Smartpaddle® as a New Monitoring Feature: A Comparison Between Inertial Measurement Unit- and Strain Gauge-Based Devices on Tethered Swimming Forces.

Smartpaddle® is a novel wearable device based on inertial measurement units (IMU) for in-field arm-stroke kinetics and kinematics analysis in swimming. However, the lack of data regarding its agreement and reliability, coupled with restricted access to raw data, emphasizes the need to evaluate it against a well-established strain gauge (SG) reference method for assessing swimming forces. Thus, this study aimed to investigate the agreement and reliability between the Smartpaddle® and strain gauge in a 30-s all-out arms-only tethered swimming test. Twelve trained young adult swimmers performed a test-retest 30-s all-out arms-only tethered swimming trial. Peak and mean forces were obtained from IMU (PFIMU and MFIMU) and SG (PFSG and MFSG) simultaneously. Statistical differences and correlations were found in both peak (PFSG = 158.46 ± 48.85 N, PFIMU = 75.47 ± 12.05 N, p < 0.001, r = 0.88) and mean (MFSG = 69.62 ± 16.36 N, MFIMU = 30.06 ± 5.42 N, p < 0.001, r = 0.84) forces between devices, presenting elevated systematic errors for both variables. No differences were found in IMU data between test-retest conditions in both peak (PFIMU = 75.47 ± 12.05 N, PFIMU = 75.45 ± 11.54 N, p = 0.99, ICC = 0.96) and mean (MFIMU = 30.06 ± 5.42 N, MFIMU = 30.21 ± 5.83 N, p = 0.80, ICC = 0.95) forces, with negligible systematic errors. In conclusion, although the Smartpaddle® device is not directly comparable to the strain gauge reference method, it has demonstrated high reliability levels in test-retest trials.

Evaluating mechanical and surface properties of zirconia-containing composites: 3D printing, subtractive, and layering techniques.

This study assessed the monotonic and fatigue flexural strength (FS), elastic modulus (E), and surface characteristics of a 3D printed zirconia-containing resin composite compared to subtractive and conventional layering methods. Specimens, including discs (n = 15; Ø = 15 mm × 1.2 mm) and bars (n = 15; 14 × 4 × 1.2 mm), were prepared and categorized into three groups: 3D printing (3D printing - PriZma 3D Bio Crown, Makertech), Subtractive (Lava Ultimate blocks, 3M), and Layering (Filtek Z350 XT, 3M). Monotonic tests were performed on the discs using a piston-on-three-balls setup, while fatigue tests employed similar parameters with a frequency of 10 Hz, initial stress at 20 MPa, and stress increments every 5000 cycles. The E was determined through three-point-bending test using bars. Surface roughness, fractographic, and topographic analyses were conducted. Statistical analyses included One-way ANOVA for monotonic FS and roughness, Kruskal-Wallis for E, and Kaplan-Meier with post-hoc Mantel-Cox and Weibull analysis for fatigue strength. Results revealed higher monotonic strength in the Subtractive group compared to 3D printing (p = 0.02) and Layering (p = 0.04), while 3D Printing and Layering exhibited similarities (p = 0.88). Fatigue data indicated significant differences across all groups (3D Printing < Layering < Subtractive; p = 0.00 and p = 0.04, respectively). Mechanical reliability was comparable across groups. 3D printing and Subtractive demonstrated similar E, both surpassing Layering. Moreover, 3D printing exhibited higher surface roughness than Subtractive and Layering (p < 0.05). Fractographic analysis indicated that fractures initiated at surface defects located in the area subjected to tensile stress concentration. A porous surface was observed in the 3D Printing group and a more compact surface in Subtractive and Layering methods. This study distinguishes the unique properties of 3D printed resin when compared to conventional layering and subtractive methods for resin-based materials. 3D printed shows comparable monotonic strength to layering but lags behind in fatigue strength, with subtractive resin demonstrating superior performance. Both 3D printed and subtractive exhibit similar elastic moduli, surpassing layering. However, 3D printed resin displays higher surface roughness compared to subtractive and layering methods. The study suggests a need for improvement in the mechanical performance of 3D printed material.

An In Silico Analysis of Genetic Variants and Structural Modeling of the Human Frataxin Protein in Friedreich's Ataxia.

