Dose-dependent effects of transcranial photobiomodulation on brain temperature in patients with major depressive disorder: a spectroscopy study.

This study aimed to evaluate the dose-dependent brain temperature effects of transcranial photobiomodulation (t-PBM). Thirty adult subjects with major depressive disorder were randomized to three t-PBM sessions with different doses (low: 50 mW/cm2, medium: 300 mW/cm2, high: 850 mW/cm2) and a sham treatment. The low and medium doses were administered in continuous wave mode, while the high dose was administered in pulsed wave mode. A 3T MRI scanner was used to perform proton magnetic resonance spectroscopy (1H-MRS). A voxel with a volume of 30 × 30 × 15 mm3 was placed on the left prefrontal region. Brain temperature (°C) was derived by analyzing 1H-MRS spectrum chemical shift differences between the water (~ 4.7 ppm) and N-acetyl aspartate (NAA) (~ 2.01 ppm) peaks. After quality control of the data, the following group numbers were available for both pre- and post-temperature estimations: sham (n = 10), low (n = 11), medium (n = 10), and high (n = 8). We did not detect significant temperature differences for any t-PBM-active or sham groups post-irradiation (p-value range = 0.105 and 0.781). We also tested for potential differences in the pre-post variability of brain temperature in each group. As for t-PBM active groups, the lowest fluctuation (variance) was observed for the medium dose (σ2 = 0.29), followed by the low dose (σ2 = 0.47), and the highest fluctuation was for the high dose (σ2 = 0.67). t-PBM sham condition showed the overall lowest fluctuation (σ2 = 0.11). Our 1H-MRS thermometry results showed no significant brain temperature elevations during t-PBM administration.

Effect of deep tissue laser therapy treatment on peripheral neuropathic pain in older adults with type 2 diabetes: a pilot randomized clinical trial.

BACKGROUND: This study assessed the safety and efficacy of deep tissue laser therapy on the management of pain, functionality, systemic inflammation, and overall quality of life of older adults with painful diabetic peripheral neuropathy. METHODS: The effects of deep tissue laser therapy (DTLT) were assessed in a randomized, double-masked, sham-controlled, interventional trial. Forty participants were randomized (1:1) to receive either DTLT or sham laser therapy (SLT). In addition to the standard-of-care treatment, participants received either DTLT or SLT twice weekly for 4 weeks and then once weekly for 8 weeks (a 12-week intervention period). The two treatments were identical, except that laser emission was disabled during SLT. Assessments for pain, functionality, serum levels of inflammatory biomarkers, and quality of life (QOL) were performed at baseline and after the 12-week intervention period. The results from the two treatments were compared using ANOVA in a pre-test-post-test design. RESULTS: All participants randomized to the DTLT group and 85% (17 of 20) of participants randomized to the SLT group completed the trial. No significant differences in baseline characteristics between the groups were observed. After the 12-week intervention period, pain levels significantly decreased in both groups and were significantly lower in the DTLT group than in the SLT group. The Timed Up and Go test times (assessing functionality) were significantly improved in both groups and were 16% shorter in the DTLT group than in the SLT group. Serum levels of IL-6 decreased significantly in both groups. Additionally, serum levels of MCP-1 decreased significantly in the DTLT group but not in the SLT group. Patients' quality of life improved significantly in the DTLT group but not in the SLT group. CONCLUSIONS: Deep tissue laser therapy significantly reduced pain and improved the quality of life of older patients with painful diabetic peripheral neuropathy. TRIAL REGISTRATION: Clinical Trial Registry-India CTRI/2017/06/008739 . [Registered on: 02/06/2017]. The trial was registered retrospectively.

Cadmium-calcium interference in the Rhinella arenarum oviduct.

