Multi-photonic Adjunctive Therapy for the Management of Periodontitis: Recent Advances and New Treatment Approach.

The efficacy of photonic therapy adjunctive to conventional root cleansing procedures for the treatment of chronic periodontitis is matter of controversy. The meta-analyses of the clinical data available in the literature have failed to reach univocal conclusions because of broad variability among the applied photonic treatments, different in terms of light-emitting devices (laser or LED), wavelengths, irradiation power and modes, clinical indications, disease grading, follow-up times, and results assessment. Hovever, this complexity can also favour a different interpretation, which assigns a specific role to each photonic treatments in order to improve the outcome of the conventional treatments, in terms of reduction of periodontopathogenic bacteria and local inflammation, and increased regeneration of alveolar bone, periodontal ligament and gingiva. In this context, distinction should be made between high- and low-energy photonic therapies: the former can be used to achieve photoablation of the infected dental/periodontal tissues, while the latter can be used for anti-bacterial, anti-inflammatory and tissue biostimulation purposes. Recently, we and others have applied a multi-photonic protocol which combines laser photoablation of the infected epithelium, standard mechanical root cleansing and low-energy antiseptic phototherapy with a λ 405 nm LED in a first surgical session. Then, antisepsis is maintained by weekly sessions of photodynamic therapy with a solution of methylene blue photoactivated with a λ 635 nm low-energy laser to release bactericidal reactive oxygen species. The satisfactory objective results and patients' liking support the view that such multi-photonic treatments are a correct approach to supportive periodontal therapy.

Photonic Therapy in Periodontal Diseases an Overview with Appraisal of the Literature and Reasoned Treatment Recommendations.

Recent reviews and meta-analyses of the literature over the past quarter-century have failed to provide enough evidence to prove or disprove the actual utility of photonic therapy in periodontitis, alone or adjunctive to conventional approaches. This apparent paradox has been explained by the many physical, molecular, biological, anatomical, and technical variables of photonic treatments, which can differ in light-emitting devices (laser or LED), wavelengths, irradiation power and modes, clinical objectives, follow-up times, disease grading, and assessment methods. This multi-faceted, controversial scenario has led practitioners to underestimate the actual potential of photonic therapy in periodontal diseases. In this critical appraisal of the literature, we have briefly summarized the main photonic therapies and instruments used in Periodontology, highlighting their main characteristics and limitations. Then, we have tried to identify and discuss the key methodological issues which can have an impact on the outcome of photonic therapies. Our main goal was to identify the best parameters, settings, and methodologies to perform effective periodontal photonic treatments and to extrapolate some recommendations for clinical use. Should these recommendations find a consensus among periodontologists and be adopted in future clinical studies, they will hopefully contribute to dissipate the present confusion and uncertainty on this complex matter.

Treatment of severe periodontitis with a laser and light-emitting diode (LED) procedure adjunctive to scaling and root planing: a double-blind, randomized, single-center, split-mouth clinical trial investigating its efficacy and patient-reported outcomes at 1 year.

Broad methodological heterogeneity makes the literature on the clinical effects of laser treatment in periodontitis, both as monotherapy and adjunct to non-surgical therapy, which is difficult to interpret. The present split-mouth study was performed: (i) to determine the efficacy and safety of a photoablative-photodynamic diode laser therapy, including antiseptic LED irradiation, in adjunct to scaling and root planing (iPAPD+SRP) vs. sham-treatment+SRP for the treatment of diffuse severe periodontitis and (ii) to estimate the patient-reported outcomes. Twenty-four patients with severe periodontitis were treated with iPAPD+SRP or sham-treatment+SRP. iPAPD+SRP consisted of the following: (1) intra-/extra-pocket de-epithelization with photoablative λ 810 nm laser, (2) disinfection with λ 405 nm LED, (3) SRP, and (4) 10 weekly antiseptic/anti-inflammatory photodynamic treatments with λ 635 nm laser and 0.1% toluidine blue as photosensitizer. Clinical and cytofluorescent periodontal markers and patient-reported results were analyzed. At 1-year follow-up, both groups showed a significant reduction of several severity markers of periodontitis, namely probing depth (PD) and bleeding on probing (BoP), as well as of bacteria, polymorphonuclear cells, erythrocytes and damaged epithelial cells in exfoliative samples, as compared with day 0. The quadrants subjected to iPAPD+SRP showed significantly better values of these parameters as well as of clinical attachment level (CAL) as compared with those undergoing sham-treatment+SRP. The patients' perceived pain/discomfort, and overall liking was also in favor of the iPAPD+SRP treatment. This study confirms the efficacy of combined phototherapy in adjunct to SRP which had emerged from previous clinical trials, extending its field of application to severe periodontitis.

