More than a decade of research has been devoted to leveraging the rich mechanical playground of periodically assembled truss metamaterials. The enormous design space of manufacturable unit cells, however, has made the inverse design a challenge: How does one efficiently identify a complex truss that has given target properties? We answer this question by a data-driven method, which instantly  generates not one but a variety of truss unit cells, whose effective response closely matches a given (fully anisotropic) stiffness tensor. Moreover, our framework to smoothly transition between different unit cells enables the design of lightweight structures with spatially varying, locally optimized properties, for applications from wave guiding to artificial bone. Inspired by crystallography, the periodic assembly of trusses into architected materials has enjoyed popularity for more than a decade and produced countless cellular structures with beneficial mechanical properties. Despite the successful and steady enrichment of the truss design space, the inverse design has remained a challenge: While predicting effective truss properties is now commonplace, efficiently identifying architectures that have homogeneous or spatially varying target properties has remained a roadblock to applications from lightweight structures to biomimetic implants. To overcome this gap, we propose a deep-learning framework, which combines neural networks with enforced physical constraints, to predict truss architectures with fully tailored anisotropic stiffness. Trained on millions of unit cells, it covers an enormous design space of topologically distinct truss lattices and accurately identifies architectures matching previously unseen stiffness responses. We demonstrate the application to patient-specific bone implants matching clinical stiffness data, and we discuss the extension to spatially graded cellular structures with locally optimal properties. Opportunities for selecting materials in the engineering design process have fundamentally changed over the past decade due to innovation in materials systems with tailored properties. Specifically with maturing additive manufacturing techniques across length scales, metamaterials or architected materials have gained momentum, whose periodic or nonperiodic structural architecture on smaller scales has enabled us to control the characteristic material behavior on larger scales. Popular examples are periodic assemblies of truss, plate, or shell networks, whose underlying unit cell (UC) architecture can be leveraged to explore a tremendous design space, including previously unattainable effective material property and functionality combinations. This includes lightweight materials with high specific stiffness and strength –3, mater48To illustrate this challenge and, moreover, to offer a solution, we focus on one of the most fundamental effective properties, the elastic stiffness of a material, which in general is direction dependent or anisotropic. The elastic stiffness not only governs the linear stress–strain response, but also is essential for, e.g., wave motion, buckling, and limit loads. Anisotropic behavior is frequently encountered in nature, e.g., in bone . Consequ18In recent years, machine-learning (ML) algorithms such as deep neural networks (NNs) have gained attention to meet the inverse design challenge. Existing approaches of single- and multiscale topology optimization commonly leverage data-driven surrogate models for the structure-to-property map, which bypass expensive computational homogenization of the microscale UC and thereby accelerate structural optimization –34. Gene3537We here propose an ML-driven inverse design framework for the instant prediction of diverse truss lattices with fully tailorable 3D anisotropic stiffness. Our framework admits an enormous, unified design space of topologically distinct lattices with an efficient design parameterization. The property space spans several orders of magnitude in stiffness, including previously unexploited shear–shear and shear–normal couplings. The inverse design admits variational sampling to propose multiple distinct architectures that exhibit a given target stiffness response—all while maintaining the ability to smoothly transition between different UCs, which is an ongoing challenge for periodic structures .SI Appendix, Fig. S1). These comprise both well-studied topologies (like the octet) and nonstandard ones to admit a wide range of anisotropic responses with a relatively small number of beam elements. From this set, we sample three lattices We start by defining a large, structured design space of truss lattices by drawing inspiration from the truss descriptors proposed by Zok et al. . Fig. 1AOwing to the symmetries of the seven chosen elementary lattices, all resulting lattices are orthotropic . To expand the achievable stiffness space in a continuous manner, we enlarge the design space by applying a series of affine geometric transformations to the obtained lattice topology, which transforms every vertex at a location Note that A rich set of anisotropic lattices is created by generating random transformations for each of the 262 topologies introduced above. To obtain physically reasonable lattices, all principal stretches are sampled from the range d of all struts in the UC (assuming circular cross-sections). Jointly with Young’s modulus bE of the base material  in the range SI Appendix, section 2) to extract the homogenized stiffness tensor  are vastly larger than those of the closest comparable approaches , 21, 49,SI Appendix, section 1) and 2) corresponding true stiffness While FE homogenization provides an accurate forward model that maps design parameters onto stiffness responses, the inverse problem has remained a challenge. We therefore introduce an inverse design framework that can efficiently reverse engineer a UC design, whose stiffness approximates any  3D anisotropic stiffness tensor characterized by its 21 independent elastic constants. To train the inverse framework, we create a large dataset of truss lattices, The inverse design problem is inherently ill-posed, as multiple combinations of design parameters may represent the same UC and, moreover, multiple distinct UCs may produce the same effective stiffness. For example, due to the cubic symmetry group of our elementary cells, all rotations ll-posed  due to tTo bypass this challenge, we propose an inverse design framework based on a combination of stochastic and physics-guided NN models, which takes inspiration from dual-network models , 50, 51 To efficiently train the inverse model lgorithm  used to lgorithm . The forOnce the forward model has been trained, the inverse model is subsequently trained to minimize the reconstruction error ]. The resulting stiffness tensor SI Appendix, Fig. S3 for details). We highlight that, unlike the presented architecture, a single neural network—without any embedded information about the lattice generation process—fails to learn the structure-to-property map. Leveraging the existing knowledge underlying the provided data to enable or accelerate the deep-learning framework aligns with the spirit of recent applications of deep learning to physical problems . Note that, contrary to the forward model, both subnetworks The sampled topology (from the Gumbel Softmax) and the target stiffness are jointly passed to the second subnetwork entation  per rotaSI Appendix, Fig. S4).The reconstruction accuracy of the inverse model for, e.g., SI Appendix, section 3.E) show that, on average, only one in 100 of the inverse-designed truss lattices share the same topology as the lattice from the training set, from which the target stiffness was computed. Notably, repeated drawing of inverse predictions for the same test set with a different random seed gives, on average, in approximately two out of three draws a different lattice realization (setting τ = 1), which highlights the generative nature of the inverse variational model. Additionally, this corroborates that Our variational inverse model (enabled by the Gumbel Softmax) attempts to find the underlying categorical probability distribution for candidate topologies matching a target stiffness and may propose different design realizations, giving the user freedom in choosing an appropriate UC, considering, e.g., manufacturability or secondary functions of importance beyond the target stiffness. To give a concrete example, experimental studies have shown that the distances between struts  are commensurate with the pore size of bone, which plays a key role in transporting nutrients into bone (and bone implants) for cell growth and also for bone ingrowth . Our resSI Appendix, section 4). We also provide the normalized mean-squared error (NMSE), defined asSI Appendix, section 3.H), we can hence efficiently sample a large variety of lattice candidates and select the one(s) with the lowest NMSE . The resulting inverse model successfully proposes different UCs of distinct topologies, which closely match the target anisotropic stiffness. We note that, if more exotic anisotropic stiffnesses cannot be matched within our design space, one may add elementary lattices to SI Appendix, section 3.G).To assess the performance of our inverse model on stiffness queries outside the proposed lattice design space, we consider two test scenarios. First, we evaluate its performance on randomly drawn  stiffnesses from a recently reported catalog (lacking a design parameterization) of over 17,000 unique topologies and corresponding stiffnesses based on crystallographic network topologies , a few rSI Appendix, section 4 and Tables S9–S12). It is hard to give a general guarantee that the network can find designs for any arbitrary  choice of the 21 elastic constants. Yet, the framework performs very well for all reasonable combinations tested . Furthermore, we can always obtain an estimate of the performance of the generated designs by using the forward model, which warns us if the generated structure is not able to mimic the given stiffness .Second, we apply our design framework to synthetic bone. The anisotropic stiffness of an anatomical site on a bone sample provides the gold standard for an ideal bone implant, which avoids stress shielding and improves long-term compatibility , 18. To =114 GPa  as base =114 GPa . The resCompared to competing methods, the proposed inverse model provides several advantages. First, the data-driven framework is highly efficient and predicts truss lattices corresponding to a prescribed 3D stiffness tensor in fractions of a second . This is orders of magnitudes faster than, e.g., classical topology optimization techniques, which iteratively optimize within an extremely large design space (restarting for every given target stiffness), typically by discretizing the UC domain into large numbers of voxels . CompareSI Appendix, section 5). In addition, we perform the aforementioned smooth grading of strut diameters to connect dissimilar UC topologies. An example is illustrated in A further advantage of the chosen design space lies in its applicability to spatially graded trusses. By introducing a smooth functional grading between any set of predicted UCs, we enable the generation of larger structures with locally tailored stiffness, as, e.g., required for bone implants that mimic the strong spatial variations in the stiffness of natural bone . UCs may1,a2,a3} B. We traSI Appendix, section 1); the computational homogenization scheme ; the machine-learning framework, training protocols, and accuracy ; the evaluation on stiffnesses outside the proposed design space ; and the method to create spatially graded lattices  are provided in SI Appendix.Details of the generated lattice design catalog (Supplementary File


