The effects of photobiomodulation therapy in individuals with tinnitus and without hearing loss.

To verify the effect of photobiomodulation therapy (PBMT) in individuals with chronic tinnitus without hearing loss, 20 patients who met the inclusion criteria were randomly divided into group 1: active low-level laser (LLL) and group 2: equipment without laser (placebo). Upon anamnesis, data collection, and audiological exams, the Tinnitus Handicap Inventory (THI) and the Visual-Analog Scale (EVA) were applied to measure the level of discomfort with tinnitus and the level of discomfort before and after laser treatment. The protocol used included 12 active LLL sessions for group 1 and not active for group 2, varying red and infrared wavelengths. There was a reduction in the disadvantage of individuals with tinnitus after the intervention and between the initial and final sessions, regardless of the intervention, although group 1 showed a greater reduction than group 2, regardless of point in time of assessment and number of session. There was no statistical difference as to group and point in time for the high-frequency audiometry and acuphenometry outcomes. Individuals with chronic tinnitus reduced the complaint, regardless of point in time and group of intervention; however, the group that received PBMT improved the level of satisfaction, regardless of point in time of assessment and number of session.

Photobiomodulation therapy preconditioning modifies nitric oxide pathway and oxidative stress in human-induced pluripotent stem cell-derived ventricular cardiomyocytes treated with doxorubicin.

Doxorubicin (DOX) is an anthracycline antibiotic that exhibits high heart toxicity. Human-induced pluripotent stem cell-derived ventricular cardiomyocytes (hiPSC-vCMs) are important in vitro models for testing drug cardiotoxicity. Photobiomodulation therapy (PBMT) is a non-invasive therapy that stimulates cells growth and self-repair using light irradiation. This study aimed to investigate the in vitro effects of PBMT preconditioning on cardiotoxicity induced by DOX. HiPSC-vCMs were treated with PBMT for 500 s, followed by the addition of 2 µM DOX. LED irradiation preconditioning parameters were at 660 nm with an irradiance of 10 mW/cm2, performing 5 J/cm2, followed by 24-h DOX exposure (2 µM). Human iPSC-vCMs treated with 2 µM DOX or irradiated with PBMT composed the second and third groups, respectively. The control group did neither receive PBMT preconditioning nor DOX and was irradiated with a white standard lamp. Cells from all groups were collected to perform mRNA and miRNA expressions quantification. PBMT, when applied before the DOX challenge, restored the viability of hiPSC-vCMs and reduced ROS levels. Although downregulated by DOX, myocardial UCP2 mRNA expression presented marked upregulation after PBMT preconditioning. Expression of eNOS and UCP2 mRNA and NO production were decreased after DOX exposure, and PBMT preconditioning before the DOX challenge reversed these changes. Moreover, our data indicated that PBMT preconditioning lowered the miR-24 expression. Our data suggested that PBMT preconditioning ameliorated in vitro DOX-induced cardiotoxicity on transcription level, restoring NO levels and reducing oxidative stress.

Photobiomodulation Therapy on Myocardial Infarction in Rats: Transcriptional and Posttranscriptional Implications to Cardiac Remodeling.

BACKGROUND AND OBJECTIVES: Induction of myocardial infarction (MI) in rats by occlusion of the left anterior descending coronary artery is an experimental model used in research to elucidate functional, structural, and molecular modifications associated with ischemic heart disease. Photobiomodulation therapy (PBMT) has become a therapeutic alternative by modulating various biological processes eliciting several effects, including anti-inflammatory and pro-proliferative actions. The main objective of this work was to evaluate the effect of PBMT in the modulation of transcriptional and post-transcriptional changes that occurred in myocardium signal transduction pathways after MI. STUDY DESIGN/MATERIALS AND METHODS: Continuous wave (CW) non-thermal laser parameters were: 660 nm wavelength, power 15 mW, with a total energy of 0.9 J, fluence of 1.15 J/cm2 , spot size of 0.785 cm2 , and time of 60 seconds. Using in silico analysis, we selected and then, quantified the expression of messenger RNA (mRNA) of 47 genes of 9 signaling pathways associated with MI (angiogenesis, cell survival, hypertrophy, oxidative stress, apoptosis, extracellular matrix, calcium kinetics, cell metabolism, and inflammation). Messenger RNA expression quantification was performed in myocardial samples by polymerase chain reaction real-time array using TaqMan customized plates. RESULTS: Our results evidenced that MI modified mRNA expression of several well-known biomarkers related to detrimental cardiac activity in almost all signaling pathways analyzed. However, PBMT reverted most of these transcriptional changes. More expressively, PBMT provoked a robust decrease in mRNA expression of molecules that participate in post-MI inflammation and ECM composition, such as IL-6, TNF receptor, TGFb1, and collagen I and III. Global microRNA (miRNA) expression analysis revealed that PBMT decreased miR-221, miR-34c, and miR-93 expressions post-MI, which are related to deleterious effects in cardiac remodeling. CONCLUSION: Thus, the identification of transcriptional and post-transcriptional changes induced by PBMT may be used to interfere in the molecular dynamics of cardiac remodeling post-MI.