T1 and T2 mapping in the identification of acute myocardial injury in patients with NSTEMI.

AIMS: To test T1 and T2 mapping in the assessment of acute myocardial injury in patients with non-ST-segment elevation myocardial infarction (NSTEMI), evaluated before revascularization. METHODS: Forty-seven patients with acute NSTEMI underwent cardiac magnetic resonance (CMR) at 1.5 T, including T1 and T2 mapping. RESULTS: Coronary angiography (CA) evidenced an obstructive coronary artery disease (CAD) in 36 patients (80%) and a non-obstructive CAD in 11 patients (20%). Edema was detected in 51.1/65.9% of patients in T1/T2 maps, respectively. This difference was due to artifacts in T1 maps. T1/T2 values were significantly higher in the infarcted myocardium (IM) compared with the remote myocardium (RM) (in T1: 1151.6 ± 53.5 ms vs. 958.2 ± 38.6 ms, respectively; in T2: 69 ± 6 ms vs. 51.9 ± 2.9 ms, respectively; p < 0.0001 for both). We found both an obstructive CAD at CA and myocardial edema at CMR in 53.2% of patients, while 8.5% of patients had a non-obstructive CAD and no edema. However, 25.5% of patients had an obstructive CAD without edema, while 12.8% of patients showed edema despite a non-obstructive CAD. Furthermore, in 6 of the edema-positive patients with multi-vessels obstructive CAD, CMR identified myocardial edema in a vascular territory different from that of the lesion supposed to be the culprit at CA. CONCLUSIONS: In a non-negligible percentage of NSTEMI patients, T1 and T2 mapping detect myocardial edema without significant stenosis at CA and vice versa. Therefore, CA and CMR edema imaging might provide complementary information in the evaluation of NSTEMI.

Red (635 nm), Near-Infrared (808 nm) and Violet-Blue (405 nm) Photobiomodulation Potentiality on Human Osteoblasts and Mesenchymal Stromal Cells: A Morphological and Molecular In Vitro Study.

Photobiomodulation (PBM) has been used for bone regenerative purposes in different fields of medicine and dentistry, but contradictory results demand a skeptical look for its potential benefits. This in vitro study compared PBM potentiality by red (635 ± 5 nm) or near-infrared (NIR, 808 ± 10 nm) diode lasers and violet-blue (405 ± 5 nm) light-emitting diode operating in a continuous wave with a 0.4 J/cm² energy density, on human osteoblast and mesenchymal stromal cell (hMSC) viability, proliferation, adhesion and osteogenic differentiation. PBM treatments did not alter viability (PI/Syto16 and MTS assays). Confocal immunofluorescence and RT-PCR analyses indicated that red PBM (i) on both cell types increased vinculin-rich clusters, osteogenic markers expression (Runx-2, alkaline phosphatase, osteopontin) and mineralized bone-like nodule structure deposition and (ii) on hMSCs induced stress fiber formation and upregulated the expression of proliferation marker Ki67. Interestingly, osteoblast responses to red light were mediated by Akt signaling activation, which seems to positively modulate reactive oxygen species levels. Violet-blue light-irradiated cells behaved essentially as untreated ones and NIR irradiated ones displayed modifications of cytoskeleton assembly, Runx-2 expression and mineralization pattern. Although within the limitations of an in vitro experimentation, this study may suggest PBM with 635 nm laser as potential effective option for promoting/improving bone regeneration.

Mesenchymal stromal cell and osteoblast responses to oxidized titanium surfaces pre-treated with λ = 808 nm GaAlAs diode laser or chlorhexidine: in vitro study.

