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Therapeutic applications of light emitting diode-red light (LED-RL) are expanding, yet data on its clinical effects are lacking. Our goal was to evaluate the safety of high fluence LED-RL (≥160 J/cm2 ). In two phase I, single-blind, dose escalation, randomized controlled trials, healthy subjects received LED-RL or mock irradiation to the forearm thrice weekly for 3 weeks at fluences of 160-640 J/cm2 for all skin types (STARS 1, n = 60) and at 480-640 J/cm2 for non-Hispanic Caucasians (STARS 2, n = 55). The primary outcome was the incidence of adverse events (AEs). The maximum tolerated dose was the highest fluence that did not elicit predefined AEs. Dose-limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm2 in STARS 1 (n = 1) and 640 J/cm2 in STARS 2 (n = 2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. We determined that LED-RL is safe up to 320 J/cm2 for skin of color and 480 J/cm2 for non-Hispanic Caucasian individuals. LED-RL may exert differential cutaneous effects depending on race and ethnicity, with darker skin being more photosensitive. These findings may guide future studies to evaluate the efficacy of LED-RL for the treatment of various diseases.

BackgroundVisible light (400 to 700 nm) is common in our environment, comprising 44% of total solar radiation and a large component of environmental light exposure. The effects of visible light on skin remain undefined. The red light portion of the visible spectrum (600 to 700 nm) may be used to treat skin diseases as a monotherapeutic modality or in combination with other agents. Light-emitting diode-red light (LED-RL) phototherapy may represent an important advance in light-based treatment modalities because it is non-invasive, inexpensive, portable, and easily combinable with other therapies. We previously determined the maximum tolerated dose (MTD) of high-fluence LED-RL (HF-LED-RL) in skin of color individuals to be 320 J/cm2. To the best of our knowledge, no clinical trials have been performed to determine the safety of higher doses of HF-LED-RL in Caucasian non-Hispanic individuals. The aim of this study is to investigate the safety of HF-LED-RL at doses of 480 and 640 J/cm2 in healthy Caucasian non-Hispanic individuals.MethodsThis is a single-blind, dose-escalation, randomized, controlled, phase I trial titled Safety Trial Assessing Red-light on Skin (STARS) 2. Healthy subjects will be randomly assigned to groups of five (three subjects randomly assigned to HF-LED-RL phototherapy and two subjects randomly assigned to mock therapy). Subjects in group 1 will receive HF-LED-RL or mock irradiation at the starting dose of 480 J/cm2, and the dose will be escalated in the subsequent group (group 2) to 640 J/cm2. The MTD is defined as the dose level below the dose at which two or more subjects (>20% of the cohort) experience a dose-limiting toxicity (DLT). After either the MTD is established or the study endpoint of 640 J/cm2 is achieved, additional HF-LED-RL phototherapy subjects and mock therapy subjects will be enrolled at that fluence (group 3) for a total number of up to 60 subjects. Each subject will receive a total of nine irradiation sessions, three times per week for three consecutive weeks.DiscussionThis follow-up study aims to provide important knowledge about safety and cutaneous effects of HF-LED-RL phototherapy of 480 and 640 J/cm2 in Caucasian non-Hispanic subjects. The importance of this clinical trial is that it may establish new treatment paradigms and a safety profile for LED-RL based on race and ethnicity.Trial registrationClinicalTrials.gov Identifier: NCT03433222 . Registered on February 1, 2018 - Retrospectively registered. Protocol date and version: January 12, 2018; version 1.