Therapeutic comparison between treatments for Vulvar Lichen Sclerosus: study protocol of a randomized prospective and controlled trial.

BACKGROUND: Vulvar lichen sclerosus (VLS) is a lymphocyte-mediated disease of unknown etiology that can cause intense itching as well stenosis, hindering the evacuation and urination. It can also limit the sex life due to severe local pruritus, pain and dyspareunia (pain during sexual intercourse). The standard treatment for this disease is the use of topical corticosteroids to reduce the clinical symptoms and to try to increase disease-free intervals. Photodynamic therapy (PDT), a treatment that associates a light radiation with a photosensitizing agent and photobiomodulation (PBM) are therapies that can promote effective immunomodulatory responses at the application site by means of photophysical and photochemical phenomena from the molecular to the systemic level, which promote their use in chronic dermatoses. The aim is to compare the effects of PDT, PBM, and topical corticosteroid in VLS evaluating clinical, histological, immunohistochemical and spectroscopic responses. METHODS: The study is prospective, randomized and controlled, in a population of 60 women with histological diagnoses of VLS. There will be 3 treatments groups: PDT, PBM and topical corticosteroid (control group), where will be allocated by randomization 20 patients in each one. The clinical course will be monitored by measuring local temperature, itching, atrophy, and the area of the lesion. Histologically, the slides will be classified and will have the ordering of collagen fibers quantified. Immunohistochemical analysis will be done using the markers IFN-γ, TGF-ß, CD4, CD8, IL-1, p53 and Ki-67. Finally, the spectroscopic evaluation will be done by reflectance. Descriptive and inferential statistical analyses will be conducted to compare the groups and make associations between different responses. The study is an open-label for patients with active symptomatic disease with a period of 1 year follow-up to determine the rate of recurrence in each groups. DISCUSSION: The immunological effects of PDT and PBM are described by several authors in inflammatory skin diseases, stimulating the production and organization of the associated collagen. Thus, it is reasonable to determine the efficacy and safety of these new treatments in VLS, in comparison to the control group, analyzing the recurrence time, the impact on the optical properties of the skin, and the benefit to patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02416531 .

The mechanistic basis for photobiomodulation therapy of neuropathic pain by near infrared laser light.

BACKGROUND AND OBJECTIVE: Various irradiances have been reported to be beneficial for the treatment of neuropathic pain with near infrared light. However, the mechanistic basis for the beneficial outcomes may vary based on the level of irradiance or fluence rate used. Using in vivo and in vitro experimental models, this study determined the mechanistic basis of photobiomodulation therapy (PBMT) for the treatment of neuropathic pain using a high irradiance. STUDY DESIGN/MATERIALS AND METHODS: In vitro experiments: Cultured, rat DRG were randomly assigned to control or laser treatment (LT) groups with different irradiation times (2, 5, 30, 60, or 120 seconds). The laser parameters were: output power = 960 mW, irradiance = 300 mW/cm2 , 808 nm wavelength, and spot size = 3 cm diameter/area = 7.07cm2 , with different fluences according to irradiation times. Mitochondrial metabolic activity was measured with the MTS assay. The DRG neurons were immunostained using a primary antibody to ß-Tubulin III. In vivo experiments: spared nerve injury surgery (SNI), an animal model of persistent peripheral neuropathic pain, was used. The injured rats were randomly divided into three groups (n = 5). (i) Control: SNI without LT; (ii) Short term: SNI with LT on day 7 and euthanized on day 7; (iii) Long term: SNI with LT on day 7 and euthanized on day 22. An 808 nm wavelength laser was used for all treatment groups. Treatment was performed once on day 7 post-surgery. The transcutaneous treatment parameters were: output power: 10 W, fluence rate: 270 mW/cm2 , treatment time: 120 seconds. The laser probe was moved along the course of the sciatic/sural nerve during the treatment. Within 1 hour of irradiation, behavior tests were performed to assess its immediate effect on sensory allodynia and hyperalgesia caused by SNI. RESULTS: In vitro experiments: Mitochondrial metabolism was significantly lower compared to controls for all LT groups. Varicosities and undulations formed in neurites of DRG neurons with a cell body diameter 30 µm or less. In neurites of DRG neurons with a cell body diameter of greater than 30 µm, varicosities formed only in the 120 seconds group. In vivo experiments: For heat hyperalgesia, there was a statistically significant reduction in sensitivity to the heat stimulus compared to the measurements done on day 7 prior to LT. A decrease in the sensitivity to the heat stimulus was found in the LT groups compared to the control group on days 15 and 21. For cold allodynia and mechanical hyperalgesia, a significant decrease in sensitivity to cold and pin prick was found within 1 hour after LT. Sensitivity to these stimuli returned to the control levels after 5 days post-LT. No significant difference was found in mechanical allodynia between control and LT groups for all time points examined. CONCLUSION: These in vitro and in vivo studies indicate that treatment with an irradiance/fluence rate at 270 mW/cm2 or higher at the level of the nerve can rapidly block pain transmission. A combination therapy is proposed to treat neuropathic pain with initial high irradiance/fluence rates for fast pain relief, followed by low irradiance/fluence rates for prolonged pain relief by altering chronic inflammation. Lasers Surg. Med. 49:516-524, 2017. © 2017 Wiley Periodicals, Inc.

