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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, CO 2 , O 2 , 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., (© 2020 Wiley Periodicals LLC.)

Allergic rhinitis (AR) is a common disease that interferes with the daily activities and reduces the quality of life. Conventional treatments often do not provide complete resolution of the symptoms, and many new treatment modalities have been tried. This study aimed to evaluate the efficacy and safety of low-level laser therapy (LLLT) for AR in a randomized, double-blind, placebo-controlled trial. Patients diagnosed with AR were randomly allocated to receive LLLT or sham treatment. The primary outcome was a change in the reflective total nasal symptom score (TNSS). The secondary outcome was quality of life scores assessed using the Rhinoconjunctivitis Quality of Life Questionnaire. Incidences of adverse events were also recorded. Among 67 randomized subjects, 41 subjects (22 in LLLT group and 19 in sham treatment group) were included for efficacy analysis. The LLLT group showed a significantly improved TNSS score compared to the sham treatment group for decreasing AR symptom severity ( p = 0.011) and improving quality of life regarding nasal symptoms ( p = 0.036) at the end of treatment. Throughout the treatment period, no severe adverse events occurred. This clinical trial showed that LLLT is an effective and safe option for the management of AR regarding symptom relief and quality of life improvement.

Objectives: The relationship of estrogen (the primary female sex hormone) with hearing function has been studied in both humans and animals. However, whether estrogen levels affect hearing remains uncertain. Therefore, in this study, we investigated changes in the vulnerability of hearing to acoustic overexposure in ovariectomized female rats., Methods: Eighteen 8-week-old female Sprague-Dawley rats were separated into four groups as follows: sham ovariectomy (OP), OP only, and OP treated with low (10 µg/kg) or high doses (100 µg/kg) of estrogen. Rats in the estrogen replacement groups were given two intraperitoneal injections. Hearing thresholds were measured before noise exposure, and at 1 day and 2 weeks after exposure., Results: The hearing thresholds of the sham OP and OP-only groups were not significantly different. However, both estrogen groups showed a lower threshold shift than the OP-only group. Histological immunostaining analyses showed that hair cell loss in the 32 kHz region was more severe in the sham OP group than in the OP-only group. Furthermore, there was little or no hair cell loss in either estrogen replacement group and significantly more hair cell loss in the OP-only group., Conclusion: These results suggest that estrogen replacement may reduce the vulnerability of hearing to noise exposure in menopausal women.

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.

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: Apc Min/+ mice-induced NPs exhibited more frequent polypoid lesions and upregulation of Wnt-related molecules, including nuclear β-catenin, WNT3A and cyclin D1. Markers of EMT were significantly overexpressed in the Apc Min/+ NP mice (p<0.001 for E-cadherin and α-smooth muscle actin), and interleukin (IL)-17A + cells and neutrophilic infiltration were increased in Apc Min/+ 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 β-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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

A multifunctional chemical neural probe fabrication process exploiting PDMS thin-film transfer to incorporate a microfluidic channel onto a silicon-based microelectrode array (MEA) platform, and enzyme microstamping to provide multi-analyte detection is described. The Si/PDMS hybrid chemtrode, modified with a nano-based on-probe IrOx reference electrode, was validated in brain phantoms and in rat brain.

Low-grade inflammation, which is related to obesity and toxic substance use in young adults, may be associated with poor physical fitness. We investigated the association between total leukocyte count and physical fitness in a military cohort of 3,453 healthy young Taiwanese males aged 20-50 years in a cross-sectional study in 2014. Low-grade inflammation was defined according to equally sized quartiles of total leukocyte counts within the suggested normal limits (4.00-9.99 × 10 3 /mm 3 ). Aerobic fitness was assessed by the time for a 3-kilometer run test, and anaerobic fitness was evaluated by the numbers of sit-ups and push-ups performed in 2 minutes. Automatic monitoring systems were used to verify the scores for all procedures. Multiple linear regression was utilized to identify the associations among variables. When compared with the lowest counts (4.00-5.49 × 10 3 /mm 3 ), the second highest (6.50-7.49 × 10 3 /mm 3 ) and highest normal leukocyte counts (7.50-9.99 × 10 3 /mm 3 ) were correlated with longer times for a 3-kilometer run (β and 95% confidence intervals =4.93 (1.61, 8.25) and 4.65 (2.20, 7.10), respectively) and fewer numbers of push-ups performed in 2 minutes (β = -0.59 (-1.15, -0.03) and -0.56 (-0.96, -0.17), respectively), after adjustments for age, service specialty, waist circumference, body mass index, alcohol consumption, tobacco smoking, and physical activity. However, the association with 2-minute sit-ups was null. Our study suggested an inverse association between total leukocyte count and not only aerobic fitness but also parts of anaerobic fitness in young males. The temporal association needs confirmation in longitudinal studies.

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., (© 2019 Wiley Periodicals, Inc.)

Photobiomodulation (PBM) stimulates different types of stem cells to migrate, proliferate, and differentiate in vitro and in vivo . However, little is known about the effects of PBM on the differentiation of embryonic stem cells (ESCs) toward the otic lineage. Only a few reports have documented the in vitro differentiation of ESCs into inner-ear hair cells (HCs) due to the complexity of HCs compared with other target cell types. In this study, we determined the optimal condition to differentiate the ESCs into the otic organoid using different culture techniques and PBM parameters. The efficiency of organoid formation within the embryoid body (EB) was dependent on the cell density of the hanging drop. PBM, using 630 nm wavelength light-emitting diodes (LEDs), further improved the differentiation of inner-ear hair cell-like cells coupled with reactive oxygen species (ROS) overexpression. Transcriptome analysis showed the factors that are responsible for the effect of PBM in the formation of otic organoids, notably, the downregulation of neural development-associated genes and the hairy and enhancer of split 5 ( Hes5 ) gene, which inhibits the differentiation of prosensory cells to hair cells. These data enrich the current differentiation protocols for generating inner-ear hair cells., (© 2020 The Author(s).)