Define relationships between quantitative magnetic resonance imaging (MRI) metrics and clinical/laboratory data in a pediatric and young adult cohort with autoimmune liver disease (AILD).This prospective, cross-sectional study was institutional review board-approved. Patients enrolled in an institutional AILD registry were divided into groups: (1) autoimmune hepatitis (AIH) or (2) primary sclerosing cholangitis (PSC)/autoimmune sclerosing cholangitis (ASC). Participants underwent serum liver biochemistry testing and research MRI examinations, including 3D magnetic resonance cholangiopancreatography (MRCP), magnetic resonance elastography (MRE), and iron-corrected T1 mapping (cT1). MRCP + and LiverMultiScan  were used to post-process 3D MRCP and cT1 data. Multiple linear regression models were used to assess relationships.p = 0.01–0.04). Seven laboratory values were significant predictors of whole liver cT1 IQR (p < 0.0001–0.04). Eight laboratory values and right hepatic bile duct median and maximum diameter were significant predictors of liver stiffness (p < 0.0001–0.03).58 patients, 35 male, median age 16 years were included; 30 in the AIH group, 28 in the PSC/ASC group. After statistical adjustments for patient age, sex, presence of inflammatory bowel disease (IBD), specific diagnosis (PSC/ASC vs. AIH), and time from diagnosis to MRI examination, left hepatic bile duct maximum diameter was a statistically significant predictor of whole liver mean cT1, cT1 interquartile range (IQR), and MRE liver stiffness (Bile duct diameters and multiple laboratory biomarkers of liver disease are independent predictors of liver stiffness and cT1 IQR in pediatric patients with AILD.The online version contains supplementary material available at 10.1007/s00261-021-03378-0. Autoimmune liver diseases (AILD) include three, sometimes overlapping, conditions: autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and autoimmune sclerosing cholangitis (ASC) –3. TheseThere is increasing evidence that quantitative MRI techniques, such as MR elastography (MRE) and T1 mapping, can be used to non-invasively measure the severity of chronic liver disease and predict liver histologic fibrosis stage –8. LiverMagnetic resonance cholangiopancreatography (MRCP) has been shown to sufficiently diagnose PSC in children, with sensitivities of 81–84% and specificity up to 100% , 18. RecThe objective of this study was to investigate relationships between quantitative MRI metrics of liver disease including (1) MRE-derived liver stiffness, (2) T1 relaxation measurements, and (3) quantitative 3D MRCP measurements, and clinical and laboratory data in a pediatric and young adult AILD cohort.This single-center, prospective, cross-sectional, Health Insurance Portability and Accountability Act (HIPAA)-compliant pilot study was approved by the institutional review board at Cincinnati Children's Hospital Medical Center (CCHMC).Patients up to 25 years of age with AILD  that were enrolled into an institutional AILD registry were included in this study. A group of pediatric hepatologists at CCHMC assigned the registry participants with a diagnosis of AIH, PSC, or ASC according to clinical guidelines , 19–21. Three-dimensional (3D) fast spin-echo (FSE) MRCP using respiratory triggering; the belt used to detect breathing was placed over the upper abdomen.Iron (T2*)-corrected T1 mapping (cT1) of the liver using a modified Look Locker (MOLLI) pulse sequence approach and complex chemical shift MRI .Two-dimensional (2D) gradient recalled echo (GRE) MRE of the liver (active driver frequency = 60 Hz), with the passive driver placed over the right upper quadrant of the abdomen and secured in place with a Velcro strap.All registry participants underwent research MRI examinations of the liver at the time of registry enrollment. Subsequent research MRI examinations using the same protocol and scanner were performed 12 and 24 months later. The current study includes baseline MRI examinations acquired on a 1.5 T scanner  using a 16-channel phased-array anterior (torso) surface coil as well as scanner table built-in spine coils (12-channels). The imaging protocol and parameters for the broader registry study have been previously published . PertinePertinent demographic and clinical data were recorded from the AILD registry. The following clinical data were recorded: patient age, sex, clinical diagnosis , time between diagnosis and research MRI (in months), and presence of inflammatory bowel disease (IBD). The following laboratory measurements also were recorded from the time of the research MRI: total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), platelets, fibrosis-4 (FIB4) score, AST to platelet ratio index (APRI), alkaline phosphatase (ALP), and matrix metalloproteinase 7 (MMP7), a novel marker of bile duct injury and liver fibrosis in AILD . MethodsPerspectum Ltd.  provided image post-processing tools and analyses for quantitative 3D MRCP metrics and iron-corrected T1 (cT1) relaxation measurements at no cost through a formal research agreement. Their analysts were blinded to all patient information, including clinical diagnosis as well as laboratory, clinical, and other imaging data.3D MRCP images were processed by a single operator at Perspectum using the MRCP + tool. This operator has more than 5 years of experience using MRCP + . To achieve this, bile ducts were identified through a series of signal enhancement and thresholding steps to detect tubular structures and generate a 3D model of the biliary tree . The folRegion-of-interest (ROI) and whole liver cT1 values were provided by Perspectum using LiverMultiScan , 24, 25,MREplus + prototype software  was utilized to measure liver stiffness values from MRE data. Under the supervision of an image analyst in the Department of Radiology who was blinded to clinical data and other imaging data, ROIs were automatically placed on elastograms with 90% confidence threshold masks across four representative axial slices. The weighted mean of the mean liver shear stiffness values (in kPa) across the four axial slices was calculated for each patient.Representative images of the quantitative MRI sequences assessed in this study are provided in Fig. U test. Categorical variables were presented as frequency counts and percentages; group differences were determined using Chi-square/Fisher’s exact test, as applicable.The patient cohort was divided into two groups, (1) AIH and (2) PSC/ASC. Patients with PSC/ASC were grouped into one cohort due to similarities in MRCP findings and clinical outcomes , 19. Conr). Relationships between three individual outcome variables  and potential predictor variables were further examined using multiple linear regression models, adjusting for patient age, sex, the presence of IBD, specific diagnosis (AIH vs. PSC/ASC), and time from diagnosis to research MRI examination. Stratified multiple linear regression models by diagnosis (AIH vs PSC/ASC) were also run, while also adjusting for patient age, sex, presence of IBD, and time from diagnosis to research MRI examination.Five variables were considered primary outcome variables: liver stiffness, ROI-based mean cT1, whole liver mean cT1, whole liver median cT1, and whole liver cT1 IQR. The following variables were considered potential predictor variables: demographic data, quantitative MRCP metrics, and serum laboratory values. Univariate associations between outcomes and predictor variables for the entire study cohort and for the AIH and PSC/ASC groups individually were assessed using Pearson correlation coefficients .Seventy-three patients were eligible for inclusion in the current study. Fifteen patients were excluded for reasons detailed in Fig. n = 30) was 16.0 years, and the median age of the PSC/ASC group (n = 28) was 15.5 years; cohort age was not statistically significantly different (p = 0.56). There were no differences in laboratory values between cohorts, with the exception of platelet count (p = 0.01) and MMP7 levels (p = 0.04).Detailed patient demographic information and laboratory value summary statistics are given in Table Summary statistics for liver stiffness, cT1 measurements, and quantitative MRCP metrics are provided in Table Univariate relationships between outcome variables and predictor variables for the entire study cohort are presented in Table r = 0.30–0.35; p values 0.008–0.02). Whole liver mean cT1, whole liver cT1 IQR, and liver stiffness positively correlated with left hepatic duct diameters . There were no other significant correlations between cT1 or liver stiffness measurements and quantitative MRCP metrics.For the overall cohort, positive correlations were detected between ROI-based mean cT1, whole liver mean cT1, whole liver median cT1, and liver stiffness and right hepatic duct diameters . There also were positive correlations between all five primary outcome variables and left hepatic bile duct diameters . Whole liver cT1 IQR positively correlated with biliary tree volume, total number and length of strictures, and total number of dilations . For the PSC/ASC cohort, none of our primary outcome variables correlated with quantitative 3D MRCP measurements (Supplementary Table 3).In the subgroup analysis for patients with AIH, there were positive correlations between all five primary outcome variables and right hepatic bile duct diameters  and cT1 IQR  positively correlated with age. There were multiple significant associations between cT1 or liver stiffness measurements and laboratory values. Liver stiffness negatively correlated with platelet count  and positively correlated with all other laboratory values . Whole liver cT1 IQR was associated with all laboratory variables except alkaline phosphatase and MMP7 ; whole liver cT1 IQR negatively correlated with platelet count . ROI-based mean cT1, whole liver mean cT1, and whole liver median cT1 were associated with APRI and FIB4 scores . Figure For the overall cohort, whole liver mean cT1  and with AST and MMP7 . Whole liver cT1 IQR positively correlated with age . For the PSC/ASC subgroup, whole liver cT1 IQR and liver stiffness positively correlated with ALT, AST, APRI, and FIB4 scores . Whole liver cT1 IQR correlated with total bilirubin and platelet count . Liver stiffness also positively correlated with GGT .For the AIH subgroup, ROI mean cT1, and whole liver mean and median cT1 positively correlated with total bilirubin, APRI, and FIB4 scores (p = 0.01). Eight predictor variables, including seven laboratory values and left hepatic bile duct maximum diameter, were significantly associated with whole liver cT1 IQR (p < 0.0001–0.04). Eleven predictor variables, including eight laboratory values and three quantitative MRCP metrics, were significantly associated with liver stiffness (p < 0.0001–0.04) , and time from diagnosis to MRI examination, only left hepatic bile duct maximum diameter was statistically significantly associated with whole liver mean cT1  and five laboratory values  were associated with whole liver mean cT1. Five quantitative MRCP metrics  and five laboratory values  as well as age (p = 0.01) were significantly associated with whole liver cT1 IQR. Four quantitative MRCP metrics (p = 0.0003–0.02) and seven laboratory values (p < 0.0001–0.047) were significantly associated with MRE liver stiffness. For the PSC/ASC group, no predictor variables were significantly associated with whole liver mean cT1. Five laboratory values (p < 0.0001–0.01) were significantly associated with whole liver cT1 IQR, while six laboratory values (p < 0.0001–0.001) were significantly associated with MRE liver stiffness. No MRCP metrics were significantly associated with cT1 IQR or MRE liver stiffness.Results from stratified [by diagnosis (AIH and PSC/ASC)] linear regression analyses are presented in Supplementary Table 4. Within the AIH group, four quantitative MRCP metrics  and between these markers and clinical variables. This suggests that each of the MRI markers and clinical markers under study are, to some degree, responsive to changes of inflammation and/or fibrosis in patients with AILD. Further, it is worth noting that there was no significant correlation between measures of cT1 or liver stiffness and time from AILD diagnosis to MRI examination. This suggests that changes in cT1 measurements and liver stiffness over time are not uniform among AILD patients, and instead may be individually specific.Quantitative MRCP metrics, inclusive of duct diameters and narrowings, would be expected to be reflective of biliary involvement by disease. Our results support this, with significant differences in quantitative MRCP metrics between the AIH and PSC/ASC subgroup. However, for the overall AILD cohort, only right and left hepatic duct diameters, and none of the other metrics, were significantly correlated with cT1 and liver stiffness, measures that may be more indicative of parenchymal disease. These results contradict prior literature demonstrating associations between liver stiffness and biliary abnormalities measured on MRCP by human observers in the setting of PSC. Tafur et al.  demonstrInterestingly, in the AIH subgroup, univariate and multivariable