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The widespread adoption of clear aligners in orthodontic treatments in recent years has necessitated a more precise examination of the mechanical properties of the devices currently available in orthodontics. Recent studies indicate that aligners, when exposed to the forces exerted during swallowing, undergo fatigue-like phenomena, leading to chip formation and cracks. The cumulative damage results in a compromised fit between the tooth and aligner, which is crucial for the effective execution of orthodontic treatment. Additionally, the formation of chips poses a potential risk to patients, as there is a possibility of inadvertently ingesting microplastics that become detached from the aligner over time. This study attempts to assess the release of microplastics from the aligners subjected to cyclic compressive loading. Three different aligners (Essix Ace, Ghost Aligner and Invisalign) are tested to simulate swallowing conditions over the aligner usage period. The mechanical performance is studied in terms of the energy absorbed by the aligner, which shows that the Essix Ace has a stable energy absorption behaviour, while the energy absorbed by the Invisalign is significantly higher than their counterparts. Ghost Aligner did not perform well in the cyclic compression tests. The microplastics (MPs) released by the aligners are examined under an optical microscope. A dimensional analysis based on k-means image segmentation and edge detection algorithm is developed to analyse the MPs. The dimensional analysis of the MPs revealed that the ingestion of the MPs released by all the three aligners does not pose a health risk. [ABSTRACT FROM AUTHOR]

The reaction-diffusion master equation (RDME) is a standard modelling approach for understanding stochastic and spatial chemical kinetics. An inherent assumption is that molecules are point-like. Here, we introduce the excluded volume reaction-diffusion master equation (vRDME) which takes into account volume exclusion effects on stochastic kinetics due to a finite molecular radius. We obtain an exact closed form solution of the RDME and of the vRDME for a general chemical system in equilibrium conditions. The difference between the two solutions increases with the ratio of molecular diameter to the compartment length scale. We show that an increase in the fraction of excluded space can (i) lead to deviations from the classical inverse square root law for the noise-strength, (ii) flip the skewness of the probability distribution from right to left-skewed, (iii) shift the equilibrium of bimolecular reactions so that more product molecules are formed, and (iv) strongly modulate the Fanofactors and coefficients of variation. These volume exclusion effects are found to be particularly pronounced for chemical species not involved in chemical conservation laws. Finally, we show that statistics obtained using the vRDME are in good agreement with those obtained from Brownian dynamics with excluded volume interactions. [ABSTRACT FROM AUTHOR]

Abstract Background The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC) patients. Functional polymorphisms within the cytochrome P450 1B1 (CYP1B1) gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen. Methods CYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition), 4326C>G (432LeuVal), and 4390A>G (453AsnSer) polymorphisms and treatment response, progression-free-survival (PFS) and overall-survival (OS) was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test. Results Patients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014), shorter progression-free-survival (P = 0.032) and overall-survival (P < 0.001). Multivariate analyses and correction for multiple comparisons confirmed its prognostic significance for OS. No significant associations were found among other polymorphisms and both response and clinical outcome. Conclusions CYP1B1-4326C>G (432LeuVal) polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.

Bone metastases are responsible for most of the morbidity associated with hormone-refractory prostate cancer (HRPC). 153Sm-ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) has been approved for palliation of painful skeletal metastases. We retrospectively investigated the possible synergistic effect on survival of 153Sm-EDTMP (given to HRPC patients for bone pain palliation) and chemotherapy. Forty-five HRPC patients were evaluated, with a median age of 71 years. The number of metastatic bone sites was ≤10 in 25 patients and >10 in 20 patients. Median serum PSA was 224 ng/ml. Bone pain was mild in 6 patients, moderate in 16, severe in 22 and intolerable in 1. Fifteen patients were only treated with 153Sm-EDTMP (group A), while 30 patients also received chemotherapy (estramustine phosphate or mitoxantrone plus prednisone) at variable times: between 3 and 5 months after 153Sm-EDTMP (14 patients, group B) or within 1 month after 153Sm-EDTMP (16 patients, group C). Haematological toxicities observed after either regimen were in general mild, consistent with common observations after either 153Sm-EDTMP or chemotherapy, and without any additive adverse effects in the patients receiving both 153Sm-EDTMP and chemotherapy. Bone pain palliation to some degree was induced by 153Sm-EDTMP in 32/45 patients (71.1%), the proportion of patients with a favourable clinical response being significantly higher in group C than in group A (87.5% vs 53.3%, p = 0.0388). Also in terms of biochemical response (serum PSA levels), patients of group C performed significantly better than patients of group A ( p = 0.0235). Overall median survival from the time of administration of 153Sm-EDTMP was 15 months in the total cohort of 45 patients, and was significantly longer in group C than in either group B (30 months vs 11 months, p = 0.023) or group A (30 months vs 10 months, p = 0.008). The results of this study confirm that 153Sm-EDTMP is effective in terms of pain relief and PSA response, with minimal toxicity. When it was administered in combination with chemotherapy, prolonged survival indicated actual clinical benefit, while there were no additive toxicities. These results provide the rationale for future prospective evaluation of combined therapeutic strategies. [ABSTRACT FROM AUTHOR]

The analysis of forces, moments and pressure points has long been of great interest in orthodontics. Hence, we set out to define a method for measuring the pressure exerted by aligners on the teeth, and specifically to identify the precise points of pressure exertion. Intraoral scans were performed on a patient with optimal alignment and levelling before and after 2º vestibularisation of the upper central incisor. Pressure sensor film was placed in a dedicated housing between the aligner and teeth in order to record the pressure exerted after 15 s of aligner application. The images captured by the film were scanned, digitised, and subsequently analysed. Areas and amounts of pressure generated by the aligners were evaluated, and the net force of each was calculated, adjusted to take into consideration passive values. The method revealed the areas of contact by which the aligner transmits force on the teeth, and the pressures at which it does so. The pressure exerted by an aligner is not evenly distributed across the entire surface of the tooth during lingual tipping of an upper incisor. The areas of force concentration were not identical, as these are influenced by factors resulting from the manufacturing and casting processes. [ABSTRACT FROM AUTHOR]

Background: Radium-223 ( 223 Ra) chloride, an alpha emitter, has been shown to improve overall survival (OS) and pain control, and to delay skeletal-related events, in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Our retrospective observational study presents the first Italian experience on the efficacy and safety of 223 Ra therapy in routine clinical practice., Methods: A total of 83 patients with metastatic CRPC were treated with 223 Ra at 3 Italian centers between August 2013 and August 2016. 223 Ra-chloride (55 kBq/kg) was administered every 4 weeks for a total of 6 cycles. Primary endpoints were OS and progression-free survival (PFS). Secondary endpoints included toxicity, pain evaluation using numeric rating scale (NRS), symptomatic skeletal-related events and biomarkers response., Results: Patients had a median age of 75 (range 53-89) years. The majority of men showed a Gleason score of 7, 8, or 9. Forty-one patients completed 6 treatment cycles; 33 stopped treatment before completing 6 cycles. Nine were still receiving therapy at the time of data collection. At the end of therapy, NRS pain scores significantly improved ( p < .000001). OS was a mean of 10.1 months, while median OS had not been attained. According to Kaplan-Meier estimation, OS and PFS were 17.5 and 7.7 months, respectively. There was a significant correlation between OS and PFS with the number of 223 Ra cycles; patients receiving all 6 cycles experienced the major benefit from the therapy. 223 Ra was well-tolerated., Conclusions: 223 Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.