Photobiomodulation of the dorsal root ganglion for the treatment of low back pain: A pilot study.

BACKGROUND AND OBJECTIVE: Chronic low back pain is a worldwide public health issue with high socioeconomic impact. The aim of this study was to determine the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for chronic axial low back pain compared to lidocaine injection and radiofrequency treatment. STUDY DESIGN/MATERIALS AND METHODS: Twenty-eight patients were randomly divided into three treatment groups: lidocaine injection, radiofrequency, or laser. The second intervertebral foramen between the second and third lumbar vertebrae was accessed by percutaneous needle puncture bilaterally, guided by fluoroscopy. In the local anesthetic group, injection of 1 ml lidocaine without epinephrine was applied through a 20-gauge (G20) Quincke tip spinal needle inserted in the second lumbar intervertebral foramen. In the radiofrequency group, the probe (150 mm long with a 5 mm active tip) was directed through a G20 needle placed in the second lumbar intervertebral foramen and neuromodulation was done with a radiofrequency of Cosman G4® in pulses of 20 ms with wash-out period of 480 ms, for 300 seconds at 42°C. A single treatment was used. In the laser treatment group, a continuous wave, 808 nm wavelength diode laser (Photon Lase III® DCM, Brazil), with an output power of 100 mW was used for a single treatment. An 18 gauge needle was placed in the second lumbar intervertebral foramen guided by fluoroscopy. Light was delivered through a 600 µm optical fiber placed in the G18 needle. The tip of the fiber extended 5 mm beyond the tip of the needle in the second lumbar intervertebral foramen. The beam spot size was 0.003 cm(2) , irradiance = 35W/cm(2) , exposure time = 84 seconds, energy density = 2800J/cm(2) , total energy was 8.4 J. The low back pain score was assessed by the visual analog scale (VAS) and Pain Relief Scale (PRS) pre, post procedure and in 1 month follow up. Temperature was measured using a digital thermometer. RESULTS: All patients in the local anesthetic and laser treatment groups reported a pain reduction of at least 50% immediately post-procedure and 10 out of 11 patients in the radiofrequency group reported a pain reduction of at least 50%. At 1 month post-treatment, the laser treatment group had the greatest number of patients who reported more than 50% pain relief based on PRS (7 out of 10 patients) while only 2 out of 7 patients and 3 out of 11 patients in the lidocaine and radiofrequency treatment groups respectively reported more than a 50% pain relief. CONCLUSION: Laser irradiation caused an immediate decrease in low back pain post-procedure similar to pain reduction caused by lidocaine injection. Both lidocaine injection and laser irradiation were more effective than radiofrequency treatment for immediate and longer term (1 month post-treatment) chronic back pain. Lasers Surg. Med. 48:653-659, 2016. © 2016 Wiley Periodicals, Inc.

Effect of photobiomodulation in the balance between effector and regulatory T cells in an experimental model of COPD.

