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The effect of photobiomodulation (PBM) treatment on wound healing and macrophage polarization was investigated in vivo. Animal models of oral ulcers were simulated through chemically induced oral ulcers in rats.PBM treatment using an infrared pulsed laser was used to treat oral ulcers in the animal models. Twelve Sprague-Dawley rats were randomly divided into four groups depending on set absorbed energy: Group 1 (control), Group 2 (30 J), Group 3 (60 J), and Group 4 (100 J). Laser treatment was performed every other day for 8 days after ulcer confirmation. Parameters used were as follows: wavelength 808 nm, power output 50 mW, spot size 10 mm, frequency 10 Hz, and pulse duration 1 millisecond. Ulcers were measured to determine the effect of the treatments over time. Histology, immunostaining, and real-time polymerase chain reaction analyses were performed to evaluate the effect of PBM treatment on macrophage-related (IL-6/IL-10) and wound-healing-related (TNF-α/TGF-β/MMP-2) cytokine expression.Histological examinations indicate that the PBM treatment stimulated a higher level of wound recovery after 8 days of treatment at 60 J absorbed energy compared to other treatment groups. Analyses of relative gene expression of proinflammatory, anti-inflammatory, and tissue remodeling cytokines indicate that the macrophages in the tissue samples were predominantly characterized as M2 subtypes (alternatively activated), which possibly accounts for the accelerated tissue repair in the animal model of oral ulcer.This preliminary study stands as a proof of concept regarding the potential use of infrared laser PBM treatment for oral ulcers which have not been previously investigated upon. PBM treatment affects macrophage polarization and enhances wound healing. Further experimentation will be conducted to expand the understanding of how PBM treatment affects the healing mechanism of ulcers.

Background and objectives Anterior knee pain (AKP) is the most common knee pathology in athletes and occurs in 15% of army recruits of elite units during basic training. Of these, 50% are symptomatic 6 years later. Photobiomodulation (PBM) is a nonthermal red-to-near-infrared irradiation used for pain reduction of a variety of etiologies. This study was designed to determine whether addition of PBM to physiotherapy (PT) for AKP in combat soldiers is superior to PT alone. Study design/materials and methods In this prospective, double-blind, sham-controlled, randomized clinical trial (NCT02845869), 26 combat soldiers/policemen (male:female, 15:11; body mass index [BMI] = 24.2 ± 3.9, n = 46 knees), with AKP due to overuse/load, received 4 weeks of PT + sham (PT + Sham) or active PBM (wavelength = 660 and 850 nm, pulsing = 2.5 Hz, LED power = 50 mW/cm2 [local tissue/regional lymph nodes]; 810 nm continuous beam, laser cluster 6 W/cm2 [analgesia] and laser pointer 4.75 W/cm2 [trigger points]) (PT + PBM). The main outcome measures were subjective pain by visual analog scale (VAS) (0 [none]-100 [intolerable]) and functional disability by Kujala score (0 [worst]-100 [best]). Evaluations were carried out at baseline, end of treatments, and 3-month follow-up. Results All participants completed the treatment protocol without any reported adverse device effects. Post-treatment pain was significantly reduced in the PT+PBM group, compared with baseline and sham (Δpain, VAS, mean ± SD: PT + PBM = -19 ± 23, P = 0.002; PT + Sham = -6 ± 21, P = 0.16; between groups, P = 0.032). At 3-month follow-up, pain reduction was similar between groups; however, the Kujala score was significantly improved only in the PBM-treated group (ΔKujala: PT + PBM = 11 ± 10, P = 0.003; PT + Sham = 5 ± 7, P = 0.059). Conclusions Addition of PBM to PT for AKP resulted in earlier reduction in pain and improved functionality, compared with PT alone. This noninvasive, nonpharmacologic, adjunctive therapeutic modality can be easily incorporated into team healthcare frameworks or end units and may lead to earlier return to competition or combat-level service. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Background and objectives Photobiomodulation (PBM) therapy uses light at various wavelengths to stimulate wound healing, grow hair, relieve pain, and more-but there is no consensus about optimal wavelengths or dosimetry. PBM therapy works through putative, wavelength-dependent mechanisms including direct stimulation of mitochondrial respiration, and/or activation of transmembrane signaling channels by changes in water activity. A common wavelength used in the visible red spectrum is ~660 nm, whereas recently ~980 nm is being explored and both have been proposed to work via different mechanisms. We aimed to gain more insight into identifying treatment parameters and the putative mechanisms involved. Study design/materials and methods Fluence-response curves were measured in cultured keratinocytes and fibroblasts exposed to 660 or 980 nm from LED sources. Metabolic activity was assessed using the MTT assay for reductases. ATP production, a major event triggered by PBM therapy, was assessed using a luminescence assay. To measure the role of mitochondria, we used an ELISA to measure COX-1 and SDH-A protein levels. The respective contributions of cytochrome c oxidase and ATP synthase to the PBM effects were gauged using specific inhibitors. Results Keratinocytes and fibroblasts responded differently to exposures at 660 nm (red) and 980 nm (NIR). Although 980 nm required much lower fluence for cell stimulation, the resulting increase in ATP levels was short-term, whereas 660 nm stimulation elevated ATP levels for at least 24 hours. COX-1 protein levels were increased following 660 nm treatment but were unaffected by 980 nm. In fibroblasts, SDH-A levels were affected by both wavelengths, whereas in keratinocytes only 660 nm light impacted SDH-A levels. Inhibition of ATP synthase nearly completely abolished the effects of both wavelengths on ATP synthesis. Interestingly, inhibiting cytochrome c oxidase did not prevent the rise in ATP levels in response to PBM treatment. Conclusion To the best of our knowledge, this is the first demonstration of differing kinetics in response to PBM therapy at red versus NIR wavelength. We also found cell-type-specific differences in PBM therapy response to the two wavelengths studied. These findings confirm that different response pathways are involved after 660 and 980 nm exposures and suggest that 660 nm causes a more durable response. © 2021 Wiley Periodicals LLC.

