Photobiomodulation by Near-Infrared 980-nm Wavelengths Regulates Pre-Osteoblast Proliferation and Viability through the PI3K/Akt/Bcl-2 Pathway.

BACKGROUND: bone tissue regeneration remains a current challenge. A growing body of evidence shows that mitochondrial dysfunction impairs osteogenesis and that this organelle may be the target for new therapeutic options. Current literature illustrates that red and near-infrared light can affect the key cellular pathways of all life forms through interactions with photoacceptors within the cells' mitochondria. The current study aims to provide an understanding of the mechanisms by which photobiomodulation (PBM) by 900-nm wavelengths can induce in vitro molecular changes in pre-osteoblasts. METHODS: The PubMed, Scopus, Cochrane, and Scholar databases were used. The manuscripts included in the narrative review were selected according to inclusion and exclusion criteria. The new experimental set-up was based on irradiation with a 980-nm laser and a hand-piece with a standard Gaussian and flat-top beam profile. MC3T3-E1 pre-osteoblasts were irradiated at 0.75, 0.45, and 0.20 W in continuous-wave emission mode for 60 s (spot-size 1 cm2) and allowed to generate a power density of 0.75, 0.45, and 0.20 W/cm2 and a fluence of 45, 27, and 12 J/cm2, respectively. The frequency of irradiation was once, three times (alternate days), or five times (every day) per week for two consecutive weeks. Differentiation, proliferation, and cell viability and their markers were investigated by immunoblotting, immunolabelling, fluorescein-FragELTM-DNA, Hoechst staining, and metabolic activity assays. RESULTS AND CONCLUSIONS: The 980-nm wavelength can photobiomodulate the pre-osteoblasts, regulating their metabolic schedule. The cellular signal activated by 45 J/cm2, 0.75 W and 0.75 W/cm2 consist of the PI3K/Akt/Bcl-2 pathway; differentiation markers were not affected, nor do other parameters seem to stimulate the cells. Our previous and present data consistently support the window effect of 980 nm, which has also been described in extracted mitochondria, through activation of signalling PI3K/Akt/Bcl-2 and cyclin family, while the Wnt and Smads 2/3-ß-catenin pathway was induced by 55 J/cm2, 0.9 W and 0.9 W/cm2.

Investigating the transmission profiles of 808 nm laser through different regions of the rat's head.

Studying light penetration in biological tissues became a very important concern in various medical applications. It is an essential factor required to resolve the optical dose in many diagnostic and therapeutic procedures. The absorption and scattering properties of the inspected tissue control how deep the light will travel inside the tissue. However, these optical properties are highly dependent on the wavelength of the light source. In this work, the light transmission through different regions of the rat's head was investigated and the minimum laser power required to reach different parts of the head is also determined using 808-nm semiconductor laser diode. The power variation in different regions of the head is estimated using Monte Carlo simulation. Absorption and scattering coefficients of the head layers were calculated using integrating sphere measurements and Kubelka-Munk model. The absorption coefficient of the skin was 0.19 ± 0.071 mm-1, 0.024 ± 0.11 mm-1 for skull, and 0.35 ± 0.13 mm-1 for the brain, while the scattering coefficients were 7.35 ± 1.09, 2.71 ± 0.37, and 13.04 ± 0.36 mm-1 for skin, skull, and brain, respectively. The obtained results provide a relationship between laser incident power and the depth in the rat's head showing a higher optical transmission at the frontal part of the head than the middle or back regions due to the variations in the skull thickness. Therefore, the study revealed that the transmitted power of 808 nm laser at different incident locations on the head is nonlinear and variable due to different skull's thickness.

Laser and LED photobiomodulation effects in osteogenic or regular medium on rat calvaria osteoblasts obtained by newly forming bone technique.