Introduction: Currently, Chronic Obstructive Pulmonary Disease (COPD) has a high impact on morbidity and mortality worldwide. The increase of CD4+, CD8+ cells expressing NF-κB, STAT4, IFN-γ and perforin are related to smoking habit, smoking history, airflow rate, obstruction and pulmonary emphysema. Furthermore, a deficiency in CD4+CD25+Foxp3+ regulatory T cells (Tregs) may impair the normal function of the immune system and lead to respiratory immune disease. On the other hand, the anti-inflammatory cytokine IL-10, produced by Treg cells and macrophages, inhibits the synthesis of several pro-inflammatory cytokines that are expressed in COPD. Therefore, immunotherapeutic strategies, such as Photobiomodulation (PBM), aim to regulate the levels of cytokines, chemokines and transcription factors in COPD. Consequently, the objective of this study was to evaluate CD4+STAT4 and CD4+CD25+Foxp3+ cells as well as the production of CD4+IFN- γ and CD4+CD25+IL-10 in the lung after PBM therapy in a COPD mice model. Methods: We induced COPD in C57BL/6 mice through an orotracheal application of cigarette smoke extract. PMB treatment was applied for the entire 7 weeks and Bronchoalveolar lavage (BAL) and lungs were collected to study production of IFN- γ and IL-10 in the lung. After the last administration with cigarette smoke extract (end of 7 weeks), 24 h later, the animals were euthanized. One-way ANOVA followed by NewmanKeuls test were used for statistical analysis with significance levels adjusted to 5% (p < 0.05). Results: This result showed that PBM improves COPD symptomatology, reducing the number of inflammatory cells (macrophages, neutrophils and lymphocytes), the levels of IFN-γ among others, and increased IL-10. We also observed a decrease of collagen, mucus, bronchoconstriction index, alveolar enlargement, CD4+, CD8+, CD4+STAT4+, and CD4+IFN-γ+ cells. In addition, in the treated group, we found an increase in CD4+CD25+Foxp3+ and CD4+IL-10+ T cells. Conclusion: This study suggests that PBM treatment could be applied as an immunotherapeutic strategy for COPD.

Assessment of the pre-emptive effect of photobiomodulation in the postoperative period of impacted lower third molar extractions: A randomized, controlled, double-blind study protocol.

Photobiomodulation is a safe option for controlling pain, edema, and trismus when applied postoperatively in third molar surgery. However, administration prior to surgery has been under-explored. This study aims to explore the effectiveness of pre-emptive photobiomodulation in reducing postoperative edema in impacted lower third molar extractions. Two groups of healthy individuals undergoing tooth extraction will be randomly assigned: Control group receiving pre-emptive corticosteroid and simulated photobiomodulation, and Photobiomodulation Group receiving intraoral low-intensity laser and extraoral LED cluster application. The primary outcome will be postoperative edema after 48 h. The secondary outcomes will be pain, trismus dysphagia, and analgesic intake (paracetamol). These outcomes will be assessed at baseline as well as two and seven days after surgery. Adverse effects will be recorded. Data will be presented as means ± SD and a p-value < 0.05 will be indicative of statistical significance.

Low-level laser in the treatment of patients with hypothyroidism induced by chronic autoimmune thyroiditis: a randomized, placebo-controlled clinical trial.

Chronic autoimmune thyroiditis (CAT) is the most common cause of acquired hypothyroidism, which requires lifelong levothyroxine replacement therapy. Currently, no effective therapy is available for CAT. Thus, the objective of this study was to evaluate the efficacy of low-level laser therapy (LLLT) in patients with CAT-induced hypothyroidism by testing thyroid function, thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and ultrasonographic echogenicity. A randomized, placebo-controlled trial with a 9-month follow-up was conducted from 2006 to 2009. Forty-three patients with a history of levothyroxine therapy for CAT-induced hypothyroidism were randomly assigned to receive either 10 sessions of LLLT (830 nm, output power of 50 mW, and fluence of 707 J/cm(2); L group, n=23) or 10 sessions of a placebo treatment (P group, n=20). The levothyroxine was suspended 30 days after the LLLT or placebo procedures. Thyroid function was estimated by the levothyroxine dose required to achieve normal concentrations of T3, T4, free-T4 (fT4), and thyrotropin after 9 months of postlevothyroxine withdrawal. Autoimmunity was assessed by measuring the TPOAb and TgAb levels. A quantitative computerized echogenicity analysis was performed pre- and 30 days postintervention. The results showed a significant difference in the mean levothyroxine dose required to treat the hypothyroidism between the L group (38.59 ± 20.22 µg/day) and the P group (106.88 ± 22.90 µg/day, P<0.001). Lower TPOAb (P=0.043) and greater echogenicity (P<0.001) were also noted in the L group. No TgAb difference was observed. These findings suggest that LLLT was effective at improving thyroid function, promoting reduced TPOAb-mediated autoimmunity and increasing thyroid echogenicity in patients with CAT hypothyroidism.