analyses demonstrated multiple quantitative MRCP metrics  to be significantly associated with cT1 measurements (including cT1 IQR) as well as liver stiffness. These results could reflect mild irregularities in biliary tree structure due to periductal fibrosis in patients with AIH, as reported previously in an adult cohort by Lewin et al. . The absr > 0.7. These associations between clinical predictive scores of fibrosis and liver stiffness are not unexpected given prior studies in adults with PSC [In the overall AILD cohort, measures of cT1, cT1 IQR, and liver stiffness all showed positive associations with numerous laboratory markers of liver disease as well as clinical predictive scores of liver fibrosis . Relationships with these predictive scores were of relatively higher strength for cT1 IQR and liver stiffness than with absolute cT1 measurements. This was similarly the case in the PSC/ASC subgroup where correlations between cT1 IQR and MRE liver stiffness and clinical predictive scores of liver fibrosis were with PSC , 28. HowOur results add to the limited literature evaluating associations between liver T1 relaxation measurements (including cT1) and other markers of chronic liver disease. Previously, Banerjee et al.  found a Our study has limitations. First, it is cross-sectional in design, including 58 subjects with AILD. As a result, small but significant correlations could have gone undetected. Such small correlations are unlikely to be clinically useful, however. Second, 25 of the 73 (~ 34%) available baseline MRI examinations could not undergo quantitative MRCP post-processing due to image quality issues, most often motion artifacts. Utilization of faster MRCP methods, such as 3D FSE sequences with compressed sensing, that shorten the acquisition time may reduce the number of datasets that are rejected for quantitative MRCP post-processing. Third, the cT1 metrics were not corrected for fat. The MOLLI sequence used is sensitive to fat as well as to the other features of liver disease such as inflammation and fibrosis. However, cT1 is not routinely corrected for fat because in patients with low liver fat, the signal is dominated by the free-water signal that is generated by the biological processes of inflammation and fibrosis. Thus, there is no need for such fat correction in order to interpret the change in the cT1 signal in response to biology in these populations . FinallyIn conclusion, we have demonstrated significant associations among automated quantitative MRCP metrics, MRE-derived liver stiffness, T1 relaxation (cT1) measurements, and liver-related laboratory measurements in children and young adults with AILD. Quantitative MRCP metrics related to the diameters of the right and left hepatic bile ducts were significantly associated with measures of cT1 and liver stiffness, especially in AIH patients. Both cT1 IQR and liver stiffness are highly associated with circulating laboratory biomarkers of liver disease, and in particular clinical fibrosis scores. Our results also suggest that T1 relaxation heterogeneity (cT1 IQR) may be a novel marker of liver fibrosis which may be less impacted by cholestasis and inflammation than MR elastography.Supplementary file1 (DOCX 32 KB)Below is the link to the electronic supplementary material.


The Israel Journal of Health Policy Research (IJHPR) was launched in January 2012. In December 2021 it will be completing 10 years of continuous publication. I have had the privilege of serving as the journal’s co-editor in chief during this period, and after ten years of service I am now preparing to step down from that role. IJHPR achievements of which I am particularly proud include remaining true to its mission, attracting manuscripts from virtually all the Israeli institutions engaged in health policy research as well as many leading institutions abroad, widening the circle of Israeli professionals who are submitting manuscripts to journals, and helping many established Israeli academics expand their repertoires to include articles with strong policy components. Several people and organizations have helped make editing the IJHPR such a wonderful experience for me. They include IJHPR co-editor Avi Israeli, IJHPR associate editor Steve Schoenbaum, the Israel National Institute for Health Policy Research , BioMed Central , the Myers-JDC-Brookdale Institute (my employer), my family , and the thousands of authors who have chosen to publish with the IJHPR. May the journal’s second decade be even better than its first one! The Israel Journal of Health Policy Research was launched in January 2012. In December 2021 it will be completing 10 years of continuous publication. I have had the privilege of serving as the journal’s co-editor in chief during this period, and after ten years of service I am now preparing to step down from that role. I am using this editorial to share several reflections on the on the journal’s evolution and achievements. I will also use the editorial to thank several of the people who have helped make editing the IJHPR such a wonderful experience for me.The journal’s mission, from its initiation until today, has always been “to promote intensive intellectual interactions among scholars and practitioners from Israel and other countries regarding all aspects of health policy… The ultimate aim of these intellectual interactions is to contribute to the development of health policy in Israel and around the world” . A decadI am particularly proud that over time we have succeeded in attracting high-quality manuscripts from a very high percentage of the Israeli researchers, universities, and research centers and others active in the health policy field. Moreover, I believe that by establishing a journal focused on Israeli health policy, and by being supportive of our authors, we have been able to widen the circle of Israeli professionals who are submitting manuscripts to journals. Many of these new authors hold analytic and managerial positions in government agencies and some of their articles have been among the journal’s most innovative and influential. No less importantly, the journal has helped many established and well-published Israeli academics expand their repertoires to include articles with strong policy components.I am also proud that we have been extremely successful in recruiting scores of leading scholars from outside of Israel to write commentaries about the original research articles written by our Israeli authors . These sSome of the key landmarks on the way have included getting the approval of the National Institute to develop concrete plans for the journal (2010), contracting with BioMed Central to serve as our publisher (2011), publishing our first set of articles (2012), being accepted into the Web of Science after just one year of publication 2013), launching our first article collection (2013), the 2015 publication of our first article by a Nobel Prize laureates , launchi and ChinOther sources of gratification are not tied to particular dates. One of the most significant of these has been the opportunity to identify numerous submissions which constituted “diamonds in the rough” and then working closely with their authors to develop them into clear, insightful, and often important, articles. Another major source of gratification is that more and more leading Israeli researchers have become regular contributors to the journal—apparently due a mix of a satisfactory author experience and recognition of the journal’s growing stature and influence.I’ve also greatly enjoyed working with my fellow editors on soliciting, editing, and publishing clusters of articles on a common theme. These have included the cluster of articles that the IJHPR published in 2018 about the relationship between research and policymaking –9 and thAlong with these achievements, it is important for me to also note two of the areas in which we have not yet done as well as I had expected. I do so, in part, because I hope that that they will get a boost when I step down from the co-EIC role.The first area in which we could do better is that, despite the recruitment of several very fine assistant editors, we have not yet done enough to expand the journal’s core editorial team. I know that Avi Israeli, who is continuing on as editor-in-chief, has some concrete ideas on how to do so, and I expect that he will succeed in this, as he has in so many of his leadership roles over the years.Another area in which we could be doing more is in connecting research and policy and strengthening ties between scholars in Israel and abroad. To that end, I have proposed to Avi, the Israel National Institute for Health Policy Research, and BioMed Central that I will transition to a new role as the IJHPR’s special projects editor. I am delighted that they have graciously agreed. In that new role I hope to launch several initiatives to strengthen the IJHPR’s policy and international linkages, and I hope that many of you will have opportunities to take part in them. Details to follow in the months ahead, so please stay tuned in.Over the past decade, co-editing the IJHPR has been one of the major foci of my life. Doing so has been consistently gratifying and at times exhilarating. I am happy to have this opportunity to acknowledge several of the key people who have contributed to my overwhelmingly positive experience.I begin with a huge thank you to Avi Israeli, with whom I have shared the editor-in-chief role from the start. Avi has brought to the journal a uniquely broad understanding of health care in Israel and beyond, along with an unwavering commitment to scholarly excellence and policy relevance. It was Avi who proposed one of the journal’s signature features: the recruitment of leading international scholars to comment on the original research articles, typically written by Israeli authors. I also want to thank Avi for going along with many of the initiatives that I proposed, despite having questions or reservations about some of them.Mid-way through the decade, Avi and I recruited Steve Schoenbaum to serve as our associate editor. This has proven to be one of our best decisions. Steve has played a central role in recruiting commentators and reviewers from beyond Israel. He has also worked intensively with many of our authors to improve their manuscripts—not just to the point where they could be accepted for publication, but also to the point where they would be widely read and cited.A big thank you also goes to the Israel National Institute for Health Policy Research, the journal’s sponsor. The key players there have included the late Haim Doron, Shlomo Mor-Yosef, Orli Manor, Alik Aviram, Haim Bitterman, Ziva Litvak, and Gili Shilat. In addition to covering the costs of publication, the National Institute has provided the journal with a home base which is respected by all of Israel’s health care and academic institutions and played a major role in promoting the journal and disseminating its articles.Thanks also to my employer, the Myers-JDC-Brookdale Institute for supporting me in my work on the journal. Both MJB executive directors under whom I have served—Jack Habib and Michael Hartal—recognized the importance of the IJHPR to me and to Israeli health care and have been supportive throughout.My investment in the journal would not have been possible without the wonderful support of my family, and in particular the support of my life partner—Professor Laura Rosen. Laura has been a great cheerleader for the journal’s accomplishments and an invaluable adviser and support to me in facing the challenges, stresses, and difficult periods involved in being a journal co-editor.Thanks also go to our publisher, BioMed Central, and particularly to Liz Hoffman, our journal development editor. Liz has been a terrific advocate for the journal, helping BMC understand, appreciate, and accommodate the IJHPR’s unique mission and needs.Finally, I want to thank the thousands of authors who have submitted manuscripts to the Israel Journal of Health Policy Research over the past decade. A very special thank you goes to those who submitted articles in our first few years, before it was clear whether the journal would make it. I am also appreciative of those who chose to wait it out during those early years, and then became consistent and valued contributors to the journal, thereby playing major roles in its continued growth and success.May the journal’s second decade be even better than its first one!