Friedreich's Ataxia (FRDA) stands out as the most prevalent form of hereditary ataxias, marked by progressive movement ataxia, loss of vibratory sensitivity, and skeletal deformities, severely affecting daily functioning. To date, the only medication available for treating FRDA is Omaveloxolone (Skyclarys®), recently approved by the FDA. Missense mutations within the human frataxin (FXN) gene, responsible for intracellular iron homeostasis regulation, are linked to FRDA development. These mutations induce FXN dysfunction, fostering mitochondrial iron accumulation and heightened oxidative stress, ultimately triggering neuronal cell death pathways. This study amalgamated 226 FXN genetic variants from the literature and database searches, with only 18 previously characterized. Predictive analyses revealed a notable prevalence of detrimental and destabilizing predictions for FXN mutations, predominantly impacting conserved residues crucial for protein function. Additionally, an accurate, comprehensive three-dimensional model of human FXN was constructed, serving as the basis for generating genetic variants I154F and W155R. These variants, selected for their severe clinical implications, underwent molecular dynamics (MD) simulations, unveiling flexibility and essential dynamic alterations in their N-terminal segments, encompassing FXN42, FXN56, and FXN78 domains pivotal for protein maturation. Thus, our findings indicate potential interaction profile disturbances in the FXN42, FXN56, and FXN78 domains induced by I154F and W155R mutations, aligning with the existing literature.

Foetal programming in sheep: Reproductive and productive implications.

The aim of this study was to evaluate the effects of pregnant ewe nutrition on the performance of offspring in terms of meat, wool production, and reproduction. Foetal programming in sheep has focused on several aspects related to foetal growth, postnatal production, behaviour, and immunological performance. Currently, significant efforts are being made to understand the endocrine, metabolic, and epigenetic mechanisms involved in offspring development. Current studies have not only evaluated the foetal period, despite the pre-conception parental nutrition has demonstrated an effect on the foetal, embryonic, and pre-implantation periods and can generate permanent effects in the foetal and postnatal phases. The performance of offspring is the result of interactions between the genome, epigenome, and environmental interventions during conception. Several factors influence the expression of phenotypic characteristics in progenies; however, this study focused on presenting data on the effect of pregnant ewe nutrition alone on foetal growth and the productive aspects of their offspring.

Geographic proximity to cardiovascular clinical trial sites: A National analysis in the United States.

INTRODUCTION: Suboptimal geographical access to cardiovascular clinical trial sites (CV-CTS) may be a cause of inadequate demographic representation in contemporary trials. Thus, we investigate access to CV-CTS in the US. METHODS: We obtained the location of CV-CTS from Clinicaltrials.gov. We calculated the distance in kilometers from each ZIP code to the nearest CV-CTS, stratifying our results based on urban/rural setting, sex and race. RESULTS: We identified a total of 10,506 studies in 4,630 US ZIP codes (10.5 %), of those only 237 (5 %) were rural. The overall median CV-CTS distance was 5.8 km (IQR: 2.7, 15.8). For urban residents, this distance was 4.5 km (IQR: 2.3, 9.2), while for rural residents, it was 24.2 km (IQR: 13.8, 42.2). RESULTS: We revealed important disparities involving geographical proximity to cardiovascular clinical trial sites. Increasing the representation of these populations in clinical trials is paramount to improving the applicability of their findings to real-world settings.

Diet-driven differential response of Akkermansia muciniphila modulates pathogen susceptibility.

The erosion of the colonic mucus layer by a dietary fiber-deprived gut microbiota results in heightened susceptibility to an attaching and effacing pathogen, Citrobacter rodentium. Nevertheless, the questions of whether and how specific mucolytic bacteria aid in the increased pathogen susceptibility remain unexplored. Here, we leverage a functionally characterized, 14-member synthetic human microbiota in gnotobiotic mice to deduce which bacteria and functions are responsible for the pathogen susceptibility. Using strain dropouts of mucolytic bacteria from the community, we show that Akkermansia muciniphila renders the host more vulnerable to the mucosal pathogen during fiber deprivation. However, the presence of A. muciniphila reduces pathogen load on a fiber-sufficient diet, highlighting the context-dependent beneficial effects of this mucin specialist. The enhanced pathogen susceptibility is not owing to altered host immune or pathogen responses, but is driven by a combination of increased mucus penetrability and altered activities of A. muciniphila and other community members. Our study provides novel insights into the mechanisms of how discrete functional responses of the same mucolytic bacterium either resist or enhance enteric pathogen susceptibility.

