Impact of Thermo-Responsive N-Acetylcysteine Hydrogel on Dermal Wound Healing and Oral Ulcer Regeneration.

This study investigates the efficacy of a thermo-responsive N-acetylcysteine (NAC) hydrogel on wound healing and oral ulcer recovery. Formulated by combining NAC with methylcellulose, the hydrogel's properties were assessed for temperature-induced gelation and cell viability using human fibroblast cells. In vivo experiments on Sprague Dawley rats compared the hydrogel's effects against saline, NAC solution, and a commercial NAC product. Results show that a 5% NAC and 1% methylcellulose solution exhibited optimal outcomes. While modest improvements in wound healing were observed, significant enhancements were noted in oral ulcer recovery, with histological analyses indicating fully regenerated mucosal tissue. The study concludes that modifying viscosity enhances NAC retention, facilitating tissue regeneration. These findings support previous research on the beneficial effects of antioxidant application on damaged tissues, suggesting the potential of NAC hydrogels in improving wound care and oral ulcer treatment.

Oral ulcer treatment using human tonsil-derived mesenchymal stem cells encapsulated in trimethyl chitosan hydrogel: an animal model study.

BACKGROUND: Oral ulcers are a common side effect of chemotherapy and affect patients' quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness. METHODS: Animals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect. RESULTS: The ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups. CONCLUSION: This study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications.

Photobiomodulation Recovers the Submandibular Gland in Vismodegib-Treated Rats.

Objective: The submandibular gland (SMG) produces the most saliva, and factors such as aging and chemotherapy can affect its structure and function. However, there are only temporary treatments available for salivary hypofunction. This study aimed to evaluate the effects of photobiomodulation (PBM) on the function of SMG by using a rat animal model and vismodegib, an antagonist of the sonic hedgehog (SHH) pathway. Methods: Vismodegib (10 mg/kg) drug was gavaged orally for 14 days in rats to significantly decrease the SHH signaling proteins [SHH, protein patched homolog 1 (PTCH1), smoothened protein (SMO), glioma-associated oncogene homolog 1 (GLI1)], induce damage in SMG tissue, and affect salivary functional markers AQP5 and Keratin5. After that, in conjunction with vismodegib administration, PBM was performed using an 850 nm high-power light-emitting diode (LED) device treated daily for 6 days at varying total energy densities of 60, 120, and 180 J/cm2 in at least 3 rats per group. The test results were confirmed by Western blot, immunofluorescence staining, and hematoxylin and eosin staining, and the statistics were t-test or one-way analysis of variance (ANOVA) with Tukey's multiple comparisons tests. Results: Significant decreases in the expression of SHH-related proteins (PTCH1, SMO, GLI1, p < 0.05) with damage of SMG ductal cells were observed with vismodegib administration. However, a significant increase in the expression levels of SHH-related proteins (SHH, SMO, GLI1, p < 0.05) and recovery of SMG ductal cells damaged after vismodegib administration were observed for PBM-treated groups. Salivary functional marker AQP5 also showed the same increase or decrease. Conclusions: This study found that vismodegib damages SMG ductal cells and decreases SHH-related proteins and associated salivary functional markers. Also, 850 nm high-power LED recovered the damaged structure of SMG and increased SHH-related proteins and salivary functional markers. The study results suggest that PBM can restore SMG structure and function through SHH signaling.

Analysis of lithotripsy efficiency and stone retropulsion displacement according to pulse characteristics of Ho: YAG laser with Moses effect.