CAD/CAM technology can enhance the dentistry application of ceramic materials that meet the more relevant biocompatibility and aesthetics demands. In implant-borne prosthesis rehabilitation, yttria-stabilized zirconia appeared to be a valid alternative to metal-alloys and titanium, with comparable mechanical properties and even better interaction with bone and soft tissues. The improvement of monolithic CAD/CAM manufacturing allows for a reliable, predictable, and rapid workflow that can correspond to a holistic treatment philosophy associated with zirconia fixtures. This reported clinical case highlights the advantages of this approach in resolving particularly functionally and aesthetically complex situations. A 40-year-old patient with permanent canine impaction and the persistence of a deciduous tooth compromised by caries was successfully rehabilitated with the surgical removal of the enclosed tooth, the seating of a mono-phase zirconia implant after the deciduous extraction and its loading with a zirconia single crown, without any clinical or radiographical alteration up to seven years follow-up. The aesthetic demands of implant-borne prosthetic rehabilitation of a mono-edentulism in the frontal zone are challenging, and often necessitate the involvement of the proximal teeth with fixed dental bridge solutions to compensate hard and soft tissue alterations . The impDigital Imaging and Communication in Medicine (DICOM) data on cone-beam tomography bone status, and 3D standard tessellation (STL) data on the topographical and superficial features of the teeth and soft tissues from an intraoral scanner (IOS), are paired using dedicated software, allowing the correct implant-prosthetic rehabilitation to be carried out according to anatomical and prosthetic demands .Computer-aided design (CAD)/computer-aided manufacturing (CAM) technology was first adopted in restorative dentistry in 1985 ,3,6,7. TThese materials evolved from a fragile feldspathic crystalline structure to zirconia oxide ceramics, with a dense monocrystalline homogeneity. Zirconia was revealed to have high flexural strength values . SubsequDespite the more customized restorative structures able to be obtained through the use of digital technology, the use of ceramic materials was reevaluated after doubts arose over the bio-inertia of titanium with possible hypersensitivity . FurtherThe major aesthetic property of ceramic materials compared to metal is the most important reason for the interest in zirconia, along with reported major biocompatibility. In the case of a thin gingival biotype and a complex anatomical situation, the dark shadow of titanium may be visible through the peri-implant tissues, particularly in the case of soft tissue retraction over time .This paper reports on a complex case of anterior zone mono-edentulism, managed with computerized technology for the planning phase and the prosthetic superstructure realization, with both fixture and crown in zirconia.A forty-year-old non-smoker patient in good health (ASA 1) with a persistent deciduous canine and bone-impacted permanent canine was referred to our dental office for a definitive aesthetic and functional rehabilitation.Different therapeutic options were proposed . Since the patient insisted on not using a metallic implant, we opted for a monotype ceramic fixture .The canine surgical extraction was performed under regional anesthesia using a piezoelectric instrument to reduce bone removal and the risk of damaging the roots of the neighboring teeth. After 4 months of healing, the bone site was assessed again with intraoral radiographs .The various formats are interpreted by the software and processed in such a way to be transferred to the CAD/CAM system. A preliminary impression of the arches was taken using an intraoral scanner (IOS). The adopted scanner was iTero . The iTero uses a red laser beam and parallel confocal imaging technology to capture up to 100,000 points of laser light with an accuracy of <20 micron. The STL files obtained with IOS were used to make a wax-up that was necessary to evaluate the correct morphology, dimension, and exact position of the prosthetic crown, as the occlusal space between the adjacent teeth had been reduced. For this analysis, the radiological DICOM files from the CBCT, the STL files from the IOS, and the laboratory scans were paired in a software platform, allowing the rehabilitation to be planned according to the anatomic and prosthetic demands.After the completion of the bone healing, the extraction of the deciduous element and the implant placement was carried out in the same surgical setting. It was not a real immediate post-extraction implant insertion as the resorption of the roots allowed the bone to completely fill the alveolar space. Particular attention was paid to the implant position, as it could not be corrected in the prosthetic portion axis, due to being a monotype implant.tm, San Paul, MN, USA) without occlusal contacts . The silicone material has a light-heavy body suitable for taking the impression of implants to better stabilize the polyether-ether-ketone (PEEK) snap-on transfer and reduce mucosal compression, resulting in a more accurate impression of the gingival area . ParticuFinally, the definitive crown in ceramic-coated zirconia was cemented with a special resinous cement, and an intra-oral X-ray was taken to confirm the prosthetic fitting .The treatment objectives were achieved with a good occlusion and improved aesthetics. The patient declared that they were completely satisfied.Seven years after the procedure, no clinical or radiographic variation was recorded apart from minimal wear of the cervical implant portion due to an incorrect method of brushing . No implThis paper aims to underline the usefulness of ceramic materials, particularly zirconia, in optimizing the treatment of a difficult aesthetically demanding implant-prosthetic rehabilitation.4) present in fossil sands, with minerals such as yttrium, manganese, and alumina. Three different types of zirconium oxide ceramic are currently available on the market: yttrium ion stabilized tetragonal zirconia (3Y-TZP), partially stabilized magnesium zirconia (Mg-PSZ) and tempered zirconia with alumina (ZTA) [Zirconia is obtained through the enrichment of silicate of zirconium (ZrSiOna (ZTA) ,16. The na (ZTA) , and a lna (ZTA) , make zina (ZTA) .The great advantage of ceramics is that they are easily workable with the current CAD/CAM milling or sintering systems, thus substantially reducing treatment timing, costs, and operative errors. The ability to directly realize the prosthetic components in a digitally designed project allows the clinician to better manage the entire treatment up to the finalization, with more precise and controlled outcomes. The digital method demonstrated better accuracy than the analog one, when compared to the original wax-up traditional molded and milled mock-ups for restorative treatment with porcelain veneers .There is little evidence for the success of zirconia monolithic crowns. A few studies showed a 100% survival rate after 36-68 months without fractures, cracks, or chipping ,20.In implant-borne prosthetic rehabilitation, metal-free zirconia crowns or bridges imply a cemented connection, and a more versatile solution in the aesthetic area, with the drawback of the impossibility of removing the prosthetic superstructure for hygiene or for repair in case of structural damage.Zirconia implants started being used as an alternative to titanium upon more frequent requirements from patients of metal-free bio-devices, based on concerns about possible immune-reactions or metal toxicity. In fact, the prevalence of titanium allergy was estimated at 0.6% in a study using the memory lymphocyte immune-stimulation assay (MELISA) . OperatiNevertheless, the first ceramic implants were in alumina oxide and, over time, proved to be too fragile . Hence tIn regard to the osseointegration of zirconia, no difference was reported with titanium in terms of bone-to-implant contact (BIC). In one study, major cell-to-implant contact with multinucleated giant cells was observed with zirconia implants (17.5%) compared to titanium ones (3.9%) at four weeks , withoutAnother aforementioned important positive property of zirconia is its non-retention of bacterial plaque, with a less marked bacterial colonization demonstrated by reduced concentrations of the metabolism products at the neck of the zirconia implant.Generally, a ceramic implant’s bed preparation requires that the producer’s directions are strictly followed to mechanically stress the structure of the fixture ,3,23. MoAnother problem with this type of implant is the necessity of preventing the extra-osseous portion from micro-traumas that can compromise the initial phase of osseointegration, with the risk of early failure. Accuracy when choosing the adequate height of the pillar is mandatory. The role of traditionally managed provisional prosthesis should not be neglected. The temporary crown, adequately out of occlusal contacts, prevents the one-piece implant from micromotions, maintaining an aesthetic function, and allows a progressive remodeling of the peri-implant soft tissues with an easy removal for clinical examinations .A further difficulty with these implants is controlling the cement flowing between the implant neck and the soft tissues, which is possibly responsible for mucositis and periimplantitis. The application of retractor wires in the cementation phase is another critical passage that complicates the procedure. Finally, in the case of pluri-edentulism with a fixed dental bridge, the necessity of an extremely precise implant seating is related to the parallelism to be obtained by the pillars.Recently, a 5 year follow-up study with these types of implants reported a 98.4% survival rate since implant insertion, with one implant lost out of 71 placed, an overall mean marginal bone loss of 0.7 mm without statistically significant bone resorption after loading, and a stable condition of the peri-implant mucosa. These data are consistent with what is observed in the literature around titanium fixtures, with a 97.2% survival rate for implants supporting SCs  and 95.6The risk of fracture in connection surfaces and screws or de-cementations of extra-osseous components, such as the abutments, marked the mono-phasic more than two-piece zirconia implants. Indeed, a three-year prospective RCT study observed worse results with zirconia CAD/CAM abutments compared to titanium ones, with an 82.2% success rate versus 100%, due to fracture occurrence at the abutment connections. For all with an internal connection, the failed abutments supported restorations in posterior areas, except for one in cuspid location . In two At present, only a few ceramic systems offer two-piece implants.Focusing on the prosthetic super-structure problems only, the monolithic approach adopted in this case report could prevent the chipping and roughening of the veneering ceramic that affected some results with zirconia recorded in the literature . AnotherThe positive results that this case presented at a long-term follow-up were the result of lengthy experience with the use of zirconia, associated with a high-level of digital technology knowledge. Hence, the possibility to treat complex cases with high aesthetic implications must be carefully evaluated and limited to selected situations. The improving technology, both for the materials and their manipulation with CAD/CAM systems, has the potential in a proximal future to fully satisfy patient requests for a more bio-compatible and aesthetic dental rehabilitation, even in the posterior areas.Digital technologies allowed us to successfully resolve a challenging aesthetic case using zirconia, with a long-term follow-up of seven years. A long-practice approach with this new therapeutic option, along with deep knowledge of aesthetic ceramics, is recommended to manage the entailed drawbacks and limitations.