Advancements in Dental Care: The Evolving Landscape of Prosthetic Dentistry.

In the dental field, the specialty of prosthodontics stands out as the frontline of innovation, continually pushing the boundaries to enhance both function and aesthetics for optimal oral rehabilitation [...].

In-Stent Restenosis Overview: From Intravascular Imaging to Optimal Percutaneous Coronary Intervention Management.

Despite ongoing progress in stent technology and deployment techniques, in-stent restenosis (ISR) still remains a major issue following percutaneous coronary intervention (PCI) and accounts for 10.6% of all interventions in the United States. With the continuous rise in ISR risk factors such as obesity and diabetes, along with an increase in the treatment of complex lesions with high-risk percutaneous coronary intervention (CHIP), a substantial growth in ISR burden is expected. This review aims to provide insight into the mechanisms, classification, and management of ISR, with a focus on exploring innovative approaches to tackle this complication comprehensively, along with a special section addressing the approach to complex calcified lesions.

How do different intraoral scanners and milling machines affect the fit and fatigue behavior of lithium disilicate and resin composite endocrowns?

The aim of this in vitro study was to evaluate the effect of the combinations of two different intraoral scanners (IOS), two milling machines, and two restorative materials on the marginal/internal fit and fatigue behavior of endocrowns produced by CAD-CAM. Eight groups (n= 10) were considered through the combination of TRIOS 3 (TR) or Primescan (PS) IOS; 4-axes (CR; CEREC MC XL) or 5-axes (PM; PrograMill PM7) milling machines; and lithium disilicate (LD; IPS e.max CAD) or resin composite (RC; Tetric CAD) restorative materials. Specific surface treatments were applied to each material, and the bonding to its corresponding Endocrown-shaped fiberglass-reinforced epoxy resin preparations was performed (Variolink Esthetic DC). Computed microtomography (µCT) was performed to assess the marginal/internal fit, as well as a mechanical fatigue test (20 Hz, initial load = 100 N/5000 cycles; step-size = 50 N/10,000 cycles until a threshold of 1500 N, then, the step-size was increased if needed to 100 N/10,000 cycles until failure or a threshold of 2800 N) to evaluate the restorations long-term behavior. Complementary analysis of the fracture features and surface topography in scanning electron microscopy was performed. Three-way ANOVA and Kaplan-Meier test (α = 0.05) were performed for marginal/internal fit, and fatigue behavior data, respectively. PS scanner, CR milling machine, and RC endocrowns resulted in a better marginal fit compared to their counterparts. Still, the PM machine resulted in a better pulpal space fit compared to the CR milling machine. Regardless of the scanner and milling machine, RC endocrowns exhibited superior fatigue behavior than LD ones. LD endocrowns presented margin chipping regardless of the milling machine used. Despite minor differences in terms of fit, the 'IOS' and 'milling machine' factors did not impair the fatigue behavior of endocrowns. Resin-composite restorations resulted in a higher survival rate compared to glass-ceramic ones, independently of the digital devices used in the workflow.

3D printed, subtractive, and conventional acrylic resins: Evaluation of monotonic versus fatigue behavior and surface characteristics.

This study assessed the mechanical properties and surface characteristics of dental prosthetic acrylic resin fabricated by 3D printing, comparing it with subtractive, pressing, and molding techniques. Bar-shaped specimens (N= 90; 65 × 10 × 3.3 mm; ISO:207951) were prepared and assigned into six groups: PRINT (3D printing vis stereolithography with PriZma 3D Bio Denture, Makertech Labs); SUB (subtractive manufacturing with Vipiblock Trilux, Vipi); PRESS Base (pressing using muffle with Thermo Vipi Wave, Vipi for base); PRESS Tooth (pressing with Onda-cryl, Clássico for tooth); MOLD Base (molding using addition silicone with Vipi Flash, Vipi for base); and MOLD Tooth (molding with Dencor, Clássico for tooth). Monotonic flexural strength (FS) and elastic modulus (E) were measured using a three-point bending approach (n= 5) on a universal testing machine at a crosshead speed of 5 mm/min. Fatigue testing (n= 10) followed similar geometry and settings, with a frequency of 2 Hz, initial stress level at 20 MPa, and stress increments of 5 MPa every 2,500 cycles. Surface roughness (n= 10) was assessed through profilometry, and fractographic and topographic analyses were conducted. Statistical analyses included One-Way ANOVA for monotonic FS, roughness, and E, along with Kaplan-Meier with Mantel-Cox post-hoc and Weibull analysis for fatigue strength. PRINT showed lower monotonic FS than the SUB and PRESS Tooth but comparable fatigue strength to these groups and superior to PRESS Base and MOLD (Base and Tooth) groups. All groups had similar Weibull moduli. Surface roughness of the PRINT group was comparable to most techniques but higher than the PRESS Tooth group. Fractographic analysis revealed fractures originating from surface defects under tensile stress, with SEM showing scratch patterns in all groups except PRINT, which had a more uniform surface. Despite its lower monotonic strength, 3D printed resin demonstrated comparable fatigue strength to subtractive and pressing methods and similar surface roughness to most methods, indicating its potential as a viable option for dental prosthesis.