BACKGROUND AND OBJECTIVES: Compared to the conventional Ho: YAG laser, a Ho: YAG laser device has been reported that has a Moses effect to reduce stone retropulsion and increase lithotripsy efficiency. The principle of this equipment is to convert a single laser pulse into two pulses. Most studies on such lasers are limited to lithotripsy efficiency and the prevention of stone retropulsion; studies according to each pulse condition have not been performed. Therefore, the purpose of this study was to quantify the bubble shape, lithotripsy efficiency, and stone retropulsion displacement in a ureteral phantom according to the modulation of the first pulse characteristics of the Moses effect laser under conditions that maintained the total energy and repetition rate. MATERIAL AND METHODS: In this study, a Ho: YAG laser system (Holinwon Pro, Wontech Inc., Korea) with an emission wavelength of 2.10 µm and a Moses effect was used. To verify the Moses effect based on the changes in the pulse, a water tank was fabricated, and the ureteral phantom was manufactured in a structure that could be easily installed in the water tank. Additionally, a spherical artificial stone in the ureteral phantom was prepared by mixing calcined gypsum (Cacinated Gypsum) and water at a ratio of 3:1. In the ureteral phantom, a high-speed camera (FASTCAM NOVA S12, Photron Inc.) and visible light were used to record pulse-dependent image analysis of bubbles and stone retropulsion. RESULT: After mounting the artificial stone in the ureteral phantom, the pulse duration and energy of the first pulse of the Moses effect laser were varied; 30 laser shots for 3 s at a repetition rate of 10 Hz were applied to quantify the lithotripsy efficiency and stone retropulsion displacement, and the experimental values were compared. The fragmentation efficiency was confirmed by measuring the mass before and after the laser pulse application, the original position of the stone retropulsion displacement, and the distance moved. The minimum value of stone retropulsion displacement appeared when the pulse duration of the first pulse was 300 µs, the pulse energy was 100 mJ, and the value was approximately 0.28 mm. The highest fragmentation efficiency was observed under the same conditions, and the mass loss of the artificial stone at that time was approximately 3.7 mg. CONCLUSION: Quantitative indices, such as lithotripsy efficiency and stone retropulsion displacement, were confirmed using ultrahigh-speed cameras to determine the effect of the first pulse energy and duration of the Ho: YAG laser with the Moses effect on stone removal. It was confirmed that the longer the duration of the primary pulse and the lower the energy, the higher the fragmentation efficiency. In this study, the possibility of manufacturing a laser with an optimal stone-removal effect was confirmed according to the first-pulse condition of the laser with the Moses effect.

Electrochemical lipolysis of subcutaneous adipose tissue in a porcine animal model.

OBJECTIVES: There is a considerable demand for noninvasive low-cost fat reduction methods with fewer side effects and shorter recovery times. This study aims to develop a fat-reduction method through electrochemical lipolysis of subcutaneous adipocytes using needle-based electrodes, body tissue fluids, and electrical current application. METHODS: Electrochemical lipolysis was performed by inserting a 4-pin needle electrode connected to a DC power supply into the pig's abdomen. Applied electrical current (0.5 and 1 mA) and treatment time (5 or 10 minutes) were varied systematically. Ultrasound imaging was performed before and after treatment to determine changes in fat thickness. Tissue samples were collected at 0, 2, and 4 weeks posttreatment for histological evaluation to determine the mechanism of action and the procedure's efficacy. RESULTS: Electrochemical subcutaneous adipose tissue lipolysis in a porcine model was achieved through hydrolysis of physiologic fluid within the vicinity of the inserted electrode where an electric current is applied, leading to localized disruption of fat cell membranes and necrosis. Electric current configuration 1.0 mA showed more pronounced lipolysis effects applied for 10 minutes, significantly decreasing adipocyte content per treatment area. The electrochemical treatment method also stimulates collagen synthesis, which helps reduce fat. CONCLUSIONS: Electrochemical lipolysis is a potential new noninvasive localized technique to reduce fat. The treatment method induces fat cell necrosis via in situ reduction-oxidation reaction by the electrochemical activation of physiologic fluid in the surrounding tissue. Electrochemical lipolysis is a simple, low-cost, fat-reducing treatment method without harmful side effects.

Analysis of penetration depth and healing process of a needleless laser lancet using swept-source optical coherence tomography.