Nodularia douglasiae, while the other was N. nipponensis.We determined the complete mitochondrial sequences of female-transmitted (F) mitogenomes of two unionid specimens from the Lake Biwa system, Japan. Their gene contents and orders agreed with those of the typical F mitogenome of freshwater mussels. Molecular phylogenetic analysis using 20 previously identified partial COI and seven (five previously identified and two newly determined) whole mitogenome sequences revealed that one of the two mitogenomes was that of  Nodularia species in Japan: Nodularia douglasiae  and N. nipponensis , the former occurring on Kyushu and Honshu Islands in the area along the Sea of Japan, and the latter being endemic to northern Honshu and Hokkaido. Before the new classification, however, two subspecies were recognized in Japan under the name, Unio douglasiae Gray, 1833: Unio douglasiae nipponensis Martens, 1877 and Unio douglasiae biwae Kobelt, 1879, with the latter endemic to the Omi Basin (Lake Biwa and adjacent area) on Honshu and the former occurring widely in Japan with the exception of the Omi Basin  are burrowing, filter-feeding bivalves. They occur in lakes and rivers worldwide but are now declining in many countries , under the registration numbers LBM-1300014505 and 1300014533. Genomic DNA was isolated from foot muscle tissue, and sequenced using Illumina MiSeq and HiSeq X Ten sequencers (Illumina). The resultant reads were assembled using CLC Genomic Workbench . Contigs were annotated by alignment with the two female (F)-transmitted mitogenomes of N. douglasiae (LC496352 and NC_026111) . The phylogenetic positions of the two mitogenomes indicated that one was that of N. nipponensis , while the other was the new N. douglasiae. This result demonstrated that there are two mitogenome lineages of Nodularia in the Omi Basin, unlike the previous classification hypothesis of Kondo (U. douglasiae biwae).The resulting supermatrix tree  containeof Kondo , which r


Revascularization of the internal iliac artery during open repair of aortoiliac aneurysms can be challenging, especially if there is a significant distance between the orifices of the internal and external iliac arteries owing to common iliac aneurysmal dilatation. We describe a technique involving insertion of an 18-mm tube graft between the proximal aortic neck and aneurysmal common iliac artery bifurcation. Revascularization of the contralateral external iliac artery is accomplished through an 8-mm side arm graft. Despite the evolution of endovascular techniques, repair of aortoiliac aneurysms is still performed by open surgery in a significant number of patients, particularly those with prolonged expected survival. Significant aneurysmal degeneration of the distal common iliac artery may lead to displacement of the orifices of the external and internal iliac arteries , making a formal end-to-end anastomosis with the graft limb of a bifurcated graft unsafe or even impossible. Several modifications of endovascular and open repair techniques have been described in the literature devised to overcome this problem. We describe an additional modification of the open reconstruction.A 79-year-old male with lower abdominal pain radiating to the lumbar spine was admitted to the hospital and underwent a computed tomography angiography that revealed an abdominal aortic aneurysm (AAA) measuring 8 cm in diameter and extending to both EIA and IIA. The infrarenal neck measured 2.8 cm in diameter. Right and left common iliac aneurysms measured 4.2 and 3.8 cm in diameter, respectively . The riThe patient was operated under general orotracheal anesthesia in the supine position. Through a standard midline laparotomy, the aortic neck and the iliac bifurcations were dissected out in the usual fashion. The AAA was opened longitudinally and an 18-mm aortic tube graft  was interposed. Proximally, the graft was sutured in an end-to-end fashion with the infrarenal aortic neck, and it was anastomosed in an end-to-end fashion with the right iliac bifurcation distally, encompassing both the orifices of the right IIA and right EIA. A separate side arm/tube graft  was then anastomosed proximally with the aortic graft (in end-to-side fashion) and distally with the left EIA (in end-to-end fashion), while the left IIA was ligated and3. Open repair of an AAA is considered complex in cases of concomitant common iliac and/or IIAs, especially if they are bilateral and involve the iliac bifurcation, requiring revascularization of at least one IIA. Approximately, 10 to 20% of AAAs are combined with iliac aneurysms. Isolated iliac aneurysm accounts for 2 to 7% and isolated IIA aneurysms for 0.3 to 0.5% of all abdominal aneurysms.An important guideline is the revascularization of at least one IIA, while the other one may be sacrificed. However, complications, such as buttock ischemia (including buttock claudication in 10–30%), erectile dysfunction, and bowel and spinal cord ischemia, may rarely develop, and are more frequent after bilateral IIA ligation.In some cases, a formal distal end-to-end anastomosis of the graft limb with the common iliac bifurcation is impossible due to long distance between the orifices of the IIA and EIA, owing to aneurysmal dilatation of the distal common iliac artery . If thiUpon review of the literature, we found some alternative techniques that have been performed at least to one side  as follows:End-to-end anastomosis of the graft limb with the IIA end reimplantation of the EIA in the graft limb.Custom-made trifurcated graft which is tailored on table and provides a separate graft limb for revascularization of the IIA.A specific tube graft with a nitinol stent at one end . It is anastomosed centrally with the graft limb of a bifurcated graft, and is fixed after deployment of its stent-portion in the IIA distally.The first AAA resection by Dubost et alIn conclusion, depending on the aneurysm morphology and the difficulties arising in a specific operation, the surgeon decides if the modification, we describe here, can help to carry out the arterial reconstruction more easily.


With the increasing demand for aesthetics in children and their parents, the treatment of decayed primary anterior teeth is one of the biggest challenges in pediatric dentistry. Zirconia crowns have provided a treatment alternative to address the aesthetic concerns and ease of placement of extracoronal restorations on primary anterior teeth.  The electronic databases including PubMed, Scopus, Google Scholar, and Embase were searched on articles published between January 2010 and January 2021. Studies relating to evaluating the clinical success and satisfaction of both parents and children about zirconia crowns in maxillary primary incisors were reviewed.  Nine studies met the criteria for final inclusion. Findings from these studies showed that parental and child satisfaction with zirconia crowns is high with clinically acceptable restorations in the maxillary primary incisors.  Parental and child satisfaction with zirconia crowns is high with clinically acceptable restorations in the maxillary primary incisors. In addition, larger sample sizes and longer follow-ups are required in future studies. Early childhood caries (ECC) is still one of the most common chronic diseases in children worldwide . ECC doeToday, aesthetic dentistry is an essential component of modern dental practice. However, the knowledge of children's aesthetic perception is relevant to dentists and their parents , but children also have dental aesthetic perception of others of the same age , 4. The Today, we have a large number of solutions available for aesthetic problems in pediatric dentistry including full-coverage crowns for primary anterior teeth, composite strip crowns, preveneered stainless steel crowns (SSCs), and prefabricated primary zirconia crowns. Resin composite strip crowns are less retentive due to their high technical sensitivity . PreveneThis systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines ; a speciPopulation: maxillary primary incisorsIntervention: zirconia crownsComparison: clinical success and child and parental satisfaction outcomes of zirconia crownsOutcome: gingival health, tooth preparation, and survival ratePICO:The Medline (through PubMed), Scopus, Google Scholar, and Embase databases were explored through advanced searches and databases for articles published between January 2010 and January 2021 to perform a literature search on studies which investigated the parental and child satisfaction and clinical success of zirconia crowns of primary incisors. These databases were searched for articles published in the English language. The search keywords were (Pediatric) AND (zirconia Anterior Crowns) OR (zirconia) AND (anterior) OR (primary incisors) AND  AND (child). All records electronically identified were independently assessed by two authors according to their titles, abstracts, and/or keywords, and the full texts of all reports considered potentially relevant were obtained. Article types such as reviews, letters, and conference proceedings were excluded. Afterwards, articles from the initial search were screened for duplicates (using EndNote software version 8), followed by screening their titles and abstracts for conformity to the eligibility criteria. Furthermore, references of retained articles were manually screened for possible inclusion of relevant studies.The obtained articles were independently subjected to clear inclusion and exclusion criteria by two authors (MHH and MK).Clinical studies with full textsCase report studies involving ZC primary incisorsInclusion criteria for the studies were as follows:Conference abstracts, review articles, letters, editorials, unpublished data, articles without full texts, and non-English articlesStudies which did not assess the efficacy of zirconia in primary incisorsFollow-up less than 6 monthsStudies in which their full texts were not availableExclusion criteria for the studies were as follows:Firstly, all retrieved articles from electronic as well as manual searches were entered into Endnote software . Thereafter, duplicates were removed. Afterwards, two authors (MHH and MK) independently reviewed the titles and abstracts of the retrieved studies for eligibility. Studies were then selected based on the predetermined inclusion and exclusion criteria. For any disagreements concerning the inclusion of studies, all authors agreed on a consensus based on factual evidence.The data were extracted from the studies according to the aim of the systematic review by two authors (SH and MHH) independently and were arranged in the following fields: general information (name of the author and year of publication), country, study type, sample description, follow-up, children's age, pulp therapy, cement, zirconia crown brand, and main outcomes. Furthermore, they were summarized and presented in tables.The literature search yielded a total of 618 articles , from whThe screening process resulted in a total of 9 articles that were included in the present systematic review . Of thesStudies comparing parental and child satisfaction with clinical success were conducted using three different tooth-colored anterior crowns which showed that parents and children had the highest satisfaction with zirconia crowns, followed by strip crowns