Despite the introduction of vacancies being a notorious practice for improving electrocatalytic performance, mechanistic elucidation and rational control of such vacancies in electrocatalytic reactions remain elusive. Furthermore, prior catalysts tend to not consider the full hydrogen evolution reaction (HER) holistically, leading to suboptimal designs. Herein, we present a vacancy structure optimization strategy for catalyzing the full Volmer–Heyrovsky reaction. The proposed method has been demonstrated using FeS nanobranches with sulfur vacancies strategically substituted by oxygens (OSV-FeS NBs). Specifically, the as-prepared sample has achieved a significantly lower overpotential of 273 mV at 200 mA cm−2 and a smaller Tafel slope of 82 mV dec−1 compared to samples with non-oxygen-substituted sulfur vacancies (SV-FeS, 357 mV/114 mV dec−1) and their pristine (p-FeS, 640 mV/160 mV dec−1) counterparts. Computational and experimental results combined reveal, for the first time, that the strategic occupation of sulfur vacancies in OSV-FeS simultaneously reduces H2O adsorption on the Fe sites, increases O–H dissociation, and weakens H* adsorption on the Fe–Fe sites, thus achieving the optimization of both the Volmer and Heyrovsky steps during the HER. This work opens a new avenue for designing high-performance electrocatalysts with enhancement of the entire Volmer–Heyrovsky reaction holistically. [ABSTRACT FROM AUTHOR]

This study sought to establish the feasibility of using in situ depth-resolved nuclear morphology measurements for detection of cervical dysplasia. Forty enrolled patients received routine cervical colposcopy with angle-resolved low coherence interferometry (a/LCI) measurements of nuclear morphology. a/LCI scans from 63 tissue sites were compared to histopathological analysis of co-registered biopsy specimens which were classified as benign, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). Results were dichotomized as dysplastic (LSIL/HSIL) versus non-dysplastic and HSIL versus LSIL/benign to determine both accuracy and potential clinical utility of a/LCI nuclear morphology measurements. Analysis of a/LCI data was conducted using both traditional Mie theory based processing and a new hybrid algorithm that provides improved processing speed to ascertain the feasibility of real-time measurements. Analysis of depth-resolved nuclear morphology data revealed a/LCI was able to detect a significant increase in the nuclear diameter at the depth bin containing the basal layer of the epithelium for dysplastic versus non-dysplastic and HSIL versus LSIL/Benign biopsy sites (both p 0.80) in identifying dysplastic biopsies and HSIL. The hybrid algorithm demonstrated a threefold decrease in processing time at a slight cost in classification accuracy. The results demonstrate the feasibility of using a/LCI as an adjunctive clinical tool for detecting cervical dysplasia and guiding the identification of optimal biopsy sites. The faster speed from the hybrid algorithm offers a promising approach for real-time clinical analysis.

BackgroundSkin fibrosis is involved in a variety of pathologic conditions ranging from scar formation secondary to surgery or trauma to immune-mediated processes. Skin fibrosis is a significant international health problem with an estimated incidence of greater than 100 million people affected per year worldwide with few effective treatment options available. Preliminary in vitro data generated by our research group suggests that red light can function as a stand-alone treatment for skin fibrosis. To our knowledge, no prior clinical trials have been performed to determine the safety of high-fluence (dose) light-emitting diode-red light (LED-RL) phototherapy. The goal of this study is to evaluate the safety of LED-RL fluences from 160 J/cm(2) up to 640 J/cm(2) in healthy subjects.Methods/designThis is a single-blind, dose escalation, randomized controlled, phase I study to evaluate the safety of high-fluence LED-RL on human skin. The protocol for dose escalation requires subjects be enrolled sequentially in groups of five. Within each group, three subjects will be randomized to LED-RL phototherapy and two subjects randomized to mock therapy. Subjects in group 1 randomized to LED-RL phototherapy will receive the maximum recommended starting dose (160 J/cm(2)). LED-RL dose will be escalated in subsequent groups (320 J/cm(2), 480 J/cm(2) and 640 J/cm(2)). The maximally tolerated dose (MTD) is defined as the dose level below the dose producing unacceptable but reversible toxicity and is considered to be the upper limit of subject tolerance. After either a MTD has been established, or the study endpoint of 640 J/cm(2) has been achieved, an additional 27 LED-RL phototherapy subjects (for a total of 30) and 18 mock therapy subjects (for a total of 20) (determined randomly) will be enrolled. Each subject will receive a total of nine procedures, three times per week for three consecutive weeks.DiscussionThis study may provide important safety information on the effects of high-fluence LED-RL phototherapy on human skin and help facilitate future phase II studies to evaluate the efficacy of high-fluence LED-RL as a potential noninvasive, safe, portable, at-home therapy for treatment of skin fibrosis.Trial registrationClinicalTrials.gov NCT02630303 . Registered on 9 December 2015.