Given that the cadmium (Cd) toxicity could be due to its interference with the calcium (Ca) homeostasis, the aim of this work was to study the effect of Cd over the presence, distribution and volume density (Vv) of Ca and Ca-ATPase in the secretory cells of the pars preconvoluta (PPC) and the pars convoluta (pc) in Rhinella arenarum. The severe effect of the xenobiotic (CdCl2 2.5 mg/kg) in sexually matured females was evaluated. Co-localization, as well as a marked reduction of Ca and Ca-ATPase, was observed in treated animals, in the areas analyzed, compared to control. Low calcium deposits were found in the secreting granules (SG) of the epithelial (ESC) and glandular secretory cells (GSC), while an increase in their cytoplasm and intracellular space was observed. The Ca-ATPase in treated and control animals was detected at the SG and the plasmatic membrane of the ESC and GSC. In relation to the Vv estimates, a substantial reduction of Ca deposits and Ca-ATPase activity was observed in the treated group, with respect to the control. Both amounts of Vv of Ca and Ca-ATPase activity were higher in PPC than in pc, and, higher in ESC than in GSC. These results were associated with the Cd concentration in the oviductal PC, determining that it is a bioaccumulator organ. Thus, this work demonstrated that the Cd interacted with Ca-ATPase, leading to an increase of cytosolic Ca, which is responsible for the possible disruptions in cellular metabolism.

Transcranial photobiomodulation in children aged 2-6 years: a randomized sham-controlled clinical trial assessing safety, efficacy, and impact on autism spectrum disorder symptoms and brain electrophysiology.

Background: Small pilot studies have suggested that transcranial photobiomodulation (tPBM) could help reduce symptoms of neurological conditions, such as depression, traumatic brain injury, and autism spectrum disorder (ASD). Objective: To examine the impact of tPBM on the symptoms of ASD in children aged two to six years. Method: We conducted a randomized, sham-controlled clinical trial involving thirty children aged two to six years with a prior diagnosis of ASD. We delivered pulses of near-infrared light (40 Hz, 850 nm) noninvasively to selected brain areas twice a week for eight weeks, using an investigational medical device designed for this purpose (Cognilum™, JelikaLite Corp., New York, United States). We used the Childhood Autism Rating Scale (CARS, 2nd Edition) to assess and compare the ASD symptoms of participants before and after the treatment course. We collected electroencephalogram (EEG) data during each session from those participants who tolerated wearing the EEG cap. Results: The difference in the change in CARS scores between the two groups was 7.23 (95% CI 2.357 to 12.107, p = 0.011). Seventeen of the thirty participants completed at least two EEGs and time-dependent trends were detected. In addition, an interaction between Active versus Sham and Scaled Time was observed in delta power (Coefficient = 7.521, 95% CI -0.517 to 15.559, p = 0.07) and theta power (Coefficient = -8.287, 95% CI -17.199 to 0.626, p = 0.07), indicating a potential trend towards a greater reduction in delta power and an increase in theta power over time with treatment in the Active group, compared to the Sham group. Furthermore, there was a significant difference in the condition (Treatment vs. Sham) in the power of theta waves (net_theta) (Coefficient = 9.547, 95% CI 0.027 to 19.067, p = 0.049). No moderate or severe side effects or adverse effects were reported or observed during the trial. Conclusion: These results indicate that tPBM may be a safe and effective treatment for ASD and should be studied in more depth in larger studies.Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04660552, identifier NCT04660552.

Three-dimensional irradiance and temperature distributions resulting from transdermal application of laser light to human knee-A numerical approach.

The use of light for therapeutic applications requires light-absorption by cellular chromophores at the target tissues and the subsequent photobiomodulation (PBM) of cellular biochemical processes. For transdermal deep tissue light therapy (tDTLT) to be clinically effective, a sufficiently large number of photons must reach and be absorbed at the targeted deep tissue sites. Thus, delivering safe and effective tDTLT requires understanding the physics of light propagation in tissue. This study simulates laser light propagation in an anatomically accurate human knee model to assess the light transmittance and light absorption-driven thermal changes for eight commonly used laser therapy wavelengths (600-1200 nm) at multiple skin-applied irradiances (W cm-2 ) with continuous wave (CW) exposures. It shows that of the simulated parameters, 2.38 W cm-2 (30 W, 20 mm beam radius) of 1064 nm light generated the least tissue heating -4°C at skin surface, after 30 s of CW irradiation, and the highest overall transmission-approximately 3%, to the innermost muscle tissue.

Pulsed light irradiation improves behavioral outcome in a rat model of chronic mild stress.