BACKGROUND AND OBJECTIVES: Needleless laser lancets have been used to reduce needle pain in people who undertake self-monitoring of blood glucose (SMBG). Although clinical trials have been conducted to understand the degree of pain associated with the developed laser blood sampling device, it is only judged by the patients' subjective judgment. This study aimed to analyze the performance and healing process of a needleless laser lancet. In particular, the penetration depth and healing process of a conventional lancet and a needleless laser lancet were quantitatively analyzed using a swept-source optical coherence tomography (SS-OCT) system. MATERIALS AND METHODS: To reduce unnecessary animal sacrifice, pig skin was used to establish and set the conditions for needleless laser lancets (wavelength of 2.94 µm; LMT-5000; Lameditech), and the penetration depth and healing process were quantitatively assessed at 0, 6, 9, and 16 h after laser (energy, 150-270 mJ in stages; voltage, 7.4 Vdc ; pulse width, approximately 200 microsecond) irradiation using 7-week-old male BALB/c nude mice. The penetration depth and healing process were measured using homemade SS-OCT, and histopathological examination was performed to observe the healing process. RESULTS: Four 7-week-old male BALB/c nude mice were tested at intensity levels of 1-3 using a needleless laser lancet and compared with the experimental values using a conventional lancet. After the lancet test, the diameter and depth of the puncture were measured using SS-OCT and the healing process was confirmed using SS-OCT and pathological slides. The puncture diameter of the needleless laser lancet was about 0.5 mm regardless of the level. In addition, the average depths at Levels 1, 2, and 3 of the measured needleless laser lancet were approximately 1.05, 1.18, and 1.52 mm, respectively, and the last common lancet was approximately 0.9 mm. In addition, the healing process of the needleless laser lancet and conventional lancet was confirmed through the SS-OCT system. CONCLUSION: After using the needleless laser lancet, quantitative indicators such as the diameter of puncture, penetration depth, and healing process were confirmed through two-dimensional and three-dimensional images of the homemade SS-OCT system and microscopic imaging of pathological slides.

Photobiomodulation regulates adult neurogenesis in the hippocampus in a status epilepticus animal model.

Status epilepticus (SE) refers to a single seizure that lasts longer than typical seizures or a series of consecutive seizures. The hippocampus, which is vulnerable to the effects of SE, has a critical role in memory storage and retrieval. The trisynaptic loop in the hippocampus connects the substructures thereof, namely the dentate gyrus (DG), CA3, and CA1. In an animal model of SE, abnormal neurogenesis in the DG and aberrant neural network formation result in sequential neural degeneration in CA3 and CA1. Photobiomodulation (PBM) therapy, previously known as low-level laser (light) therapy (LLLT), is a novel therapy for the treatment of various neurological disorders including SE. However, the effects of this novel therapeutic approach on the recovery process are poorly understood. In the present study, we found that PBM transformed SE-induced abnormal neurogenesis to normal neurogenesis. We demonstrated that PBM plays a key role in normal hippocampal neurogenesis by enhancing the migration of maturing granular cells (early neuronal cells) to the GCL, and that normal neurogenesis induced by PBM prevents SE-induced hippocampal neuronal loss in CA1. Thus, PBM is a novel approach to prevent seizure-induced neuronal degeneration, for which light devices may be developed in the future.

Evaluation of the safety and efficacy of long pulsed Nd: YAG laser in the treatment of vascular lesions in vivo.

Long-pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers have recently been used for the treatment of vascular lesions refractory to conventional vascular lasers. The aim of this study was to evaluate the clinical efficacy and safety of long-pulsed Nd:YAG laser treatment for vascular disorders. Laser irradiation was performed using two approaches: the 532 nm Nd:YAG laser was used to irradiate the dorsal skin fold in mice and the 1064 nm Nd:YAG laser was used to irradiate the leg of mice without skin incision. The specimens were observed immediately after laser treatment using a laser Doppler perfusion imaging system. Red blood cell (RBC) extravasation and hemorrhage were observed using the hematoxylin and eosin stain. The diameter of blood vessel under 30 µm was disrupted with a laser pulse at a fluence of 12 J/cm2 and a wavelength of 532 nm regardless of pulse duration. The veins and arteries of approximately 1 mm in size were ablated with laser pulses at a fluence of 140 J/cm2 and above and a wavelength of 1064 nm. Selective photopyrolysis can be achieved with either 532- or 1064 nm Nd:YAG laser pulses in vascular diseases based on the depth and size of the vessel.