The purposes of this study are to evaluate the effects of photobiomodulation (PBM) with laser and LED on rat calvaria osteoblasts (rGO lineage), cultured in osteogenic (OST) or regular (REG) medium, after induction of a quiescent state and to test if PBM is capable of osteogenic induction and if there is a sum of effects when combining OST medium with PBM. Before irradiation, the cells were put in a quiescent state (1% FBS) 24 h, when red (AlGaInP-660 nm) and infrared laser (GaAlAs-808 nm) and LED (637 ± 15 nm) were applied. The groups were as follows: red laser (RL3-5 J/cm2, 3 s and RL5-8.3 J/cm2, 5 s, 1.66 W/cm2); infrared laser (IrL3-5 J/cm2, 3 s and IrL5-8.3 J/cm2, 5 s); LED (LED3-3 s and LED5-5 s, 0.02 J/cm2, 0.885 W/cm2); positive (C+, 10% FBS) and negative control (C-, 1% FBS). For alkaline phosphatase (ALP) and mineralization assays, the cells were cultured in REG (DMEM 10% FBS) and OST medium (DMEM 10% FBS, 50 µg/mL ascorbic acid, 10 mM ß-glycerophosphate). Statistical analysis was performed using ANOVA and Tukey's tests (p < 0.05). RL5 and LED5 increased proliferation, in vitro wound closure, ALP, and mineralization in rGO cells (p < 0.05). PBM with red laser and LED induced mineralization by itself, without osteogenic medium, not observed for infrared laser (p < 0.05). A sum of effects was observed in osteogenic medium and PBM by infrared, red laser, and LED (5 s). Red laser and LED increased proliferation, migration, and secretory phases in rGO cells in a dose-dependent manner. PBM with red laser and LED promotes osteogenic induction by itself. PBM with infrared laser and osteogenic medium potentializes mineralization.

Experimental and Computational Investigation of Guided Waves in a Human Skull.

We investigate guided (Lamb) waves in a human cadaver skull through experiments and computational simulations. Ultrasonic wedge transducers and scanning laser Doppler vibrometry are used respectively to excite and measure Lamb waves propagating in the cranial bone of a degassed skull. Measurements are performed over a section of the parietal bone and temporal bone spanning the squamous suture. The experimental data are analyzed for the identification of wave modes and the characterization of dispersion properties. In the parietal bone, for instance, the A0 wave mode is excited between 200 and 600 kHz, and higher-order Lamb waves are excited from 1 to 1.8 MHz. From the experimental dispersion curves and average thickness extracted from the skull computed tomography scan, we estimate average isotropic material properties that capture the essential dispersion characteristics using a semi-analytical finite-element model. We also explore the leaky and non-leaky wave behavior of the degassed skull with water loading in the cranial cavity. Successful excitation of leaky Lamb waves is confirmed (for higher-order wave modes with phase velocity faster than the speed of sound in water) from 500 kHz to 1.5 MHz, which may find applications in imaging and therapeutics at the brain periphery or skull-brain interface (e.g., for metastases). The non-leaky A0 Lamb wave mode propagates between 200 and 600 kHz, with or without fluid loading, for potential use in skull-related diagnostics and imaging (e.g., for sutures).

Role and limitations of the geometric mean method regarding head rotation in salivary gland scintigraphy: a phantom study.

To investigate the possible influence of head rotation on the results of salivary gland scintigraphy, a phantom study was designed to simulate clinical salivary gland scintigraphy. The quantitative accuracy of regional activity counts was compared for two data acquisition methods involving head rotation: (i) an anterior planar projection-only (ANT) method and (ii) a geometric mean (GM) method using both the anterior and posterior planar projections. The roles and limitations of the GM and ANT methods when used at different head rotation angles were examined. Parallel planar projections of a head phantom with four salivary gland simulators, containing 3.7 MBq 99mTc-sodium pertechnetate, at various rotational settings were acquired using a dual-head gamma camera. The difference between the standard activity counts (no phantom rotation) and the activity counts affected by the phantom rotation was calculated and defined as the rotational bias that decreased the accuracy of activity quantification. For small-angle rotation (≤10°), use of the GM method decreased the bias for all salivary gland simulators. In contrast, the bias of large-angle rotation (>10°) between four salivary gland simulators became conspicuous and complex in both methods. This bias may reflect different attenuation effects caused by displacement of the structures. Our data suggest that the GM method can be used when the head rotation angle is small (≤10°); however, when the head rotation angle is >10°, the non-negligible influence of head rotation should be considered during image acquisition.