Preservation of implant biocompatibility following peri-implantitis treatments is a crucial issue in odontostomatological practice, being closely linked to implant re-osseointegration. Our aim was to assess the responses of osteoblast-like Saos2 cells and adult human bone marrow-mesenchymal stromal cells (MSCs) to oxidized titanium surfaces (TiUnite®, TiU) pre-treated with a 808 ± 10 nm GaAlAs diode laser operating in non-contact mode, in continuous (2 W, 400 J/cm2; CW) or pulsed (20 kHz, 7 µs, 0.44 W, 88 J/cm2; PW) wave, previously demonstrated to have a strong bactericidal effect and proposed as optional treatment for peri-implantitis. The biocompatibility of TiU surfaces pre-treated with chlorhexidine digluconate (CHX) was also evaluated. In particular, in order to mimic the in vivo approach, TiU surfaces were pre-treated with CHX (0.2%, 5 min); CHX and rinse; and CHX, rinse and air drying. In some experiments, the cells were cultured on untreated TiU before being exposed to CHX. Cell viability (MTS assay), proliferation (EdU incorporation assay; Ki67 confocal immunofluorescence analysis), adhesion (morphological analysis of actin cytoskeleton organization), and osteogenic differentiation (osteopontin confocal immunofluorescence analysis; mineralized bone-like nodule formation) analyses were performed. CHX resulted cytotoxic in all experimental conditions. Diode laser irradiation preserved TiU surface biocompatibility. Notably, laser treatment appeared even to improve the known osteoconductive properties of TiU surfaces. Within the limitations of an in vitro experimentation, this study contributes to provide additional experimental basis to support the potential use of 808 ± 10 nm GaAlAs diode laser at the indicated irradiation setting, in the treatment of peri-implantitis and to discourage the use of CHX.

Effects of photodynamic laser and violet-blue led irradiation on Staphylococcus aureus biofilm and Escherichia coli lipopolysaccharide attached to moderately rough titanium surface: in vitro study.

Effective decontamination of biofilm and bacterial toxins from the surface of dental implants is a yet unresolved issue. This study investigates the in vitro efficacy of photodynamic treatment (PDT) with methylene blue (MB) photoactivated with λ 635 nm diode laser and of λ 405 nm violet-blue LED phototreatment for the reduction of bacterial biofilm and lipopolysaccharide (LPS) adherent to titanium surface mimicking the bone-implant interface. Staphylococcus aureus biofilm grown on titanium discs with a moderately rough surface was subjected to either PDT (0.1% MB and λ 635 nm diode laser) or λ 405 nm LED phototreatment for 1 and 5 min. Bactericidal effect was evaluated by vital staining and residual colony-forming unit count. Biofilm and titanium surface morphology were analyzed by scanning electron microscopy (SEM). In parallel experiments, discs coated with Escherichia coli LPS were treated as above before seeding with RAW 264.7 macrophages to quantify LPS-driven inflammatory cell activation by measuring the enhanced generation of nitric oxide (NO). Both PDT and LED phototreatment induced a statistically significant (p < 0.05 or higher) reduction of viable bacteria, up to -99 and -98% (5 min), respectively. Moreover, besides bactericidal effect, PDT and LED phototreatment also inhibited LPS bioactivity, assayed as nitrite formation, up to -42%, thereby blunting host inflammatory response. Non-invasive phototherapy emerges as an attractive alternative in the treatment of peri-implantitis to reduce bacteria and LPS adherent to titanium implant surface without causing damage of surface microstructure. Its efficacy in the clinical setting remains to be investigated.

Quality assurance multicenter comparison of different MR scanners for quantitative diffusion-weighted imaging.