Background and objective To compare changes in skin sensitivity before and after treatment with a 1064-nm Q-switched Nd:YAG laser in healthy individuals, and to provide a reference for clinicians to use this laser reasonably. Study design/materials and methods Nineteen healthy female volunteers underwent 10 random unilateral 1064-nm Q-switched Nd:YAG laser treatments. The skin transepidermal water loss rate (TEWL), skin glossiness, epidermal and dermal thickness and density, current perception threshold (CPT) value, facial blood perfusion were determined before and after treatment at different time points. Moreover, the changes in skin barrier function, blood vessels, and sensory nerve reaction in the treated and untreated sides of the face were recorded before and after treatment. Results Seventeen volunteers completed the 12-month follow-up study after 1064-nm Q-switched Nd:YAG laser treatment. At D3, M3, and M6, skin TEWL was decreased on the treated side of the face. Skin glossiness was significantly improved in the early post-treatment period (D1-D7) and M3, M6, and M12 compared with the untreated side of the face. There was no significant change in dermal and epidermal thickness or density at all time points before and after treatment. There were no significant differences in sensory nerve CPT values and local blood flow volume or velocity between the treated side of the face and the untreated side before and after treatment. Conclusion Multiple low-energy 1064-nm Q-switched Nd:YAG laser treatments will not affect the barrier function of facial skin, skin nerve sensitivity, or local microcirculation of healthy skin over the long term. Therefore, 1064-nm Q-switched Nd:YAG laser treatment is safe, and does not alter skin sensitivity. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Author(s): Mehrabi, Joseph N; Kelly, Kristen M; Holmes, Jon D; Zachary, Christopher B | Abstract: BACKGROUND ANDnOBJECTIVE: Long-term benefits can be predicted by the incorporation of more intelligent systems in lasers and other devices. Such systems can produce more reliable zones of thermal injury when used in association with non-invasive monitoring and precise laser energy delivery. The more classical endpoint of tumor destruction with radiofrequency or long-pulsed (LP) 1064 nm laser is the non-specific appearance of tissue graying and tissue contraction.nHerein we discuss combining non-invasive LP 1064 nm Nd:YAG treatment with the assistance of optical coherence tomography (OCT) and the forward-looking infrared (FLIR) thermal camera while testing literature-based formulaenfor thermal destruction.Study design/materials and methodsThe skin on the forearm and back of two consenting volunteers was marked and anesthetized with lidocaine with epinephrine. The parameters of a scanner-equipped LP 1064 nm Nd:YAG laser were adjusted to achieve an epidermal/superficial dermal heating of between 50°C and 60°C over a specified time course. Experimental single treatments examined various adjusted parameters including, fluence, pulse overlap, pulse duration, scan size, and pulse rate. A FLIR camera was used to record skin temperature. Outcome measures included skin temperature, post-treatment appearance, and OCT assessment of skin and vascular damage. The clinical response of each treatment was followed daily for 4 weeks.ResultsOptimal protocols initially raised the skin temperature to between 55°C and 60°C, which was carefully maintained using subsequent laser passes over a 60-second time course. Immediately post laser, clinical responses included erythema, edema, and blistering. Immediate OCT revealed increased vascularity with intact, dilated blood vessels. Prolonged exposure above 60°C resulted in sub-epidermal blistering and an absence of blood flow in the treatment area with prolonged healing.ConclusionThe LP 1064 nm laser can be used to achieve heat-related tissue injury, though the narrow parameters necessary for the desired endpoint require the assistance of IR thermal regulation to avoid unacceptable outcomes. The use of the laser scanner ensures precise energy delivery over a defined treatment area. Future studies might explore this as a selective hyperthermic method for the treatment of non-melanoma skin cancer. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Background and objectives Transdermal differentiation of human adipose stem cells (ASCs) to other cell types is still a challenge in regenerative medicine. Studies using primary ASCs are also limited as they may undergo replicative senescence during repeated passages in vitro. However, ASCs immortalized (iASCs) with human telomerase enzyme expressing plasmid exhibits a uniform population suitable for differentiation in vitro. A right combination of biological and physical stimuli may induce transdermal differentiation of iASCs into neurons in vitro. Study design/materials and methods iASCs were differentiated to free-floating neural stem cell aggregates (neurospheres) using a combination of growth inducers. Cells in these spheres were induced to differentiate into neurons using low-intensity lasers by a process called photobiomodulation (PBM). Results Laser at the near infrared (NIR) wavelength 825 nm and fluences 5, 10, and 15 J/cm2 was capable of increasing the differentiation of neurospheres to neurons. Precisely, there was a statistically significant increase in the early neuronal marker at 5 J/cm2 and a much appreciable increase at 15 J/cm2 in correlation with the biphasic dose response of PBM. However, these differentiated cells failed to express late neuronal markers in vitro. Comparison of these differentiating iASCs with the primary ASCs revealed a sharp distinction between the metabolic processes of the primary ASCs, neurospheres, and newly differentiated neurons. Conclusion We found that PBM increased the yield of neurons and effected stem cell differentiation through modulation of cellular metabolism and redox status. Our study also identifies that iASCs are an excellent model for analysis of stem cell biology and for performing transdermal differentiation. Significance This study demonstrates that a combination of biological and physical inducers can advance the differentiation of adipose stem cells to neurons. We were able to establish the optimal energy for the neuronal differentiation of iASCs in vitro. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