In critical limb ischemia (CLI), overproduction of reactive oxygen species (ROS) and impairment of neovascularization contribute to muscle damage and limb loss. Cerium oxide nanoparticles (CNP, or 'nanoceria') possess oxygen-modulating properties which have shown therapeutic utility in various disease models. Here we show that CNP exhibit pro-angiogenic activity in a mouse hindlimb ischemia model, and investigate the molecular mechanism underlying the pro-angiogenic effect. CNP were injected into a ligated region of a femoral artery, and tissue reperfusion and hindlimb salvage were monitored for 3 weeks. Tissue analysis revealed stimulation of pro-angiogenic markers, maturation of blood vessels, and remodeling of muscle tissue following CNP administration. At a dose of 0.6 mg CNP, mice showed reperfusion of blood vessels in the hindlimb and a high rate of limb salvage (71%, n = 7), while all untreated mice (n = 7) suffered foot necrosis or limb loss. In vitro, CNP promoted endothelial cell tubule formation via the Ref-1/APE1 signaling pathway, and the involvement of this pathway in the CNP response was confirmed in vivo using immunocompetent and immunodeficient mice and by siRNA knockdown of APE1. These results demonstrate that CNP provide an effective treatment of CLI with excessive ROS by scavenging ROS to improve endothelial survival and by inducing Ref-1/APE1-dependent angiogenesis to revascularize an ischemic limb., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The aim of study is to investigate the role of transient receptor potential cation channel subfamily V member 1 (TRPV1) on xerostomia-induced inflammatory response in vivo., Methods: Parotid, submandibular, and lingual gland were removed for xerostomia induction. The expression of inflammatory cytokines, TRPV1, NFkB, and MAPK in xerostomia was evaluated and compared in both TRPV1 wild and knockout mice., Results: The level of interleukin-6 (IL-6) and IL-17, neutrophil/CD4 T-cell infiltration, phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N terminal kinase, TRPV1, and the localization of NFkB were elevated in xerostomia-induced TRPV1 wild-type mice. In contrast, inflammatory cytokines and MAPK were decreased in xerostomia-induced TRPV1 knockout mice. TRPV1 antagonist treatment also reduced tongue ulceration, neutrophil/CD4 + T-cell expression, IL-6, and IL-17 in TRPV1 wild-type mice., Conclusion: TRPV1 had a crucial role in modulating inflammation in xerostomia and targeting TRPV1 might be a promising therapeutic strategy for xerostomia., (© 2019 Wiley Periodicals, Inc.)

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.

Accumulated evidence suggests that sporadic cases of Alzheimer's disease (AD) make up more than 95% of total AD patients, and diabetes has been implicated as a strong risk factor for the development of AD. Diabetes shares pathological features of AD, such as impaired insulin signaling, increased oxidative stress, increased amyloid-beta (Aβ) production, tauopathy and cerebrovascular complication. Due to shared pathologies between the two diseases, anti-diabetic drugs may be a suitable therapeutic option for AD treatment. In this article, we will discuss the well-known pathologies of AD, including Aβ plaques and tau tangles, as well as other mechanisms shared in AD and diabetes including reactive glia and the breakdown of blood brain barrier in order to evaluate the presence of any potential, indirect or direct links of pre-diabetic conditions to AD pathology. In addition, clinical evidence of high incidence of diabetic patients to the development of AD are described together with application of anti-diabetic medications to AD patients., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

Arbitrary patterning of micro-objects in liquid is crucial to many biomedical applications. Among conventional methodologies, acoustic approaches provide superior biocompatibility but are intrinsically limited to producing periodic patterns at low resolution due to the nature of standing waves and the coupling between fluid and structure vibrations. This work demonstrates a near-field acoustic platform capable of synthesizing high resolution, complex and non-periodic energy potential wells. A thin and viscoelastic membrane is utilized to modulate the acoustic wavefront on a deep, sub-wavelength scale by suppressing the structural vibration selectively on the platform. Using 3 MHz excitation (λ∼ 500 μm in water), we have experimentally validated such a concept by realizing patterning of microparticles and cells with a line resolution of 50 μm (one tenth of the wavelength). Furthermore, massively parallel patterning across a 3 × 3 mm 2 area has been achieved. This new acoustic wavefront modulation mechanism is powerful for manufacturing complex biologic products.

A certain degree of noise can cause hearing problems without a permanent change in the hearing threshold, which is called hidden hearing loss and results from partial loss of auditory synapses. Photobiomodulation (PBM) enhances neural growth and connections in the peripheral nervous systems. In this study, we assessed whether PBM could rescue cochlear synaptopathy after acoustic overexposure in rat. PBM was performed for 7 days after noise exposure. The auditory brainstem responses (ABRs) were acquired before and after noise exposure using a tone and a paired-click stimulus. Auditory response to paired click sound with short time interval was performed to evaluate auditory temporal processing ability. In the result, hearing threshold recovered 2 weeks after noise exposure in both groups. Peak wave 1 amplitude of the ABR and ABR recovery threshold did not recover in the noise only group, whereas it fully recovered in the noise + PBM group. The number of synaptic ribbons was significantly different in the control and noise only groups, while there was no difference between the control and noise + PBM group. These results indicate that PBM rescued peak wave 1 amplitude and maintained the auditory temporal processing ability resulting from a loss of synaptic ribbons after acoustic overexposure., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Elevated levels of plasma homocysteine could, through homocysteine oxidation, induce the overproduction of reactive oxygen species, leading to a reduction in glutathione-related antioxidants, and may impair graft functions in patients with renal transplants. The purpose of this study was to determine whether plasma homocysteine, glutathione, or its related antioxidants were related to graft functions in patients with renal transplants., Patients and Methods: We recruited 66 patients (mean age 48.4 years) with renal transplants (mean transplant duration 8.3 years). Patients were divided into 2 groups, based on their estimated glomerular filtration rate (eGFR): the moderate graft function group (eGFR ≥ 60 mL/min/1.73 m 2 , n = 37) and low graft function group (eGFR < 60 mL/min/1.73 m 2 , n = 29). We then determined their fasting levels of the following: malondialdehyde (MDA), homocysteine, cysteine, pyridoxal 5'-phosphate (PLP), glutathione (GSH), oxidized glutathione (GSSG), GSH/GSH ratio, glutathione peroxidase (GSH-Px) activity., Results: We found in the low graft function group significantly higher levels of plasma homocysteine, cysteine, GSH, and GSH/GSSG ratios. But an intergroup difference was not found regarding levels of MDA, PLP, GSSG, and GSH-Px activity. After adjusting for potential confounders, the increased plasma homocysteine and GSH levels were independently associated with lower eGFR. No interaction existed between homocysteine and GSH levels in association with eGFR., Conclusion: Increased plasma homocysteine and GSH levels appeared to be independent indicators of decreased graft functions in patients with renal transplants., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Efficient intracellular delivery of biomolecules into cells that grow in suspension is of great interest for biomedical research, such as for applications in cancer immunotherapy. Although tremendous effort has been expended, it remains challenging for existing transfer platforms to deliver materials efficiently into suspension cells. Here, we demonstrate a high-efficiency photothermal delivery approach for suspension cells using sharp nanoscale metal-coated tips positioned at the edge of microwells, which provide controllable membrane disruption for each cell in an array. Self-aligned microfabrication generates a uniform microwell array with three-dimensional nanoscale metallic sharp tip structures. Suspension cells self-position by gravity within each microwell in direct contact with eight sharp tips, where laser-induced cavitation bubbles generate transient pores in the cell membrane to facilitate intracellular delivery of extracellular cargo. A range of cargo sizes were tested on this platform using Ramos suspension B cells with an efficiency of >84% for Calcein green (0.6 kDa) and >45% for FITC-dextran (2000 kDa), with retained viability of >96% and a throughput of >100 000 cells delivered per minute. The bacterial enzyme β-lactamase (29 kDa) was delivered into Ramos B cells and retained its biological activity, whereas a green fluorescence protein expression plasmid was delivered into Ramos B cells with a transfection efficiency of >58%, and a viability of >89% achieved.