BACKGROUND AND OBJECTIVE: Transcranial laser therapy (TLT) has been used successfully for the treatment of stroke in animal models and clinical trials. These results support the hypothesis that TLT could be used to treat other central nervous system conditions, such as depression. Current therapy for depression emphasizes pharmaco-therapeutics. However, these interventions often cause unwanted side effects. Here, TLT as a treatment for depression was studied in a rat model of chronic mild stress (CMS). STUDY DESIGN/MATERIAL AND METHODS: Wistar rats were randomized into four experimental groups (n = 8): (1) No-stress; (2) stress without treatment (Stress); (3) stress treated with an antidepressant (Drug); and (4) stress treated with TLT (TLT). The rats in the stress groups were exposed sequentially to a variety of mild stressors for 8 weeks. Rats were weighed weekly. After 5 weeks of stressing, the Drug group received a daily injection of fluoxetine (10 mg/kg), and the TLT group was irradiated transcranially 3 times a week (810 nm wavelength laser, 3 mm diameter probe, 350 mW peak power, 100 Hz with 20% duty cycle, 2-minute treatment time, 120 J/cm(2) average energy density on skin surface). After 3 weeks of treatment, a forced swimming test (FST) was performed and recorded for behavioral assessment. Animals were euthanized after 8 weeks of the study. RESULTS: The No-stress group had significantly higher body weight than stress groups from week 5 (P < 0.05). No weight difference was found between the stress groups before treatment. However, the Drug group had significantly less body weight than both Stress and TLT groups after 2 weeks of treatment (P < 0.05). FST showed that the Stress group had significantly more immobility than the No-stress group (P < 0.05). Both Drug and TLT groups had significantly less immobility than the stress group (P < 0.05). There was no significant difference in immobility between both Drug and TLT groups (P = 0.62). CONCLUSIONS: TLT was comparable to fluoxetine in improving the behavioral outcome after CMS. TLT did not cause weight loss, which is consistently seen in patients treated with fluoxetine. This study demonstrates that TLT has potential as an effective treatment for depression.

Successful Treatment With Daptomycin of MRSA Empyema Complicated by Right-Sided Loculated Pleural Effusion Refractory to Vancomycin.

Empyema is a serious complication of pneumonia and has been reported to have a mortality rate of 8.7%. For methicillin-resistant Staphylococcus aureus (MRSA) empyema, treatment includes drainage and specific antibiotics such as vancomycin and linezolid. Strikingly, there are increasing incidences of empyema refractory to vancomycin and linezolid. Despite being inactivated in the lung parenchyma by pulmonary surfactant, daptomycin can penetrate the pleural space and may be better at treating MRSA empyema than vancomycin and linezolid. Some case reports have shown that daptomycin has been used to successfully treat MRSA empyema refractory to linezolid and vancomycin-resistant enterococcus (VRE) empyema. Here, we present a 26-year-old male with a past medical history of intravenous (IV) drug use, newly diagnosed HIV, HCV, and multifocal pneumonia complicated by a left-sided MRSA empyema that partially resolved with vancomycin and drainage. However, he subsequently developed a right-sided loculated pleural effusion. After the patient was switched to daptomycin with continued drainage, the right and left pleural effusions improved significantly. Once medically stable, he was discharged to a rehabilitation facility for further recovery. Our case report demonstrates that daptomycin could be considered as an effective treatment for MRSA empyema, particularly when refractory to vancomycin.

Very Low-Level Transcranial Photobiomodulation for Major Depressive Disorder: The ELATED-3 Multicenter, Randomized, Sham-Controlled Trial.

