and dynamic pain scores, and analgesic consumption at 2 h, 24 h and 48 h postoperatively. An analysis of the dose–response relationship was performed using multiple comparison procedure‐modelling. The median (IQR range) duration of analgesia was significantly prolonged in a dose‐dependent manner: control 685 (590–860 453–1272) min; 1 mg 835 (740–1110 450–1375) min; 2 mg 904 (710–1130 525–1365) min; 3 mg 965 (875–1025 730–1390) min; 4 mg 1023 (838–1239 518–1500) min (p = 0.03). There were no significant differences between the secondary outcomes. Perineural administration of dexamethasone with doses between 1 mg and 4 mg, combined with ropivacaine for interscalene brachial plexus block, prolongs duration of analgesia in a dose‐dependent manner.
Emotions experienced by healthy individuals in response to tasting or eating food were examined in two studies. In the first study, 42 participants reported the frequency with which 22 emotion types ...were experienced in everyday interactions with food products, and the conditions that elicited these emotions. In the second study, 124 participants reported the extent to which they experienced each emotion type during sample tasting tests for sweet bakery snacks, savoury snacks, and pasta meals. Although all emotions occurred from time to time in response to eating or tasting food, pleasant emotions were reported more often than unpleasant ones. Satisfaction, enjoyment, and desire were experienced most often, and sadness, anger, and jealousy least often. Participants reported a wide variety of eliciting conditions, including statements that referred directly to sensory properties and experienced consequences, and statements that referred to more indirect conditions, such as expectations and associations. Five different sources of food emotions are proposed to represent the various reported eliciting conditions: sensory attributes, experienced consequences, anticipated consequences, personal or cultural meanings, and actions of associated agents.
Abstract
STUDY QUESTION
Do two different concentrations of human adipose tissue-derived stem cells (ASCs) embedded inside a fibrin scaffold have the potential to differentiate into vessels and aid ...vascularization in a peritoneal grafting site intended for ovarian tissue transplantation?
SUMMARY ANSWER
Human ASCs in low and high concentrations differentiated into vessels when transplanted to mouse peritoneum inside a fibrin matrix, but only high ASC concentrations significantly increased human vessel area 14 days after transplantation.
WHAT IS KNOWN ALREADY
ASCs have multilineage differentiation potential, including proangiogenic properties and have been used in tissue engineering to enhance vascularization in transplanted tissues. Fibrin has been studied and used as an ASC-compatible biomaterial.
STUDY DESIGN, SIZE, DURATION
In vivo experimental model using 22 severe combined immunodeficient mice. In total, 16 mice (eight per group) were intraperitoneally grafted with a fibrin scaffold loaded with two different human ASC concentrations (either 150 000 L-ASC or 1 500 000 H-ASC cells) and lithium phthalocyanine (LiPc) crystals as oxygen-sensitive probes. Six mice were grafted with an empty fibrin (EF) implant containing only LiPc and served as controls. Levels of partial pressure of oxygen (pO2) in implants were monitored in vivo by electron paramagnetic resonance oximetry (EPR). ASC identification, proliferation, and host and human vascularization were analyzed by immunohistochemistry (IHC). All analyses were performed on post-grafting Days 3, 7 and 14.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Prospective experimental study conducted at the Gynecology Research Unit, Université Catholique de Louvain. All materials were used to perform pO2 measurements (EPR oximetry), as well as histological (hematoxylin-eosin staining) and IHC (anti-human vimentin, anti-human Ki67, anti-mouse and human double CD34) analyses.
MAIN RESULTS AND THE ROLE OF CHANCE
A significant increase in pO2 in implants was observed in all groups between Days 3 and 7 (P < 0.001). ASC-loaded implants displayed a tendency towards increased pO2 levels from Days 7 to 14, not observed in EF implants. ASC-loaded implants showed differentiation into human CD34-positive vessels. Total CD34-positive endothelial area was correlated to pO2 values obtained by EPR oximetry (r = 0.6506, P = 0.0019). In the H-ASC group, a greater human CD34-positive vascular surface area was found compared to the L-ASC group 14 days after transplantation (P < 0.0049).