BACKGROUND AND OBJECTIVES Actinic keratoses (AK) are common pre-cancerous lesions, which are associated with ultraviolet light exposure and aging. Wounding therapies such as fractionated laser resurfacing (FLR) have been previously demonstrated to effectively treat facial AK. However, the effectiveness of FLR on other sites commonly afflicted with AK has not been studied in detail. Previously, our group has reported that treatment of aged skin with wounding therapies including dermabrasion and ablative fractionated resurfacing results in the removal of senescent fibroblasts and normalizing the pro-carcinogenic acute ultraviolet B radiation responses associated with aged skin. The current studies were designed to test the effectiveness of FLR of the forearm skin of subjects aged 60 and older to remove AKs. STUDY DESIGN/MATERIALS AND METHODS Between February 2018 and March 2019, 30 subjects were enrolled in a study, in which they underwent a single FLR treatment of one extremity including the dorsal forearm, wrist, and dorsal hand. The number of AKs was recorded on both extremities at baseline, 3 and 6 months in a blinded fashion. Side effects of the FLR were documented. RESULTS A single FLR treatment resulted in a 62% reduction in the absolute number of AK in the treated arm at 6 months post-treatment. The laser treatment was well-tolerated without major complications. CONCLUSIONS These studies demonstrate that FLR using settings, which have demonstrated to remove senescent fibroblasts and normalize the pro-carcinogenic UVB-response of aged skin is a potentially effective and safe field therapy treatment that should be studied for long-term efficacy for use in treating upper extremity AKs. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Background and objectives Treatment of photoaging and intrinsic aging of the chest, with the associated concerns of skin roughness, uneven pigmentation, laxity, atrophy, and telangiectasias, can be problematic because of the potential for worsened esthetic outcomes with existing treatments. This study assessed the efficacy and safety of using nonablative fractional laser therapy (FLT) pretreatment with photodynamic therapy (PDT) versus PDT alone for chest rejuvenation. Study design/materials and methods In a randomized, evaluator-blinded, split-sided study, adult female patients with photodamage to the chest received three treatment courses over an 8-week period with follow-up visits at Weeks 12 and 20. FLT was applied to one side of the chest, randomly assigned at baseline, followed by aminolevulinic acid-based PDT, delivered using a thermal, short incubation, broad area technique, to both sides of the chest. In-person and photographic assessments were conducted using five-point scales to evaluate outcomes including rhytides, pigmentation, skin texture, and telangiectasias. Results Eleven adults completed the study, of whom 11 had improved scores for rhytides and 10 had improved scores for skin texture at Week 20. There was no significant difference in any efficacy outcome between FLT and PDT and standard PDT alone. The severity of adverse events was rated significantly greater with the combined FLT-PDT treatment vs PDT alone. Conclusions Significant improvements were observed vs baseline for both sides of the chest treated with FLT-PDT or standard PDT following three treatment sessions. No significant difference in efficacy was observed between treatment approaches, although adverse events were more severe on the FLT-pretreated side. This study was not registered as it qualified as a nonsignificant risk study. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Background and objectives Laser hair removal is the most common laser therapy and the third most commonly performed procedure with more than one million treatments in United States in 2016. This retrospective study was conducted to assess long-term efficacy and safety of the 755 nm laser for hair removal. Study design/materials and methods Nearly, 3,606 laser treatments were performed with the long-pulsed 755 nm wavelength laser equipped with an epidermal cooling device between 1997 and 2005 and were followed till 2013. Standardized assessments were conducted by two treating physicians and patients at two follow-up intervals. At first follow-up, clearance was assessed by two physicians and clearance and satisfaction by patients. At the second follow-up, patients were assessed if hair clearance sustained compared with the first follow-up. Results Nine hundred and forty-eight patients with Fitzpatrick skin types I-IV were treated with a total of 3,606 laser treatments in this study. The mean age at the beginning of the study was 35 years (±11), 95.1% of patients were female (n = 902) and 4.9% male (n = 46). Five hundred and seventy-four patients received a minimum of three treatments and an average of 5.31 (3-16) treatments on axilla, back, bikini, breast, abdomen, face, lower extremity, or upper extremity region. First, follow-up was conducted 3.9 (±1.5) years after the final laser treatment. Seventy-four percent of these patients received 75-100% clearance as reported by the physician and 48% clearance as reported by the patient. Fifty-two percent of patients reported slower hair growth and 42% change in hair texture. Ninety percent of patients treated on axilla, 82% treated on the bikini area, and 79% treated on lower extremities experienced 75% or more clearance after three treatments. Facial, as well as breast and abdomen treatments, only showed a 66% and 62%, respectively, after three treatments. For these locations, five and more treatments were needed to achieve a quote of 79% (face) or 80% (breast and abdomen) for a 75-100% clearance. Upper extremity and back treatments did not have enough physician ratings to draw conclusions. Long-term adverse events were minimal and were all located on the face (one patient scar, four patients herpes infection). Second follow-up of 173 patients was conducted after 11.5 years (±2.0) and 87.9% of patients reported that their improvement sustained. Conclusions The long-pulsed 755 nm alexandrite laser is a safe and efficacious treatment for the reduction of unwanted body hair with permanent results and high patient satisfaction. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Background and Objectives The ability to provide improved tattoo fading using multiple laser passes in a single office laser tattoo removal session is limited. In part, this is due to the loss of laser effectiveness caused by epidermal and dermal vacuole “whitening” generated during the initial laser pass at the tattoo site. The Rapid Acoustic Pulse (RAP) device generates acoustic shock wave pulses that clear epidermal and dermal vacuoles to enable multiple laser passes in a single office laser tattoo removal session. The objectives of this study were to determine if the RAP device, when used as an accessory to the 1064 nm Nd:YAG Q‐switched (QS) laser can enable delivery of multiple laser passes in a single office laser tattoo removal session, and therefore result in increased tattoo fading compared to the clinical standard single‐pass QS laser tattoo removal session. Study Design/Materials and Methods The RAP device was evaluated in a single‐center (SkinCare Physicians), prospective, IRB approved study. A total of 32 black ink tattoos, from 21 participants, were divided into three zones and treated with either multiple QS laser passes, each followed by 1 minute of RAP device application (Laser + RAP) in zone one and single‐pass QS laser treatment (Laser‐Only) in zone two, separated by an untreated control zone. The treatment sites were assessed for the number of laser passes and adverse events immediately, 6 weeks, and 12 weeks following the treatment session. Photographs of the treatment sites were assessed for percent fading at 12 weeks post‐treatment by three blinded reviewers. Results When the RAP device was applied as an accessory to the QS laser in a multi‐pass laser tattoo removal treatment, an average of 4.2 laser passes were delivered in a single session, with no unexpected or serious RAP device‐related adverse events. At the 12‐week follow‐up, tattoos treated with Laser + RAP showed a statistically significant increase in average fading (44.2%) compared with tattoos treated with Laser‐Only (24.8%) (P 50% fading compared with tattoos treated with QS Laser‐Only (9.4%) (P 75% fading from Laser + RAP treatment (21.9%) compared with Laser‐Only treatment (3.1%) (P

OBJECTIVES To evaluate the efficacy of nonablative fractional 1,540 nm laser to treat the atrophic scars caused by the cutaneous leishmaniasis (CL). METHODS This clinical trial with a pre- and a posttreatment measurement was conducted on patients with atrophic CL scars. The lesions were treated with nonablative fractional 1,540 nm laser. We evaluated the patients initially and then monthly, before each treatment session. The final follow-up was done 6 months after the end of study for all patients. Patient assessment was performed by two physicians using the modified Manchester Scar Scale (MSS) as well as the interpretation of captured digital photographs. Moreover, the patients performed a self-assessment by filling in a researcher-made questionnaire. The data were statistically analyzed by SPSS software. P

Background and objectives Hospital-acquired infections (HAIs) and multidrug resistant bacteria pose a significant threat to the U.S. healthcare system. With a dearth of new antibiotic approvals, novel antimicrobial strategies are required to help solve this problem. Violet-blue visible light (400-470 nm) has been shown to elicit strong antimicrobial effects toward many pathogens, including representatives of the ESKAPE bacterial pathogens, which have a high propensity to cause HAIs. However, phototherapeutic solutions to prevention or treating infections are currently limited by efficient and nonobtrusive light-delivery mechanisms. Study design/materials and methods Here, we investigate the in vitro antimicrobial properties of flexible Corning® light-diffusing fiber (LDF) toward members of the ESKAPE pathogens in a variety of growth states and in the context of biological materials. Bacteria were grown on agar surfaces, in liquid culture and on abiotic surfaces. We also explored the effects of 405 nm light within the presence of lung surfactant, human serum, and on eukaryotic cells. Pathogens tested include Enterococcus spp, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Staphylococcus epidermidis, Streptococcus pyogenes, Candida albicans, and Escherichia coli. Results Overall, the LDF delivery of 405 nm violet-blue light exerted a significant degree of microbicidal activity against a wide range of pathogens under diverse experimental conditions. Conclusions The results exemplify the fiber's promise as a non-traditional approach for the prevention and/or therapeutic intervention of HAIs. