Identification of DSPP novel variants and phenotype analysis in dentinogenesis dysplasia Shields type II patients.

OBJECTIVES: To investigate the genetic causes and teeth characteristics of dentin dysplasia Shields type II(DD-II) in three Chinese families. MATERIALS AND METHODS: Data from three Chinese families affected with DD-II were collected. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were conducted to screen for variations, and Sanger sequencing was used to verify mutation sites. The physical and chemical characteristics of the affected teeth including tooth structure, hardness, mineral content, and ultrastructure were investigated. RESULTS: A novel frameshift deletion mutation c.1871_1874del(p.Ser624fs) in DSPP was found in families A and B, while no pathogenic mutation was found in family C. The affected teeth's pulp cavities were obliterated, and the root canals were smaller than normal teeth and irregularly distributed comprising a network. The patients' teeth also had reduced dentin hardness and highly irregular dentinal tubules. The Mg content of the teeth was significantly lower than that of the controls, but the Na content was obviously higher than that of the controls. CONCLUSIONS: A novel frameshift deletion mutation, c.1871_1874del (p.Ser624fs), in the DPP region of the DSPP gene causes DD-II. The DD-II teeth demonstrated compromised mechanical properties and changed ultrastructure, suggesting an impaired function of DPP. Our findings expand the mutational spectrum of the DSPP gene and strengthen the understanding of clinical phenotypes related to the frameshift deletion in the DPP region of the DSPP gene. CLINICAL RELEVANCE: A DSPP mutation can alter the characteristics of the affected teeth, including tooth structure, hardness, mineral content, and ultrastructure.

In Silico Analysis of Adjuvant Head and Neck Online Adaptive Radiation Therapy.

Purpose: Recently developed online adaptive radiation therapy (OnART) systems enable frequent treatment plan adaptation, but data supporting a dosimetric benefit in postoperative head and neck radiation therapy (RT) are sparse. We performed an in silico dosimetric study to assess the potential benefits of a single versus weekly OnART in the treatment of patients with head and neck squamous cell carcinoma in the adjuvant setting. Methods and Materials: Twelve patients receiving conventionally fractionated RT over 6 weeks and 12 patients receiving hypofractionated RT over 3 weeks on a clinical trial were analyzed. The OnART emulator was used to virtually adapt either once midtreatment or weekly based on the patient's routinely performed cone beam computed tomography. The planning target volume (PTV) coverage, dose heterogeneity, and cumulative dose to the organs at risk for these 2 adaptive approaches were compared with the nonadapted plan. Results: In total, 13, 8, and 3 patients had oral cavity, oropharynx, and larynx primaries, respectively. In the conventionally fractionated RT cohort, weekly OnART led to a significant improvement in PTV V100% coverage (6.2%), hot spot (-1.2 Gy), and maximum cord dose (-3.1 Gy), whereas the mean ipsilateral parotid dose increased modestly (1.8 Gy) versus the nonadapted plan. When adapting once midtreatment, PTV coverage improved with a smaller magnitude (0.2%-2.5%), whereas dose increased to the ipsilateral parotid (1.0-1.1 Gy) and mandible (0.2-0.7 Gy). For the hypofractionated RT cohort, similar benefit was observed with weekly OnART, including significant improvement in PTV coverage, hot spot, and maximum cord dose, whereas no consistent dosimetric advantage was seen when adapting once midtreatment. Conclusions: For head and neck squamous cell carcinoma adjuvant RT, there was a limited benefit of single OnART, but weekly adaptations meaningfully improved the dosimetric criteria, predominantly PTV coverage and dose heterogeneity. A prospective study is ongoing to determine the clinical benefit of OnART in this setting.

A Y-shape-structured electrochemiluminescence biosensor based on carbon quantum dots and locked nucleic acid probe for microRNA determination with single-base resolution.