Effect of Photobiomodulation Combined with Physiotherapy on Functional Performance in Children with Myelomeningo-Cele-Randomized, Blind, Clinical Trial.

BACKGROUND: This study aimed to evaluate the electrical activity of the rectus femoris, tibialis anterior, and lateral gastrocnemius muscles during the sit-to-stand task and functional mobility after a neurofunctional physiotherapy protocol associated with PBM. METHODS: Twenty-five children were randomly allocated to either Active PBM + physiotherapy (n = 13) or PBM sham + physiotherapy (n = 12). PBM was carried out with a LED device (850 nm, 25 J, 50 s per point and 200 mW) at four points over the area with absence of a spiny process. Both groups completed a twelve-week supervised program with two weekly 45-60 min sessions. Pre-training and post-training assessments involved the Pediatric Evaluation of Disability Inventory (PEDI). Muscle activity was assessed using portable electromyography (BTS Engineering) and the electrodes were positioned on the lateral gastrocnemius, anterior tibialis, and rectus femoris muscles. The RMS data were recorded and analyzed. RESULTS: After 24 sessions of the treatment protocol, improvements were found in the PEDI score. The participants presented greater independence in performing the tasks, requiring less assistance from their caregivers. More significant electrical activity was found in the three muscles evaluated between the rest period and execution of the sit-to-stand tasks, both in the more compromised or less compromised lower limbs. CONCLUSION: Neurofunctional physiotherapy with or without PBM improved functional mobility and electrical muscle activity in children with myelomeningocele.

Analysis of the Potential of Blood Transvascular Sublingual with Light-Emitting Diode Irradiation in COVID-19 Patients: A Pilot Clinical Study.

Background: Due to the high morbidity and mortality rates of this century, the COVID-19 pandemic has had a devastating impact on the health of the global population. Objective: The aim was to evaluate the disturbing impact of in-hospital stay length and the appeal of severe problems for supplemental oxygen for our patients with COVID-19 in moderate stage who were undergoing transvascular blood irradiation onto sublingual vessels. The demand for supplemental oxygen and the serum oxygen levels were measured, and the impact on the length of hospital stay was assessed. Methods: This randomized, prospective, clinical pilot study evaluated the diagnosis of COVID-19 patients admitted to the ventilatory care unit and undergoing treatment protocol usage of light-emitting diode (LED) irradiation by transvascular application onto the sublingual vessels daily. Patients were selected and enrolled into two groups: the Placebo group (n = 7) that received conventional treatment by the device off (LED-off), and the photobiomodulation therapy (PBMT) group (n = 7) that also received the same therapy plus LED irradiation. Results: There was a statistically significant clinical improvement, such as a reduction in serum creatinine, and oxygen usage per few days less in the PBMT group compared with the Placebo group. All patients in the PBMT group had normalized SatO2, while a quarter of patients in the Placebo group required longer O2 supplementation until hospital discharge. Conclusions: The surveillance of clinical improvement in moderate stage indicated that the daily PBMT was able to diminish oxygen supplementation within a short time, besides reducing the hospital stay length in the PBMT group, particularly, when compared with the Placebo group. Clinical Trial Registration number: The study was reviewed by the Ethics Committee in UNINOVE research under number 42325020.6.0000.5511 and approved through number 5,090,119.

Evaluation of the Combination of CO2 Laser and Bifunctional Bonding Agents for Composite Resin Repairs After 1 Year of Aging.

Objective: to evaluate the bond strength of repairs to composite resin restorations treated with CO2 laser and bifunctional monomers after 1 year of aging. Background: Adequate bond strength between a composite restoration and resin repair agent can be achieved through mechanical and/or chemical treatment. However, the longevity of such repairs is unknown. Methods: Resin blocks (volume: 125 mm3) were created. Failure surfaces were either not treated or were treated before the repair with a universal adhesive, a silane bonding agent and/or CO2 laser. The blocks were distributed into six groups (n = 6 per group): resin+resin group (RRG), universal adhesive+resin group (ARG), silane+universal adhesive group (SAG), laser+silane+universal adhesive group (LSAG), laser+universal adhesive group (LAG), and laser+silane group (LSG). After treatment, repairs were made with another resin composite. "Sticks" (1.0 mm2 in area and 1.0 cm in length) were cut from the specimens in each group and immersed in distilled water at 37°C. Microtensile bond strength was evaluated after 1 year of aging. Bond strength values were compared using the Kruskal-Wallis test and Dunn's test. Results: Bond strength was significantly higher in the LSAG compared with the RRG, adhesive system, LSG, whereas statistically similar results were found for the SAG, LSAG, and LAG. Bond strength was lowest in the RRG. The LSAG and LAG presented predominantly cohesive fractures. Conclusions: The bond strength of composite resin repairs was satisfactory over time. Treatment with CO2 laser contributed to the maintenance of bond strength during the 1-year storage period and bifunctional monomers present in the universal adhesive on the irradiated repair surface were of fundamental importance to the maintenance of bond strength values, as demonstrated by microtensile bond test and fracture pattern analysis.