and preveneered SSCs in primary anterior maxillary teeth. Zirconia crowns were found to have better aesthetics, retention, and gingival health at their follow-up , 22, 24.The case reports showed that zirconia crowns offer high-end aesthetics, superior durability, and easy placement compared to composite restorations and strip crowns. Therefore, they can be considered as a method of aesthetic rehabilitation in pediatric patients , 19.One study compared prefabricated primary zirconia with resin composite strip crowns on primary maxillary central and lateral incisors with regard to gingival health, plaque accumulation, recurrent caries, restoration failure, and opposing tooth wear over a period of 3, 6, and 12 months. Zirconia crowns showed significantly less gingival bleeding, better gingival health, and plaque accumulation, as well as less loss of material . One croOne study conducted by El Shahawy and O'Connell showed a simple reliable technique for restoring severely mutilated primary anterior teeth. A rigid glass-ionomer post was created over which zirconia crowns can be fitted to achieve a long-term stable aesthetic restoration for primary anterior teeth. The use of zirconia crowns offered superior aesthetic, durable restorations with remarkable gingival response up to 24 months .To our knowledge, this is the first study to systematically review the clinical evaluation and parental and child satisfaction with zirconia crowns in maxillary primary incisors. Our findings from the reviewed studies showed that parental satisfaction with zirconia crowns is high with clinically acceptable restorations in the maxillary primary incisors. The aesthetic of the primary anterior teeth with ECC has been a major challenge for pediatric dentists. However, the request of their parents has improved aesthetic solutions . RecentlZirconia crowns are less technique sensitive and more moisture tolerant. However, the potential disadvantages of the zirconia restoration are the inability to crimp the crown for mechanical retention, the inability to change its color, the limited ability to trim the crown or alter its shape, and the need for more tooth reduction than a traditional preformed metal crown . Some drZirconia crowns have been used successfully as clinical advantages were extended to pediatric dentistry. Zirconia crowns have gained popularity among pediatric dentists and have shown high parental and child satisfactory ratings compared to full-coverage crowns . Thus, sIt is important to understand that aesthetic harmony can lead to better psychological health and higher self-assurance. It improves peer relationships and strengthens self-confidence in a growing child. Zirconia crowns offer high-end aesthetics, superior durability, and easy placement compared to composite restorations and strip crowns. Therefore, they can be considered as a method of aesthetic rehabilitation in pediatric patients .Despite the limited number of published clinical trials, the available studies showed that parental and child satisfaction with zirconia crowns is high with clinically acceptable restorations in the maxillary primary incisors , 13, 21.Findings from the reviewed studies have shown that parental and child satisfaction with zirconia crowns is high with clinically acceptable restorations in the maxillary primary incisors. However, there still remains a lot of work to be done in ensuring their full clinical translation. Further research studies are necessary, including in vitro, in vivo, and clinical studies with larger sample sizes and longer follow-ups.


Highland barley (HB) is commonly milled into flour for direct consumption or further processed with other food formulations. Nevertheless, the association between milling and HB flour properties remains lacking. This work studied the effect of particle sizes  on physicochemical and nutritional properties of raw and sand-roasted HB flour. Gelatinization enthalpy decreased with increasing particle sizes of raw HB flour, while no endothermic transitions were observed in sand-roasted flour. Sand roasting destroyed starch granules and decreased short-range molecular order. Starch digestibility increased while total short-chain fatty acids (SCFAs) production decreased with decreasing particle sizes in all samples. The relative crystallinity of sand-roasted HB flour decreased by 80–88% compared with raw samples. Sand roasting raised in vitro starch digestibility, while total SCFAs during in vitro fecal fermentation decreased. Sand-roasted HB flour with particle sizes <150 μm had the highest starch digestibility (94.0%) but the lowest production of total SCFAs (1.89–2.24 mM). Pearson’s correlation analysis confirmed the relationship between the nutritional qualities of HB flour and milling. Recently, the effects of food processing on the sensory and nutritional qualities of whole grain flours and their finished products have attracted increasing interest. Milling not only influences the interaction between proximate compositions  and digestive enzymes, but also concentrates unique bioactive compounds  in the different proportions of the tissues present ,2,3. HarMilling, a common method to produce flours with a wide range of particle sizes, causes varied distributions of components, bioavailability of nutrients, and baking properties of grain flours. Until now, milling affects textural and pasting qualities of starch, which are detrimental for finished product properties, such as stability, flow, functionality, texture, mouth feel, and structure ,5,6. TheHordeum vulgare L. var. nudum hook. f, HB), one of the varieties of the Gramineae wheat family, is mainly cultivated in highland areas of Tibet, Qinghai, west Sichuan, northwest Yunnan, and southwest Gansu, China. Tsampa, flour milled from sand-roasted HB and consumed with ghee, milk dregs, and sugar, has been a traditional Qinghai–Tibetan staple food for centuries. Due to the low glycemic index (39.4–47.5) of HB starch, it is regarded as an ideal staple food for diabetics [β-glucan, phytosterols, and tocols, which are beneficial for health due to their antioxidant, anti-inflammatory [Highland barley  on changes of physicochemical, morphological, and thermal properties of raw and sand-roasted HB flour, with a focus on in vitro starch digestion and fermentation properties. This study might provide a theoretical basis for understanding the relationship between the utility of HB flour and its acceptable physiochemical and functional qualities when mixed with other food formulations in industrialized production.β-glucan (mixed linkage) kit, total dietary fiber kit, and total starch kit were obtained via Megazyme International Ireland, Ltd. . α-amylase from porcine pancreas type VI-B  and pepsin from porcine gastric mucosa  were obtained via Sigma Chemical Co. . Pancreatic enzyme  was obtained via the Shanghai yuanye Bio-Technology Co. . Other chemicals and reagents used were of analytical grade.HB was obtained from Lhasa, Tibet. Acetic acid ≥98%, propionic acid ≥99%, butyric acid ≥99%, valeric acid ≥99%, and 2-ethylbutyric acid ≥98% were obtained from Aladdin Bio-Chem Technology Co., Ltd., . Total glucose oxidase/peroxidase (GOPOD) kit, w/w) and vigorously stirred at 220 ± 5 °C for 30 s using an electromagnetic oven . Sand roasting was carefully operated so that it led to maximum expansion of HB grains without burning. Then, sand-roasted HB was immediately separated from hot sand and cooled down to room temperature. Sand-roasted HB was ground into flour by a high-speed multifunction mill  and fractionated sequentially into three fractions by sieves of 35, 60, and 100 meshes. The flours were designated as Roasted-35 , Roasted-60 , and Roasted-100 , respectively. Raw barley was ground as mentioned above and designated as Raw-35 , Raw-60 , and Raw-100 , respectively.First, 100 g HB (conditioned to 30% moisture content at 4 °C) was mixed with 100 μm fine sand , 50th or median (d50), and 90th percentile (d90), respectively.Particle size distributions (PSDs) of tall flours were determined by a Mastersizer Malvern Hydro2000MU . HB flour was suspended in circulating distilled water at 2000 rpm. The particle size of HB flour was recorded within the range of 0.02–2000 μm under an obscuration of 10–12%. The particle refractive absorption indexes were 1.52 and 0.1, respectively. The refractive index of water as the dispersant was 1.33. The particle sizes were recorded as the 10th percentile ; starch digested during 20–120 min was designated as slowly digestible starch (SDS); starch undigested after 120 min was designated as resistant starch (RS) [The crude lipid, crude protein, and ash contents of all flours were analyzed according to AOAC methods 960.39 (2000), 955.04 (2000), and 923.03 (2000) . The conrch (RS) . The polrch (RS) . Color vPolarized light microscopy images of starch granules were analyzed according to a modified method using a BX53 microscope  with a polarized light accessory. Briefly, 5 mg flour (dry basis) was dispersed in 150 μL of 50% glycerol in a glass vial. A drop of flour suspension was then put onto a slide and observed at 400 × magnification (40 × 10).For scanning electron microscopy (SEM), all flours were analyzed with a scanning electron microscope Phenom Pro 10,102 at 10 kV . The flour was packed on the plate using a double-faced conductive tape and sputter-coated with a thin film of gold. Nitrogen was used to remove the non-attached flour using a blowing device and observed at 3000× magnification.−1 were obtained from three different positions under a 785 nm green diode. As an indicator of the short-range ordered structures in starch [−1 was acquired by Peak Fit v4.12 software.A DXR2 Raman microscopy system was used to acquire laser confocal micro-Raman spectra  with an Olympus BX51 microscope . Spectra of 3200–100 cmn starch , the fulθ) using an X’Pert3 Powder XRD system . The flour was mounted tightly on a round glass cell at a rate of 2°/min under 1600 W (40 kV × 40 mA). The ratio of the crystalline area/the total diffraction area was used for calculating relative crystallinity (RC) by MDI Jade 5.0 software .The crystallinity structures of all flours were scanned at 4–40° (2H), onset temperature (OT), peak temperature (PT), and conclusion temperature (CT) were acquired by TRIOS data recording software. An empty aluminum pan was used as the control.A Discovery DSC  was used to determine the thermal properties of all flours. To the precisely weighed sample (3 mg) was added 12 mg distilled water in an aluminum pan, which was then sealed and put at 4 °C. After 24 h of equilibration, the pan was heated from 40 to 100 °C at a rate of 10 °C/min. The gelatinization enthalpy  for 10 min. The released glucose in the supernatant was analyzed using the Megazyme GOPOD kit and converted into starch by multiplying factor 0.9. The starch digestograms were fixed with the first-order equation as described previously [tC = starch digested at time t, C∞ = starch digested at the reaction end point, and k = the first order rate coefficient calculated from the slope of a linear least squares fit of a plot of ln (1 − C/C∞) against t.An in vitro simulation of saliva–gastrointestinal digestion was studied according to a previous method with modifications . First, eviously :Ct = C∞ g for 10 min to obtain the precipitate, which