Response to GH Treatment After Radiation Therapy Depends on Location of Irradiation.

OBJECTIVES: Cancer survivors with GH deficiency (GHD) receive GH therapy (GHT) after 1+ year observation to ensure stable tumor status/resolution. HYPOTHESIS: Radiation therapy (RT) to brain, spine, or extremities alters growth response to GHT. AIM: Identify differences in growth response to GHT according to type/location of RT. METHODS: The Pfizer International Growth Database was searched for cancer survivors on GHT for ≥5 years. Patient data, grouped by tumor type, were analyzed for therapy (surgery, chemotherapy, RT of the focal central nervous system, cranial, craniospinal, or total body irradiation [TBI] as part of bone marrow transplantation), sex, peak stimulated GH, age at GHT start, and duration from RT to GHT start. Kruskal-Wallis test and quantile regression modeling were performed. RESULTS: Of 1149 GHD survivors on GHT for ≥5 years (male 733; median age 8.4 years; GH peak 2.8 ng/mL), 431 had craniopharyngioma (251, cranial RT), 224 medulloblastoma (craniospinal RT), 134 leukemia (72 TBI), and 360 other tumors. Median age differed by tumor group (P < 0.001). Five-year delta height SD score (SDS) (5-year ∆HtSDS; median [10th-90th percentile]) was greatest for craniopharyngioma, 1.6 (0.3-3.0); for medulloblastoma, 5-year ∆HtSDS 0.9 (0.0-1.9); for leukemia 5-year ∆HtSDS, after TBI (0.3, 0-0.7) versus without RT (0.5, 0-0.9), direct comparison P < 0.001. Adverse events included 40 treatment-related, but none unexpected. CONCLUSIONS: TBI for leukemia had significant impact on growth response to GHT. Medulloblastoma survivors had intermediate GHT response, whereas craniopharyngioma cranial RT did not alter GHT response. Both craniospinal and epiphyseal irradiation negatively affect growth response to GH therapy compared with only cranial RT or no RT.

Feasibility of customizing titanium implant with three-dimensional CT imaging of low dose in skull.

OBJECT: To explore the feasibility and practicability of making virtual three-dimensional model of skull defect and customizing titanium implant by skull three-dimensional CT examination of low dose. METHODS: Sixty patients with skull defects who underwent skull three-dimensional CT before cranioplasty were randomly divided into 4 groups: group A (conventional dose 120 peak Kilovoltage (kVp), 150 tube current time product (mAs)), low dose group B (120 kVp, 50 mAs), low dose group C (100 kVp, 50 mAs), low dose group D (100 kVp, 30 mAs). After the scanning, we compared radiation doses and image quality among the groups. The CT data were sent to the reconstruction company to produce accurate titanium implants, and neurosurgeons performed cranioplasty. After the operation, patients immediately underwent head CT scans to confirm the accuracy of the implantation position, and a series of clinical functions were evaluated. RESULTS: There were significant differences in dose length product (DLP) and effective dose (ED) among the 4 groups (P < .001). The volume CT dose index (CDTIvol), DLP, and ED in group D were, respectively, 87.1%, 86.9%, and 87.3% lower than those in group A (P < .001). All images quality were at or above the general level, and there was no statistical difference (P > .05). Titanium implants were successfully manufactured, every cranioplasty was carried out smoothly, and the clinical function of patients recovered well. CONCLUSION: Customizing titanium implant with three-dimensional CT imaging of low dose in skull not only met the clinical requirements, but also significantly reduced the radiation dose and hazard.

Initial damage produced by a single 15-Gy x-ray irradiation to the rat calvaria skin.