Photobiomodulation Therapy Restores IL-10 Secretion in a Murine Model of Chronic Asthma: Relevance to the Population of CD4+CD25+Foxp3+ Cells in Lung.

It is largely known that photobiomodulation (PBM) has beneficial effects on allergic pulmonary inflammation. Our previous study showed an anti-inflammatory effect of the PBM in an acute experimental model of asthma, and we see that this mechanism is partly dependent on IL-10. However, it remains unclear whether the activation of regulatory T cells is mediated by PBM in a chronic experimental model of asthma. In this sense, the objective of this study was to verify the anti-inflammatory role of the PBM in the pulmonary inflammatory response in a chronic experimental asthma model. The protocol used for asthma induction was the administration of OVA subcutaneously (days 0 and 14) and intranasally (3 times/week, for 5 weeks). On day 50, the animals were sacrificed for the evaluation of the different parameters. The PBM used was the diode, with a wavelength of 660 nm, a power of 100 mW, and 5 J for 50 s/point, in three different application points. Our results showed that PBM decreases macrophages, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid (BALF). Moreover, PBM decreased the release of cytokines by the lung, mucus, and collagen in the airways and pulmonary mechanics. When we analyzed the percentage of Treg cells in the group irradiated with laser, we verified an increase in these cells, as well as the release of IL-10 in the BALF. Therefore, we conclude that the use of PBM therapy in chronic airway inflammation attenuated the inflammatory process, as well as the pulmonary functional and structural parameters, probably due to an increase in Treg cells.

Effect of photobiomodulation combined with physical therapy on functional performance in children with myelomeningocele: A protocol randomized clinical blind study.

INTRODUCTION: Myelomeningocele is a severe type of spina bifida, resulting from improper closure of the neural tube. This condition drastically affects the structures of the spinal cord resulting in deficiencies. The combination of these deficiencies results in an overall decrease in mobility and functional participation amongst this population. Physiotherapy plays an essential role in rehabilitating people with MMC. The current literature shows that resources such as photobiomodulation (PBM) may support the rehabilitation of neurological conditions. The aim of the proposed study is to evaluate the effects of photobiomodulation (PBM) combined with physical therapy on functional performance in children with low lumbosacral myelomeningocele. MATERIALS AND METHODS: This is a protocol randomized clinical blind study, that will include 30 individuals of both sexes, aged between 5 to 8 years, diagnosed with low and sacral lumbar myelomeningocele and capable of performing the sit-to-stand task. The participants will be randomly assigned into two treatment groups: PBM + physiotherapeutic exercises and sham PBM + physiotherapeutic exercises. Irradiation will be carried out with light emitting diode (LED) at a wavelength of 850 nm, energy of 25 J per point, 50 seconds per point and a power of 200 mW. The same device will be used in the placebo group but will not emit light. Muscle activity will be assessed using a portable electromyograph (BTS Engineering) and the sit-to-stand task will be performed as a measure of functioning. Electrodes will be positioned on the lateral gastrocnemius, tibialis anterior and rectus femoris muscles. The Pediatric Evaluation of Disability Inventory will be used to assess functional independence. Quality of life will be assessed using the Child Health Questionnaire-Parent Form 50. Changes in participation will be assessed using the Participation and Environment Measure for Children and Youth. The data will be analyzed with the aid of GraphPad PRISM. DISCUSSION: The results of this study can contribute to a better understanding of the effectiveness of PBM on functioning and quality of life in children with myelomeningocele. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04425330.

Low-level laser therapy in chronic autoimmune thyroiditis: a pilot study.