Since microRNAs (miRNAs) are predictors of tumorigenesis, accurate identification and quantification of miRNAs with highly similar sequences are expected to reflect tumor diagnosis and treatment. In this study, a highly selective and sensitive electrochemiluminescence (ECL) biosensor was constructed for miRNAs determination based on Y-shaped junction structure equipped with locked nucleic acids (LNA), graphene oxide-based nanocomposite to enrich luminophores, and conductive matrix. Specifically, two LNA-modified probes were designed for specific miRNA recognition, that is, a dual-amine functionalized hairpin capture probe and a signal probe. A Y-shaped DNA junction structure was generated on the electrode surface upon miRNA hybridizing across the two branches, so as to enhance the selectivity. Carbon quantum dots-polyethylene imine-graphene oxide (CQDs-PEI-GO) nanocomposites were developed to enrich luminophores CQDs, and thus enhancing the ECL intensity. For indirect signal amplification, an electrochemically activated poly(2-aminoterephthalic acid) (ATA) film decorated with gold nanoparticles was prepared on electrode as an effective matrix to accelerate the electron transfer. The fabricated ECL biosensor achieved sensitive determination of miRNA-222 with a limit-of-detection (LOD) as low as 1.95 fM (S/N = 3). Notably, Y-shaped junction structures equipped with LNA probes endowed ECL biosensor with salient single-base discrimination ability and anti-interference capacity. Overall, the proposed Y-shaped ECL biosensor has considerable promise for clinical biomarker determination.

Measurement-based Monte Carlo dose calculation system for IMRT pretreatment and on-line transit dose verifications.

The aim of this study was to develop a dose simulation system based on portal dosimetry measurements and the BEAM Monte Carlo code for intensity-modulated (IM) radiotherapy dose verification. This measurement-based Monte Carlo (MBMC) system can perform, within one systematic calculation, both pretreatment and on-line transit dose verifications. BEAMnrc and DOSXYZnrc 2006 were used to simulate radiation transport from the treatment head, through the patient, to the plane of the aS500 electronic portal imaging device (EPID). In order to represent the nonuniform fluence distribution of an IM field within the MBMC simulation, an EPID-measured efficiency map was used to redistribute particle weightings of the simulated phase space distribution of an open field at a plane above a patient/phantom. This efficiency map was obtained by dividing the measured energy fluence distribution of an IM field to that of an open field at the EPID plane. The simulated dose distribution at the midplane of a homogeneous polystyrene phantom was compared to the corresponding distribution obtained from the Eclipse treatment planning system (TPS) for pretreatment verification. It also generated a simulated transit dose distribution to serve as the on-line verification reference for comparison to that measured by the EPID. Two head-and-neck (NPC1 and NPC2) and one prostate cancer fields were tested in this study. To validate the accuracy of the MBMC system, film dosimetry was performed and served as the dosimetry reference. Excellent agreement between the film dosimetry and the MBMC simulation was obtained for pretreatment verification. For all three cases tested, gamma evaluation with 3%/3 mm criteria showed a high pass percentage (> 99.7%) within the area in which the dose was greater than 30% of the maximum dose. In contrast to the TPS, the MBMC system was able to preserve multileaf collimator delivery effects such as the tongue-and-groove effect and interleaf leakage. In the NPC1 field, the TPS showed 16.5% overdose due to the tongue-and-groove effect and 14.6% overdose due to improper leaf stepping. Similarly, in the NPC2 field, the TPS showed 14.1% overdose due to the tongue-and-groove effect and 8.9% overdose due to improper leaf stepping. In the prostate cancer field, the TPS showed 6.8% overdose due to improper leaf stepping. No tongue-and-groove effect was observed for this field. For transit dose verification, agreements among the EPID measurement, the film dosimetry, and the MBMC system were also excellent with a minimum gamma pass percentage of 99.6%.

Surgical removal of extravasated epidural and neuroforaminal polymethylmethacrylate after percutaneous vertebroplasty in the thoracic spine.

Although extravasations of polymethylmetharylate during percutaneous vertebroplasty are usually of little clinical consequence, surgical decompression is occasionally required if resultant neurologic deficits are severe. Surgical removal of epidural polymethylmetharylate is usually necessary to achieve good neurologic recovery. Because mobilizing the squeezed spinal cord in a compromised canal can cause further deterioration, attempts to remove epidural polymethylmetharylate in the thoracic region need special consideration. A 66-year-old man had incomplete paraparesis and radicular pain on the chest wall after percutaneous vertebroplasty for osteoporotic compression fracture of T7. Radiological studies revealed polymethylmetharylate extravasations into the right lateral aspect of spinal canal that caused marked encroachment of the thecal sac and right neuroforamina. Progressive neurologic deficit and poor responses to medical managements were observed; therefore, surgical decompression was performed 4 months later. After laminectomy and removal of facet joints and T7 pedicle on the affected side, extravasated polymethylmetharylate posterior and anterior to the thecal sac was completely removed without retracting the dura mater. Spinal stability was reconstructed by supplemental spinal instrumentation and intertransverse arthrodesis with banked cancellous allografts. Myelopathy and radicular pain gradually resolved after decompression surgery. The patient was free of sensory abnormality and regained satisfactory ambulation two years after surgical decompression.