PURPOSE: To propose a magnetic resonance imaging (MRI) quality assurance procedure that can be used for multicenter comparison of different MR scanners for quantitative diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Twenty-six centers (35 MR scanners with field strengths: 1T, 1.5T, and 3T) were enrolled in the study. Two different DWI acquisition series (b-value ranges 0-1000 and 0-3000 s/mm(2) , respectively) were performed for each MR scanner. All DWI acquisitions were performed by using a cylindrical doped water phantom. Mean apparent diffusion coefficient (ADC) values as well as ADC values along each of the three main orthogonal directions of the diffusion gradients (x, y, and z) were calculated. Short-term repeatability of ADC measurement was evaluated for 26 MR scanners. RESULTS: A good agreement was found between the nominal and measured mean ADC over all the centers. More than 80% of mean ADC measurements were within 5% from the nominal value, and the highest deviation and overall standard deviation were 9.3% and 3.5%, respectively. Short-term repeatability of ADC measurement was found <2.5% for all MR scanners. CONCLUSION: A specific and widely accepted protocol for quality controls in DWI is still lacking. The DWI quality assurance protocol proposed in this study can be applied in order to assess the reliability of DWI-derived indices before tackling single- as well as multicenter studies.

Low intensity 635 nm diode laser irradiation inhibits fibroblast-myofibroblast transition reducing TRPC1 channel expression/activity: New perspectives for tissue fibrosis treatment.

BACKGROUND AND OBJECTIVE: Low-level laser therapy (LLLT) or photobiomodulation therapy is emerging as a promising new therapeutic option for fibrosis in different damaged and/or diseased organs. However, the anti-fibrotic potential of this treatment needs to be elucidated and the cellular and molecular targets of the laser clarified. Here, we investigated the effects of a low intensity 635 ± 5 nm diode laser irradiation on fibroblast-myofibroblast transition, a key event in the onset of fibrosis, and elucidated some of the underlying molecular mechanisms. MATERIALS AND METHODS: NIH/3T3 fibroblasts were cultured in a low serum medium in the presence of transforming growth factor (TGF)-ß1 and irradiated with a 635 ± 5 nm diode laser (continuous wave, 89 mW, 0.3 J/cm(2) ). Fibroblast-myofibroblast differentiation was assayed by morphological, biochemical, and electrophysiological approaches. Expression of matrix metalloproteinase (MMP)-2 and MMP-9 and of Tissue inhibitor of MMPs, namely TIMP-1 and TIMP-2, after laser exposure was also evaluated by confocal immunofluorescence analyses. Moreover, the effect of the diode laser on transient receptor potential canonical channel (TRPC) 1/stretch-activated channel (SAC) expression and activity and on TGF-ß1/Smad3 signaling was investigated. RESULTS: Diode laser treatment inhibited TGF-ß1-induced fibroblast-myofibroblast transition as judged by reduction of stress fibers formation, α-smooth muscle actin (sma) and type-1 collagen expression and by changes in electrophysiological properties such as resting membrane potential, cell capacitance and inwardly rectifying K(+) currents. In addition, the irradiation up-regulated the expression of MMP-2 and MMP-9 and downregulated that of TIMP-1 and TIMP-2 in TGF-ß1-treated cells. This laser effect was shown to involve TRPC1/SAC channel functionality. Finally, diode laser stimulation and TRPC1 functionality negatively affected fibroblast-myofibroblast transition by interfering with TGF-ß1 signaling, namely reducing the expression of Smad3, the TGF-ß1 downstream signaling molecule. CONCLUSION: Low intensity irradiation with 635 ± 5 nm diode laser inhibited TGF-ß1/Smad3-mediated fibroblast-myofibroblast transition and this effect involved the modulation of TRPC1 ion channels. These data contribute to support the potential anti-fibrotic effect of LLLT and may offer further informations for considering this therapy as a promising therapeutic tool for the treatment of tissue fibrosis.

The effects of diode laser on Staphylococcus aureus biofilm and Escherichia coli lipopolysaccharide adherent to titanium oxide surface of dental implants. An in vitro study.