Background: Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light might represent a treatment for major depressive disorder (MDD). However, the dosimetry of administered t-PBM varies widely. We tested the efficacy of t-PBM with low irradiance, low energy per session, and low number of sessions in individuals with MDD.Methods: A 2-site, double-blind, sham-controlled study was conducted of adjunct t-PBM NIR (830 nm; continuous wave; 35.8 cm2 treatment area; 54.8 mW/cm2 irradiance; 65.8 J/cm2 fluence, 20 min/session; ~2 W total power; 2.3 kJ total energy per session), delivered to the prefrontal cortex, bilaterally, twice a week for 6 weeks, in subjects diagnosed with MDD per the DSM-IV criteria. Subjects were recruited between August 2016 and May 2018. A sequential parallel comparison design was used: 18 nonresponders to sham in phase 1 (6 weeks) were re-randomized in phase 2. The primary outcome was reduction in depression severity (Hamilton Depression Rating Scale [HDRS-17] and Quick Inventory of Depressive Symptomatology-Clinician Rating [QIDS-C] scores) from baseline. Statistical analyses used R package SPCDAnalyze2, including all subjects with ≥ 1 post-randomization evaluation.Results: Of the 54 subjects recruited, we included 49 MDD subjects in the analysis (71% female, mean ± SD age 40.8 ± 16.1 years). There were no significant differences between t-PBM and sham with respect to the change in HDRS-17 (t = -0.319, P = .751) or QIDS-C (t = -0.499, P = .620) scores. The sham effect was reasonably low.Conclusions: Mostly uncontrolled studies suggest the efficacy of t-PBM for MDD; however, its optimal dose is still to be defined. A minimal dose threshold is likely necessary, similarly to other neuromodulation techniques in MDD (electroconvulsive therapy, transcranial magnetic stimulation). We established a threshold of inefficacy of t-PBM for MDD, based on combined low irradiance, low energy per session, and low number of sessions.Trial Registration: ClinicalTrials.gov identifier: NCT02959307.

Baseline situational analysis in Bangladesh, Jordan, Paraguay, the Philippines, Ukraine, and Zimbabwe for the WHO Special Initiative for Mental Health: Universal Health Coverage for Mental Health.

INTRODUCTION: Mental, neurological and substance use conditions lead to tremendous suffering, yet globally access to effective care is limited. In line with the 13th General Programme of Work (GPW 13), in 2019 the World Health Organization (WHO) launched the WHO Special Initiative for Mental Health: Universal Health Coverage for Mental Health to advance mental health policies, advocacy, and human rights and to scale up access to quality and affordable care for people living with mental health conditions. Six countries were selected as 'early-adopter' countries for the WHO Special Initiative for Mental Health in the initial phase. Our objective was to rapidly and comprehensively assess the strength of mental health systems in each country with the goal of informing national priority-setting at the outset of the Initiative. METHODS: We used a modified version of the Program for Improving Mental Health Care (PRIME) situational analysis tool. We used a participatory process to document national demographic and population health characteristics; environmental, sociopolitical, and health-related threats; the status of mental health policies and plans; the prevalence of mental disorders and treatment coverage; and the availability of resources for mental health. RESULTS: Each country had distinct needs, though several common themes emerged. Most were dealing with crises with serious implications for population mental health. None had sufficient mental health services to meet their needs. All aimed to decentralize and deinstitutionalize mental health services, to integrate mental health care into primary health care, and to devote more financial and human resources to mental health systems. All cited insufficient and inequitably distributed specialist human resources for mental health as a major impediment. CONCLUSIONS: This rapid assessment facilitated priority-setting for mental health system strengthening by national stakeholders. Next steps include convening design workshops in each country and initiating monitoring and evaluation procedures.

Dose response effects of 810 nm laser light on mouse primary cortical neurons.

BACKGROUND AND OBJECTIVES: In the past four decades numerous studies have reported the efficacy of low level light (laser) therapy (LLLT) as a treatment for diverse diseases and injuries. Recent studies have shown that LLLT can biomodulate processes in the central nervous system and has been extensively studied as a stroke treatment. However there is still a lack of knowledge on the effects of LLLT at the cellular level in neurons. The present study aimed to study the effect of 810 nm laser on several cellular processes in primary cortical neurons cultured from embryonic mouse brains. STUDY DESIGN/MATERIALS AND METHODS: Neurons were irradiated with fluences of 0.03, 0.3, 3, 10, or 30 J/cm(2) of 810-nm laser delivered over varying times at 25 mW/cm(2) and intracellular levels of reactive oxygen species (ROS), nitric oxide and calcium were measured using fluorescent probes within 5 minutes of the end of irradiation. The changes in mitochondrial function in response to light were studied in terms of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP). RESULTS: Light induced a significant increase in calcium, ATP and MMP at lower fluences and a decrease at higher fluences. ROS was significantly induced at low fluences, followed by a decrease and a second larger increase at 30 J/cm(2). Nitric oxide levels showed a similar pattern of a double peak but values were less significant compared to ROS. CONCLUSIONS: The results suggest that LLLT at lower fluences is capable of inducing mediators of cell signaling processes which in turn may be responsible for the beneficial stimulatory effects of the low level laser. At higher fluences beneficial mediators are reduced and high levels of Janus-type mediators such as ROS and NO (beneficial at low concentrations and harmful at high concentrations) may be responsible for the damaging effects of high-fluence light and the overall biphasic dose response.