BACKGROUND: Calvaria skin has a reduced thickness, and its initial damage produced by irradiation was scarcely reported. We aimed to identify the initial effects of x-ray irradiation in the rat calvaria skin. METHODS: After approval by the Animal Ethical Committee, calvaria skin sections of five Wistar rats per time point were evaluated on days 4, 9, 14, and 25 following a single 15-Gy x-ray irradiation of the head. The control group was composed of five rats and evaluated on day 4. Sections were assessed using hematoxylin-eosin and Masson's trichrome staining for morphology, inflammation, and fibrosis. Fibrosis was also evaluated by the collagen maturation index from Picrosirius red staining and by cell proliferation using the immunohistochemistry, after 5-bromo-2-deoxyuridine intraperitoneal injection. RESULTS: In irradiated rats, we observed a reduction in epithelial cell proliferation (p = 0.004) and in matrix metalloproteinase-9 expression (p < 0.001), an increase in the maturation index, and with a predominance in the type I collagen fibers, on days 9 and 14 (1.19 and 1.17, respectively). A progressive disorganization in the morphology of the collagen fibers at all time points and changes in morphology of the sebaceous gland cells and hair follicle were present until day 14. CONCLUSIONS: The initial damage produced by a single 15-Gy x-ray irradiation to the rat calvaria skin was a change in the normal morphology of collagen fibers to an amorphous aspect, a temporary absence of the sebaceous gland and hair follicles, and without a visible inflammatory process, cell proliferation, or fibrosis process in the dermis.

Effect of Low- Level Laser Therapy on Bone Regeneration of Critical-Size Bone Defects: A Systematic Review of In Vivo Studies and Meta-Analysis.

OBJECTIVE: Low-level laser therapy is a method for osteogenesis since it stimulates cell proliferation, vascularization and osteoblastic activity. Various protocols applying low-level laser with different outcomes exist. The aim of the present study was to review the result of different methods on bone formation in critical-size defects of in vivo studies. DESIGN: According to PRISMA statement, electronic search of PubMed, google scholar, Scopus and Web of Science and a hand search limited to in vivo English language studies until December 2019. Studies used low-level laser therapy in bone regeneration of critical-size defects met the inclusion criteria and which used high power lasers or a defect size smaller than 5 mm, were excluded. RESULTS: Finally, 18 studies were included. Fourteen studies utilized low-level laser with a wavelength ranging from 606 to 980 nm and 53 % of studies applied low-level laser in a single session. Ten studies utilized continuous wave mode of laser. Highest and lowest values of power density were 1.5 W/cm2 and 0.1 W/cm2 in order. Eleven studies evaluated low-lever laser therapy on defects of 5 mm in calvaria. Meta-analysis showed the positive effect of low-level laser therapy on osteogenesis after 30 days compared to control group and no significant difference after 60 days. CONCLUSIONS: New bone formation can be increased in early stage by applying low-level laser therapy through stimulating osteoblasts and fibroblasts' proliferation. This effect would be more remarkable by combining with bone substitutes. Hence, for each case, protocol selection should be performed according defect's properties, attentively.

Inter-patient variations in relative biological effectiveness for cranio-spinal irradiation with protons.

Cranio-spinal irradiation (CSI) using protons has dosimetric advantages compared to photons and is expected to reduce risk of adverse effects. The proton relative biological effectiveness (RBE) varies with linear energy transfer (LET), tissue type and dose, but a variable RBE has not replaced the constant RBE of 1.1 in clinical treatment planning. We examined inter-patient variations in RBE for ten proton CSI patients. Variable RBE models were used to obtain RBE and RBE-weighted doses. RBE was quantified in terms of dose weighted organ-mean RBE ([Formula: see text] = mean RBE-weighted dose/mean physical dose) and effective RBE of the near maximum dose (D2%), i.e. RBED2% = [Formula: see text], where subscripts RBE and phys indicate that the D2% is calculated based on an RBE model and the physical dose, respectively. Compared to the median [Formula: see text] of the patient population, differences up to 15% were observed for the individual [Formula: see text] values found for the thyroid, while more modest variations were seen for the heart (6%), lungs (2%) and brainstem (<1%). Large inter-patient variation in RBE could be correlated to large spread in LET and dose for these organs at risk (OARs). For OARs with small inter-patient variations, the results show that applying a population based RBE in treatment planning may be a step forward compared to using RBE of 1.1. OARs with large inter-patient RBE variations should ideally be selected for patient-specific biological or RBE robustness analysis if the physical doses are close to known dose thresholds.

Gamma Knife radiosurgery: Scenarios and support for re-irradiation.

