Er:YAG laser-induced damage to a dental composite in simulated clinical scenarios for inadvertent irradiation: an in vitro study.

Inadvertent Er:YAG laser irradiation occurs in dentistry and may harm restorative materials in teeth. The aim of this in vitro study was to quantify Er:YAG laser-induced damage to a nanohybrid composite in simulated clinical scenarios for inadvertent direct and indirect (reflection) laser irradiation. The simulation was performed by varying the output energy (OE;direct˃indirect) reaching the specimen and the operating distance (OD;direct˂indirect). Composite specimens were irradiated by an Er:YAG laser. The ablation threshold was determined and clinically relevant parameters were applied (n = 6 for each OE/OD combination) for direct (OE: 570 mJ/OD: 10 mm, OE: 190 mJ/OD: 10 mm) and indirect irradiation (OE: 466 mJ/OD: 15 mm, OE: 57 mJ/OD: 15 mm, OE: 155 mJ/OD: 15 mm, OE: 19 mJ/OD: 15 mm). The extent of damage in the form of craters was evaluated using a laser scanning microscope (LSM) and a conventional light microscope (LM). The ablation threshold was determined to be 2.6 J/cm2. The crater diameter showed the highest value (LM: 1075 ± 18 µm/LSM: 1082 ± 17 µm) for indirect irradiation (reflectant:dental mirror) (OE: 466 mJ/OD: 15 mm). The crater depth showed the highest and comparable value for direct (OE: 570 mJ/OD: 10 mm; LSM: 89 ± 2 µm) and indirect irradiation (OE: 466 mJ/OD: 15 mm; LSM: 90 ± 4 µm). For each OD, the crater diameter, depth, and volume increased with higher laser fluence. However, the OD-and thus the laser spot diameter-also had an enlarging effect. Thus, indirect irradiation (reflectant:dental mirror) with only 47% of the laser fluence of direct irradiation led to a larger diameter and a comparable depth. The three-dimensional extent of the crater was large enough to cause roughening, which may lead to plaque accumulation and encourage caries, gingivitis, and periodontitis under clinical conditions. Clinicians should be aware that reflected irradiation can still create such craters.

Obstructive sleep apnea and craniofacial appearance in MPS type I-Hurler children after hematopoietic stem cell transplantation.

OBJECTIVES: Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disorder characterized by severe multi-systemic organ manifestations including obstructive sleep apnea syndrome (OSAS). Hematopoietic stem cell transplantation (HSCT) is the treatment of choice in severe MPS I (MPS IH, Hurler syndrome). However, the effect of HSCT on OSAS in MPS IH still remains unclear. The purpose of this study was to analyze respiratory patterns during sleep following HSCT in MPS IH children and to relate these findings to craniofacial abnormalities. METHODS: Overnight polysomnographies of nine MPS IH children (mean age: 8.2 years) previously treated with HSCT were retrospectively analyzed. Magnetic resonance images of the head were assessed with regard to soft and hard tissue abnormalities of the upper respiratory tract. RESULTS: The mean apnea hypopnea index (AHI) was 5.3 events/h (range, 0.3-12.2), and the majority of apnea/hypopneas were obstructive. Whereas two patients had severe OSAS (AHI > 10) and two moderate OSAS (5 > AHI < 10), five patients had no evidence of OSAS (AHI < 2.0). Donor cell chimerism was significantly lower in MPS IH patients with OSAS as compared to patients without OSAS (p < 0.001). The upper airway space and the maxilla were significantly smaller and the adenoids larger in MPS IH patients with OSAS as compared to those of non-OSAS patients. CONCLUSION: OSAS was only observed in MPS IH patients with graft failure or low donor cell chimerism. Conversely, successful HSCT seems to ameliorate adenoid hyperplasia and maxillary constriction in MPS IH patients and thereby minimizes the risk of OSAS at least at younger ages.

Characterization of the transmission behavior of dental filling materials and cements for the diode lasers' and the Nd:YAG laser's wavelengths.