Effective decontamination of biofilm and bacterial toxins from the surface of dental implants is a yet unresolved issue. This in vitro study aims at providing the experimental basis for possible use of diode laser (λ 808 nm) in the treatment of peri-implantitis. Staphylococcus aureus biofilm was grown for 48 h on titanium discs with porous surface corresponding to the bone-implant interface and then irradiated with a diode laser (λ 808 nm) in noncontact mode with airflow cooling for 1 min using a Ø 600-µm fiber. Setting parameters were 2 W (400 J/cm2) for continuous wave mode; 22 µJ, 20 kHz, 7 µs (88 J/cm2) for pulsed wave mode. Bactericidal effect was evaluated using fluorescence microscopy and counting the residual colony-forming units. Biofilm and titanium surface morphology were analyzed by scanning electron microscopy (SEM). In parallel experiments, the titanium discs were coated with Escherichia coli lipopolysaccharide (LPS), laser-irradiated and seeded with RAW 264.7 macrophages to quantify LPS-driven inflammatory cell activation by measuring the enhanced generation of nitric oxide (NO). Diode laser irradiation in both continuous and pulsed modes induced a statistically significant reduction of viable bacteria and nitrite levels. These results indicate that in addition to its bactericidal effect laser irradiation can also inhibit LPS-induced macrophage activation and thus blunt the inflammatory response. The λ 808-nm diode laser emerges as a valuable tool for decontamination/detoxification of the titanium implant surface and may be used in the treatment of peri-implantitis.

Thermal effects of λ = 808 nm GaAlAs diode laser irradiation on different titanium surfaces.

Diode lasers are widely used in dental laser treatment, but little is known about their thermal effects on different titanium implant surfaces. This is a key issue because already a 10 °C increase over the normal body temperature can induce bone injury and compromise osseo-integration. The present study aimed at evaluating the temperature changes and surface alterations experienced by different titanium surfaces upon irradiation with a λ = 808 nm diode laser with different settings and modalities. Titanium discs with surfaces mimicking different dental implant surfaces including TiUnite and anodized, machined surfaces were laser-irradiated in contact and non-contact mode, and with and without airflow cooling. Settings were 0.5-2.0 W for the continuous wave mode and 10-45 µJ, 20 kHz, 5-20 µs for the pulsed wave mode. The results show that the surface characteristics have a marked influence on temperature changes in response to irradiation. The TiUnite surface, corresponding to the osseous interface of dental implants, was the most susceptible to thermal rise, while the machined surfaces, corresponding to the implant collar, were less affected. In non-contact mode and upon continuous wave emission, the temperature rose above the 50 °C tissue damage threshold. Scanning electron microscopy investigation of surface alterations revealed that laser treatment in contact mode resulted in surface scratches even when no irradiation was performed. These findings indicate that the effects of diode laser irradiation on implant surfaces depend on physical features of the titanium coating and that in order to avoid thermal or physical damage to implant surface the irradiation treatment has to be carefully selected.

Progression of brain atrophy in the early stages of Parkinson's disease: a longitudinal tensor-based morphometry study in de novo patients without cognitive impairment.

The presence of brain atrophy and its progression in early Parkinson's disease (PD) are still a matter of debate, particularly in patients without cognitive impairment. The aim of this longitudinal study was to assess whether PD patients who remain cognitively intact develop progressive atrophic changes in the early stages of the disease. For this purpose, we employed high-resolution T1-weighted MR imaging to compare 22 drug-naïve de novo PD patients without cognitive impairment to 17 age-matched control subjects, both at baseline and at three-year follow-up. We used tensor-based morphometry to explore the presence of atrophic changes at baseline and to compute yearly atrophy rates, after which we performed voxel-wise group comparisons using threshold-free cluster enhancement. At baseline, we did not observe significant differences in regional atrophy in PD patients with respect to control subjects. In contrast, PD patients showed significantly higher yearly atrophy rates in the prefrontal cortex, anterior cingulum, caudate nucleus, and thalamus when compared to control subjects. Our results indicate that even cognitively preserved PD patients show progressive cortical and subcortical atrophic changes in regions related to cognitive functions and that these changes are already detectable in the early stages of the disease.

Gender, age-related, and regional differences of the magnetization transfer ratio of the cortical and subcortical brain gray matter.