Trends in tracheal, bronchial and lung cancer attributed to smoking in South America: Global Burden of Disease analysis 1990-2019.

Objective: To investigate the burden of tracheal, bronchus, and lung (TBL) cancer due to tobacco exposure in the last 30 years in 12 South American countries. Methods: We used the Global Burden of Disease (GBD) 2019 exposure-response function to analyze the total tobacco, smoking, and secondhand smoke exposure-related TBL cancer deaths and disability-adjusted life years (DALYs), for 12 South American countries, between 1990 and 2019. Metrics were described as absolute numbers or rates per 100 000 individuals. The relative change in burden was assessed by comparing the 1990-1994 to 2015-2019 periods. Results: In 2019, the all-ages number of TBL cancer deaths and DALYs associated with tobacco exposure in South America was 29 348 and 658 204 in males and 14 106 and 318 277 in females, respectively. Age-adjusted death and DALYs rates for the region in 2019 were 182.8 and 4035 in males and 50.8 and 1162 in females, respectively. In males, 10/12 countries observed relative declines in TBL death rates attributed to tobacco exposure while only 4 countries reduced their mortality in females. Conclusion: While significant efforts on tobacco control are under place in South America, substantial burden of TBL cancer persists in the region with significant sex-specific disparities. Increased country-specific primary data on TBL cancer and tobacco exposure is needed to optimize healthcare strategies and improve comprehension of regional trends.

Effect of brushing simulation on the wear behavior of repaired CAD-CAM restorations.

OBJECTIVE: The aim of the present study was to evaluate the influence of multidirectional brushing on the surface roughness, morphology, and bonding interface of resin-repaired CAD-CAM ceramic and composite restorations. MATERIALS AND METHODS: Twelve (N = 12) blocks (4 mm × 4 mm × 2 mm for parallel axis; 5 mm × 4 mm × 2 mm for perpendicular axis) of lithium disilicate glass-ceramic (IPS e.max CAD, Ivoclar AG) and CAD-CAM resin composite (Tetric CAD, Ivoclar AG) were obtained and repaired with direct resin composite (Clearfil AP-X, Kuraray). An abrasive slurry was prepared and the brushing was performed according to each restorative material and axis of brushing (n = 6; perpendicular to repair interface and parallel to repair interface) during 3,650 cycles (240 strokes per minute) to simulate 3 years of brushing. The surface roughness (Ra) and the profile variation for each material (restoration and direct repair resin composite) were measured at the baseline condition and after brushing, and the mean roughness and presence of steps at the repair interface were evaluated through factorial analysis of Variance (ANOVA). Scanning Electron Microscopy (SEM) images were taken to evaluate the surface topography of the repaired materials after brushing. RESULTS: The mean roughness of the repaired CAD-CAM restorations was affected by the brushing (P < .05), mainly when evaluating the repair material and the interface (P < .05), while the restorative CAD-CAM materials presented more stable values. The profile evaluation showed higher steps at the interface when repairing lithium disilicate than for CAD-CAM resin composite. CONCLUSION: Repaired CAD-CAM restorations were susceptible to wear after brushing simulation. The surface roughness of the direct resin composite was the most affected leading to step development at the interface, particularly in the repaired lithium disilicate samples. Cinical maintenance recalls and polishing protocols must be considered to enhance the longevity of such restorations.

Effect of Radiotherapy and Taper of Root Canal Preparation on the Biomechanical Behavior of Mesial Roots of Mandibular Molars.