BackgroundSkin care products make up the largest part (36%) of the cosmetic market globally, of which the United States plays the largest role. In 2015, approximately 115 billion USD was spent globally on skin care products. Skin care products, in contradistinction to pharmaceuticals, are not strictly regulated by the FDA. A key factor for evaluation of a skin care product or topical drug is skin barrier function and effect on super cial skin. Thus, it is critical to have quantitative and qualitative methods to study the effects of skin care products on skin barrier and the super cial skin. Currently, no imaging method exists that can evaluate and track super cial skin changes visually in real-time.ObjectiveTo report using a novel imaging modality, Microscopy using Ultraviolet Surface Excitation (MUSE), to provide real-time, high- resolution, in vivo characterization of super cial skin and moisturizing properties of topical moisturizer, and to highlight key bene ts of using MUSE to visualize the super cial skin and serve as an excellent complementary tool to current quantitative methods.Methods and materialsThe methodology of MUSE is based upon two main principles inherent to ultraviolet (UV) light and uorescent staining agents. In this study, the author's (JJ) index ngertip was imaged using the MUSE instrument without and with moisturizer.ResultsDermatoglyphics of the fingertip consists of ridges (cristae super ciales) and grooves (sulci super ciales) proved to be straightforward to visualize at high resolution. Desquamation of superficial corneocytes and opening of an acrosyringium (the most superficial portion of eccrine ducts) were visualized in high-resolution. Post-application of a moisturizer, a uniform layer of moisturizer could be seen superficial to the corneocytes along the ridges and CONCLUSIONS: Real-time, high-resolution, in vivo characterization of super cial skin and moisturizing properties of moisturizer using MUSE is feasible. Its utility can be enhanced with downstream quantification using imaging software. J Drugs Dermatol. 2016;15(11):1344-1346..

BackgroundIn this paper we determined the benefits of image registration on estimating longitudinal retinal nerve fiber layer thickness (RNFLT) changes.MethodsRNFLT maps around the optic nerve head (ONH) of healthy primate eyes were measured using Optical Coherence Tomography (OCT) weekly for 30 weeks. One automatic algorithm based on mutual information (MI) and the other semi-automatic algorithm based on log-polar transform cross-correlation using manually segmented blood vessels (LPCC_MSBV), were used to register retinal maps longitudinally. We compared the precision and recall between manually segmented image pairs for the two algorithms using a linear mixed effects model.ResultsWe found that the precision calculated between manually segmented image pairs following registration by LPCC_MSBV algorithm is significantly better than the one following registration by MI algorithm (p

Accuracy of IVOCT for measurement of neointimal thickness and effect of neointima in the appearance of metallic struts in IVOCT images was investigated. Phantom vessels were constructed and coronary stents were deployed and covered with thick (250-400 μm) and thin (30-70 μm) phantom neointima. High resolution Micro-CT images of the stent struts were recorded as a gold standard. IVOCT images of the phantom vessels were acquired with various luminal blood scattering strengths and measured neointimal thicknesses from IVOCT and Micro-CT images were compared. In transparent lumen, comparison of IVOCT and Micro-CT neointima thickness measurements found no significant difference (p > 0.05) in the thick neointima phantom but a significant difference (p < 0.05) in the thin neointima phantom. For both thick and thin neointima, IVOCT neointimal thickness measurements varied from Micro-CT values by as much as ±35%. Increased luminal scattering due to presence of blood at concentrations

We sought to elucidate the mechanisms underlying two common intravascular optical coherence tomography (IV-OCT) artifacts that occur when imaging metallic stents: “merry-go-rounding” (MGR), which is an increase in strut arc length (SAL), and “blooming,” which is an increase in the strut reflection thickness (blooming thickness). Due to uncontrollable variables that occur in vivo, we performed an in vitro assessment of MGR and blooming in stented vessel phantoms. Using Xience V and Driver stents, we examined the effects of catheter offset, intimal strut coverage, and residual blood on SAL and blooming thickness in IV-OCT images. Catheter offset and strut coverage both caused minor MGR, while the greatest MGR effect resulted from light scattering by residual blood in the vessel lumen, with 1% hematocrit (Hct) causing a more than fourfold increase in SAL compared with saline (p