Pilot Study on Dose-Dependent Effects of Transcranial Photobiomodulation on Brain Electrical Oscillations: A Potential Therapeutic Target in Alzheimer's Disease.

BACKGROUND: Transcranial photobiomodulation (tPBM) has recently emerged as a potential cognitive enhancement technique and clinical treatment for various neuropsychiatric and neurodegenerative disorders by delivering invisible near-infrared light to the scalp and increasing energy metabolism in the brain. OBJECTIVE: We assessed whether transcranial photobiomodulation with near-infrared light modulates cerebral electrical activity through electroencephalogram (EEG) and cerebral blood flow (CBF). METHODS: We conducted a single-blind, sham-controlled pilot study to test the effect of continuous (c-tPBM), pulse (p-tPBM), and sham (s-tPBM) transcranial photobiomodulation on EEG oscillations and CBF using diffuse correlation spectroscopy (DCS) in a sample of ten healthy subjects [6F/4 M; mean age 28.6±12.9 years]. c-tPBM near-infrared radiation (NIR) (830 nm; 54.8 mW/cm2; 65.8 J/cm2; 2.3 kJ) and p-tPBM (830 nm; 10 Hz; 54.8 mW/cm2; 33%; 21.7 J/cm2; 0.8 kJ) were delivered concurrently to the frontal areas by four LED clusters. EEG and DCS recordings were performed weekly before, during, and after each tPBM session. RESULTS: c-tPBM significantly boosted gamma (t = 3.02, df = 7, p < 0.02) and beta (t = 2.91, df = 7, p < 0.03) EEG spectral powers in eyes-open recordings and gamma power (t = 3.61, df = 6, p < 0.015) in eyes-closed recordings, with a widespread increase over frontal-central scalp regions. There was no significant effect of tPBM on CBF compared to sham. CONCLUSION: Our data suggest a dose-dependent effect of tPBM with NIR on cerebral gamma and beta neuronal activity. Altogether, our findings support the neuromodulatory effect of transcranial NIR.

Effect of pulsing in low-level light therapy.

BACKGROUND AND OBJECTIVE: Low level light (or laser) therapy (LLLT) is a rapidly growing modality used in physical therapy, chiropractic, sports medicine and increasingly in mainstream medicine. LLLT is used to increase wound healing and tissue regeneration, to relieve pain and inflammation, to prevent tissue death, to mitigate degeneration in many neurological indications. While some agreement has emerged on the best wavelengths of light and a range of acceptable dosages to be used (irradiance and fluence), there is no agreement on whether continuous wave or pulsed light is best and on what factors govern the pulse parameters to be chosen. STUDY DESIGN/MATERIALS AND METHODS: The published peer-reviewed literature was reviewed between 1970 and 2010. RESULTS: The basic molecular and cellular mechanisms of LLLT are discussed. The type of pulsed light sources available and the parameters that govern their pulse structure are outlined. Studies that have compared continuous wave and pulsed light in both animals and patients are reviewed. Frequencies used in other pulsed modalities used in physical therapy and biomedicine are compared to those used in LLLT. CONCLUSION: There is some evidence that pulsed light does have effects that are different from those of continuous wave light. However further work is needed to define these effects for different disease conditions and pulse structures.

Retrospective Observational Study and Analysis of Two Different Photobiomodulation Therapy Protocols Combined with Rehabilitation Therapy as Therapeutic Interventions for Canine Degenerative Myelopathy.