INTRODUCTION: This study aimed to investigate the effect of radiotherapy and taper of root canal preparation on the biomechanical behavior of mesial roots of mandibular molars. METHODS: Eighty mandibular molars with 2 canals in the mesial root were randomly allocated into 2 groups (n = 40): one group underwent irradiation (60 Gy), while the other did not. Subsequently, the mesial roots were sectioned and each group was subdivided into 5 subgroups (n = 8), according to the preparation taper: no preparation (control); 25.03; 25.04; 25.06; and 25.08. All groups were considered homogeneous regarding their dimensions, weight, and morphology. The prepared specimens were embedded in cylindrical plastic molds and subjected to a cyclic fatigue test. A failure analysis was performed according to the extension and course of the fractures. Two-way ANOVA, Tukey's post-hoc, Fisher's exact, and Kaplan-Meier tests were conducted to evaluate the obtained data (α = 5%). RESULTS: Fatigue resistance decreased as the taper of the preparation increased (P < .05). Preparation 25.03 presented significantly higher values only than 25.08 (P < .05), while 25.04, 25.06, and 25.08 were considered similar (P > .05). Irradiation significantly reduced the biomechanical performance (P < .05). Survival analysis corroborated these findings. There were no differences in the distribution of fracture types among the groups (P > .05). CONCLUSION: The biomechanical behavior of the mesial roots of the mandibular molars decreased significantly in the face of irradiation and as the taper of the preparation increased.

Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host.

Inflammatory bowel diseases (IBDs) are chronic conditions characterized by periods of spontaneous intestinal inflammation and are increasing in industrialized populations. Combined with host genetics, diet and gut bacteria are thought to contribute prominently to IBDs, but mechanisms are still emerging. In mice lacking the IBD-associated cytokine, interleukin-10, we show that a fiber-deprived gut microbiota promotes the deterioration of colonic mucus, leading to lethal colitis. Inflammation starts with the expansion of natural killer cells and altered immunoglobulin-A coating of some bacteria. Lethal colitis is then driven by Th1 immune responses to increased activities of mucin-degrading bacteria that cause inflammation first in regions with thinner mucus. A fiber-free exclusive enteral nutrition diet also induces mucus erosion but inhibits inflammation by simultaneously increasing an anti-inflammatory bacterial metabolite, isobutyrate. Our findings underscore the importance of focusing on microbial functions-not taxa-contributing to IBDs and that some diet-mediated functions can oppose those that promote disease.

Influence of CAD-CAM milling strategies on the outcome of indirect restorations: A scoping review.

STATEMENT OF PROBLEM: The influence of computer-aided manufacturing (CAM) parameters and settings on the outcomes of milled indirect restorations is poorly understood. PURPOSE: The purpose of this scoping review was to summarize the current CAM systems, parameters, and setting changes, and their effects on different outcomes of milled indirect restorations and aspects related to their manufacture. MATERIAL AND METHODS: The protocol of this review is available online (https://osf.io/x28ps/). Studies that used at least 2 different parameters (CAM units, number of axes, digital spacers, or protocols with different rotatory instruments, grit-sizes, milling speed, or others) for milling indirect restorations were included. A structured search up to July 2023 was performed by 2 independent reviewers for articles written in English in LILACS, MEDLINE via PubMed, EMBASE, Web of Science, and Scopus. RESULTS: Of 1546 studies identified, 22 were included in the review. Discrepancies were found between the planned and actual measured cement space, with a decreasing linear relationship impacting restoration adaptation at different points. The CEREC MC XL milling machine was the most used system in the included studies, with variations in bur types, milling modes, and number of burs uses affecting internal fit and surface trueness. The results demonstrated the better adaptation of restorations made with 5-axis over 3-axis milling machines. Lithium disilicate and zirconia were the most commonly used materials, and crowns and inlays were popular designs. Marginal and internal adaptation were the primary outcomes assessed using the various techniques. CONCLUSIONS: The study presented a comprehensive exploration of CAM systems and parameters, and their influence on indirect restorations. The planned cement space was not properly reproduced by the milling. Bur characteristics can affect restoration fit and trueness. The 5-axis units seem to result in better-adapted restorations compared with 3- and 4-axis units.

Repair protocols for indirect monolithic restorations: a literature review.