OBJECTIVES: Diode lasers and the Nd:YAG laser are used in periodontal therapy and soft tissue surgery. Dental filling materials or cements might be inadvertently damaged. The underlying mechanism of the damage is based on the dental material's specific transmission and thus absorption behavior. MATERIALS AND METHODS: Twenty-four material representatives for composites, glass ionomer cements and other material classes (e.g., compomer) were processed to 100 µm and 200 µm planar specimens and spectroscopically measured for their collimated transmission in the photo spectrometer Varian Cary 5000. The (1) mean intensity of transmitted light was determined for the laser wavelengths of interest (810 nm, 940 nm, 980 nm, 1,064 nm) and used to calculate the (2) absorption lengths. RESULTS: The (1) mean intensity of transmitted light ranged between 9.51 % (Panavia F 2.0 for 810 nm) and 96.79% (Artegral Cem for 1,064 nm) for the composite specimens (100 µm) and was-with few exceptions-near zero for the representatives of glass ionomer cement and the other material classes. The (2) absorption lengths were between 0.06 mm (Panavia F 2.0 for all wavelengths of interest) and 1.33 mm (Coltène Duo Cement Plus for 1,064 nm) for the composites and below or equal 0.15 mm (PermaCem for 1,064 nm) for the few representatives of glass ionomer cements and the other material classes with mean intensities of transmitted light, which were not near zero and thus permitted to calculate absorption lengths. CONCLUSIONS: The transmission behavior varied between the different material classes and even within, albeit less pronounced. Composites generally showed the highest intensities of transmitted light and are thus least susceptible to surface damage by laser light (810 nm, 940 nm, 980 nm, 1,064 nm). The results can be used to improve and develop laser applications involving purposeful interactions between laser light and dental materials. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

The neural basis of visual dominance in the context of audio-visual object processing.

Visual dominance refers to the observation that in bimodal environments vision often has an advantage over other senses in human. Therefore, a better memory performance for visual compared to, e.g., auditory material is assumed. However, the reason for this preferential processing and the relation to the memory formation is largely unknown. In this fMRI experiment, we manipulated cross-modal competition and attention, two factors that both modulate bimodal stimulus processing and can affect memory formation. Pictures and sounds of objects were presented simultaneously in two levels of recognisability, thus manipulating the amount of cross-modal competition. Attention was manipulated via task instruction and directed either to the visual or the auditory modality. The factorial design allowed a direct comparison of the effects between both modalities. The resulting memory performance showed that visual dominance was limited to a distinct task setting. Visual was superior to auditory object memory only when allocating attention towards the competing modality. During encoding, cross-modal competition and attention towards the opponent domain reduced fMRI signals in both neural systems, but cross-modal competition was more pronounced in the auditory system and only in auditory cortex this competition was further modulated by attention. Furthermore, neural activity reduction in auditory cortex during encoding was closely related to the behavioural auditory memory impairment. These results indicate that visual dominance emerges from a less pronounced vulnerability of the visual system against competition from the auditory domain.

Non-consensus GLI binding sites in Hedgehog target gene regulation.

BACKGROUND: The GLI transcription factors, mediators of the hedgehog signal bind with high affinity to the consensus sequence GACCACCCA. The affinity of variant single substitutions in GLI binding sites has been measured systematically, but the affinities of the variant binding sites appears low compared to the frequency of occurrence of variant sites in known GLI target gene promoters. RESULTS: We quantified transcriptional activation by GLI using PTCH1 promoter based luciferase reporters containing all single substitutions of the GLI consensus binding site. As expected variants with very low affinity did not activate the reporter. Many lower affinity binding sequences are, however, functional in the presence of moderate GLI concentration. Using two natural non-consensus GLI site promoters we showed that substitution of the variant sequences by consensus leads to comparable activity. CONCLUSIONS: Variant GLI binding sites with relatively low affinity can within natural promoters lead to strong transcriptional activation. This may facilitate the identification of additional direct GLI target genes.

GLI2-specific transcriptional activation of the bone morphogenetic protein/activin antagonist follistatin in human epidermal cells.

Hedgehog (HH) signaling in the epidermis is primarily mediated by the zinc finger transcription factors GLI1 and GLI2. Exquisite regulation of HH/GLI signaling is crucial for proper specification of the epidermal lineage and development of its derivatives, whereas dysregulation of HH/GLI signaling disrupts tissue homeostasis and causes basal cell carcinoma (BCC). Similarly, bone morphogenetic proteins (BMPs) and activins have been described as key signaling factors in the complex regulation of epidermal fate decisions, although their precise interplay with HH/GLI is largely elusive. Here we show that, in human epidermal cells, expression of the activin/BMP antagonist follistatin (FST) is predominantly up-regulated by the HH effector GLI2. Consistently, we found strong FST expression in the outer root sheath of human hair follicles and BCC. Detailed promoter analysis showed that two sequences with homology to the GLI consensus binding site are required for GLI2-mediated activation. Interestingly, activation of the FST promoter is highly GLI2-specific, because neither GLI1 nor GLI3 can significantly increase FST transcription. GLI2 specificity requires the presence of a 518-bp fragment in the proximal FST promoter region. On the protein level, sequences C-terminal to the zinc finger are responsible for GLI2-specific activation of FST transcription, pointing to the existence of GLI-interacting cofactors that modulate GLI target specificity. Our results reveal a key role of GLI2 in activation of the activin/BMP antagonist FST in response to HH signaling and provide new evidence for a regulatory interaction between HH and activin/BMP signaling in hair follicle development and BCC.