We evaluated changes in cell viability and morphology in response to low-level light irradiation and underlying variations in the levels of heat shock proteins (HSPs). Human fibroblasts were irradiated with a light-emitting diode (LED) array at 660 nm (50 mW for 15, 30, and 60 minutes). Cell viability and morphological changes were evaluated via epifluorescence analysis; we also assessed cell viability and length changes. The expression levels of adenosine triphosphate (ATP) and various HSPs (HSP27, 60, 70, and 90) were analyzed by immunohistochemical staining, Western blotting and microarray analysis. After LED irradiation, cellular viability and morphology changed. Of the several HSPs analyzed, the HSP90 level increased significantly, suggesting that this protein played roles in the morphological and cellular changes. Thus, low-level irradiation triggered cellular changes mediated by increased HSP90 expression; this may explain why skin irradiation enhances wound-healing., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Subglottic stenosis (SGS) is a challenging disease to diagnose in neonates. Long-range optical coherence tomography (OCT) is an optical imaging modality that has been described to image the subglottis in intubated neonates. A major challenge associated with OCT imaging is the lack of an automated method for image analysis and micrometry of large volumes of data that are acquired with each airway scan (1 to 2 Gb). We developed a tissue segmentation algorithm that identifies, measures, and conducts image analysis on tissue layers within the mucosa and submucosa and compared these automated tissue measurements with manual tracings. We noted small but statistically significant differences in thickness measurements of the mucosa and submucosa layers in the larynx (p  <  0.001), subglottis (p  =  0.015), and trachea (p  =  0.012). The automated algorithm was also shown to be over 8 times faster than the manual approach. Moderate Pearson correlations were found between different tissue texture parameters and the patient’s gestational age at birth, age in days, duration of intubation, and differences with age (mean age 17 days). Automated OCT data analysis is necessary in the diagnosis and monitoring of SGS, as it can provide vital information about the airway in real time and aid clinicians in making management decisions for intubated neonates.

Anemia defined as reduced hemoglobin levels of red blood cells may carry less oxygen to skeletal muscle and impair physical performance. Previous studies have shown that exercise intolerance was related to moderate or severe anemia, however, the relationship to mild anemia was unknown. We investigated the cross-sectional association of mild anemia defined as a hemoglobin level of 10.0-13.9 g/dL with physical fitness in 3,666 military young males in Taiwan in 2014. Aerobic fitness was evaluated by 3000-meter run test, and anaerobic fitness was evaluated by 2-minute sit-ups and 2-minute push-ups, respectively. Multiple logistic regressions for the best 10% and the worst 10% performers were used to determine the relationship. There were 343 mild anemic males in whom 47.8% were microcytic anemia and 3,323 non-anemic males for the analysis. The multiple logistic regression shows that as compared with non-anemic males, mild anemic males were more likely to be the worst 10% performers in the 3000-meter run test (odds ratios (OR) and 95% confidence intervals: 1.47, 1.01-2.14) after adjusting for age, service specialty, body mass index, waist size, mean blood pressure, unhealthy behaviors, lipid profiles, and exercise frequency. On the contrary, mild anemic males had higher possibility to be the best 10% performers in the 2-minute push-ups test (OR: 1.48, 1.08-2.04). However, there was no association between mild anemia and 2-minute sit-ups. Our findings suggest that unspecified mild anemia might be associated with lower cardiorespiratory fitness but not with anaerobic fitness in physically active military males.

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to provide guidance on the implementation of a surgical treatment of oral cancer. MEDLINE databases were searched for articles on subjects related to "surgical management of oral cancer" published in English. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. The quality of evidence was rated with use RoBANS (Risk of Bias Assessment Tool for Nonrandomized Studies) and AMSTAR (A Measurement Tool to Assess the Methodological Quality of Systematic Reviews). Evidence-based recommendations for practice were ranked according to the American College of Physicians grading system. Additional directives are provided as expert opinions and Delphi questionnaire when insufficient evidence existed. The Committee developed 68 evidence-based recommendations in 34 categories intended to assist clinicians and patients and counselors, and health policy-makers. Proper surgical treatment selection for oral cancer, which is directed by patient- and subsite-specific factors, remains the greatest predictor of successful treatment outcomes. These guidelines are intended for use in conjunction with the individual patient's treatment goals.

Background: To determine whether photobiomodulation (PBM) rescued the disruption of Na + /Ca 2+ homeostasis and mitochondrial membrane potential by ouabain; the Na, K-ATPase inhibitor. For PBM in this study, a 660 nm LED array was used at energy densities of 0.78, 1.56, 3.12, 6.24, and 9.36 J/cm 2 ., Results: HCN-2 neuronal cells treated with ouabain showed loss of cell polarity, disrupted cell morphology, and decreased cell viability, which were improved after PBM treatment. We found that ouabain-induced Na, K-ATPase inhibition promoted activation of downstream signaling through Src, Ras, and mitogen-activated protein kinase (MAPK), which were suppressed after PBM treatment. This provided evidence of Na, K-ATPase α-subunit inactivation and intracellular Ca 2+ increase. In response to ouabain, we observed activation of Src and MAPK by Na, K-ATPase, decreased mitochondrial membrane potential, and Na + -dependent Ca 2+ increases, which were restored by PBM treatment., Conclusions: This study demonstrated that Na + /K + imbalance could be regulated by PBM treatment in neuronal cells, and we suggest that PBM is a potential therapeutic tool for Na, K-ATPase targeted neuronal diseases.