BACKGROUND AND OBJECTIVES: Chronic autoimmune thyroiditis (CAT) remains the most common cause of acquired hypothyroidism. There is currently no therapy that is capable of regenerating CAT-damaged thyroid tissue. The objective of this study was to gauge the value of applying low-level laser therapy (LLLT) in CAT patients based on both ultrasound studies (USs) and evaluations of thyroid function and thyroid autoantibodies. STUDY DESIGN/MATERIALS AND METHODS: Fifteen patients who had hypothyroidism caused by CAT and were undergoing levothyroxine (LT4) treatment were selected to participate in the study. Patients received 10 applications of LLLT (830 nm, output power 50 mW) in continuous mode, twice a week, using either the punctual technique (8 patients) or the sweep technique (7 patients), with fluence in the range of 38-108 J/cm(2). USs were performed prior to and 30 days after LLLT. USs included a quantitative analysis of echogenicity through a gray-scale computerized histogram index (EI). Following the second ultrasound (30 days after LLLT), LT4 was discontinued in all patients and, if required, reintroduced. Triiodothyronine, thyroxine (T4), free T4, thyrotropin, thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) antibodies levels were assessed before LLLT and then 1, 2, 3, 6, and 9 months after LT4 withdrawal. RESULTS: We noted all patients' reduced LT4 dosage needs, including 7 (47%) who did not require any LT4 through the 9-month follow-up. The LT4 dosage used pre-LLLT (96 +/- 22 microg/day) decreased in the 9th month of follow-up (38 +/- 23 microg/day; P < 0.0001). TPOAb levels also decreased (pre-LLLT = 982 +/- 530 U/ml, post-LLLT = 579 +/- 454 U/ml; P = 0.016). TgAb levels were not reduced, though we did observe a post-LLLT increase in the EI (pre-LLLT = 0.99 +/- 0.09, post-LLLT = 1.21 +/- 0.19; P = 0.001). CONCLUSION: The preliminary results indicate that LLLT promotes the improvement of thyroid function, as patients experienced a decreased need for LT4, a reduction in TPOAb levels, and an increase in parenchymal echogenicity.

Effects of low-level laser therapy on collagen expression and neutrophil infiltrate in 5-fluorouracil-induced oral mucositis in hamsters.

BACKGROUND AND OBJECTIVES: Several studies have suggested that low-level laser therapy (LLLT) can ameliorate oral mucositis; however, the mechanisms involved are not well understood. The aim of this study was to investigate the mechanisms of action of LLLT on chemotherapy-induced oral mucositis, as related to effects on collagen expression and inflammation. MATERIALS AND METHODS: A hamster cheek pouch model of oral mucositis was used with all animals receiving intraperitoneal 5-fluorouracil, followed by surface irritation. Animals were randomly allocated into three groups, and treated with an InGaAIP diode laser at a wavelength of 660 nm and output power of 35 or 100 mW laser, or no laser. Clinical severity of mucositis was assessed at four time-points by a blinded examiner. Buccal pouch tissue was harvested from a subgroup of animals in each group at four time-points. Collagen was qualitatively and quantitatively evaluated after picrosirius staining. The density of the neutrophil infiltrate was also scored. RESULTS: Peak clinical severity of mucositis was reduced in the 35 mW laser group as compared to the 100 mW and control groups. The reduced peak clinical severity of mucositis in the 35 mW laser group was accompanied by a decrease in the number of neutrophils and an increase in the proportion of mature collagen as compared to the other two groups. The total quantity of collagen was significantly higher in the control (no laser) group at the day 11 time-point, as compared to the 35 mW laser group, consistent with a more prolonged inflammatory response in the control group. CONCLUSION: This study supports two mechanisms of action for LLLT in reducing mucositis severity. The increase in collagen organization in response to the 35 mW laser indicates that LLLT promotes wound healing. In addition, LLLT also appears to have an anti-inflammatory effect, as evidenced by the reduction in neutrophil infiltrate.

Effect of Isolated Proteins from Crotalus Durissus Terrificus Venom on Leishmania (Leishmania) Amazonensis-Infected Macrophages.

BACKGROUND: Cutaneous and mucocutaneous leishmaniasis are parasitic diseases characterized by skin manifestations. In Brazil, Leishmania (Leishmania) amazonensis is one of the etiological agents of cutaneous leishmaniasis. The therapeutic arsenal routinely employed to treat infected patients is unsatisfactory, especially for pentavalent antimonials, as they are often highly toxic, poorly tolerated and of variable effectiveness. This study aimed to evaluate in vitro the leishmanicidal activity of toxins isolated from Crotalus durissus terrificus venom as a new approach for the treatment of leishmaniasis. METHODS: The comparative effects of crotamine, crotoxin, gyrotoxin, convulxin and PLA2 on bone marrow-derived macrophages infected with L. (L.) amazonensis as well as the release of TGF-ß from the treated macrophages were studied. RESULTS AND DISCUSSION: Crotamine had the strongest inhibitory effect on parasite growth rate (IC50: 25.65±0.52 µg/mL), while convulxin showed the weakest inhibitory effect (IC50: 52.7±2.21 µg/mL). In addition, TGF-ß was significantly reduced after the treatment with all toxins evaluated. CONCLUSION: The Crotalus durissus terrificus toxins used in this study displayed significant activity against L. (L.) amazonensis, indicating that all of them could be a potential alternative for the treatment of cutaneous leishmaniasis.