Despite the advancements in indirect monolithic restorations, technical complications may occur during function. To overcome this issues, intraoral repair using resin composite is a practical and low-cost procedure, being able to increase the restoration's longevity. This review aimed to evaluate the need for repair and suggest a standardized repair protocol to the main indirect restorative materials. For this, studies were surveyed from PubMed with no language or date restriction, to investigate the scientific evidence of indirect monolithic restoration repair with direct resin composite. A classification to guide clinical decisions was made based on the FDI World Dental Federation criteria about defective indirect restorations considering esthetic and functional standards, along with the patient's view, to decide when polishing, repairing or replacing a defective restoration. Based on 38 surveyed studies, different resin composite intraoral repair protocols, that included mechanical and chemical aspects, were defined depending on the substrate considering resin-based, glass-ceramic or zirconia restorations. The presented criteria and protocols were developed to guide the clinician's decision-making process regarding defective indirect monolithic restorations, prolonging longevity and increasing clinical success.

Repair of monolithic zirconia restorations with different direct resin composites: effect on the fatigue bonding and mechanical performance.

OBJECTIVE: The study aims to evaluate the shear bond and flexural strength fatigue behavior of yttrium-stabilized zirconia (4YSZ) repaired using different resin composites. MATERIALS AND METHODS: Cylindric specimens of 4YSZ were obtained for the bond strength (Ø = 6 mm, 1.5 mm of thickness) and biaxial flexural strength (Ø = 15 mm, 1 mm of thickness) fatigue tests and divided into 3 groups according to the repair resin composite: EVO (nanohybrid), BULK (bulk-fill), and FLOW (flowable). The zirconia surface was air-abraded with alumina particles, a 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) primer was applied, and the resin composite was build-up over the zirconia. Fatigue shear bond strength and flexural fatigue strength tests were performed (n = 15). One-way ANOVA and Tukey post hoc tests were carried out for both outcomes, besides scanning electron microscopy and finite element analysis. RESULTS: The repair material affected the fatigue shear bond strength of zirconia ceramic. The BULK group (18.9 MPa) depicted higher bond strength values than FLOW (14.8 MPa) (p = 0.04), while EVO (18.0 MPa) showed similar results to both groups. No effect was observed for the mechanical behavior (p = 0.53). The stress distribution was similar for all groups. CONCLUSION: The repair of yttrium-stabilized zirconia (4YSZ) ceramics with bulk-fill resin composites was the best option for high fatigue bond strength. However, the fatigue mechanical performance was similar regardless of the applied repair material. CLINICAL RELEVANCE: The repair of yttrium-stabilized zirconia (4YSZ) monolithic restorations may be performed with nanohybrid and bulk-fill resin composites in order to promote longevity in the treatment.

In silico analysis of alpha-synuclein protein variants and posttranslational modifications related to Parkinson's disease.

Parkinson's disease (PD) is among the most prevalent neurodegenerative disorders, affecting over 10 million people worldwide. The protein encoded by the SNCA gene, alpha-synuclein (ASYN), is the major component of Lewy body (LB) aggregates, a histopathological hallmark of PD. Mutations and posttranslational modifications (PTMs) in ASYN are known to influence protein aggregation and LB formation, possibly playing a crucial role in PD pathogenesis. In this work, we applied computational methods to characterize the effects of missense mutations and PTMs on the structure and function of ASYN. Missense mutations in ASYN were compiled from the literature/databases and underwent a comprehensive predictive analysis. Phosphorylation and SUMOylation sites of ASYN were retrieved from databases and predicted by algorithms. ConSurf was used to estimate the evolutionary conservation of ASYN amino acids. Molecular dynamics (MD) simulations of ASYN wild-type and variants A30G, A30P, A53T, and G51D were performed using the GROMACS package. Seventy-seven missense mutations in ASYN were compiled. Although most mutations were not predicted to affect ASYN stability, aggregation propensity, amyloid formation, and chaperone binding, the analyzed mutations received relatively high rates of deleterious predictions and predominantly occurred at evolutionarily conserved sites within the protein. Moreover, our predictive analyses suggested that the following mutations may be possibly harmful to ASYN and, consequently, potential targets for future investigation: K6N, T22I, K34E, G36R, G36S, V37F, L38P, G41D, and K102E. The MD analyses pointed to remarkable flexibility and essential dynamics alterations at nearly all domains of the studied variants, which could lead to impaired contact between NAC and the C-terminal domain triggering protein aggregation. These alterations may have functional implications for ASYN and provide important insight into the molecular mechanism of PD, supporting the design of future biomedical research and improvements in existing therapies for the disease.