Flexible neural probes have been pursued previously to minimize the mechanical mismatch between soft neural tissues and implants and thereby improve long-term performance. However, difficulties with insertion of such probes deep into the brain severely restricts their utility. We describe a solution to this problem using gallium (Ga) in probe construction, taking advantage of the solid-to-liquid phase change of the metal at body temperature and probe shape deformation to provide temperature-dependent control of stiffness over 5 orders of magnitude. Probes in the stiff state were successfully inserted 2 cm-deep into agarose gel "brain phantoms" and into rat brains under cooled conditions where, upon Ga melting, they became ultra soft, flexible, and stretchable in all directions. The current 30 μm-thick probes incorporated multilayer, deformable microfluidic channels for chemical agent delivery, electrical interconnects through Ga wires, and high-performance electrochemical glutamate sensing. These PDMS-based microprobes of ultra-large tunable stiffness (ULTS) should serve as an attractive platform for multifunctional chronic neural implants., (Copyright © 2019 Elsevier B.V. All rights reserved.)

While colonoscopy is the gold standard for diagnosis and classification of colorectal cancer (CRC), its sensitivity and specificity are operator-dependent and are especially poor for small and flat lesions. Contemporary imaging modalities, such as optical coherence tomography (OCT) and near-infrared (NIR) fluorescence, have been investigated to visualize microvasculature and morphological changes for detecting early stage CRC in the gastrointestinal (GI) tract. In our study, we developed a multimodal endoscopic system with simultaneous co-registered OCT and NIR fluorescence imaging. By introducing a contrast agent into the vascular network, NIR fluorescence is able to highlight the cancer-suspected area based on significant change of tumor vascular density and morphology caused by angiogenesis. With the addition of co-registered OCT images to reveal subsurface tissue layer architecture, the suspected regions can be further investigated by the altered light scattering resulting from the morphological abnormality. Using this multimodal imaging system, an in vivo animal study was performed using a F344-Apc Pirc Uwm rat, in which the layered architecture and microvasculature of the colorectal wall at different time points were demonstrated. The co-registered OCT and NIR fluorescence images allowed the identification and differentiation of normal colon, hyperplastic polyp, adenomatous polyp, and adenocarcinoma. This multimodal imaging strategy using a single imaging probe has demonstrated the enhanced capability of identification and classification of CRC compared to using any of these technologies alone, thus has the potential to provide a new clinical tool to advance gastroenterology practice., Competing Interests: Dr. Chen has a financial interest in OCT Medical Imaging, Inc., which, however, did not support this work.

Gene therapy is the delivery of a therapeutic gene into target cells to treat disorders by replacing disease-causing mutated genes with healthy ones. Gene therapy of the inner ear has been recently described, with applications for sensorineural hearing loss. However, gene delivery to the location of the inner ear, and thus efficacy of therapy, is challenging. Photobiomodulation (PBM) with a low-level laser has been suggested to have a therapeutic effect and has the potential to augment gene therapy. To investigate whether PBM improves the rate of adenovirus (Ad)-mediated viral delivery, we compared low-level laser therapy (LLLT) and non-LLLT HEI-OC1 cells treated with an Ad viral vector carrying green fluorescent protein (GFP). Cultured HEI-OC1 cells were divided into six groups: no treatment control, LLLT only, 1 μL Ad-GFP, 3 μL Ad-GFP, 1 μL Ad-GFP + LLLT, and 3 μL Ad-GFP + LLLT (LLLT: 808 nm at 15 mW for 15 min). Cells were irradiated twice: at 2 h and again at 24 h. A nonparametric Mann-Whitney U test was used to statistically analyze differences between the control and treatment groups. The viral inoculations used in this study did not change the amount of viable HEI-OC1 cells (N = 4-8). The 1 μL Ad-GFP + LLLT and 3 μL Ad-GFP + LLLT groups showed an increased density of GFP-positive cells compared to 1 μL and 3 μL Ad-GFP cells (N = 5-8, 1 μL: p = 0.0159; 3 μL: p = 0.0168,). The quantitative analysis of the epifluorescence of the 1 μL Ad-GFP + LLLT, and 3 μL Ad-GFP + LLLT groups revealed increased GFP expression/cell compared to 1 μL and 3 μL Ad-GFP cells (N = 6-15, 1 μL: p = 0.0082; 3 μL: p = 0.0012). The RT-qPCR results were consistent (N = 4-5, p = 0.0159). These findings suggest that PBM may enhance the gene delivery of Ad-mediated viral transduction, and the combination of the two may be a promising tool for gene therapy for sensorineural hearing loss.

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.

Laryngeal squamous cell carcinoma (LSCC) is currently a serious public health problem in China; thus, it is urgent to identify effective treatment strategies for this disease. Previous studies demonstrated that reactive oxygen species (ROS) serve important roles in the apoptosis of LSCC cells. It has also been indicated that carboplatin (CBDCA), a second-generation platinum compound with broad antineoplastic properties, is able to induce oxidative stress to produce ROS, which in turn promotes apoptosis. Thus, the present study investigated if CBDCA is cytotoxic in LSCC cells due to the oxidative stress caused by ROS. Therefore, an MTT assay was performed to determine the cell viability of HN-3 LSCC cells following treatment with different doses of CBDCA. Subsequently, the expression levels of ROS and the rate of apoptosis/necrosis were evaluated in the cells. Following this, the HN-3 cells were co-treated with CBDCA and glutathione (GSH) or H 2 O2, followed by an MTT assay, a cell migration assay and western blot analysis. The results demonstrated that CBDCA reduced the viability of HN-3 cells in a time- and dose-dependent manner and promoted the production of ROS and apoptosis at certain doses. Additionally, the combination treatment of CBDCA and H2O2 enhanced the inhibitory effects of CBDCA on cell viability and migration ability, and promoted apoptosis in HN-3 cells; whereas the combined treatment of CBDCA and GSH exerted opposite effects. The results of the present study demonstrated that CBDCA promotes the apoptosis of HN-3 cells through accumulation of ROS, which may provide a novel treatment strategy for treating LSCC.