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Background and objectives Fibrosis is a highly prevalent disease, which is responsible for 45% of deaths through pathological effects in developed countries. Previous studies have reported that low-level laser therapy (LLLT) can modulate fibrotic activity, but significant enhancement of therapeutic efficacy is still required for clinical translation. The aim of this study is to evaluate the feasible effect of LLLT combined with phloroglucinol (PHL) on the inhibition of fibrosis in vitro. Study design/materials and methods NIH/3T3 murine embryonic fibroblasts cells were cultured and transforming growth factor-β1 (TGF-β1) was treated for transition of fibroblasts. After TGF-β1 treatment, LLLT and PHL were used, respectively, and in combination to suppress fibrosis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and BrdU assays were performed to estimate the cell viability and proliferation. To evaluate the expression of fibrotic markers, we used confocal immunofluorescence and western blot. Results When compared with respectively treated groups, the group with the combined treatment of LLLT and PHL significantly reduced cell viability and proliferation. Immunofluorescence staining showed that the combined group minimized more α-smooth muscle actin (α-SMA) and type I collagen than the other groups. Western blot analysis showed that the combined treatment had significant decreases in α-SMA, TGF-β1, and type I collagen. Conclusions PHL-assisted LLLT may be an effective treatment to inhibit fibrosis due to its additive effects. The combined treatment has a potential to be an alternative treatment for fibrosis. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Background and objective Recent advances in low-level light devices have opened new treatment options for mild to moderate acne patients. Light therapies have been used to treat a variety of skin conditions over the years but were typically only available as treatments provided by professional clinicians. Clinical application of blue light has proven to be effective for a broader spectral range and at lower fluences than previously utilized. Herein, we tested the hypothesis that sub-milliwatt/cm2 levels of long-wave blue light (449 nm) effectively kills Propionibacterium acnes, a causative agent of acne vulgaris, in vitro. Materials and methods Two types of LED light boards were designed to facilitate in vitro blue light irradiation to either six-well plates containing fluid culture or a petri plate containing solid medium. P. acnes. Survival was determined by counting colony forming units (CFU) following irradiation. P. acnes was exposed in the presence and absence of oxygen. Coproporphyrin III (CPIII) photoexcitation was spectrophotometrically evaluated at 415 and 440 nm to compare the relative photochemical activities of these wavelengths. Results 422 and 449 nm blue light killed P. acnes in planktonic culture. Irradiation with 449 nm light also effectively killed P. acnes on a solid agar surface. Variation of time or intensity of light exposure resulted in a fluence-dependent improvement of antimicrobial activity. The presence of oxygen was necessary for killing of P. acnes with 449 nm light. CPIII displayed clear photoexcitation at both 415 and 440 nm, indicating that both wavelengths are capable of initiating CPIII photoexcitation at low incident light intensities (50 uW/cm2 ). Conclusion Herein we demonstrate that sub-milliwatt/cm2 levels of long-wave blue light (449 nm) effectively kill P. acnes. The methods and results presented allow for deeper exploration and design of light therapy treatments. Results from these studies are expanding our understanding of the mode of action and functionality of blue light, allowing for improved options for acne patients. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Objectives Photoepilation is a commonly used technology in home-use devices (HUDs) and in professional systems to remove unwanted body hair using pulses of laser or intense pulsed light (IPL). Albeit HUDs and professional systems operate at different fluences and treatment regimes, both demonstrate high hair reduction. The underlying mechanisms, however, remain unknown partly due to high divergence of the existing literature data. The objective of this study was to develop an ex vivo photoepilation model with a set of criteria evaluating response to light pulses; and to investigate dose-response behavior of hair follicles (HFs) subjected to a range of fluences. Methods After ex vivo treatment (single pulse, 810 nm, 1.7-26.4 J/cm2 , 4-64 ms pulse) human anagen HFs were isolated and maintained in culture for 7-10 days. Response to light was evaluated based on gross-morphology and histological examination (H&E and TUNEL stainings). Results HFs treated ex vivo demonstrated a dose-dependent response to light with five distinct classes defined by macroscopic and microscopic criteria. Fluences below 13.2 J/cm2 provoked catagen-like transition, higher fluences resulted in coagulation in HF compartments. Conclusion Observed changes in the HF organ culture model were reflected by clinical efficacy. The developed photoepilation model provides an easy and fast method to predict clinical efficacy and permanency of light-based hair removal devices. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

BACKGROUND Currently, low-level laser therapy (LLLT) has been approved as a new treatment for androgenetic alopecia (AGA). However, it has not been elucidated how LLLT promotes hair growth in vivo. OBJECTIVES To investigate the change in protein expression from dermal papilla (DP) tissues in male AGA patients after LLLT treatment using liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. METHODS This is an open-label, prospective, single-arm study obtained punch scalp biopsy specimens from patients with AGA before and after LLLT treatment. Each subject was self-treated with helmet type of LLLT (655 nm, 5 mW) device at home for 25 minutes per treatment every other day for 24 weeks. LC-MS/MS analysis based on the dimethyl labeling strategy for protein quantification was used to identify proteins expressed in DP tissues from AGA patients. RESULTS Proteomic analysis revealed 11 statistically significant up-regulated and 2 down-regulated proteins in LLLT treated DP compared with baseline (P