Cyclic fatigue of a repaired 4 YSZ ceramic: Effect of the repair protocol on the adhesive and mechanical behavior.

Objective: To evaluate the effect of different surface treatments on the morphology, shear bond, and flexural fatigue strength of a repaired translucent zirconia. Methods: Monolithic disc-shaped specimens of translucent zirconia were prepared and ground to simulate repair areas. Four groups underwent different treatments: Air-MDP (air-abrasion with alumina particles and 10-MDP primer), Si-Sil (silica-coated alumina particles with MDP-containing silane), Si-MDP (silica coating with 10-MDP primer), and Uni adhe (universal adhesive). After roughness measurements and treatments, repairs were done using resin composite. Shear bond and flexural (n = 15) fatigue tests were performed. Surface topography, interfacial analysis, fractographic, and finite element analysis were conducted. Results: The zirconia roughness was similar between the groups, however, the surface topography was modified according to the surface treatments. Si-Sil generated higher and more stable bond strength values (20.69 MPa) between translucent zirconia and resin composite when compared to Uni adhe (15.75 MPa) considering the fatigue bond strength scenario, while it was similar to Si-MDP (17.70 MPa) and Air-MDP (18.97 MPa). Regarding the mechanical behavior, Si-Sil (680.83 MPa) also showed higher and significantly different fatigue strength when compared to Uni adhe (584.55 MPa), while both were similar to Si-MDP (634.22 MPa) and Air-MDP (641.86 MPa). Conclusion: The association of mechanical and chemical approaches is essential for long-term bond strength and optimized mechanical behavior, being air-abrasion protocols and the use of silane and/or MDP-based primers suitable for zirconia repair protocols. It was found that relying solely on a universal adhesive was not as effective as other options available. Clinical significance: The surface treatment of repair protocols affects translucent zirconia's morphology. To enhance fatigue behavior in repaired monolithic zirconia, air abrasion is crucial. Exclusive use of a universal adhesive is less effective than other choices. A primer containing silane/MDP holds the potential for stable bond strength and optimized mechanical performance.

Conventional-, bulk-fill- or flowable-resin composites as prosthetic core build-up: Influence on the load-bearing capacity under fatigue of bonded leucite-reinforced glass-ceramic.

This study aimed to evaluate the fatigue performance of simplified ceramic restorations (leucite-reinforced glass ceramic) adhesively cemented onto substrates of different resin composites. Three options from the same commercial line were selected (Tetric N-Line, Ivoclar), classified as Conventional (CRC), Bulk-fill (BRC) and Flowable (FRC), which were used to make discs using a cylindrical metallic device (n = 19; Ø = 10 mm, thickness = 2.0 mm). A total of 57 discs (Ø = 10 mm, thickness = 1.0 mm) were made from CAD/CAM prefabricated blocks of a leucite reinforced glass-ceramic (Empress CAD, Ivoclar) to simulate a monolithic restoration, then were randomly distributed to be bonded on 19 discs of each three different resin composite substrates (CRC; BRC; or FRC) with a dual resin cement (Multilink N; Ivoclar). The samples were subjected to a compression test with a hemispherical stainless-steel piston (Ø = 40 mm) at a monotonic regimen (n = 4; 1 mm/min loading rate and 500 kgf loading cell until fracture). The cyclic fatigue test was performed underwater at a frequency of 20 Hz (n = 15). The first step was applied using 200N for 5000 cycles, followed by increments of 50N at each step of 10,000 until failure. The outcome considered for both tests was the occurrence of radial crack. Specific statistical tests (α = 0.05) were performed for monotonic (One-way ANOVA; Tukey's test) and fatigue data (Kaplan-Meier test; Log-rank test). Fractography of fractured samples were also performed. The FRC group had the lowest failure load in both test regimes (p < 0.05; monotonic: 726.64N; fatigue: 716.67N). There were no differences between the CRC and BRC groups (p > 0.05; monotonic: 989.30 and 990.11N; fatigue: 810.00 and 833.33N, respectively). The same result was obtained considering cycles for fatigue failure (FRC < CRC=BRC). Leucite glass-ceramic bonded to substrates made of flowable resin composite behaves worse mechanically than bonding to conventional or bulk-fill resin composite substrates.