was freeze-dried and then subject to in vitro simulated fecal fermentation [w/v). Secondly, 100 mg digesta precipitate was dissolved in 9 mL of autoclaved basal nutrient medium 7, 0.01 g/L CaCl2, 2.0 g/L NaHCO3, 0.5 g/L bile salts, 0.5 g/L L-Cysteine-HCL, 0.02 g/L chlorhematin, 1.0 mg/L resazurin, 9.8 mg/L vitamin K, and 2 mL Tween-80). Thirdly, the resultant mixture was thoroughly mixed with fecal slurry (1 mL) and incubated in a thermostatic shaker ZWY-2102C  at 37 °C. Anaerobic condition was kept during in vitro fermentation using an anaerobic chamber . The fermented samples were obtained at 6, 12, 24, and 48 h, respectively, which were then centrifuged at 25 °C, 2809× g for 10 min to collect the supernatant. Test tubes without digesta precipitates were used as blanks.The digesta obtained from simulated in vitro saliva–gastrointestinal digestion was centrifuged at 25 °C, 2151× entation . Three hg  for 20 min to obtain the supernatant. Short-chain fatty acids were analyzed on a Shimadzu GC-2010 gas chromatograph  with a CP-FFAP-CB capillary column . Short-chain fatty acids were determined by the retention times of authentic standards and quantified by the amount of 2-ethylbutyric acid.The pH value of the supernatant obtained from in vitro fecal fermentation was determined using a pH meter . Short-chain fatty acids were analyzed according to a previous method with minor modifications . Brieflyn = 3). Any significant difference among six groups was analyzed using one-way analysis of variance (ANOVA) followed by post hoc LSD analysis at p < 0.05 using IBM SPSS 25.0 software . The partial correlation coefficients between particle size and starch digestibility and fermentation properties were investigated using SPSS Statistics 25.0 followed by a two-tailed Pearson’ correlation analysis. Asterisks “*” and “**” indicate the different levels of associations significant at p < 0.05 and p < 0.01, respectively.Data was presented as means ± standard deviations (d50) of 584 μm (Raw-35), 317 μm (Raw-60), 665 μm (Roasted-35), 367 μm (Roasted-60), and 129 μm (Roasted-100), respectively. However, Raw-100 (d50 = 103 μm) showed a clear bimodal distribution, which represented free starch granules of about 25 μm [The PSD of all flours are presented in ut 25 μm .The polarized light microscopic images of all flours are shown in L*) increased as particle size decreased, while redness (a*) and yellowness (b*) showed a reverse trend. This was because of the presence of more bran particles in coarse and medium fractions [L*) and increased redness (a*) and yellowness (b*), indicating Maillard reactions caused by the thermal breakdown of starch [The anisotropic structure color values of all samples are shown in ractions . Sand rof starch .β-glucan-rich fragments evenly distributed in each flour fraction (4.5–4.9%). Raw and sand-roasted samples had similar contents of crude lipids and soluble dietary fiber (SDF) but varied in other compositions. Compared with raw samples, sand roasting significantly raised the contents of RDS and SDS while it reduced the contents of RS, β-glucan, total polyphenols (TPs), and free polyphenols (FPs).The chemical compositions of all samples are demonstrated in −1 in all flours are presented in −1. Little difference was observed in FWHM of the Raman band at 480 cm−1 among raw or sand-roasted samples, indicating that milling barely affected the short-range molecular order. Compared with raw flours (16.57–17.41), sand roasting increased the FWHM of the Raman band at 480 cm−1 (18.10–18.88), indicating destroyed crystalline structure and increased amorphous regions of starch.The FWHM of the Raman band at 480 cmThe XRD profiles of all flours are shown in OT, PT, and CT than Raw-35, indicating that starch granules entrapped inside the cell walls of coarse HB flour were more resistant to gelatinization [H of Raw-35 significantly decreased in comparison to Raw-100, possibly due to the fact that cell wall encapsulation limited starch swelling and gelatinization [Starch gelatinization, an endothermic transition, is associated with the dissociation of amylopectin double helices from the ordered structure to an amorphous conformation. The DSC thermograms of all flours are shown in nization . Our resnization  and Faronization , who repnization ,36. No ek and C∞ of starch in all samples are presented in C∞ increased with decreasing particle sizes among either raw or sand-roasted flours. Similarly, Farooq et al. [k, 0.008–0.011) and extent  of raw flours were much lower than those of sand-roasted samples , demonstrating that sand roasting significantly enhanced in vitro starch digestion rates.Digestograms and values of q et al.  found thChanges of pH and total short-chain fatty acids of in vitro fermentation in digesta precipitates at 6–48 h are presented in Bifidobacterium and Lactobacillus [The decreased pH was in agreement with the increased production of total short-chain fatty acids B, which bacillus ,39. Compbacillus . Howeverbacillus  found noβ-glucan produced higher proportions of propionate than lactulose and inulin did during in vitro fermentation. Propionate is beneficial in modulating blood glucose, insulin sensitivity, and lipid homeostasis [Changes in individual short-chain fatty acid production during in vitro fermentation at 6–48 h are presented in eostasis ,44. Howep < 0.05). RS showed a very strong positive association with particle size . In addition, RS had very strong positive correlations with acetate production.The correlations between particle size and parameters related to the digestion and fermentation properties of all samples are shown in Overall, medium and fine particles in HB flour might be responsible for the improved hydrolysis rate and extent of starch. More starch remained undigested in raw coarse flours after 180 min enzymatic digestion, leading to higher in vitro fecal short-chain fatty acids production. Raw HB flour with coarse particle sizes might be developed as a functional component or nutraceutical in formulated foods. This study might provide fundamentals for the milling and application of HB flour in industrialized production.


The aim of this study was to investigate the effects of different surface treatment methods on shear bond strength between composite resin and different levels of zirconia ceramic. Laser surface-conditioning procedures have been reported as effective method to increase repair bond strength of composite to zirconia ceramics. Detailed information of effects of Er,Cr:YSGG laser treatment with different pulse rates on the zirconia ceramics is lacking in the literature. 120 disc-shaped specimens were prepared including zirconia, veneering ceramic, and 50% veneering ceramic-50% zirconia surfaces. Four different surface treatments were applied to the specimens. These were grinding with diamond bur, sandblasting, and short and long pulse rates of Er,Cr:YSGG laser irradiation. An intraoral ceramic repair kit was used to repair specimens, and shear bond strength was performed on the composite resin to each specimen. The highest mean bond strength was seen in the veneering ceramic surface that was ground using a diamond bur, and the lowest mean bond strength value was observed in the same surface that was treated with long pulse laser irradiation. The sandblasting with alumina particles exhibited lower mean repairing bond strength among the rest of used methods in this study for the group which contained half of the veneering ceramic and half of the zirconia. Sandblasting and Er,Cr:YSGG laser using surface treatment procedures obtained appropriate bond strength for the group that included 50% veneering ceramic-50% zirconia, because of no significant differences observed among the applied surface conditioning methods in this group. All-ceramic crowns, for example, aluminum-based porcelains, zirconium oxide ceramics, and leucite or lithium-disilicate-reinforced glass ceramics, can be considered an alternative treatment option to porcelain fused to metal fixed partial dentures in daily clinical practice of restorative dentistry , 2. AmonZirconia core ceramics have been demonstrated to be used more safely as framework from single crowns to multiunit bridgeworks. The zirconia core materials are veneered with a stratified feldspathic porcelain to achieve superior esthetics. Although high survival rates of the zirconia ceramics (73.9%-100% after 2-5 years) have been reported in anterior and posterior fixed partial dentures [Fracture in the zirconia framework has been reported as a rarely observed complication with an annual failure rate ranging from 1.88% to 4.24%. On the other hand, minor chipping and complete fracture of the porcelain have been most frequent technical complication. Chipping or crack of porcelain layer can be fracture originating from either zirconia core-porcelain junction or the porcelain itself. Porcelain cracks have been referred to tensile stresses that result from flaws regardless of internal or external characteristics. Stresses in the veneering porcelain throughout the cooling procedure and incompatibility of the coefficient of thermal expansion between zirconia framework and veneering porcelain are other possible causes for beginning and propagation of the crack .When a fracture occurs in veneer ceramics, intraoral repair methods are easier than complete replacement or application of extraoral repair techniques. Also, that is less traumatic for the patient and do not require additional time, efforts, and costs , 8.2O3 particles, acid etching, liner application, grinding with diamond disc, and laser application. Among these methods, benefits of laser application, namely, erbium:yttrium aluminum garnet (Er:YAG), carbon dioxide (CO2), neodymium-doped yttrium garnet (ND:YAG), and erbium chromium:yttrium scandium gallium garnet  lasers, as a chair-side application have become popular and commonly used method recently [Intraoral porcelain repair kits include a bonding system to bond dental composite resin to a fractured porcelain restoration . Strong recently , 11–25.This study is aimed at investigating the efficacy of Er:Cr:YSGG laser application with short and long pulse durations in comparison to other surface roughening procedures for the repair of zirconia ceramics with different surface configurations. The null hypothesis of this study was that the laser irradiation and sandblasting applications have no effect on the repair bond strength of the different level of zirconia ceramics.Group I: testing surfaces of the specimens were merely fabricated from zirconia (zirconia 100%) . (Zirconia Group); Group II: testing surfaces of the specimens were only fabricated from veneering ceramic (veneering ceramic 100%) . (Veneering Group); Group III: testing surfaces of the specimens were fabricated from 50% veneering ceramic and 50% zirconia (Zirconia-Veneering Group).Totally, 120 disc-shaped specimens (5 mm in diameter and 2 mm in height) were manufactured to analyze the shear bond strength of porcelain repair system to various ceramic surfaces treated with different methods. 3 main groups were determined, so that 40 discs were randomly selected for each group. The following surface configurations were defined for these groups: Disc-shaped zirconia specimens were milled using a machine-milling technique from the presintered zirconia green blocks. Afterwards, the final sintering was performed at 1500°C according to manufacturer's recommendations. 