Stereotactic radiosurgery (SRS) involves the focal delivery of large, cytotoxic doses of radiation to small targets within the brain, often located in close proximity to radiosensitive normal tissue structures and requiring very low procedural uncertainties to perform safely. Historically, neurosurgeons considered SRS as a one-time, single session procedure. However therapeutic advances and a better understanding of the clinical response to SRS have caused a renewal of interest in a variety of re-irradiation scenarios; including re-irradiation of the same target after prior SRS, SRS treatments after prior broad-field radiation, hypofractionated treatments, and volume-staged treatments. Re-irradiation may in some cases require even greater effort towards minimizing treatment uncertainties as compared to one-time-only treatments. Gamma Knife radiosurgery (GKRS) has evolved over time in ways that directly supports many re-irradiation scenarios while helping to minimize overall procedural uncertainty.

Simulation of nonlinear trans-skull focusing and formation of shocks in brain using a fully populated ultrasound array with aberration correction.

Multi-element high-intensity focused ultrasound phased arrays in the shape of hemispheres are currently used in clinics for thermal lesioning in deep brain structures. Certain side effects of overheating non-targeted tissues and skull bones have been revealed. Here, an approach is developed to mitigate these effects. A specific design of a fully populated 256-element 1-MHz array shaped as a spherical segment (F-number, F# = 1) and filled by randomly distributed equal-area polygonal elements is proposed. Capability of the array to generate high-amplitude shock fronts at the focus is tested in simulations by combining three numerical algorithms for linear and nonlinear field modeling and aberration correction. The algorithms are based on the combination of the Rayleigh integral, a linear pseudo-spectral time domain Kelvin-Voigt model, and nonlinear Westervelt model to account for the effects of inhomogeneities, aberrations, reflections, absorption, nonlinearity, and shear waves in the skull. It is shown that the proposed array can generate nonlinear waveforms with shock amplitudes >60 MPa at the focus deep inside the brain without exceeding the existing technical limitation on the intensity of 40 W/cm2 at the array elements. Such shock amplitudes are sufficient for mechanical ablation of brain tissues using the boiling histotripsy approach and implementation of other shock-based therapies.

Transcranial Photobiomodulation with Near-Infrared Light for Generalized Anxiety Disorder: A Pilot Study.

Objective: Our aim was to test the anxiolytic effect of transcranial photobiomodulation (t-PBM) with near-infrared light (NIR) in subjects suffering from generalized anxiety disorder (GAD). Background: t-PBM with NIR is an experimental, noninvasive treatment for mood and anxiety disorders. Preliminary evidence indicates a potential anxiolytic effect of transcranial NIR. Methods: Fifteen subjects suffering from GAD were recruited in an open-label 8-week study. Each participant self-administered t-PBM daily, for 20 min (continuous wave; 830 nm peak wavelength; average irradiance 30 mW/cm2; average fluence 36 J/cm2; total energy delivered per session 2.9 kJ: total output power 2.4 W) broadly on the forehead (total area 80 cm2) with an LED-cluster headband (Cerebral Sciences). Outcome measures were the reduction in total scores of the Hamilton Anxiety Scale (SIGH-A), the Clinical Global Impressions-Severity (CGI-S) subscale and the Pittsburgh Sleep Quality Index (PSQI) subscales from baseline to last observation carried forward. Results: Of the 15 recruited subjects (mean age 30 ± 14 years; 67% women), 12 (80%) completed the open trial. Results show a significant reduction in the total scores of SIGH-A (from 17.27 ± 4.89 to 8.47 ± 4.87; p < 0.001; Cohen's d effect size = 1.47), in the CGI-S subscale (from 4.53 ± 0.52 to 2.87 ± 0.83; p < 0.001; Cohen's d effect size = 2.04), as well as significant improvements in sleep at the PSQI. t-PBM was well tolerated with no serious adverse events. Conclusions: Based on our pilot study, t-PBM with NIR is a promising alternative treatment for GAD. Larger, randomized, double-blind, sham-controlled studies are needed.

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.

Transcranial Photobiomodulation Improves Cognitive Performance in Young Healthy Adults: A Systematic Review and Meta-Analysis.