LARGE SCALE DATA
N/A.
LIMITATIONS REASONS FOR CAUTION
As demonstrated by our results, ASCs transplanted inside a fibrin matrix can differentiate into CD34-positive human vessels. However, other possible mechanisms involved in ASC angiogenic behavior remain to be investigated.
WIDER IMPLICATIONS OF THE FINDINGS
High concentrations of ASCs loaded inside a fibrin scaffold could serve as a substrate to prepare a peritoneal grafting site over 14 days, in order to enhance vascularization once human ovarian tissue is grafted. Our proposed preparation of the grafting site would not only benefit ovarian tissue transplantation, but also other experimental avascular grafting procedures.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR Convention T.0077.14, Télévie Grant no. 7.6515.16F awarded to DDM and Grant 5/4/150/5 awarded to M.M.D. CAA is FRS-FNRS research associate), Fonds Spéciaux de Recherche, and Fondation St Luc, Foundation Against Cancer, and donations from the Ferrero family. None of the authors have any competing interests to declare.
As ubiquitous technology is increasingly mediating our relationships with the world and others, we argue that the sublime is struggling to find room in product design primarily aimed at commercial ...and transactional goals such as speed and efficiency. We suggest a new category of products to promote deeper and more meaningful experiences, specifically those offering liminality, transcendence, and personal transformation. This paper introduces a conceptual framework and three-step design approach looking at narrative participation in design through abstractions to promote, hold and deepen more complex emotions. We explore implications from a theoretical point of view and suggest product examples for how the model might be applied in practice.
The sternocostal and clavicular regions of the pectoralis major are independently harvested to provide shoulder stability, but surgical decision making does not consider the biomechanical ...consequences that disinsertion of one fiber region over the other has on shoulder function. Differences in material properties between the fiber regions could influence which tissue is more optimal for surgical harvesting. The current study utilized ultrasound shear wave elastography (SWE) to investigate whether the in vivo material properties differ between the fiber regions. Shear wave velocities (SWVs) were collected from the sternocostal and clavicular fiber regions of the pectoralis major from ten healthy young male participants. Participants produced isometric shoulder torques of varying magnitudes (passive, 15%, and 30% MVC) and directions (horizontal and vertical adduction). Four shoulder positions encompassing different vertical abduction and external rotation angles were examined. One-way ANOVAs tested the hypotheses that differences in SWVs during rest existed between the fiber regions asa function of shoulder position, and differences in SWVs during contraction existed asa function of shoulder position and torque direction. In all shoulder positions, the clavicular region exhibited greater SWVs during rest than the sternocostal region (P<0.001). In shoulder positions that did not include external rotation, the clavicular region exhibited greater SWVs during contraction when producing horizontal adduction torques (P<0.001), while the sternocostal region exhibited greater SWVs during contraction when producing vertical adduction torques at 30% MVC (P<0.01). Our results suggest that each fiber region of the pectoralis major provides unique contributions to passive and active shoulder function.
A lack of oxygen is classically described as a major cause of impaired wound healing in diabetic patients. Even if the role of oxygen in the wound healing process is well recognized, measurement of ...oxygen levels in a wound remains challenging. The purpose of the present study was to assess the value of electron paramagnetic resonance (EPR) oximetry to monitor pO2 in wounds during the healing process in diabetic mouse models. Kinetics of wound closure were carried out in streptozotocin (STZ)-treated and db/db mice. The pO2 was followed repeatedly during the healing process by 1 GHz EPR spectroscopy with lithium phthalocyanine (LiPc) crystals used as oxygen sensor in two different wound models: a full-thickness excisional skin wound and a pedicled skin flap. Wound closure kinetics were dramatically slower in 12-week-old db/db compared to control (db/+) mice, whereas kinetics were not statistically different in STZ-treated compared to control mice. At the center of excisional wounds, measurements were highly influenced by atmospheric oxygen early in the healing process. In pedicled flaps, hypoxia was observed early after wounding. While reoxygenation occurred over time in db/+ mice, hypoxia was prolonged in the diabetic db/db model. This observation was consistent with impaired healing and microangiopathies observed using intravital microscopy. In conclusion, EPR oximetry using LiPc crystals as the oxygen sensor is an appropriate technique to follow wound oxygenation in acute and chronic wounds, in normal and diabetic animals. Nevertheless, the technique is limited for measurements in pedicled skin flaps and cannot be applied to excisional wounds in which diffusion of atmospheric oxygen significantly affects the measurements.