[Key frames extraction and application in intravascular ultrasound pullback sequences based on manifold learning].

OBJECTIVE: We propose an image-based key frames gating method for intravascular ultrasound (IVUS) sequence based on manifold learning to reduce motion artifacts in IVUS longitudinal cuts. METHODS: We achieved the gating with Laplacian eigenmaps, a manifold learning technique, to determine the low-dimensional manifold embedded in the high-dimensional image space. A distance function was constructed by the low-dimensional feature vectors to reflect the heart movement. The IVUS images were classified as end-diastolic and non-end-diastolic based on the distance function, and the IVUS images collected in end-diastolic stage constitutes the key frames gating sequences. RESULTS: We tested the algorithm on 13 in vivo clinical IVUS sequences (images 915±142 frames, coronary segments length 15.24±2.37 mm) to calculate the vessel volume, lumen volume, and the mean plaque burden of the original and gated sequences. Statistical results showed that both the vessel volume and lumen volume measured from the gated sequences were significantly smaller than the original ones, indicating that the gated sequences were more stable; the mean plaque burden was comparable between the original and gated sequences to meet the need in clinical diagnosis and treatment. In the longitudinal views, the gated sequences had less saw tooth shape than the original ones with a similar trend and a good continuity. We also compared our method with an existing gating method. CONCLUSION: The proposed algorithm is simple and robust, and the gating sequences can effectively reduce motion artifacts in IVUS longitudinal cuts.

[Effects of periodontal mechanical therapy with local and systemic drugs on carotid artery and serum high-sensitivity C-reactive protein in rats with chronic periodontitis associated with atherosclerosis].

OBJECTIVE: The aim of this study is to investigate the effects of serum high-sensitivity C-reactive protein (hsCRP) and the pathological changes in the carotid artery after periodontal mechanical therapy with local and systemic drugs in SD rats with chronic periodontitis (CP) associated with atherosclerosis (As). METHODS: Thirty-five SD rats were randomly divided into two groups: control group (group A) and CP+As group (group B). Group B was further divided into the natural process group (B1), the periodontal mechanical treatment group (B2), the periodontal mechanical treatment plus local drugs group (B3), and the periodontal mechanical treatment plus local and systemic drugs group (B4). Each group comprised seven rats. Serum hsCRP levels were evaluated at baseline 1 week after the first periodontal therapy and 1, 3, and 5 weeks after the second periodontal therapy by enzyme linked immunosorbent assay (ELISA). The pathological lesion in the carotid artery plaque was stained with hematine and eosin. RESULTS: The levels of serum hsCRP in group B1 increased gradually as time passed and became significantly higher than that of the other groups five weeks after periodontal therapy (P < 0.001). The levels of serum hsCRP in groups B2, B3, and B4 increased gradually and reached the peak 1 week after the second periodontal therapy. After that, the levels of serum hsCRP decreased gradually but were still higher than that of group A (P < 0.05). The levels of serum hsCRP in groups B3 and B4 were significantly lower than that in group B2 3 and 5 weeks after the second periodontal therapy (P < 0.001). Histologic sections revealed increased foam cell infiltration and disordered and destructed elastic fibers in groups B1 and B2. The thickness of the blood vessels in groups B3 and B4 was more uniform than that in groups B1 and B2. The elastic fibers in groups B3 and B4 were lined up in order. CONCLUSION: Direct periodontal mechanical treatment results in acute, short-term, systemic inflammation and might increase the risk of atherosclerosis in SD rats. However, the levels of serum hsCRP decreased gradually 3 to 5 weeks after therapy. With periodontal mechanical treatment, the benefits of local and systemic drugs are associated with improvement in atherosclerotic lesion progression.

The dosimetric impact of dental implants on head-and-neck volumetric modulated arc therapy.