Trimethyl chitosan postoperative irrigation solution modulates inflammatory cytokines related to adhesion formation.

Lavage or irrigation has been instilled in surgical practice for wound clearance and surgical site infection prevention during and after surgery. Herein, we developed a new irrigation solution using trimethyl chitosan (TMC), a quaternized chitosan derivative. The TMC-saline irrigation solution developed in the study possesses highly effective bactericidal properties with hemostatic and anti-adhesion properties. The anti-adhesion property of TMC was investigated in relation to inflammatory cytokine response and wound healing. TMC-saline irrigation solution showed reduced pro-inflammatory cytokine protein and gene expressions relevant in the cascade of wound healing and cytokine-related orchestration of postoperative adhesion formation. Further development of this multifunctional TMC-saline irrigation solution can be beneficial for surgical applications and postoperative wound management.

Improved healing and macrophage polarization in oral ulcers treated with photobiomodulation (PBM).

OBJECTIVES: 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. MATERIALS AND METHODS: 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-ß/MMP-2) cytokine expression. RESULTS: 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. CONCLUSION: 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.

Role of Transient Receptor Potential Vanilloid 1 in Sonic Hedgehog-Dependent Taste Bud Differentiation.

Taste bud cell differentiation is extremely important for taste sensation. Immature taste bud cells cannot function during taste perception transmission to the nerve. In this study, we investigated whether hedgehog signaling affected taste bud cell differentiation and whether transient receptor potential vanilloid 1 (TRPV1) played a key role in dry mouth. The induction of dry mouth due to salivary gland resection (SGR) was confirmed on the basis of reduced salivation and disrupted fungiform papillae. The expression of keratin 8 (K8) of taste bud cells, neurofilament (NF), sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (Gli1) around taste bud cells was downregulated; however, the expression of TRPV1, P2X purinoceptor 3 (P2X3), and hematopoietic stem cell factor (c-Kit) was upregulated at the NF ends in the dry mouth group. To investigate the effect of TRPV1 defect on dry mouth, we induced dry mouth in the TRPV-/- group. The K8, NF, and P2X3 expression patterns were the same in the TRPV1 wild-type and TRPV1-/- dry mouth groups. However, Shh and c-Kit expression decreased regardless of dry mouth in the case of TRPV1 deficiency. These results indicated that TRPV1 positively regulated proliferation during taste bud cell injury by blocking the Shh/Gli1 pathway. In addition, not only cell proliferation but also differentiation of taste bud cells could not be regulated under TRPV1-deficiency conditions. Thus, TRPV1 positively regulates taste bud cell innervation and differentiation; this finding could be valuable in the clinical treatment of dry mouth-related taste dysfunction.

Effect of Photobiomodulation on Restoration of Ionization Radiation-Induced Thyroid Dysfunction Through p53 and Retinoblastoma Signaling.

Objective: This study aimed to investigate whether photobiomodulation (PBM) restores normal thyroid follicular cells affected by ionizing radiation, and to determine the mechanism of PBM on thyroid function. Background: Despite diverse applications of PBM to medical therapy, there has been no evidence of its involvement with thyroid function. Methods: A light emission diode (850 nm) array was used at 2, 5, and 10 J/cm2 for in vitro analysis in human thyroid N-Thy-3.1 cells, and at 120 J/cm2 for in vivo analysis in C58BL6 mice. Cell survival and proliferation were evaluated through clonogenic and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] assays. Cell cycle was measured using flow cytometry. Cell cycle markers, such as p53, retinoblastoma (Rb), and E2F1, were investigated by western blot analysis. In vitro levels of cyclic adenosine monophosphate (cAMP) and thyroglobulin (TG) and in vivo levels of cAMP, TG, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were measured using enzyme-linked immunosorbent assay. Results: A lethal dose for N-Thy-3.1 cells was 6 Gy. PBM at 2 J/cm2 was the most effective for causing cell cycle arrest by ionizing radiation. PBM regulated p53, Rb, and cAMP expression levels in vitro. PBM restored proliferation by regulating Rb and p53 in ionizing radiated thyroid follicular tissues. PBM also recovered cAMP, TG, and thyroid function marker expression (TSH, T3, and T4) by ionizing radiation in vivo. Conclusions: PBM restored ionizing radiation-induced thyroid follicular cell dysfunction by increasing cAMP proliferation and expression. PBM is effective for ionizing radiation-induced hypothyroidism by complementing cell proliferation and cAMP, presenting a novel method for clinical application.