Laryngeal carcinomas have been recognized as a serious health threat worldwide. In the present study, the mechanism of apoptosis in HN‑3 cells induced by carboplatin (CBCDA), a widely used anti‑cancer drug, was investigated. The pro‑apoptotic effect of CBCDA in HN‑3 cells was demonstrated to be time‑ and dose‑dependent. Therefore, the stages of apoptosis were investigated in chronological order. The results demonstrated that excessive generation of cytosolic Ca2+ in HN‑3 cells was initially triggered when cells were exposed to CBCDA, followed by the appearance of mitochondrial depolarization and oxidative stress, leading to the release of apoptosis‑inducing factor. At later stages, expression of caspase‑8 was increased due to the apoptotic signals originating from CBCDA‑induced DNA damage, as well as caspase‑9 and poly ADP ribose polymerase (PARP) expression upregulation. Glutathione decreased the available CBDCA concentration, decreased apoptosis and alleviating oxidative stress, thus reducing the actual effective concentration. Mechanistic research may benefit the rational design of more efficient therapeutic strategies as well as development of novel platinum‑based agents.

We developed a highly efficient method for patterning cells by a novel and simple technique called lift-off cell lithography (LCL). Our approach borrows the key concept of lift-off lithography from microfabrication and utilizes a fully biocompatible process to achieve high-throughput, high-efficiency cell patterning with nearly zero background defects across a large surface area. Using LCL, we reproducibly achieved >70% patterning efficiency for both adherent and non-adherent cells with <1% defects in undesired areas.

The overall goal is to study the effect of low-level laser therapy (LLLT) on membrane distribution of major water channel protein aquaporin 5 (AQP5) in salivary gland during hyperglycemia. Par C10 cells treated with high glucose (50 mM) showed a reduced membrane distribution of AQP5. The functional expression of AQP5 was downregulated due to intracellular Ca 2+ overload and ER stress. This reduction in AQP5 expression impairs water permeability and therefore results in hypo-salivation. A reduced salivary flow was also observed in streptozotocin (STZ)-induced diabetic mice model and the expression of AQP5 and phospho-AQP5 was downregulated. Low-level laser treatment with 850 nm (30 mW, 10 min = 18 J/cm 2 ) reduced ER stress and recovered AQP5 membrane distribution via serine phosphorylation in the cells. In the STZ-induced diabetic mouse, LLLT with 850 nm (60 J/cm 2 ) increased salivary flow and upregulated of AQP5 and p-AQP5. ER stress was also reduced via downregulation of caspase 12 and CHOP. In silico analysis confirmed that the serine 156 is one of the most favorable phosphorylation sites of AQP5 and may contribute to the stability of the protein. Therefore, this study suggests high glucose inhibits phosphorylation-dependent AQP5 membrane distribution. High glucose induces intracellular Ca 2+ overload and ER stress that disrupt AQP5 functional expression. Low-level laser therapy with 850 nm improves salivary function by increasing AQP5 membrane distribution in hyperglycemia-induced hyposalivation., (Copyright © 2018. Published by Elsevier B.V.)

In this study, we developed a new immunosensor that can achieve an ultralow detection limit and high sensitivity. This new device has an electrokinetic trapping (EKT)-based nanofluidic preconcentrator, which was integrated with oscillating bubble valves, to trap concentrated antigen and immunobeads. During the immunoassay process, oscillating bubbles rapidly grew and acted as control valves and to block the microchannel. Thereafter, the trapped preconcentrated antigen plug and antibody-coated nanobeads were preserved in the region between these two valves. Finally, the antigen concentration was quantitatively analyzed by a real-time measurement of Brownian diffusion of the immunobeads. In this work, the test sample used was C-reactive protein (CRP) which is a risk indicator of coronary heart disease and atherosclerosis.

This study aimed to evaluate the effect of aqueous extract of Lespedeza cuneata (ALC) on men menopause induced erectile dysfunction (ED) and testosterone deficiency syndrome (TDS) in vitro and in vivo. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) have been fundamental factors of ED, and free testosterone such as dihydrotestosterone (DHT) has a crucial role in mitigation of TDS. ALC increased the production of NO in a dose-dependent manner in vitro and in vivo. The level of neuronal nitric oxide synthase and cGMP was increased in the ALC group. The level of DHT and 17-beta hydroxysteroid dehydrogenases (17β-HSD) was also increased in the ALC group. There was no significant change of hepatotoxicity, renal toxicity, lipid metabolism, and glucose. These results suggest that ALC enhanced NO, cGMP and free testosterone which could be developed as a health supplement for improving male menopause., Competing Interests: Compliance with ethical standardsThe authors declare that they have no competing interests.

Background: Adipocyte differentiation of human mesenchymal stem cells (hMSCs) is dependent on mitochondrial metabolism and reactive oxygen species (ROS) to initiate adipocyte differentiation. Although anethole has been known as an anti-oxidant and lipid peroxidation inhibitor, there is little investigated about its role in adipogenic differentiation., Methods: The effects on cytotoxicity and proliferation of anethole in hMSCs were measured by the MTT assay. The anti-adipogenic effect of anethole on hMSCs was analyzed by Oil Red O staining and western blot analysis. The anti-oxidant activity of anethole on hMSC was assessed by flowcytometry and fluorescence staining using 2',7' -dichlorofluorescin diacetate (DCFDA). The western blotting was used to detect of phospho-Akt, phospho-mTOR, phospho-p70S6K, PPARγ, and phsopho-AMP-activated kinase (AMPK)., Results: Anethole suppressed the adipogenic differentiation of hMSCs through down-regulation of Akt-mTOR-p70S6K-PPARγ and up-regulation of AMPK. Anethole affected oxidative conditions through ROS generation. Anethole also rescued AMPK activity and reduced activation of mTOR-p70S6K-PPARγ under oxidative conditions in presence of exogenous hydrogen peroxide., Conclusion: ROS and mTOR regulation is a crucial factor in adipogenic differentiation, anethole has an important role in regulating activities of mTOR/PPARγ and ROS control in adipogenic differentiation of hMSCs.

A novel manufacturing approach to fabricate liquid metal-based, multifunctional microcapillary pipettes able to provide electrodes with high electrical conductivity for high-frequency electrical stimulation and measurement is proposed. 4D single cell manipulation is realized by applying multifrequency, multiamplitude, and multiphase electrical signals to the microelectrodes near the pipette tip to create 3D dielectrophoretic trap and 1D electrorotation, simultaneously. Functions such as single cell trapping, patterning, transfer, and rotation are accomplished. Cell viability and multiday proliferation characterization has confirmed the biocompatibility of this approach. This is a simple, low-cost, and fast fabrication process that requires no cleanroom and photolithography step to manufacture 3D microelectrodes and microchannels for easy access to a wide user base for broad applications.