Selective modulation of Hedgehog/GLI target gene expression by epidermal growth factor signaling in human keratinocytes.

Hedgehog (HH)/GLI signaling plays a critical role in epidermal development and basal cell carcinoma. Here, we provide evidence that epidermal growth factor receptor (EGFR) signaling modulates the target gene expression profile of GLI transcription factors in epidermal cells. Using expression profiling and quantitative reverse transcriptase PCR, we identified a set of 19 genes whose transcription is synergistically induced by GLI1 and parallel EGF treatment. Promoter studies of a subset of GLI/EGF-regulated genes, including the genes encoding interleukin-1 antagonist IL1R2, Jagged 2, cyclin D1, S100A7, and S100A9, suggest convergence of EGFR and HH/GLI signaling at the level of promoters of selected direct GLI target genes. Inhibition of EGFR and MEK/ERK but not of phosphatidylinositol 3-kinase/AKT abrogated synergistic activation of GLI/EGF target genes, showing that EGFR can signal via RAF/MEK/ERK to cooperate with GLI proteins in selective target gene regulation. Coexpression of the GLI/EGF target IL1R2, EGFR, and activated ERK1/2 in human anagen hair follicles argues for a cooperative role of EGFR and HH/GLI signaling in specifying the fate of outer root sheath (ORS) cells. We also show that EGF treatment neutralizes GLI-mediated induction of epidermal stem cell marker expression and provide evidence that EGFR signaling is essential for GLI-induced cell cycle progression in epidermal cells. The results suggest that EGFR signaling modulates GLI target gene profiles which may play an important regulatory role in ORS specification, hair growth, and possibly cancer.

Overlapping and distinct transcriptional regulator properties of the GLI1 and GLI2 oncogenes.

The GLI transcription factors mediate the hedgehog signal in development and carcinogenesis. Basal cell carcinoma can be caused by overexpression of either GLI1 or GLI2. Though GLI1 and GLI2 have identical or very similar DNA binding specificities, some of their activities are overlapping, some are clearly distinct. We analyzed target gene specificities of GLI1 and constitutively active GLI2 (GLI2DeltaN) by global expression profiling in an inducible, well-characterized HaCaT keratinocyte expression system. Four hundred fifty-six genes up- or downregulated at least twofold were identified. GLI target gene profiles correlated well with the biological activities of these transcription factors in hair follicles and basal cell carcinoma. Upregulation of largely overlapping sets of target genes was effected by both factors, repression occurred predominantly in response to GLI2. Also, significant quantitative differences in response to GLI1 and GLI2DeltaN were found for a small number of activated genes. Since we have not detected a putative processed GLI2 repressor, these results point to specific but indirect target gene repression by GLI2DeltaN via preferential activation of one or more negative regulators.

The functional and temporal characteristics of top-down modulation in visual selection.

Perceptual load of an attended task influences the processing of irrelevant background stimuli. In a series of behavioral, functional magnetic resonance (fMRI) and electroencephalography (EEG) experiments we examined the influence of working memory (WM) load related to a relevant visual stimulus on the processing of irrelevant backgrounds. We further addressed two open questions about the mechanism of load-dependent modulation: (i) is this modulation dependent on regional activity (i.e. phasic)? (ii) At what processing stage does this modulation take place? Load was manipulated by a WM task and concurrently the processing of irrelevant visual objects was assessed with fMRI and EEG. To examine the dependency of this modulation on intrinsic activity, we varied the activity level of visual areas by presenting objects with different levels of degradation. Activity in the lateral occipital complex (LOC) increased with object visibility and was phasically modulated by WM load. Event related potentials revealed that this phasic modulation occurred approximately 170 ms after stimulus onset, indicative of an early selection under high load. The results indicate a phasic modulatory effect of WM load on visual object processing in the LOC that is comparable to the effects found for perceptual load manipulations.