Background: Transcranial photobiomodulation (t-PBM) is a noninvasive modality that may improve cognitive function in both healthy and diseased subjects. Objective: This systematic review and meta-analysis addresses the question of whether t-PBM improves cognitive function in healthy adults. Methods: We searched MEDLINE using PubMed, EMBASE, SCOPUS, Web of Science, and Cochrane Library up to March 2019. We also searched ProQuest and Google Scholar databases for unpublished material. The search was limited to articles on the procognitive effects of t-PBM in healthy adults. The initial search resulted in 871 studies, of which nine publications met our criteria for inclusion and exclusion. Seven studies were performed on young, healthy subjects (17-35 years), and two studies were conducted on older (≥49 years), normal subjects. A meta-analysis was performed on six full-text publications whose subjects were young adults. Results: t-PBM administration improved cognition-related outcomes by an 0.833 standardized mean difference (SMD; 95% confidence interval (CI): 0.458-1.209, 14 comparisons) in young, healthy participants. Funnel plotting revealed asymmetry, which was validated using Egger's (p = 0.030) and Begg's regression (p = 0.006) tests. However after reanalysis, this asymmetry disappeared in the attention subgroup, but not in the memory subgroup. The trim-and-fill analysis indicated two studies were lacking required data. Thus, the effect size was adjusted from an SMD of 0.761 (95% CI: 0.573-0.949) to 0.949 (0.779-1.120). The overall quality score of the studies was modest. Conclusions: We demonstrated a significant, beneficial effect of t-PBM on cognitive performance of young, healthy individuals; however, the heterogeneity of the data was high. This could be due to the modest quality or to the low number of included studies, or to the differences between the various subdomains assessed. These shortcomings should be meticulously addressed before concluding that t-PBM is a cognitive-enhancing intervention in healthy individuals.

Bioglass/PLGA associated to photobiomodulation: effects on the healing process in an experimental model of calvarial bone defect.

Bioactive glasses (BG) are known for their ability to bond to bone tissue. However, in critical situations, even the osteogenic properties of BG may be not enough to induce bone consolidation. Thus, the enrichment of BG with polymers such as Poly (D, L-lactic-co-glycolic) acid (PLGA) and associated to photobiomodulation (PBM) may be a promising strategy to promote bone tissue healing. The aim of the present study was to investigate the in vivo performance of PLGA supplemented BG, associated to PBM therapy, using an experimental model of cranial bone defect in rats. Rats were distributed in 4 different groups (Bioglass, Bioglass/PBM, Bioglas/PLGA and BG/PLGA/PBM). After the surgical procedure to induce cranial bone defects, the pre-set samples were implanted and PBM treatment (low-level laser therapy) started (808 nm, 100 mW, 30 J/cm2). After 2 and 6 weeks, animals were euthanized, and the samples were retrieved for the histopathological, histomorphometric, picrosirius red staining and immunohistochemistry analysis. At 2 weeks post-surgery, it was observed granulation tissue and areas of newly formed bone in all experimental groups. At 6 weeks post-surgery, BG/PLGA (with or without PBM) more mature tissue around the biomaterial particles. Furthermore, there was a higher deposition of collagen for BG/PLGA in comparison with BG/PLGA/PBM, at second time-point. Histomorphometric analysis demonstrated higher values of BM.V/TV for BG compared to BG/PLGA (2 weeks post-surgery) and N.Ob/T.Ar for BG/PLGA compared to BG and BG/PBM (6 weeks post-surgery). This current study concluded that the use of BG/PLGA composites, associated or not to PBM, is a promising strategy for bone tissue engineering.

Effects of an Er,Cr:YSGG Laser on Bone Regeneration in Critical-Sized Calvarial Defects of Rats Exposed to Inhalation of Cigarette Smoke.