Objective: The objective of this retrospective review was to examine the impact that adding photobiomodulation therapy (PBMt) to rehabilitation therapy had on the pathology of degenerative myelopathy (DM) in canine patients. Background: Canine DM is a progressive, fatal neurodegenerative disease for which there exists a dearth of effective treatments, limiting clinicians to pursue symptom palliation. Methods: Clinical records of dogs referred for presumed DM to a specialty rehabilitation facility were screened for patients meeting study criteria. Qualifying patients were divided into two groups: Protocol A (PTCL-A) and Protocol B (PTCL-B) group, based on the PBMt protocol used. Data related to demographics, diagnostics, rehabilitation protocols, and progression of clinical signs were collected. Data were analyzed to determine differences in outcomes between the two treated groups and historical data expectations, as given by a previously published study. Results: The times between symptom onset and euthanasia of dogs in the PTCL-B group: 38.2 ± 14.67 months (mean ± SD), were significantly longer than those of dogs in the PTCL-A group: 11.09 ± 2.68 months. Similarly, the times between symptom onset and nonambulatory paresis (NAP) or paralysis of dogs in the PTCL-B group: 31.76 ± 12.53 months, were significantly longer than those of dogs in the PTCL-A group: 8.79 ± 1.60 months. Further, Kaplan-Meier survival analysis showed that the times from symptom onset to NAP of dogs in the PTCL-B group were significantly longer than those of dogs in the PTCL-A group (Mantel-Cox Log Rank statistic = 20.434, p < 0.05) or the historical data group (Mantel-Cox Log Rank statistic = 16.334, p < 0.05). Conclusions: The data reviewed show significantly slower disease progression-longer survival times-for patients in the PTCL-B group than those in the PTCL-A group or published historical data. Further studies are warranted.

Photobiomodulation does not influence maturation and mildly improves functional healing of mouse achilles tendons.

Tendon rupture can occur at any age and is commonly treated nonoperatively, yet can result in persisting symptoms. Thus, a need exists to improve nonoperative treatments of injured tendons. Photobiomodulation (PBM) therapy has shown promise in the clinic and is hypothesized to stimulate mitochondrial-related metabolism and improve healing. However, the effect of PBM therapy on mitochondrial function during tendon maturation and healing are unknown, and its effect on tendon structure and function remain unclear. In this study, near-infrared light (980:810 nm blend, 2.5 J/cm2 ) was applied at low (30 mW/cm2 ) or high (300 mW/cm2 ) irradiance to unilateral Achilles tendons of CD-1 mice during postnatal growth (maturation) as well as adult mice with bilateral Achilles tenotomy (healing). The chronic effect of PBM therapy on tendon structure and function was determined using histology and mechanics, and the acute effect of PBM therapy on mitochondrial-related gene expression was assessed. During maturation and healing, collagen alignment, cell number, and nuclear shape were unaffected by chronic PBM therapy. We found a sex-dependent effect of PBM therapy during healing on mechanical outcomes (eg, increased stiffness and Young's modulus for PBM-treated females, and increased strain at ultimate stress for PBM-treated males). Mitochondria-related gene expression was marginally influenced by PBM therapy for both maturation and healing studies. This study was the first to implement PBM therapy during both growth and healing of the murine tendon. PBM therapy resulted in marginal and sex-dependent effects on the murine tendon. Clinical significance: PBM may be beneficial for tendon healing because functional remodeling improves without adverse effects.

Near infrared light amplifies endothelial progenitor cell accumulation after stroke.

Damage-associated molecular pattern signals may play key roles in mediating non-cell autonomous effects of pre and post-conditioning. Here, we show that near-infrared (NIR) light stimulation of astrocytes increases a calcium-dependent secretion of the prototypical DAMP, HMGB1, which may then accelerate endothelial progenitor cell (EPC) accumulation after stroke. Conditioned media from NIR-stimulated astrocytes increased EPC proliferation in vitro, and blockade of HMGB1 with siRNA diminished the effect. In vivo transcranial NIR treatment confirmed that approximately 40% of NIR could penetrate the scalp and skull. Concomitantly, NIR increased GFAP expression in normal mouse brain at 30 min after the irradiation. In a mouse model of focal ischemia, repeated irradiation of NIR at days 5, 9, and 13 successfully increased HMGB1 in peri-infarct cortex, leading to a higher accumulation of EPCs at 14 days post-stroke. Conditioning and tolerance are now known to involve cell-cell signaling between all cell types in the neurovascular unit. Taken together, our proof-of-concept study suggest that NIR light may be an effective conditioning tool to stimulate astrocytic signaling and promote EPC accumulation after stroke.