Photobiomodulation by low-level laser therapy in patients with obstructive sleep apnea: Study protocol clinical trial (SPIRIT compliant).

Obstructive sleep apnea (OSA) increases morbidity and mortality and it is associated with an increased cardiovascular risk. The gold standard treatment for OSA is positive airway pressure therapy (CPAP). However, it is an expensive treatment and several patients do not adapt to CPAP. GOAL: The researchers will verify the effects of low-level laser therapy (LLLT) on OSA, when applied to the soft palate and on the tongue base. METHODS: The researchers will select individuals of both sexes aged 30 to 60 years old who are sedentary and that present a high risk of OSA by the Berlin questionnaire. The evaluations pre and post interventions will be polysomnography; anthropometric and body composition measurements (Bioimpedance); metabolic syndrome risk factors (International Diabetes Federation); physical capacity (VO2 peak at the cardiopulmonary exercise test, CPET); endothelial function (flow-mediated dilatation, FMD); autonomic control (heart rate variability and sympathovagal balance). Those diagnosed with moderate and severe OSA (apnea/hypopnea index, AHI ≥15 events/h) will be invited to participate in the study and they will be randomized into 2 groups: LLLT treatment or placebo (C). The LLLT group will receive applications at 8 points on the soft palate and on the base of the tongue for 8 seconds for each point. The applications of LLLT will occur twice a week, with a minimum interval of 2 days between the applications for 2 months, when using a Therapy Plus NS 13678 Laser. The C group will have similar applications, but with the device turned off. EXPECTED RESULTS: In the individuals with OSA, photobiomodulation through LLLT will decrease the AHI. Additionally, when LLLT is applied in the oral cavity, a highly vascularized region, this may cause improvements in the vascular function and in the autonomic and hemodynamic control. ETHICS AND DISSEMINATION: This protocol was approved by the Research Ethics Committee of the Nove de Julho University, São Paulo, Brazil, on the date of March 11, 2019 (CAAE: 06025618.2.0000.5511 - Acceptance Number: 3.191.077). This trial has been registered with the Brazilian Registry of Clinical Trials (REBEC TRIAL RBR-42v548). This study is not yet recruiting. Issue date: November 4, 2019.

Effects of photobiomodulation on interleukin-10 and nitrites in individuals with relapsing-remitting multiple sclerosis - Randomized clinical trial.

OBJECTIVE: Investigate the effects of photobiomodulation (PBM) on the expression of IL-10 and nitrites in individuals with Relapsing-Remitting multiple sclerosis (MS), as these biomarkers play a fundamental role in the physiopathology of the disease. The modulation of IL-10 and nitrites through treatment with PBM may be a novel treatment modality for MS. METHODS: A randomized, uncontrolled, clinical trial was conducted involving 14 individuals with a diagnosis of Relapsing-Remitting MS and a score of up to 6.0 on the Expanded Disability Status Scale (EDSS). THE PARTICIPANTS WERE RANDOMIZED TO TWO GROUPS: Group 1 -PBM in the sublingual region; Group 2 -PBM over the radial artery. Irradiation was administered with a wavelength of 808 nm and output power of 100 mW for 360 seconds twice a week, totaling 24 sessions. Peripheral blood was analyzed for the determination of serum levels of IL-10 and nitrites. RESULTS: After treatment with PBM, the expression of IL-10 increased in both the sublingual group (pre-treatment: 2.8 ± 1.4 pg/ml; post-treatment: 8.3 ± 2.4 pg/ml) and the radial artery group (pre-treatment: 2.7 pg/ml ± 1.4; post-treatment: 11.7 ± 3.8 pg/ml). In contrast, nitrite levels were not modulated in the sublingual group (pre-treatment: 65 ± 50 nmol/mg protein; post-treatment: 51 ± 42 nmol/mg protein) or the radial artery group (pre-treatment: 51 ± 16 nmol/mg protein; post-treatment: 42 ± 7 nmol/mg protein). CONCLUSION: Treatment with PBM positively modulated the expression of IL-10 but had no effect on nitrite levels. Further studies should be conducted with a larger sample and a control group, as PBM may be a promising complementary treatment for the management of MS. This trial is registered at ClinicalTrials.gov. Identifier: NCT03360487.