Objective: To evaluate the effect of the Er,Cr:YSGG laser on healing of critical-sized calvarial defects (CSDs) in rats submitted to inhalation of cigarette smoke. Background: Smoking has been implicated with the delay in the bone healing after osteotomy procedures, then the use of the Er,Cr:YSGG laser for osteotomy in smokers could be an alternative to the conventional drills. Methods: One hundred animals were randomly allocated into four groups: trephine-the CSDs were made with a trephine drill in healthy rats; Er,Cr:YSGG-the CSDs were made with the Er,Cr:YSGG laser in healthy rats; Trephine-S-the CSDs were made with a trephine drill in rats exposed to cigarette smoke; and Er,Cr:YSGG-S-the CSDs were made with the Er,Cr:YSGG laser in rats exposed to cigarette smoke. The inhalation of cigarette smoke started 7 days before the surgical procedure until euthanasia (immediately, 7, 15, 30, or 60 days after the surgical procedure). A histometric analysis and a histological description were performed to evaluate (1) the residual linear lengths and bone formation in the CSDs; (2) the quality of bone healing. Results: The use of Er,Cr:YSGG laser induces more bone formation compared with the trephine in smokers; however, the closure of the CSD was only superior in the Er,Cr:YSGG-S group compared to the Trephine-S group at the 60-day period. Conclusions: The use of the Er,Cr:YSGG laser stimulated the bone repair process after osteotomy procedures in animals submitted to exposure of inhalation of cigarette smoke.

The influence of LLLT applied on applied on calvarial defect in rats under effect of cigarette smoke.

OBJECTIVE: Considering the global public health problem of smoking, which can negatively influence bone tissue repair, the aim of this study is to analyze the influence of photobiomodulation therapy (PBM) on calvaria defects created surgically in specimens under the effect of cigarette smoke and analyzed with use of histomorphometric and immunohistochemistry techniques. METHODOLOGY: Calvaria defects 4.1 mm in diameter were surgically created in the calvaria of 90-day-old rats (n=60) that were randomly divided into 4 experimental groups containing 15 animals each: control group (C), smoking group (S), laser group (L), and smoke associated with laser group (S+L). The animals were subjected to surgery for calvaria defects and underwent PBM, being evaluated at 21, 45, and 60 days post-surgery. The specimens were then processed for histomorphometric and immunohistochemistry analyses. The area of bone neoformation (ABN), percentage of bone neoformation (PBNF), and the remaining distance between the edges of the defects (D) were analyzed histometrically. Quantitative analysis of the TRAP immunolabeled cells was also performed. The data were subjected to analysis of variance (ANOVA) in conjunction with Tukey's test to verify the statistical differences between groups (p<0.05). RESULTS: The smoking group showed less ABN compared to the other experimental groups in all periods, and it also showed more D at 21 days compared to the remaining groups and at 45 days compared to the laser group. The smoking group showed a lower PNBF compared to the laser group in all experimental periods and compared to smoking combined with LLLT group at 21 days. CONCLUSIONS: PBM acted on bone biomodulation, thus stimulating new bone formation and compensating for the negative factor of smoking, which can be used as a supportive therapy during bone repair processes.

Diagnostic Reference Levels for conventional radiography and fluoroscopy in Austria: Results and updated National Diagnostic Reference Levels derived from a nationwide survey.

OBJECTIVE: Evaluation and updating of Austrian National Diagnostic Reference Levels (NDRLs). METHODS: A nationwide survey on common conventional radiography and fluoroscopy examinations was conducted. In line with Austrian radiation protection standards, all relevant Austrian hospitals and radiology offices/centers were asked to report a minimum sample of 10 representative dose-area product (DAP) values together with patient weight and fluoroscopy time, if applicable. Examinations included for conventional radiography were skull, chest, abdomen, pelvis, lumbar spine and bedside chest x-ray, for fluoroscopy barium enema (single and double contrast) and swallowing (video). Participants were invited via e-mail, followed up by reminders to increase participation rates. Plausibility checks were performed to increase data quality. 3rd quartiles of facility median and mean DAP were calculated and compared to Austrian and international NDRLs. RESULTS: 59% of invited facilities submitted DAP data, 43% submitted additional data on patient weight and 41% on fluoroscopy time. DAP case numbers varied from 1005 to 2121 for conventional radiography and from 182 to 1380 for fluoroscopy. Average patient weight was 75 kg for conventional radiography and 77 kg for fluoroscopy. CONCLUSION: 3rd quartiles derived from the survey are substantially lower than the old Austrian NDRLs (valid till early 2018). Since 3rd quartiles correspond well to European NDRLs, the update would be in accordance with European DRL harmonisation efforts.