Penetration Profiles of Visible and Near-Infrared Lasers and Light-Emitting Diode Light Through the Head Tissues in Animal and Human Species: A Review of Literature.

Background and objective: Photobiomodulation (PBM) therapy is a promising and noninvasive approach to stimulate neuronal function and improve brain repair. The optimization of PBM parameters is important to maximize effectiveness and tolerability. Several studies have reported on the penetration of visible-to-near-infrared (NIR) light through various animal and human tissues. Scientific findings on the penetration of PBM light vary, likely due to use of different irradiation parameters and to different characteristics of the subject such as species, age, and gender. Materials and methods: In this article, we review published data on PBM penetration through the tissues of the head in both animal and human species. The patterns of visible-to-NIR light penetration are summarized based on the following study specifications: wavelength, coherence, operation mode, beam type and size, irradiation site, species, age, and gender. Results: The average penetration of transcranial red/NIR (630-810 nm) light ranged 60-70% in C57BL/6 mouse (skull), 1-10% in BALB/c mouse (skull), 10-40% in Sprague-Dawley rats (scalp plus skull), 20% in Oryctolagus cuniculus rabbit (skull), 0.11% in pig (scalp plus skull), and 0.2-10% in humans (scalp plus skull). The observed variation in the reported values is due to the difference in factors (e.g., wavelengths, light coherence, tissue thickness, and anatomic irradiation site) used by researchers. It seems that these data challenge the applicability of the animal model data on transcranial PBM to humans. Nevertheless, two animal models seem particularly promising, as they approximate penetration in humans: (I) Penetration of 808 nm laser through the scalp plus skull was 0.11% in the pig head; (II) Penetration of 810 nm laser through intact skull was 1.75% in BALB/c mouse. Conclusions: In conclusion, it is worthwhile mentioning that since the effectiveness of brain PBM is closely dependent on the amount of light energy reaching the target neurons, further quantitative estimation of light penetration depth should be performed to validate the current findings.

Sensitivity and Specificity of a Weight Distribution Platform for the Detection of Objective Lameness and Orthopaedic Disease.

INTRODUCTION: Weight distribution and off-loading at the stance are commonly used subjective assessments during the orthopaedic examination. The clinical relevance, sensitivity and specificity of limb off-loading have not yet been established. The aim of the study was to assess off-loading on a weight distribution platform (WDP) and determine the sensitivity and specificity at various cut-off points for the detection of objective lameness (OL) and orthopaedic disease (OD). MATERIALS AND METHODS: The total pressure index was used to determine OL on a pressure-sensitive walkway (PSW). Normal weight distribution on both the PSW and WDP was considered 30/30/20/20. A total pressure index standard deviation of 2 was used. The sensitivity and specificity of the WDP for the identification of OL and OD was determined at cut-off points 1 to 6 below normal weight distribution values. RESULTS: All patients in the study (n = 50) had confirmed OD. The PSW identified 36/50 (74%) patients as OL; these were deemed to be OL for sensitivity and specificity analysis of WDP data. At cut-off point 1, the WDP had the highest sensitivity for OD (84%) and OL (97%). At cut-off point 6, the WDP had the highest specificity for OD (98%) and OL (98%). The highest combination of sensitivity and specificity for both OD (1.65) and OL (1.80) was at cut-off point 2. DISCUSSION/CONCLUSION: The WDP provided the highest combined sensitivity and specificity at cut-off point 2 below the normal value for the detection of both OL and OD.

Flexible nine-channel photodetector probe facilitated intraspinal multisite transcutaneous photobiomodulation therapy dosimetry in cadaver dogs.