Hair cells in the cochlea can be damaged by various causes. Damaged hair cells can lead to additional destruction of parts of the auditory afferent pathway sequentially, which is called secondary degeneration. Recently, researches regarding cochlear implants have been actively carried out for clinical purposes; secondary degeneration in animals is a much more practical model for identifying the prognosis of cochlear implants. However, an appropriate model for this research is not established yet. Thus, we developed a secondary degeneration model using an ototoxic drug. 35 gerbils were separated into four different groups and kanamycin was applied via various approaches. ABR was measured several times after drug administration. SGCs were also counted to identify any secondary degeneration. The results showed that outer and inner HCs were damaged in all kanamycin-treated groups. Twelve weeks after kanamycin treatment, the round window membrane injection group showed severe subject differences in hair cells and SGC damage, whereas the gelfoam group showed consistent and severe damage in hair cells and SGCs. In this study, we successfully induced secondary degeneration in hair cells in a gerbil model. This model can be used for various purposes in the hearing research area either for treatment or for preservation.

Sulforaphene (SFE), a natural isothiocyanate from cruciferous vegetables has shown a potential anticancer effect against cervical and lung cancer. Palliative treatments like photodynamic therapy (PDT) are being implemented for a long time however, the results are still not promising in case of aggressive cancers like anaplastic thyroid cancer. The objective of this work is to establish an alternative method with the combination of photofrin-PDT and sulforaphene, a natural isothiocyanate from cruciferous vegetables, against human anaplastic thyroid cancer to enhance the efficacy of PDT. In this study, cell viability of FRO cells due to combination treatment was analyzed by MTT assay, Cell cycle arrest, MMP depolarization and ROS generation, analyzed by flow cytometry. Western blot analysis of various proliferative proteins was performed to assess the activity of combination treatment against FRO cells. From the results, sulforaphene alone showed no cytotoxicity against normal cells, however, combination of sulforaphene and photofrin mediated PDT showed a noticeable decrease in cell proliferation against FRO cells. Combination treatment synergistically caused cell cycle arrest via ROS generation and MMP depolarization. The expressions of Ras, MEK, ERK, B-Raf proteins significantly modulated due to combination treatment. PDT and SFE can induce apoptosis in anaplastic thyroid cancer cells individually but while treated in combination, it enhanced the apoptotic and anti-proliferative effect, much higher than the individual doses. In summary, our work designates sulforaphene as a unique natural enhancer of efficacy with PDT against anaplastic thyroid cancer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this study is to examine the enhanced survival effect of ischemic skin flap by combined treatment with bone marrow-derived stem cells (BMSCs) and low-level light irradiation (LLLI). The neovasculogenic effect of BMSCs induced by LLLI was detected using a wound healing and tube formation assay. ICR mice were divided into four groups: control group, LLLI group, BMSCs group, and combine-treated group. The percentage of skin flap necrosis area was calculated on the seventh post-operative day. Specimens were harvested for histologic analyses. LLLI promoted BMSC migration and tube formation. The flap survival rate of combined treated group was significantly higher than that of the control group. Histologic results demonstrated a significant increase in neovascularization in the combined treatment group. This study demonstrates that combination treatment of BMSCs and LLLI could enhance the survival of ischemic skin flap in a mouse model.

Background: Lack of familiarity with collection and inspection procedures, incorrect bone-packaging procedures, and unclear instructions for bone placement during storage are primary reasons for the resultant low bone collection pass rate of bone banks. Moreover, 8 cases / operations were directly affected by this problem, which caused bone-nail dislocations during the post-operative period that nearly caused medical disputes., Purpose: The present project was designed to improve the pass rate of the bone of the human organ to 95%., Methods: Education and training programs were planned, visual-aid posters depicting standard procedures were produced, the repository was remarked and relabeled, and a regular audit system was established with the medical team., Results: The pass rate for the collection of the bone of the human organ increased from 71.4% pre-intervention to 96% post-intervention., Conclusions: The project reduced patient complaints and raised the accuracy of the bone collection process.

Skin flap grafting is a form of transplantation widely used in plastic surgery. However, ischemia/reperfusion injury is the main factor which reduces the survival rate of flaps following grafting. We investigated whether photobiomodulation (PBM) precondition prior to human adipose-derived stromal cell (hASC) spheroid (PBM-spheroid) transplantation improved skin tissue functional recovery by the stimulation of angiogenesis and tissue regeneration in skin flap of mice. The LED had an emission wavelength peaked at 660 ± 20 nm (6 J/cm 2 , 10 mW/cm 2 ). The expression of angiogenic growth factors in PBM-spheroid hASCs was much greater than that of not-PBM-treated spheroid or monolayer-cultured hASCs. From immunochemical staining analysis, the hASCs of PBM-spheroid were CD31 + , KDR + , and CD34 + , whereas monolayer-cultured hASCs were negative for these markers. To evaluate the therapeutic effect of hASC PBM-spheroid in vivo, PBS, monolayer-cultured hASCs, and not-PBM-spheroid were transplanted into a skin flap model. The animals were observed for 14 days. The PBM-spheroid hASCs transplanted into the skin flap ischemia differentiated into endothelial cells and remained differentiated. Transplantation of PBM-spheroid hASCs into the skin flap ischemia significantly elevated the density of vascular formations through angiogenic factors released by the skin flap ischemia and enhanced tissue regeneration at the lesion site. Consistent with these results, the transplantation of PBM-spheroid hASCs significantly improved functional recovery compared with PBS, monolayer-cultured hASCs, and not-PBM-spheroid treatment. These findings suggest that transplantation of PBM-spheroid hASCs may be an effective stem cell therapy for the treatment of skin flap ischemia.