PURPOSE: To explore gender, age-related, and regional differences of magnetization transfer ratio (MTR) of brain cortical and subcortical gray matter (GM). MATERIALS AND METHODS: In all, 102 healthy subjects (51 women and 51 men; range 25-84 years) were examined with 3-mm thick MT images. We assessed MTR in automatically segmented GM structures including frontal, parietal-insular, temporal, and occipital cortex, caudate, pallidus and putamen, and cerebellar cortex. A general linear model analysis was conducted to ascertain the linear and quadratic relationship among the MTR and gender, age, and anatomical structure. RESULTS: The effect of gender was borderline (P = 0.07) in all GM structures (with higher MTR values in men), whereas age showed a significant linear as well as quadratic effect in all cortical and subcortical GM structures (P ≤ 0.001). Quadratic age-related decrease in MTR began at about 40 years of age. Mean and standard deviation (SD) of MTR had the following decreasing order: thalamus (58.3 + 0.8), pallidus (56.8 ± 1.3), caudate (55.5 ± 1.6) and putamen (54.6 ± 1.1); temporal (56.8 ± 0.9), parietal-insular (56.8 ± 1.1), frontal (56.5 ± 1.1), occipital (55.4 ± 1.0) and cerebellar (53.2 ± 1.0) cortex. In post-hoc testing, all regional pairwise differences were statistically significant except pallidus vs. temporal or parietal-insular cortex, caudate vs. occipital cortex, frontal vs. parietal-insular or temporal cortex. CONCLUSION: MTR of the cortical and subcortical brain GM structures decreases quadratically after midlife and shows significant regional differences.

Soft-Tissue Augmentation Around Dental Implants by a New Laser-Aided Pouch Roll Technique: Volumetric and Clinical Evaluation After 1 Year.

The ultimate goal in implantology is to restore the whole tooth-gingival complex in a fashion that cannot be distinguished from the rest of the natural dentition. This study assesses the volumetric and clinical changes in vestibular gingival soft tissues, crucial for satisfactory engraftment and esthetic results, upon treatment with laser-aided pouch roll augmentation in second-stage surgery for dental implant uncovering. Twelve patients with mild ridge deficiencies in 16 edentulous sites, including distal elements, were enrolled and reevaluated for up to 1 year. Digital impressions, taken with an intraoral laser scanner and software, were analyzed before (day 0) and after (month 12) treatment. The digital STL files were superimposed to assess volumetric and linear dimensional variations in selected peri-implant regions of interest by 3D analysis software. Clinical periodontal parameters (probing depth [PD], bleeding on probing [BoP], plaque index [PI]) and subjective patient-reported outcomes were also evaluated. In all patients, the applied technique induced a substantial increase in the volume of the vestibular peri-implant gingiva at 12-month follow-up (range, 24%-69%, mean 40.4%) with respect to day 0. The gingival mucosa appeared normal at both inspection and evaluation of the periodontal parameters (PD 2.7 ± 1 mm; BoP 0.11 ± 0.2 seconds; PI 0.19 ± 0). Patients' satisfaction with perceived pain/discomfort and esthetic outcome was high. These findings indicate that laser-aided pouch roll flap is a safe, patient-liked procedure whose long-term effectiveness has been objectively demonstrated by volumetric and clinical assessment.

Efficacy of MRI data harmonization in the age of machine learning: a multicenter study across 36 datasets.

Pooling publicly-available MRI data from multiple sites allows to assemble extensive groups of subjects, increase statistical power, and promote data reuse with machine learning techniques. The harmonization of multicenter data is necessary to reduce the confounding effect associated with non-biological sources of variability in the data. However, when applied to the entire dataset before machine learning, the harmonization leads to data leakage, because information outside the training set may affect model building, and potentially falsely overestimate performance. We propose a 1) measurement of the efficacy of data harmonization; 2) harmonizer transformer, i.e., an implementation of the ComBat harmonization allowing its encapsulation among the preprocessing steps of a machine learning pipeline, avoiding data leakage by design. We tested these tools using brain T1-weighted MRI data from 1740 healthy subjects acquired at 36 sites. After harmonization, the site effect was removed or reduced, and we showed the data leakage effect in predicting individual age from MRI data, highlighting that introducing the harmonizer transformer into a machine learning pipeline allows for avoiding data leakage by design.

Photoactivation of bone marrow mesenchymal stromal cells with diode laser: effects and mechanisms of action.