Texturing metallic zinc anodes (MZAs) for selective exposure of (002)Zn plane with high thermodynamical stability is an efficient scheme for dendrite‐free Zn electrodeposition. However, fundamental factors that influence Zn deposition morphology via surface crystallographic texture engineering are not well understood. Herein, different from traditional cognition, MZAs with preferential exposure of (101)Zn facet are demonstrated to be equally effective in promoting dendrite‐free Zn deposition, which is enabled by introducing trace amount (0.01 m) of theophylline into ZnSO4 electrolyte. Experimental results and mathematical model corroborate, indicating mechanistically that the theophylline derived cations preferentially adsorb on the (002)Zn crystal plane due to higher adsorption energy, thereby accelerating its growth through increased binding affinity with Zn2+ ions. Consequently, this phenomenon facilitates the texture exposure of (101)Zn facet to achieve ordered surface crystallographic orientation of MZAs (101‐Zn), thus enabling electrodeposition/dissolution cycling over 650 h under a depth of discharge up to 40% and significantly boosting the rechargeability (76.7% capacity retention after 1000 cycles) of the 101‐Zn||carbon‐cloth@MnO2 full battery relative to counterpart without theophylline additive (36.3%). The work offers deep insights on the scientific links between the surface crystallographic orientation of MZAs and Zn deposition morphology, while opens up vast untapped opportunities to realize dendrite‐free MZAs. [ABSTRACT FROM AUTHOR]

Conventional MXene‐based thick electrodes with stacked and tortuous microstructures suffer from sluggish charge transport and low‐utilization of active substances, thus a limited boost in areal energy density of the assembled micro‐supercapacitors (MSCs). Herein, the duplication of wood‐like microstructure is realized in MXene/Ag‐nanowires (AgNWs) hybrid aerogel electrode (WL‐M/A‐AE) via directional freeze‐drying technique. Benefitting from the uniform 3D vertically‐aligned microchannels as the highways for ions transport throughout the matrix, the WL‐M/A‐AE with a thickness of up to 2000 µm can achieve a 50‐times higher of Cl− diffusion coefficient relative to closely restacked film electrode with the same mass loading of MXene. Furthermore, the evenly interspersed AgNWs serving as percolation network within the electrode matrix can facilitate horizontal electrons transmission between vertically‐aligned loose MXene flakes, while reversibly capture/release Cl− ions via phase conversion (Ag⇔AgCl) to raise the charge storage capacity of the WL‐M/A‐AE. Thus, when coupling with Zn anode, the assembled micro‐redoxcapacitor adopting polyacrylamide/ZnCl2+NH4Cl hydrogel electrolyte can deliver an areal energy density up to 292.5 µWh cm−2 in a more stable way (a smooth discharge plateau contributing 40.9% of the energy). The demonstrated hybrid thick electrode with wood‐like low‐tortuosity microstructure promises an effective avenue for tackling the performance bottlenecks facing traditional MSCs. [ABSTRACT FROM AUTHOR]

Piezoionic materials consisting of a polymer matrix and mobile ions can produce an electrical output upon an applied pressure inducing an ion concentration gradient. Distinct from charges generated by the piezoelectric or triboelectric effects, the use of generated mobile ions to carry a signal closely resembles many ionic biological processes. Due to this similarity to biology, the piezoionic effect has great potential to enable seamless integration with biological systems, which accelerates the advancement of medical devices and personalized medicine. In this review, a comprehensive description of the piezoionic mechanism, methods, and applications are presented, with the aim to facilitate a dialogue among relevant scientific communities. First, the piezoionic effect is briefly introduced, then the development of mechanistic understanding over time is surveyed. Next, different types of piezoionic materials are reviewed and methods to enhance the piezoionic output via materials properties, electrode interfaces, and device architectures are detailed. Finally, applications, challenges, and outlooks are provided. With its novel properties, piezoionics is expected to play a key role in the overcoming of grand challenges in the areas of sensing, biointerfaces, and energy harvesting. [ABSTRACT FROM AUTHOR]