Background Aims: We investigated whether low-level light irradiation (LLLI) before adipose-derived stromal cells (ASCs) spheroid transplantation improved hind-limb functional recovery by stimulation of angiogenesis., Methods: The spheroid, composed of ASCs, was irradiated with low-level light and expressed angiogenic factors, including vascular endothelial growth factor and basic fibroblast growth factor. From immunochemical staining analysis, the spheroid of ASCs included CD31 + , KDR + and CD34 + , whereas monolayer-cultured ASCs were negative for these markers. To evaluate the therapeutic effect of the ASC spheroid treated with LLLI in vivo, phosphate-buffered saline, monolayer ASCs, LLLI-monolayer ASCs, spheroid ASCs and LLLI-spheroid ASCs were transplanted into a hind-limb ischemia model., Results: The LLLI-spheroid ASCs transplanted into the hind-limb ischemia differentiated into endothelial cells and remained differentiated. Transplantation of LLLI-spheroid ASCs into the hind-limb ischemia significantly elevated the density of vascular formations through angiogenic factors released by the ASCs and enhanced tissue regeneration at the lesion site. Consistent with these results, the transplantation of LLLI-spheroid ASCs significantly improved functional recovery compared with ASC or spheroid ASC transplantation and PBS treatment., Conclusions: These findings suggest that transplantation of ASC spheroid treated with LLLI may be an effective stem cell therapy for the treatment of hind-limb ischemia and peripheral vascular disease., (Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Gentamicin, which is still used in modern medicine, is a known vestibular toxic agent, and various degrees of balance problems have been observed after exposure to this pharmacologic agent. Photobiomodulation is a candidate therapy for vertigo due to its ability to reach deep inner ear organs such as the cochlea. Previous reports have suggested that photobiomodulation can improve hearing and cochlea function. However, few studies have examined the effect of photobiomodulation on balance dysfunction. We used a rat model to mimic human vestibulopathy resulting from gentamicin treatment and evaluated the effect of photobiomodulation on vestibular toxicity. Slow harmonic acceleration (SHA) rotating platform testing was used for functional evaluation and both qualitative and quantitative epifluorescence analyses of cupula histopathology were performed. Animals were divided into gentamicin only and gentamicin plus laser treatment groups. Laser treatment was applied to one ear, and function and histopathology were evaluated in both ears. Decreased function was observed in both ears after gentamicin treatment, demonstrated by low gain and no SHA asymmetry. Laser treatment minimized the damage resulting from gentamicin treatment as shown by SHA asymmetry and recovered gain in the treated ear. Histology results reflected the functional results, showing increased hair cell density and epifluorescence intensity in laser-treated cupulae., ((2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

Background: The Korean Society of Thyroid Head and Neck Surgery established a nationwide multicenter registry of anaplastic thyroid carcinoma (ATC) and evaluated the prognostic factors and treatment outcomes of ATC., Methods: The present study enrolled 329 patients who were diagnosed with ATC between January 2000 and December 2012 at 19 medical centers in Korea. Survival outcomes were evaluated according to various clinical factors and treatments., Results: Multivariate analysis identified age ≥70 years old, the presence of initial clinical symptoms, distant metastasis, and treatment modality as significant risk factors (p <.05). The patients who underwent curative resection and adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CRT) showed the best survival on multivariate analysis (p < 0.05)., Conclusion: Although ATC is a lethal neoplasm, long-term survival may be acquired in cases in which the aggressive management, including curative resection or RT/concurrent CRT, is possible for therapeutic intent. © 2016 Wiley Periodicals, Inc. Head Neck 39: 133-139, 2017., (© 2016 Wiley Periodicals, Inc.)

Auditory neuropathy is a hearing disorder caused by impaired auditory nerve function. The lack of information about the pathophysiology of this disease limits early diagnosis and further treatment. Laser therapy is a novel approach to enhance nerve growth or induce axonal regeneration. We induced auditory neural degeneration sparing the sensory epithelium with local ouabain application in an animal model and observed the rescue effect of photobiomodulation (PBM), showing recovered auditory function and favorable histologic outcome. Hearing was evaluated using the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). Seven days after ouabain application, the animals were sacrificed to evaluate the morphological changes. DPOAE change was not observed in all groups after ouabain application indicating no changes of outer hair cell function. Ouabain application increased the ABR thresholds increase, while the use of ouabain plus laser produced lower threshold compared to the ouabain group. Hematoxylin and Eosin staining of cochlea mid-modiolar sections in animals treated with ouabain showed damaged spiral ganglion cells, neurofilaments, and post synaptic puncta. Ouabain plus laser group showed higher number of spiral ganglion cells, higher density of neurofilaments, and higher number post synaptic puncta counts compared with ouabain application group. Short-term application of ouabain caused spiral ganglion cell damage while sparing the inner and outer hair cells in gerbils. Photobiomodulation alleviated the hearing loss caused by ouabain induced auditory neuropathy. The results indicate the possible role of photobiomodulation therapy for inner ear diseases accompanied by spiral ganglion degeneration., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The present study aimed to investigate the effect, and elucidate the potential mechanisms, of 9-hydroxypheophorbide α-based photodynamic therapy (9-HPbD-PDT) on apoptosis and necrosis induction, and migration suppression of laryngeal cancer AMC-HN-3 (HN-3) cells. Phototoxicity initiated by 9-HPbD-PDT on HN-3 cells was observed in a photosensitizer dose-dependent pattern. There was an initial increase of apoptotic cells coupled with gradual enhancement of reactive oxygen series (ROS) generation at lower doses of 9-HPbD. By contrast, at a higher dose of 9-HPbD, there was a clear increase of necrotic cells with a gradual decrease of ROS generation. Following PDT, an elevated percentage of apoptotic cells with shrinkage or condensing nuclei was observed using Hoechst 33342/propidium iodide double staining, and an upregulated expression of poly ADP-ribose polymerase was detected through western blotting. A disruption of the mitochondrial membrane potential was detected 2 h following PDT. Significant suppression of cell migration and downregulation of epidermal growth factor receptor (EGFR) expression were recorded following PDT. These results indicate that the distribution of photosensitizer leads to differences in the generation of ROS, which subsequently determines the type of cell death. Overall, mitochondrial activation under oxidative stress is important in the 9-HPbD-PDT-induced apoptosis of HN-3 cells. Migration suppression of HN-3 cells following PDT may be associated with the inhibited expression of EGFR, due to oxidative stress.

Noise-induced hearing loss is a common type of hearing loss. The effects of laser therapy have been investigated from various perspectives, including in wound healing, inflammation reduction, and nerve regeneration, as well as in hearing research. A promising feature of the laser is its capability to penetrate soft tissue; depending on the wavelength, laser energy can penetrate into the deepest part of the body without damaging non-target soft tissues. Based on this idea, we developed bilateral transtympanic laser therapy, which uses simultaneous laser irradiation in both ears, and evaluated the effects of bilateral laser therapy on cochlear damage caused by noise overexposure. Thus, the purpose of this research was to assess the benefits of simultaneous bilateral laser therapy compared with unilateral laser therapy and a control. Eighteen Sprague-Dawley rats were exposed to narrow-band noise at 115 dB SPL for 6 h. Multiple auditory brainstem responses were measured after each laser irradiation, and cochlear hair cells were counted after the 15th such irradiation. The penetration depth of the 808 nm laser was also measured after sacrifice. Approximately 5% of the laser energy reached the contralateral cochlea. Both bilateral and unilateral laser therapy decreased the hearing threshold after noise overstimulation in the rat model. The bilateral laser therapy group showed faster functional recovery at all tested frequencies compared with the unilateral laser therapy group. However, there was no difference in the endpoint ABR results or final hair cell survival, which was analyzed histologically.