This work aims to investigate the dosimetric impact of dental implants on volumetric modulated arc therapy (VMAT) for head-and-neck patients and to evaluate the effectiveness of using the material's electron-density ratio for the correction. An in-house Monte Carlo (MC) code was utilized for the dose calculation to account for the scattering and attenuation caused by the high-Z implant material. Three different dental implant materials were studied in this work: titanium, Degubond®4 and gold. The dose perturbations caused by the dental implant materials were first investigated in a water phantom with a 1 cm(3) insert. The per cent depth dose distributions of a 3 × 3 cm(2) photon field were compared with the insert material as water and the three selected dental implant materials. To evaluate the impact of the dental implant on VMAT patient dose calculation, four head-and-neck cases were selected. For each case, the VMAT plan was designed based on the artifact-corrected patient geometry using a treatment planning system (TPS) that was typically utilized for routine patient treatment. The plans were re-calculated using the MC code for five situations: uncorrected geometry, artifact-corrected geometry and artifact-corrected geometry with one of the three different implant materials. The isodose distributions and the dose-volume histograms were cross-compared with each other. To evaluate the effectiveness of using the material's electron-density ratio for dental implant correction, the implant region was set as water with the material's electron-density ratio and the calculated dose was compared with the MC simulation with the real material. The main effect of the dental implant was the severe attenuation in the downstream. The 1 cm(3) dental implant can lower the downstream dose by 10% (Ti) to 51% (Au) for a 3 × 3 cm(2) field. The TPS failed to account for the dose perturbation if the dental implant material was not precisely defined. For the VMAT patient dose calculation, the presence of dental implants degrades the PTV coverage significantly. With the material's electron-density ratio applied, the dose calculation accuracy in the water phantom and the VMAT patient was improved to a clinically acceptable level. The effects of the dental implant material can be clinically significant and its impact varies with the density of the dental implant material. We demonstrated that it was effective to use the material's electron-density ratio to account for the dosimetric impact of the dental implant.

Evaluation of the cone beam CT for internal target volume localization in lung stereotactic radiotherapy in comparison with 4D MIP images.

PURPOSE: To investigate whether the three-dimensional cone-beam CT (CBCT) is clinically equivalent to the four-dimensional computed tomography (4DCT) maximum intensity projection (MIP) reconstructed images for internal target volume (ITV) localization in image-guided lung stereotactic radiotherapy. METHODS: A ball-shaped polystyrene phantom with built-in cube, sphere, and cone of known volumes was attached to a motor-driven platform, which simulates a sinusoidal movement with changeable motion amplitude and frequency. Target motion was simulated in the patient in a superior-inferior (S-I) direction with three motion periods and 2 cm peak-to-peak amplitudes. The Varian onboard Exact-Arms kV CBCT system and the GE LightSpeed four-slice CT integrated with the respiratory-position-management 4DCT scanner were used to scan the moving phantom. MIP images were generated from the 4DCT images. The clinical equivalence of the two sets of images was evaluated by comparing the extreme locations of the moving objects along the motion direction, the centroid position of the ITV, and the ITV volumes that were contoured automatically by Velocity or calculated with an imaging gradient method. The authors compared the ITV volumes determined by the above methods with those theoretically predicted by taking into account the physical object dimensions and the motion amplitudes. The extreme locations were determined by the gradient method along the S-I axis through the center of the object. The centroid positions were determined by autocenter functions. The effect of motion period on the volume sizes was also studied. RESULTS: It was found that the extreme locations of the objects determined from the two image modalities agreed with each other satisfactorily. They were not affected by the motion period. The average difference between the two modalities in the extreme locations was 0.68% for the cube, 1.35% for the sphere, and 0.5% for the cone, respectively. The maximum difference in the centroid position of the cylinder, sphere, and cone was less than 1.4 mm between the two modalities for all motion periods studied. For the ITV volume evaluation, the authors found that both MIP-based and CBCT-based ITVs increased with increases of motion period. Furthermore, the MIP-based ITV volumes were generally larger than those determined from the CBCT images, with the difference in autocontoured volumes being 2.57%, 1.66%, and 1.82% for the sphere, cylinder, and cone, respectively, while these differences increased to 9.57%, 3.52%, 8.71% for the above objects when the gradient method was used. The authors found that the autocontour method was accurate enough to predict the actual ITV values with the absolute differences less than 2.4% comparing to the theoretically predicted values. CONCLUSIONS: The extreme location and the centroid position of the objects agree with each other between the two image modalities when the breathing motion is sinusoidal. Although the ITV volumes delineated from both image modalities changed with the motion period, the differences in ITV between the two modalities were minimal when an optimized window level was used. The authors' results suggest that CBCT and MIP images are equivalent in determining an ITV's position in the conditions studied. The CBCT is adequate in providing imaging-guidance for lung cancer treatment.