Effects of N-acetylcysteine inhalation therapy on the quality of life of patients with head and neck cancer who are receiving radiation therapy: a prospective non-randomized controlled multi-center study.

BACKGROUNDS AND PURPOSE: Radiation therapy is an important mode of treatment for patients with head and neck cancers, but some associated complications can reduce the quality of life. We investigated whether N-acetylcysteine inhalation therapy improved the quality of life of such patients. MATERIALS AND METHODS: We designed a prospective, non-randomized controlled multi-center study involving 10 institutions. We enrolled 120 patients (80 in the experimental group and 40 in the control group). Patients in the experimental group inhaled nebulized liquid N-acetylcysteine (2400 mg daily) for 8 weeks from the start of radiation therapy. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N 35. RESULTS: N-acetylcysteine inhalation was not associated with any side effect or discomfort. The reduction in painkiller use from the end of N-acetylcysteine inhalation therapy to the 1-month follow-up was greater in the experimental group than in the control group (P = 0.014). Dry mouth symptoms also improved significantly in the experimental group (P = 0.019). CONCLUSION: N-acetylcysteine inhalation improves the quality of life of patients with head and neck cancers who are receiving radiation therapy, without any specific side effect.

Biochemical and Pain Comparisons Between the Laser Lancing Device and Needle Lancets for Capillary Blood Sampling: A Randomized Control Trial.

BACKGROUND AND OBJECTIVES: Patients around the world use a lancing device to perform self-monitoring of blood sugar (SMBG). However, there are always fears of needles and pain. Therefore, less painful devices are being developed. The purpose of this study was to compare the usefulness and safety of a laser lancing device (without a needle) to a conventional needle lancet (with a needle) for capillary blood sampling. STUDY DESIGN/MATERIALS AND METHODS: A total of 40 healthy subjects were enrolled in the study. Capillary blood was collected from a laser lancing device (without a needle) and a conventional needle lancet (with a needle) on opposite fingers, the choice of which was randomly selected. The laser lancing device (LMT-3000) uses a 2940 nm mono-pulse laser, a radiation field of 350 µm, laser energy of 210 mJ, and a 3.7 V battery. One week later, capillary blood was obtained by switching the devices and fingers. The biochemical measurements and pain were compared between the two groups. Puncture pain was measured on a pain scale from 0 to 10. RESULT: All patients were tested with both a laser lancing device and a conventional needle lancet. In the biochemical analysis, the blood glucose level was 103.21 ± 17.20 mg/dl in laser lancing device group and 102.25 ± 22.44 mg/dl in the conventional needle lancet group, and there were no significant differences between the two groups (P = 0.940). The pH, CO2 , O2 , lactate and hematocrit levels of the blood were no significant differences between the two groups. In the first trial, the median pain score (interquartile range) of patients using laser lancing device was 2.0 (1.0-3.0), whereas it was 2.5 (2.0-4.0) in patients using a conventional needle lancet (P = 0.029). In the second trial, one week later, the median pain score in the laser lancing device group was 2.5 (1.0-4.0), whereas it was 3.5 (2.25-5.0) in the conventional needle lancet group (P = 0.001). The difference in pain scores between the first and second trials was significant in the conventional needle lancet group (P = 0.007), but not in the laser lancing device group (P = 0.150). CONCLUSION: There was no difference in biochemical results between the laser lancing device group and the conventional needle lancet group. The laser lancing device demonstrated comparatively lower pain than the conventional needle lancet. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Survival Benefits From Surgery for Stage IVa Head and Neck Squamous Cell Carcinoma: A Multi-institutional Analysis of 1,033 Cases.