Background and objectives Low-level light therapies using visible to infrared light are known to activate several cellular functions, such as adenosine triphosphate and nitric oxide synthesis. However, few clinical observations report its biological consequences for skin and scalp homeostasis. Since scalp inflammation was recognized as a potential physiological obstacle to the efficacy of the reference hair regrowth drug Minoxidil in vivo and since perifollicular inflammation is the hallmark of about 50%-70% follicular units in androgenetic alopecia, we decided to investigate whether the anti-inflammatory activity of LLLT/GentleWaves® device were assigned to L'Oreal by Light BioScience L.L.C., Virginia Beach, VA (US) could enhance hair regrowth activity of Minoxidil. Study design/materials and methods We conducted a first experimental clinical study on 64 men with androgenetic alopecia using LLLT/GentleWaves®, 590-nm predominant wavelength 70 seconds, specifically pulsed once per day, for 3 days, and we performed a whole-genome analysis of treated scalp biopsies. In a second clinical study, including 135 alopecic volunteers, we evaluated the hair regrowth activity in response to the upgraded LLLT/GentleWaves® device and Minoxidil. Results In the first clinical study, whole-genome analysis of treated scalp biopsies showed downregulation of scalp inflammatory biomarkers, such as AP1/FOSB messenger RNA (mRNA) and mir21, together with the disappearance of CD69 mRNA, specific to scalp-infiltrating T cells of about 50% of the studied volunteers prior to the LLLT/GentleWaves® treatment. In the second clinical study, we observed that LLLT/GentleWaves® was able to boost the hair regrowth activity of a Minoxidil 2% lotion to the extent of the highest concentration (5%) in terms of efficacy, number of responders, and perceived performance. Conclusions Altogether, these observations suggest the potential benefit of LLLT/GentleWaves® as a noninvasive adjunctive technology for skin and scalp conditions, where a mild perifollicular inflammation is involved. Lasers Surg. Med. 2021. Copyright © 2021 Wiley Periodicals LLC.

Background and Objective: Striae distensae (SD) are cutaneous lesions that often occur on the breasts, abdomen, hips, and thighs. The aim of this study is to evaluate the effectiveness of a new technique using a non-invasive Er:YAG laser combined with Spatially Modulated Ablation (SMA) module for the treatment of SD. Study Design/Materials and Methods: This prospective pilot clinical study included 20 patients with skin phototypes I to IV who are affected by SD. The Er:YAG 2940 nm laser with SMA module was used in scanning mode with fluences of 2.3 J/cm 2 , frequency of 3 Hz, and pulse duration of 0.3 milliseconds. The laser beam is split into several microspots and penetrates only by 50 μm in the epidermis thickness. This technology induces also the generation of acoustic waves to stimulate tissue regeneration. Each patient underwent six laser sessions. An objective and subjective assessment of SD were used. All adverse events were reported. Results: Most patients reported good improvement and expressed their satisfaction with the treatment. Cutometric analysis showed significant improvement in skin elasticity at the end of study. Moreover, ultrasound analysis revealed an increase in dermal thickness (P < 0.01). POSAS scores decreased significantly at 3 and 6 months, reflecting improved skin quality. The average recovery time was 5 days, with no adverse effects reported. Conclusion: Using Er:YAG laser (2,940 nm) with SMA technology to treat SD resulted in improved volume and textural appearance without side effects. The elasticity and thickness of the dermis also improved. The Er:YAG laser with SMA module may be considered as a novel and effective technique to treat SD lesions with minimal time recovery. Lasers Surg. Med. 51:230–238, 2019. © 2018 Wiley Periodicals, Inc.

Background and objective Visible light has beneficial effects on cutaneous wound healing, but the role of potential photoreceptors in human skin is unknown. In addition, inconsistency in the parameters of blue and red light-based therapies for skin conditions makes interpretation difficult. Red light can activate cytochrome c oxidase and has been proposed as a wound healing therapy. UV-blue light can activate Opsin 1-SW, Opsin 2, Opsin 3, Opsin 4, and Opsin 5 receptors, triggering biological responses, but their role in human skin physiology is unclear. Materials and methods Localization of Opsins was analyzed in situ in human skin derived from face and abdomen by immunohistochemistry. An ex vivo human skin wound healing model was established and expression of Opsins confirmed by immunohistochemistry. The rate of wound closure was quantitated after irradiation with blue and red light and mRNA was extracted from the regenerating epithelial tongue by laser micro-dissection to detect changes in Opsin 3 (OPN3) expression. Retention of the expression of Opsins in primary cultures of human epidermal keratinocytes and dermal fibroblasts was confirmed by qRT-PCR and immunocytochemistry. Modulation of metabolic activity by visible light was studied. Furthermore, migration in a scratch-wound assay, DNA synthesis and differentiation of epidermal keratinocytes was established following irradiation with blue light. A role for OPN3 in keratinocytes was investigated by gene silencing. Results Opsin receptors (OPN1-SW, 3 and 5) were similarly localized in the epidermis of human facial and abdominal skin in situ. Corresponding expression was confirmed in the regenerating epithelial tongue of ex vivo wounds after 2 days in culture, and irradiation with blue light stimulated wound closure, with a