To successfully traverse their environment, humans often perform maneuvers to achieve desired task goals while simultaneously maintaining balance. Humans accomplish these tasks primarily by ...modulating their foot placements. As humans are more unstable laterally, we must better understand how humans modulate lateral foot placement. We previously developed a theoretical framework and corresponding computational models to describe how humans regulate lateral stepping during straight-ahead continuous walking. We identified goal functions for step width and lateral body position that define the walking task and determine the set of all possible task solutions as Goal Equivalent Manifolds (GEMs). Here, we used this framework to determine if humans can regulate lateral stepping during non-steady-state lateral maneuvers by minimizing errors consistent with these goal functions. Twenty young healthy adults each performed four lateral lane-change maneuvers in a virtual reality environment. Extending our general lateral stepping regulation framework, we first re-examined the requirements of such transient walking tasks. Doing so yielded new theoretical predictions regarding how steps during any such maneuver should be regulated to minimize error costs, consistent with the goals required at each step and with how these costs are adapted at each step during the maneuver. Humans performed the experimental lateral maneuvers in a manner consistent with our theoretical predictions. Furthermore, their stepping behavior was well modeled by allowing the parameters of our previous lateral stepping models to adapt from step to step. To our knowledge, our results are the first to demonstrate humans might use evolving cost landscapes in real time to perform such an adaptive motor task and, furthermore, that such adaptation can occur quickly-over only one step. Thus, the predictive capabilities of our general stepping regulation framework extend to a much greater range of walking tasks beyond just normal, straight-ahead walking.
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Oxygen is essential in physiology and pathophysiology. Electron paramagnetic resonance (EPR) oximetry, using oxygen sensitive paramagnetic materials, could be attractive for measuring ...oxygen in tissues. The aim of the present study was to assess the properties of lipid nanocapsules (LNCs) loaded with the nitroxide tempo-benzoate (TB) or tetrathiatriarylmethyl (TAM) radicals. LNCs loaded with the EPR probes were successfully prepared by the phase inversion process leading to nanocapsules of about 60 nm. LNCs protected the TB radical against reduction in vitro. The calibration of the EPR line width (LW) as a function of the pO2 showed a two-fold increase in sensitivity with TAM-LNC compared to hydrophilic trityl radical. The TAM-LNCs were evaluated in vivo. Contrarily to unencapsulated TAM, for which a rapid decrease in EPR signal was observed, the half-life of TAM-LNCs administered in muscles or in tumours exceeded an hour. Carbogen-challenges in mice demonstrated that the TAM-LNCs responded well to changes in oxygen environment. However, the apparent pO2 values acquired were higher than the expected physiological values. These results warrant further investigation in the formulation of stable nano-objects encapsulating EPR oxygen sensitive probes.
Melanoma is the most aggressive skin tumour type. Although complete cure can be achieved when the whole tumour is resected, prognostic dramatically drops when melanoma cells reach deeper tissues and ...lymph nodes. Hence, there is an urgent need to develop accurate tools allowing (i) discriminating benign naevi from malignant tumours and (ii) being able to characterise melanoma infiltration. For that purpose, we exploited the paramagnetic properties of melanin by using electron paramagnetic resonance (EPR) spectroscopy to measure the melanin content in pigmented (B16F10 cancer cells) and non-pigmented melanomas (WM2664 cancer cells) inoculated intradermally in nude mice. Specifically, we took advantage of a new clinical EPR device (1 GHz), which provides sensitive measurements of radical species in vivo. Results showed that the melanin-specific EPR signal increased with tumour growth in pigmented tumours, whereas no EPR signal could be detected in achromic melanomas. These data plead for the development of new EPR spectrometers/imagers with an improved in-depth resolution for the detection of invasive melanomas.
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