This PDF file contains the front matter associated with SPIE Proceedings Volume 12362, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.

It is known from the literature that foot ulcers are a frequent complication of diabetes mellitus with a yearly incidence of 2-4% in high income countries. Hard to heal ulcers are a major cause of morbidity, mortality and financial costs. Data from the Swedish quality registry RiksSar for ulcer treatment 2020, show that patients with diabetes mellitus heals more slowly than other ulcer patients. This study compared Photobiomodulation PBM time to heal in frail elderly patients with and without diabetes mellitus. Patients ulcer diagnosis were arterial ulcer, pressure ulcer category two to four and venous leg ulcer. The patients with diabetes mellitus had a median of one comorbidity more than the patients without diabetes diagnosis. The patients in this study received infrared and red laser PBM two times per week from the municipality home healthcare in their private residence or nursing home. In the study no significant difference in PBM treatment time to heal was found between patients with and without diabetes mellitus per ulcer diagnosis. Conclusion, the study shows that hard to heal ulcers in frail elderly patients with diabetes mellitus respond at least as good and as fast to laser PBM as frail elderly patients with hard to heal ulcers, without diabetes mellitus.

The term photobiomodulation (PBM), where modulation usually implies a positive or negative response, has been used to describe a photostimulation effect on cells and tissues that leads to beneficial physiological outcomes, such as increased cellular energetics (ATP) and faster healing. Literature points to multiple hypotheses for the mechanism of PBM therapy when using light in the wavelength range of red to near infrared (NIR). We have used a variety of methods and experimental systems to measure light-dependent biological effects in response to laser parameters that would be expected to produce the physiological effects associated with PBM. Here, we highlight two in vitro experiments addressing two different hypotheses for the mechanism of PBM initiation. First, based on wavelength-dependent efficiencies for nitric oxide (NO) release in hTERT-RPE1 cells, we have used these dependences to determine if optimal NO release correlates to increased activity of complex C-IV in the electron transport chain (ETC). Second, to find any indication that water vibration can lead to stimulation of C-IV activity, we exposed isolated mitochondria with laser light at a frequency of 2.52 terahertz (THz) and compared the results with photostimulation of C-IV activity at 808 nm.

Silicon phantom models have been utilized to calculate light fluence in patients being treated with Photodynamic Therapy (PDT). This application can be utilized for other non-ionizing wavelength therapies such as Photobiomodulation (PBM). We have developed a novel protocol to validate homogeneity for 3-dimensional silicon phantom models of the human maxilla. Accurately quantifying the light profiles of human tissue can accommodate for varying optical properties that occur between subjects. More importantly, this can help optimize light fluence dosimetry calculations to achieve intended results. Silicon models of identical composition were fabricated into two different shapes: 1 flat-planar cylindrical shaped model, 2) non-flat planar (3-dimensional) mold of the human maxilla.

Fabricating homogenous silicon phantom models continues to be a challenge as micro-bubbles can contaminate the compound during the curing process. Integrating both proprietary CBCT and handheld surface acquisition imaging devices confirmed our results to be within 0.5mm of accuracy. This protocol was specifically used to cross-reference and validate homogeneity at various depths of penetration. These results present the first known successful validation of identical silicon tissue phantoms with a flat-planar surface vs. a non-flat 3D planar surface. This proof-of-concept phantom validation protocol is sensitive to the specific variations of 3-dimensional surfaces and can be applied to a workflow used to capture accurate light fluence calculations in the clinical setting.

Applications of red and near infrared LED light with diverse pulsing frequencies over the head and on the nose were proven effective in improving the cognitive capability of the Alzheimer's disease patients. A protocol for clinical trial for the patients with Alzheimer’s disease using flexible LED photobiomodulation therapy devices with 660nm, 850nm, and 940nm LEDs over the head, nose, neck, and abdominal area with 40Hz light pulsing frequency is described for this case study.

Mitochondria are proposed to be the main target of photobiomodulation (PBM) at the cell level, where photon absorption would lead to therapeutic results. However, there is still plenty to be explored and understood about the effects of photons on mitochondria. This study investigates photon interactions at 635 nm on mitochondrial bioenergetics measuring mitochondrial respiration through high-resolution respirometry (HRR) techniques. Mice (C57BL/6 females) liver mitochondria were isolated and immediately irradiated with a LASER beam emitting at 635 nm while measuring mitochondrial respiration. The selected protocol for respiration analysis allowed the evaluation of oxidative phosphorylation, non-oxidative phosphorylation and the maximal capacity of electron transport chain. The following experimental conditions were applied: temperature (37 and 28 °C), sample concentration (0.5 and 0.25 mg.mL^-1) and LASER power intensities (200 to 800 mW). At 37 °C and 0.5 mg.mL^-1, the effects were small, but indicated that higher powers might be more promising, and subsequent experiments followed with power intensities ranging from 600 to 800 mW. At 28 °C and 0.25 mg.mL^-1 there was a photothermal influence of irradiation, interfering with the oxygen consumption measurements. These results entail the search for a way to correct such effect, aiming to bring the experimental conditions closer to those idealized for this study, that proposes to measure light effects in real time.

Emerging evidence in animal models suggests external photobiomodulation (PBM) improves glucose intolerance and insulin resistance. But data on therapeutic targets is limited. Recently, duodenum has been gaining attention to the therapeutic potential for metabolic disease including type 2 diabetes (T2DM). We investigated the role and underlying mechanism on the duodenal light emitting diode PBM whether this modality could lower serum glucose level and improve hepatic parameters in T2DM animal model. This study identifies single session of duodenal multi-wavelength light emitting diode PBM affects improving hyperglycemia and hepatic parameters through increased serum insulin level, decreased insulin resistance, enhanced expression of insulin the pancreas, and change of gut microbiome and, thus representing the duodenum as an attractive therapeutic target for T2DM.

About 80% of the patients recovering from COVID-19 have inflammation symptoms, like brain fog, myopathy, myalgia, muscle weariness, headache, mental tiredness, asthenia, adynamia, dizziness, tinnitus, hearing loss, telogenic effluvium and mood disturbances. Here, we demonstrate how transcranial and systemic photobiomodulation using near-infrared LEDs emitting 850 nm wavelength light enhanced cognition and reduced pain. Participants were separated into transcranial photobiomodulation with near-infrared LEDs (850 nm, 10W, 10 minutes), photobiomodulation with a punctual cutaneous application (850nm, 10W, 10-40 minutes), and both treatments. All patients underwent 10-day treatments at least.

Neuroinflammation induced by activated microglia is a typical pathological feature in most neurodegenerative diseases. Generally, inhibition of neuroinflammation could attenuate damage of brain in neurodegenerative diseases. Photobiomodulation (PBM) has been proved to suppress neuroinflammation by decreasing microglial activation. However, the underlying mechanisms of PBM on microglial inflammation remain unclear. Herein, we studied the effects of mitochondrial function on PBM regulated microglial inflammation. The results showed that PBM attenuates lipopolysaccharide (LPS)-induced microglial proinflammatory response while ameliorating mitochondrial dysfunction. Further study revealed that PBM promotes mitophagy in microglia exposed to LPS. In addition, we found that 3- methyladenine (3-MA), the autophagy inhibitor, disrupts microglial mitophagy and reverses the protective effect of PBM on inflammation. Taken together, these studies underline the significance of mitophagy in suppressing inflammation and enhancing mitochondrial function in activated microglia under PBM treatment. Our research may supply a potential strategy to control the progression of neuroinflammation.