corresponding increase in OPN3 expression. Expression of Opsins was retained in primary cultures of epidermal keratinocytes and dermal fibroblasts. Both blue and red light stimulated the metabolic activity of cultured keratinocytes. Low levels of blue light reduced DNA synthesis and stimulated differentiation of keratinocytes. While low levels of blue light did not alter keratinocyte migration in a scratch wound assay, higher levels inhibited migration. Gene silencing of OPN3 in keratinocytes was effective (87% reduction). The rate of DNA synthesis in OPN3 knockdown keratinocytes did not change following irradiation with blue light, however, the level of differentiation was decreased. Conclusions Opsins are expressed in the epidermis and dermis of human skin and in the newly regenerating epidermis following wounding. An increase in OPN3 expression in the epithelial tongue may be a potential mechanism for the stimulation of wound closure by blue light. Since keratinocytes and fibroblasts retain their expression of Opsins in culture, they provide a good model to investigate the mechanism of blue light in wound healing responses. Knockdown of OPN3 led to a reduction in early differentiation of keratinocytes following irradiation with blue light, suggesting OPN3 is required for restoration of the barrier function. Understanding the function and relationship of different photoreceptors and their response to specific light parameters will lead to the development of reliable light-based therapies for cutaneous wound healing. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Background and Objectives Fractional treatment with a dual wavelength 1,064 and 532 nm picosecond‐domain laser, delivering a 10 × 10 array of highly focused beamlets via a holographic optic, was investigated for the treatment of acne scars. Study Twenty‐seven of 31 subjects completed the study, 19 were treated using 1,064 nm and 8 were treated at 532 nm, all having four‐monthly treatments. Blinded evaluation of digital images by three physician evaluators comparing pre‐ and 3‐month post‐treatment images measured efficacy using a 10‐point scale. Subject self‐assessment of treatment effects were also recorded. Safety was measured by recording subject discomfort scores and adverse effects. Results Blinded reviewers correctly identified the baseline image in 61 of the 81 image sets (75%), and baseline acne scar scores were 1.8 ± 0.7 and 1.8 ± 0.5 for the 1,064 and 532 nm cohorts, and decreased to 1.1 ± 0.5 (P

BACKGROUND AND OBJECTIVES Post inflammatory hyperpigmentation (PIH) can be difficult to treat especially in patients with darker skin types as darker skin carries increased epidermal melanin content. Various treatments available to improve the appearance of PIH may incite further pigmentation thus making treatment extremely difficult and frustrating. The purpose of this study was to perform a retrospective chart and photographic review to evaluate the efficacy and safety profile of a low energy low density non-ablative fractional1927 nm wavelength laser treatment for PIH in patients with Fitzpatrick skin types IV-VI. STUDY DESIGN A retrospective evaluation of 61 patients with PIH treated with a 1927 nm laser was conducted at a single center. Inclusion criteria required at least 2 treatment sessions so that before and after treatment photographs would be available for comparison and study purposes. Two blinded physician-evaluators using a visual analog scale for percentage of pigmentary clearance in standard photographs assessed treatment efficacy. RESULTS The mean percent improvement after treatment, evaluated by two dermatologists was 43.24%. The correlation between raters was statistically significant (Pearson's correlation coefficienct of r = 0.59, p

Background and objectives Erythema is one of the most common cosmetic concerns and usually responds well to pulsed dye laser (PDL) treatment. As this laser can cause significant discomfort, topical anesthesia is sometimes offered. However, it is still uncertain whether topical anesthetics can affect the outcome of the laser therapy. We performed a retrospective single site study to compare the efficacy of PDL for the treatment of erythema in patients with and without pretreatment with topical anesthetic. Study design/materials and methods A chart review was performed and patients who presented with erythema of face, neck, chest, and extremities pretreated with topical anesthesia (23% lidocaine/7% tetracaine ointment or 7% lidocaine/7% tetracaine ointment) undergoing PDL were reviewed and compared with another group without anesthesia. Two blinded dermatologists evaluated the postlaser procedure photographs and gave an assessment compared with baseline. Results A total of 69 patient charts were reviewed. The erythema resulted from various skin conditions including telangiectasia, cherry angioma, striae, and rosacea. The mean improvement was 2.2581 in the anesthesia group and 2.2632 in the nonanesthesia group. There was no significant difference between both groups as confirmed by a noninferiority test. Conclusions Topical anesthesia with lidocaine and tetracaine ointment do not interfere with the efficacy of the PDL. Since pain management is essential for any cosmetic procedure, the application of a local anesthetic will enhance patient comfort and satisfaction during treatment with PDL. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Background and objectives To evaluate the antiallergic effect of low-level laser irradiation (LLLI) at 650 nm in a mouse model of allergic rhinitis (AR), and to examine the underlying mechanisms. Study design/materials and methods BALB/c mice were sensitized with ovalbumin (OVA) and alum and challenged intranasally with OVA. Straight- and diffusion-type LLLI were applied directly into the intranasal cavity of the mice once daily for 10 days (650 nm, 5 mW, 15 min/day) and multiple allergic parameters were evaluated. Results LLLI reduced allergic symptoms, such as rubbing and sneezing, and suppressed the serum total immunoglobulin E (IgE), OVA-specific IgE, and OVA-specific IgG1 levels. Diffusion-type LLLI significantly reduced eosinophil infiltration of nasal mucosa and lymph nodes (LNs). LLLI reduced the expression of interleukin-4 (IL-4) and IL-17 in cervical LN and splenocyte culture supernatant, as well as their messenger RNA levels in nasal mucosa. However, the expression of interferonγ (IFN-γ) and IL-6 was unaffected by LLLI. The levels of reactive oxygen species (ROS) and nitric oxide (NO) in LN cells and the nasal mucosa, which were increased in the AR group, were reduced by LLLI, suggesting involvement of ROS and NO within their mechanism. Conclusions LLLI exerted an antiallergic effect by decreasing local and systemic IL-4, IL-17, and IgE levels, as well as eosinophilic infiltration into the nasal mucosa, in a mouse model of AR by modulating ROS and NO levels. Diffusion-type LLLI exhibited greater efficacy against AR than straight-type LLLI. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Background and objectives This study was aimed at determining the effects of blue light photobiomodulation on primary adult mouse dermal fibroblasts (AMDFs) and the associated signaling pathways. Study design/materials and methods Cultured AMDFs from adult C57BL/6 mice were irradiated by blue light from a light-emitting diode (wavelength = 463 ± 50 nm; irradiance = 5 mW/cm2 ; energy density = 4-8 J/cm2 ). The cells were analyzed using mass spectrometry for proteomics/phosphoproteomics, AlamarBlue assay for mitochondrial activity, time-lapse video for cell migration, quantitative polymerase chain reaction for gene expression, and immunofluorescence for protein expression. Results Proteomic/phosphoproteomic analysis showed inhibition of extracellular signal-regulated kinases/mammalian target of rapamycin and casein kinase 2 pathways, cell motility-related networks, and multiple metabolic processes, including carbon metabolism, biosynthesis of amino acid, glycolysis/gluconeogenesis, and the pentose phosphate pathway. Functional analysis demonstrated inhibition of mitochondrial activities, cell migration, and mitosis. Expression of growth promoting insulin-like growth factor 1 and fibrosis-related genes, including transforming growth factor β1 (TGFβ1) and collagen type 1 ɑ2 chain diminished. Protein expression of α-smooth muscle actin, an important regulator of myofibroblast functions, was also suppressed. Conclusions Low-level blue light exerted suppressive effects on AMDFs, including suppression of mitochondrial activity, metabolism, cell motility, proliferation, TGFβ1 levels, and collagen I production. Low-level blue light can be a potential treatment for the prevention and reduction of tissue fibrosis, such as hypertrophic scar and keloids. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Scar rehabilitation is a complex process that incorporates medical, surgical, and physical therapeutic measures to best restore function and visual normalcy. Lasers have emerged as essential tools in the management of scars, with devices available to address scar size, dyschromia, and contour irregularities. As different lasers treat these different features, multi-laser, same session therapeutic approaches may offer a more comprehensive approach to scar revision. In this study, we aim to demonstrate the effect of a combinatorial, same session treatment with intense pulsed light (IPL) and fractional ablative COThis institutional review board-approved, randomized controlled trial, enrolled 23 healthy adults with large (100 cmAs compared to control and COTreatment with combined IPL and CO

Objectives: The effectiveness of transcranial photobiomodulation (TPBM) in treating anxiety and depression disorders is a demonstrated and identified issue. However, the optimum therapeutic dose and the underlying mechanism of action are not fully understood. In this study, the therapeutic effects of three different near-infrared (NIR) doses on anxiety- and depression-like behaviors as well as cerebral levels of serotonin (5-HT) and nitric oxide (NO) were evaluated in a mouse model of chronic restraint stress (CRS). Materials and Methods: CRS procedure (3 hours/day, over 3 weeks) was performed as a typical stress model to study anxiety and depression along with laser treatment (3 times/week, over 3 weeks), which began simultaneously with CRS. A NIR diode laser (810nm wavelength, 10 Hz) with the output power of 200mW and power density of 4.75 W/cm2 was implemented to deliver three different doses of 4, 8, and 16 J/cm2 to the cerebral cortex of mice. Behavioral experiments including open field, tail suspension, and elevated plus maze tests as well as serum cortisol levels were assessed to evaluate the anti-anxiety and antidepressive effects of NIR TPBM. The changes of 5-HT and NO levels in the prefrontal cortex (PFC) and hippocampus (Hipp) were assessed. Results: CRS procedure induced anxiety- and depressionlike behaviors, increased serum cortisol levels, decreased 5-HT and increased NO levels in the PFC and Hipp areas. NIR TPBM improved behavioral results, decreased serum cortisol levels, increased 5-HT and decreased NO concentrations in the PFC and Hipp. A dose of 8 J/cm2 of NIR TPBM showed the maximum effects on behavioral and molecular results, while a decline was observed from the optimum effects at both lower (4 J/cm2) and higher (16 J/ cm2) doses. Conclusion: Our results demonstrated that NIR TPBM had an anti-anxiety and anti-depressive effect in CRS mice, which is probably linked to increasing 5-HT and decreasing NO levels in the PFC and Hipp areas. Also, the maximum anti-anxiety and anti-depressive effect was produced at dose of 8 J/cm2. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.