Young patients with dense breasts have a relatively low-positive biopsy rate for breast cancer (∼1 in 7). South Korean women have higher breast density than Westerners. We investigated the benefit of using a functional and metabolic imaging technique, diffuse optical spectroscopic imaging (DOSI), to help the standard of care imaging tools to distinguish benign from malignant lesions in premenopausal Korean women. DOSI uses near-infrared light to measure breast tissue composition by quantifying tissue concentrations of water (ctH2O), bulk lipid (ctLipid), deoxygenated (ctHHb), and oxygenated (ctHbO2) hemoglobin. DOSI spectral signatures specific to abnormal tissue and absent in healthy tissue were also used to form a malignancy index. This study included 19 premenopausal subjects (average age 41±9), corresponding to 11 benign and 10 malignant lesions. Elevated lesion to normal ratio of ctH2O, ctHHb, ctHbO2, total hemoglobin (THb=ctHHb+ctHbO2), and tissue optical index (ctHHb×ctH2O/ctLipid) were observed in the malignant lesions compared to the benign lesions (p<0.02). THb and malignancy index were the two best single predictors of malignancy, with >90% sensitivity and specificity. Malignant lesions showed significantly higher metabolism and perfusion than benign lesions. DOSI spectral features showed high discriminatory power for distinguishing malignant and benign lesions in dense breasts of the Korean population.

Background: Bacterial flagellin, a Toll-like receptor 5 agonist, is used as an adjuvant for immunomodulation. In this study, we aimed to evaluate the effect and its mechanism following intralymphatic administration of OVA-flagellin (FlaB) mixture in the mouse model of allergic rhinitis., Materials and Methods: BALB/c mice were sensitized with OVA and treated with an OVA-FlaB mixture via intranasal, sublingual, and intralymphatic routes to evaluate the effect of each treatment. Several parameters for allergic inflammation and its underlying mechanisms were then evaluated., Results: Intralymphatic injection of the OVA-FlaB mixture reduced symptom scores, eosinophil infiltration in the nasal mucosa, and total and OVA-specific IgE levels more significantly than intranasal and sublingual administration. Systemic cytokine (IL-4, IL-5, IL-6, IL-17, and IFN-γ) production and local cytokine (IL-4 and IL-5) production were also reduced significantly after intralymphatic injection with OVA-FlaB. Double intralymphatic injection of the mixture was more effective than single injection. Moreover, the expression of innate cytokines such as IL-25 and IL-33 in nasal epithelial cells was reduced, and the expression of chemokines such as CCL24 (eotaxin-2), CXCL1, and CXCL2 was decreased in the nasal mucosa, suggesting the underlying mechanism for intralymphatic administration of the OVA-FlaB mixture., Conclusion: Intralymphatic administration of an OVA-FlaB mixture was more effective in alleviating allergic inflammation than intranasal and sublingual administration in a mouse model of allergic rhinitis. This effect may be attributed to the reduced expression of innate cytokines and chemokines. This treatment modality can be considered as a new therapeutic method and agent., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Molecularly thin perfluoropolyether (PFPE) has been used extensively as a high-performance lubricant in various applications and, more importantly, on carbon overcoats to enhance the reliability and lubrication of micro-/nanoelectro-mechanical systems, where the tribological performance caused by its molecular architecture is a critical issue, as are its physical properties and rheological characteristics. This Highlight addresses recent trends in the development of fluoro-polymeric lubricant films with regard to their tribology, rheology, and physio-chemical properties as they relate to heat-assisted magnetic recording. Nanorheology has been employed to examine the dynamic response of nonfunctional and functional PFPEs, while the viscoelastic properties of nanoscale PFPE films and the relaxation processes as a function of molecular structure and end-group functionality were analyzed experimentally; furthermore, the characteristics of binary blends were reported.

We evaluated functional and morphological changes after trans-tympanic laser application using several different powers of photobiomodulation (PBM). The left (L) ears of 17 rats were irradiated for 30 min daily over 14 days using a power density of 909.1 (group A, 5040 J), 1136.4 (group B, 6300 J), and 1363.6 (group C, 7560 J) mW/cm(2). The right (N) ears served as controls. The safety of PBM was determined by endoscopic findings, auditory brainstem response (ABR) thresholds, and histological images of hair cells using confocal microscopy, and light microscopic images of the external auditory canal (EAC) and tympanic membrane (TM). Endoscopic findings revealed severe inflammation in the TM of C group; no other group showed damage in the TM. No significant difference in ABR threshold was found in the PBM-treated groups (excluding the group with TM damage). Confocal microscopy showed no histological difference between the AL and AN, or BL and BN groups. However, light microscopy showed more prominent edema, inflammation, and vascular congestion in the TM of BL ears. This study found a dose-response relationship between laser power parameters and TM changes. These results will be useful for defining future allowance criteria for trans-tympanic laser therapies.

Transient receptor potential vanilloid 1 (TRPV1), which has been identified as a molecular target for the activation of sensory neurons by various painful stimuli, was reported to regulate the signaling and activation of CD4+ T cells. However, the role of TRPV1 in CD4+ T cell in allergic rhinitis remains poorly understood. In this study, TRPV1 expression was localized in CD4+ T cells. Both knockout and chemical inhibition of TRPV1 suppressed Th2/Th17 cytokine production in CD4 T cells and Jurkat T cells, respectively, and can suppress T cell receptor signaling pathways including NF-κB, MAP kinase, and NFAT. In TRPV1 knockout allergic rhinitis (AR) mice, eosinophil infiltration, Th2/Th17 cytokines in the nasal mucosa, and total and ova-specific IgE levels in serum decreased, compared with wild-type AR mice. The TRPV1 antagonists, BCTC or theobromine, showed similar inhibitory immunologic effects on AR mice models. In addition, the number of TRPV1+/CD4+ inflammatory cells increased in the nasal mucosa of patients with AR, compared with that of control subjects. Thus, TRPV1 activation on CD4+ T cells is involved in T cell receptor signaling, and it could be a novel therapeutic target in AR.