OBJECTIVES: Head and neck squamous cell carcinomas (HNSCs) are frequently diagnosed at the locoregional advanced stage (stage IVa), but controversy remains regarding whether stage IVa HSNCs should be treated with upfront surgery or definitive chemoradiation therapy (CRT). The purpose of this study was to compare overall survival (OS) and disease-free survival (DFS) in patients with stage IVa HNSC treated primarily by surgery with curative intent with/without (neo)adjuvant treatment (surgery group) versus those treated primarily with CRT (CRT group). METHODS: We reviewed data of 1,033 patients with stage IVa HNSC treated with curative intent at 17 cancer centers between 2010 and 2016. RESULTS: Among 1,033 patients, 765 (74.1%) received upfront surgery and 268 (25.9%) received CRT. The 5-year OS and DFS rates were 64.4% and 62.0% in the surgery group and 49.5% and 45.4% in the CRT group, respectively. In multivariate analyses, OS and DFS were better in the surgery group than in the CRT group (odds ratio [OR] for death, 0.762; 95% confidence interval [CI], 0.592-0.981; OR for recurrence, 0.628; 95% CI, 0.492-0.802). In subgroup analyses, the OS and DFS of patients with oropharyngeal cancer were better in the surgery group (OR for death, 0.548; 95% CI, 0.341-0.879; OR for recurrence, 0.598; 95% CI, 0.377-0.948). In the surgery group, patients with laryngeal cancer showed better OS (OR for death, 0.432; 95% CI, 0.211-0.882), while those with hypopharyngeal cancer DFS was improved (OR for recurrence, 0.506; 95% CI, 0.328-0.780). CONCLUSION: A survival benefit from surgery may be achieved even in patients with stage IVa HNSC, particularly those with oropharyngeal and laryngeal cancer. Surgery led to a reduction in the recurrence rate in patients with hypopharyngeal cancer.

Intraoperative use of optical coherence tomography to differentiate normal and diseased thyroid and parathyroid tissues from lymph node and fat.

The purpose of this study is twofold: (1) to determine the feasibility of optical coherence tomography (OCT) to differentiate normal and diseased tissue of the neck region intraoperatively and (2) to evaluate how accurately a cohort of test subjects can identify various tissue types when shown a sample set of OCT images. In this in vivo, prospective, single institutional study, an OCT imaging system (Niris, Imalux, Cleveland, OH) was used to image parathyroid, thyroid, lymph node, and fat tissue in 76 patients during neck surgery. Biopsies were performed for comparison of OCT images with histology in select cases (n = 20). Finally, a group of either surgeons or scientists familiar with OCT (n = 17) were shown a sample of OCT images and asked to identify the tissue. A total of 437 OCT images were analyzed, and characteristic features of each tissue type were identified. OCT demonstrated distinct differences in structural architecture and signal intensity that allows differentiation between thyroid and parathyroid tissues, lymph nodes, and fat. OCT images were also compared with histology with good correlation. There was no difference in correctly identifying OCT-imaged tissue type between surgeons and scientists. This study is the first in vivo OCT imaging study to evaluate both normal and diseased tissues that may be encountered during neck surgery. OCT has the potential to become a valuable intraoperative tool to differentiate diseased and normal thyroid tissue intraoperatively to obtain an "optical biopsy" in real time without fixation, staining, or tissue resection.