Noninvasive photobiomodulation therapy (PBMT) of spinal cord disease remains speculative due to the lack of evidence for whether photobiomodulatory irradiances can be transcutaneously delivered to the spinal cord under a clinically acceptable PBMT surface irradiation protocol. We developed a flexible nine-channel photodetection probe for deployment within the spinal canal of a cadaver dog after hemilaminectomy to measure transcutaneously transmitted PBMT irradiance at nine sites over an eight-cm spinal canal length. The probe was built upon a 6.325-mm tubular stem, to the surface of which nine photodiodes were epoxied at approximately 1 cm apart. The photodiode has a form factor of 4.80 mm×2.10 mm×1.15 mm (length×width×height). Each photodiode was individually calibrated to deliver 1 V per 7.58 µW/cm2 continuous irradiance at 850 nm. The outputs of eight photodiodes were logged concurrently using a data acquisition module interfacing eight channels of differential analog signals, while the output of the ninth photodiode was measured by a precision multimeter. This flexible probe rendered simultaneous intraspinal (nine-site) measurements of transcutaneous PBMT irradiations at 980 nm in a pilot cadaver dog model. At a surface continuous irradiance of 3.14 W/cm2 applied off-contact between L1 and L2, intraspinal irradiances picked up by nine photodiodes had a maximum of 327.48 µW/cm2 without the skin and 5.68 µW/cm2 with the skin.

A Protocol for Transcranial Photobiomodulation Therapy in Mice.

Transcranial photobiomodulation is a potential innovative noninvasive therapeutic approach for improving brain bioenergetics, brain function in a wide range of neurological and psychiatric disorders, and memory enhancement in age-related cognitive decline and neurodegenerative diseases. We describe a laboratory protocol for transcranial photobiomodulation therapy (PBMT) in mice. Aged BALB/c mice (18 months old) are treated with a 660 nm laser transcranially, once daily for 2 weeks. Laser transmittance data shows that approximately 1% of the incident red light on the scalp reaches a 1 mm depth from the cortical surface, penetrating the dorsal hippocampus. Treatment outcomes are assessed by two methods: a Barnes maze test, which is a hippocampus-dependent spatial learning and memory task evaluation, and measuring hippocampal ATP levels, which is used as a bioenergetics index. The results from the Barnes task show an enhancement of the spatial memory in laser-treated aged mice when compared with age-matched controls. Biochemical analysis after laser treatment indicates increased hippocampal ATP levels. We postulate that the enhancement of memory performance is potentially due to an improvement in hippocampal energy metabolism induced by the red laser treatment. The observations in mice could be extended to other animal models since this protocol could potentially be adapted to other species frequently used in translational neuroscience, such as rabbit, cat, dog, or monkey. Transcranial photobiomodulation is a safe and cost-effective modality which may be a promising therapeutic approach in age-related cognitive impairment.

Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial.

Objective: Our objective was to test the antidepressant effect of transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD). Background: t-PBM with NIR light is a new treatment for MDD. NIR light is absorbed by mitochondria; it boosts cerebral metabolism, promotes neuroplasticity, and modulates endogenous opioids, while decreasing inflammation and oxidative stress. Materials and methods: We conducted a double-blind, sham-controlled study on the safety and efficacy [change in Hamilton Depression Rating Scale (HAM-D17) total score at end-point] of adjunct t-PBM NIR [823 nm; continuous wave (CW); 28.7 × 2 cm2; 36.2 mW/cm2; up to 65.2 J/cm2; 20-30 min/session], delivered to dorsolateral prefrontal cortex, bilaterally and simultaneously, twice a week, for 8 weeks, in subjects with MDD. Baseline observation carried forward (BOCF), last observation carried forward (LOCF), and completers analyses were performed. Results: The effect size for the antidepressant effect of t-PBM, based on change in HAM-D17 total score at end-point, was 0.90, 0.75, and 1.5 (Cohen's d), respectively for BOCF (n = 21), LOCF (n = 19), and completers (n = 13). Further, t-PBM was fairly well tolerated, with no serious adverse events. Conclusions: t-PBM with NIR light demonstrated antidepressant properties with a medium to large effect size in patients with MDD. Replication is warranted, especially in consideration of the small sample size.