Mesenchymal stromal cells (MSCs) are a promising cell candidate in tissue engineering and regenerative medicine. Their proliferative potential can be increased by low-level laser irradiation (LLLI), but the mechanisms involved remain to be clarified. With the aim of expanding the therapeutic application of LLLI to MSC therapy, in the present study we investigated the effects of 635 nm diode laser on mouse MSC proliferation and investigated the underlying cellular and molecular mechanisms, focusing the attention on the effects of laser irradiation on Notch-1 signal activation and membrane ion channel modulation. It was found that MSC proliferation was significantly enhanced after laser irradiation, as judged by time lapse videomicroscopy and EdU incorporation. This phenomenon was associated with the up-regulation and activation of Notch-1 pathway, and with increased membrane conductance through voltage-gated K(+) , BK and Kir, channels and T- and L-type Ca(2+) channels. We also showed that MSC proliferation was mainly dependent on Kir channel activity, on the basis that the cell growth and Notch-1 up-regulation were severely decreased by the pre-treatment with the channel inhibitor Ba(2+) (0.5 mM). Interestingly, the channel inhibition was also able to attenuate the stimulatory effects of diode laser on MSCs, thus providing novel evidence to expand our knowledge on the mechanisms of biostimulation after LLLI. In conclusions, our findings suggest that diode laser may be a valid approach for the preconditioning of MSCs in vitro prior cell transplantation.

Collinearity and Dimensionality Reduction in Radiomics: Effect of Preprocessing Parameters in Hypertrophic Cardiomyopathy Magnetic Resonance T1 and T2 Mapping.

Radiomics and artificial intelligence have the potential to become a valuable tool in clinical applications. Frequently, radiomic analyses through machine learning methods present issues caused by high dimensionality and multicollinearity, and redundant radiomic features are usually removed based on correlation analysis. We assessed the effect of preprocessing-in terms of voxel size resampling, discretization, and filtering-on correlation-based dimensionality reduction in radiomic features from cardiac T1 and T2 maps of patients with hypertrophic cardiomyopathy. For different combinations of preprocessing parameters, we performed a dimensionality reduction of radiomic features based on either Pearson's or Spearman's correlation coefficient, followed by the computation of the stability index. With varying resampling voxel size and discretization bin width, for both T1 and T2 maps, Pearson's and Spearman's dimensionality reduction produced a slightly different percentage of remaining radiomic features, with a relatively high stability index. For different filters, the remaining features' stability was instead relatively low. Overall, the percentage of eliminated radiomic features through correlation-based dimensionality reduction was more dependent on resampling voxel size and discretization bin width for textural features than for shape or first-order features. Notably, correlation-based dimensionality reduction was less sensitive to preprocessing when considering radiomic features from T2 compared with T1 maps.

Neurodegeneration in friedreich's ataxia is associated with a mixed activation pattern of the brain. A fMRI study.

Friedreich's ataxia (FRDA) is associated with a distributed pattern of neurodegeneration in the spinal cord and the brain secondary to selective neuronal loss. We used functional MR Imaging (fMRI) to explore brain activation in FRDA patients during two motor-sensory tasks of different complexity, i.e. continuous hand tapping and writing of "8" figure, with the right dominant hand and without visual feedback. Seventeen FRDA patients and two groups of age-matched healthy controls were recruited. Task execution was monitored and recorded using MR-compatible devices. Hand tapping was correctly performed by 11 (65%) patients and writing of the "8" by 7 (41%) patients. After correction for behavioral variables, FRDA patients showed in both tasks areas of significantly lower activation in the left primary sensory-motor cortex and right cerebellum. Also left thalamus and right dorsolateral prefrontal cortex showed hypo-activation during hand tapping. During writing of the "8" task FRDA patients showed areas of higher activation in the right parietal and precentral cortex, globus pallidus, and putamen. Activation of right parietal cortex, anterior cingulum, globus pallidus, and putamen during writing of the "8" increased with severity of the neurological deficit. In conclusion fMRI demonstrates in FRDA a mixed pattern constituted by areas of decreased activation and areas of increased activation. The decreased activation in the primary motor cortex and cerebellum presumably reflects a regional neuronal damage, the decreased activation of the left thalamus and primary sensory cortex could be secondary to deafferentation phenomena, and the increased activation of right parietal cortex and striatum might have a possible compensatory significance.