Effects of Wnt signaling on epithelial to mesenchymal transition in chronic rhinosinusitis with nasal polyp.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP). Wnt signaling is causative for EMT, whereas the mechanism in CRSwNP is not fully understood. OBJECTIVE: We sought to evaluate the role of Wnt signaling in EMT of CRSwNP using a murine nasal polyp (NP) model and human tissues. METHODS: Inflammatory markers and EMT-related molecules were evaluated in NP models using adenomatosis polyposis coli (Apc)Min/+ mice with activated Wnt signaling and NP models treated with Wnt signaling inhibitor, indocyanine green-001 (ICG-001). EMT markers and Wnt signaling-associated mediators were analysed using human sinonasal tissues from control subjects and CRSwNP patients. RESULTS: ApcMin/+ mice-induced NPs exhibited more frequent polypoid lesions and upregulation of Wnt-related molecules, including nuclear ß-catenin, WNT3A and cyclin D1. Markers of EMT were significantly overexpressed in the ApcMin/+ NP mice (p<0.001 for E-cadherin and α-smooth muscle actin), and interleukin (IL)-17A+ cells and neutrophilic infiltration were increased in ApcMin/+ NP mice (p<0.001). Inhibition of Wnt signaling via ICG-001 resulted in significantly decreased nasal polypoid lesions (p<0.001), EMT-related markers (p=0.019 for E-cadherin and p=0.002 for vimentin) and the mRNA levels of IL-4 (p<0.001) and IL-17A (p=0.004) compared with the positive control group. Finally, nuclear ß-catenin (p=0.042) was significantly increased compared with the control, and the expression levels of Wnt ligands and receptors were upregulated in human NP tissues (p=0.045 for WNT3A and p=0.042 for FZD2), suggesting increased Wnt signaling and EMT in CRSwNP. CONCLUSION: Wnt signaling may contribute to the pathogenesis of NPs through EMT. Therefore, inhibition of Wnt signaling may be a potential therapeutic strategy for patients with CRSwNP.

Effects of Low-Level Laser Irradiation in a Mouse Model of Allergic Rhinitis.

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.

Enhanced mitochondrial membrane potential and ATP synthesis by photobiomodulation increases viability of the auditory cell line after gentamicin-induced intrinsic apoptosis.

Photobiomodulation (PBM) has been suggested to have a therapeutic effect on irreversible hearing loss induced by aminoglycosides, including gentamicin (GM). However, its intracellular mechanism(s) in GM-induced ototoxicity remain poorly understood. In the present study, we investigated the effect of PBM in GM-induced ototoxicity in auditory cells. We tried to characterize the downstream process by PBM, and the process that triggered the increased cell viability of auditory cells. As a result, the effects of PBM against GM-induced ototoxicity by increasing ATP levels and mitochondrial membrane potential was confirmed. These results suggest a theory to explain the therapeutic effects and support the use of PBM for aminoglycoside-induced hearing loss.

A preliminary study on the efficacy and safety of low level light therapy in the management of cochlear tinnitus: A single blind randomized clinical trial.

OBJECTIVES: To evaluate the efficacy and safety of low-level light therapy (LLLT) using new irradiation parameters for chronic unilateral tinnitus with cochlear dysfunction. DESIGN: A single-blind, randomized clinical trial. SETTING: Tertiary-care hospital center. PARTICIPANTS: Participants who had a history of chronic unilateral tinnitus (≥ 3 months) and pure-tone thresholds greater than 15dB (averaged for 3k, 4k, and 6k Hz). MAIN OUTCOME MEASURES: Numerical rating scales (NRS) measuring loudness, duration, and annoyance, the tinnitus handicap inventory (THI), and psychoacoustical matches of tinnitus loudness and minimum masking levels (MML). RESULTS: Thirty-eight participants were received either a 100-mW diode laser at 830-nm (TINI group; n=19) or placebo (sham group; n=19) irradiation through the tympanic membrane. No adverse events were reported during 2 weeks of 10-interventions (20 minutes/day, five days/week). The NRS measuring duration of tinnitus and psychoacoustical matches of tinnitus loudness significantly decreased over times in the TINI group (p<0.05). However, post-hoc analysis revealed that there was no significant decrease of tinnitus among different time points (baseline, during LLLT, immediately after LLLT, and two weeks after LLLT). There was no placebo effect in the Sham group. Participants who improved the duration by at least one point or improved the loudness matches by more than 5 dB SL two weeks after LLLT tended to have worse pure-tone thresholds. It may suggest that further study is needed in patients with worse pure-tone thresholds to evaluate the therapeutic efficacy of LLLT. CONCLUSION: Although this preliminary result is insufficient to support the therapeutic efficacy of new laser device for chronic tinnitus, further study is needed in a large number of selected patients.