40 specimens were left as only zirconia specimens (Group I). For fabricating 40 zirconia specimens coated with veneering ceramics (Group II), the veneer ceramic powder and liquid were mixed, and the slurry obtained was applied into the disc shaped metal mold that wrapped around the preprepared zirconia discs. This metal mold had sufficient space in it to provide the veneering ceramic as thick as the zirconia specimens that was coated. Then, zirconia and veneering ceramic assembly was fired in a computer-assisted oven owing to the instructions manual. Subsequently, a slot measuring 1 mm in depth was prepared into half of the testing surface of the 40 remaining zirconia specimens as was shown in Subgroup I: control group, surface grinding with wheel grinding diamond bur  (10 strokes); Subgroup II: airborne particle abrasion group, sandblasting with Rondo flex plus 360 . 50 μm Al2O3 particles were applied at an air pressure of 4 bar and water pressure of 1.5 bar for 20 s at a distance of 1 mm, perpendicularly to the surface; Subgroup III: laser application with long pulse, bonding surfaces of the specimens were irradiated by the Er,Cr:YSGG laser  at a 2.78 μm wavelength. The optical fiber of laser  was placed perpendicularly to the surface at a distance of 10 mm. The pulse duration was 200 μs with a repetition rate of 20 Hz (pulses/s), and the pulsed laser-powered hydrokinetics, energy, and power densities were 5.6 J/cm2 and 111 W/cm2 at 1.5 W, respectively. Water and air flows of 50% and 50%, respectively, were used continuously during the 20 s irradiation; and Subgroup IV: laser application with short pulse, bonding surfaces of the specimens were irradiated by Er,Cr:YSGG laser  with a 2.78 μm. The pulse duration was 140 μs with a repetition rate of 20 Hz (pulses/s), while the other conditions of this laser were similar to that of Subgroup III.40 specimens of each group were randomly distributed into 4 subgroups of 10 discs each. Different surface treatments were applied to the testing surfaces of specimens of each subgroup. Surface treatments applied were as follows: After the surface treatments were completed, the surfaces were examined with the scanning electron microscope  in order to observe the topographic surface changes. The samples were first dried, and a sputter-coating device was used to sputter-coat with gold and palladium. The SEM images were then obtained using an electron microscope with a magnification of 1000x, 2000x, and 5000x. SEM pictures with 5000x magnification are shown in After the SEM examination, all specimens were bathed in ultrasonic cleaner with 96% isopropyl alcohol  for 3 mins. Then, the intraoral ceramic repair kit  and composite material  were used to apply to surface of the specimens following the manufacturer's recommendations. In short, following the instructions, the conditioned testing surfaces of the specimens involving veneering ceramic (Group II and III) were etched with 40% phosphoric acid  for 5 s (no need for zirconia surfaces) and rinsed with water for 15 s. Following air drying, the Clearfil SE Bond Primer and Clearfil Porcelain Bond Activator were mixed at a 1 : 1 ratio and put on to the surfaces for 5 s and air thinned. The SE Bond was applied, air dried, and photopolymerized for 10 s. The composite resin material  was applied to the specimen surfaces with the aid of the Teflon mold which had 2x2x2 mm dimension. The mold was incrementally filled up, and each layer was light-polymerized for 20 s at a distance of 1 mm using a light-polymerizing unit  with an output power of 11 W and 1.2 A. Before the shear bond test, specimens were stepped in 37°C distilled water for 24 h.2).Each specimen was placed in a metal holder in a universal testing machine . Loading parallel to the long axis of the specimen was applied at the interface between composite block and testing surface at a 0.5 mm/min crosshead speed until fracture . The maxFollowing the shear bond test, observation on the fractured surfaces was carefully carried out, and the failure modes in the interfaces were determined by a single researcher. The observed failure modes were adhesive, cohesive failures, and mixed of them. Completely separated composite resin from the zirconia surface is determined as adhesive failure; the complete fracture in the composite resin is defined as cohesive failure, and the failure which includes both of the failures (adhesive and cohesive failures) is rendered as mixed failure.p < 0.05 was considered statistically significant.The Shapiro-Wilk normality analysis and the homogeneity test of variance analysis revealed that group distributions were normal. Through the results of those tests, the parametric one-way analysis of variance (one-way ANOVA) was performed among the groups applying a statistical analysis software program . p < 0.05). Differences between the Subgroups II and III and the Subgroups I and IV were not statistically significant (p > 0.05). According to results of Group II, the Subgroup IV showed the lowest bond strength value, and there were statistically significant differences between the values of the Subgroups I and III and between the Subgroups I and IV (p < 0.05). The Subgroup II illustrated any statistically significant differences among the other subgroups. In Group III, the Subgroup II presented the lowest bond strength value, but this was not statistically significant among all other subgroups (p > 0.05).The shear bond strength values including means and standard deviations are presented in Moreover, the failure modes are assessed and presented in Evaluation of the SEM images was performed after the surface treatment procedures  under at a magnification of 5000x . DiverseOutstanding mechanical properties such as high fracture toughness and natural appearance are a key to increase clinical application of zirconia ceramics. Despite the popularity and high clinical success rates of zirconia-based fixed restorations, a considerable amount of veneering ceramic material fracture has been reported by some clinical studies –28. The The clinical achievement is frequently reliant on the integrity of the bonding strength in the interface of the fractured surface of zirconia/veneering ceramic and repairing material. Thus, several researches have been conducted related to outcomes of Er,Cr:YSGG laser application to zirconia ceramics, due to the aiming improvement of bond strength between the resin composite and the zirconia surface –25. In tThe shear bond test is one of the most commonly used bond strength tests , 29, 30,2O3 abrasion is another common treatment that is used to increase surface roughness, but there is no consensus on the bonding effectiveness to zirconia among researchers. Some of them stated that sandblasting caused superior bonding to zirconia, while rest of the others reported that this method did not significantly ascend the bonding strength between the zirconia ceramics and the composite.Previous studies proved that the mechanical conditioning that creates microretentions and improves adhesion has been efficient in surface treatment of zirconia and veneer ceramic material , 32. In 2 lasers in terms of surface conditioning of ceramics have been published, the data including the influence of Er,Cr:YSGG laser on the bond strength of composite resin to ceramic, zirconia, or 50% ceramic-50% zirconia surfaces are scarce. Thus, grinding with coarse diamond bur, sandblasting with Al2O3 particles, and laser treatment via Er,Cr:YSGG were preferred to be used in this study.Recently, investigators have focused on the use of laser treatment to roughen the surface of ceramic substrates. Despite many studies , 33–35 rIt is evident from the present study that grinding with diamond bur resulted in the highest shear bond strength values among other subgroups. The clinically acceptable level of shear bond strength between composite resin and ceramic materials has been reported in previous studies as 10-13 MPa. In the current study, the mean bond strength values were around the range of the recommended level, except those determined for short- and long-pulsed laser treatments applied on the zirconia surfaces. However, it should be taken into account that oral environment, mastication patterns, and long-term usage of the restoration were not able to simulate in the study, which can be caused to decrease on bond strength of the repair system over time. While the in vitro results cannot be exactly depicted to the in vivo conditions, the findings are beneficial predictor of a material's performance or a treatment method.For Group I that consists only zirconia specimens, grinding with diamond bur showed higher mean shear bond strength value than other surface treatment methods, but only the differences between grinding and laser treatments were statistically significant. The possible reason for that finding is the rougher surface areas that can be confirmed by the SEM images for either grinding or sandblasting. While the surface roughness increase, it can result in not only higher surface area but also ascending surface energy. First of them enables micromechanical retention, and the latter can lead to wettability and adhesion.According to our findings in this study, these were compatible with those presented in the study of Derand and Derand , in whicGhasemi et al.  presenteIn the present study, lower values of shear bond strength were obtained applying short- or long-pulsed Er,Cr:YSGG laser treatments than sandblasting and control groups on zirconia surfaces. It can be considered that the power output setting of 1.5 W used in this study could be insufficient to modify and roughen the zirconia surface. It has been conferred that the lower energy settings created minor changes on the surface of Y-TZP, while the higher parameters showed up excessive deterioration on the material, with strong occurrence of cracks and carbonization .The failure mode analysis demonstrated different fracture patterns for zirconia specimens. All specimens in laser-treated groups had adhesive fractures, whereas some specimens in grinding and sandblasting groups had mix failures. This can be predicted as another indicator of the insufficient performance of Er,Cr:YSGG laser conditioning on zirconia surfaces compared to other surface methods. It may be suggested that zirconia samples irradiated with Er,Cr:YSGG laser do not guarantee a convenient clinical service.Irrespective of the laser pulse duration, the difference between grinding and laser treatments was statistically significant, whereas the difference between sandblasting and laser treatments was insignificant. There was inconsistency of the findings compared to the results of research paper of Ghasemi et al. , in whicOn the other hand, the study of Kirmali et al.  reportedHigher shear bond strength values were achieved for specimens involving veneering ceramic surfaces, irrespective of the surface treatment methods used in this study. It could be attributed to higher vitreous proportion in ceramic than zirconia . Since mIn this study, the mean shear bond strength values obtained between the Clearfil Repair system and pretreated veneering ceramic surfaces in terms of grinding with bur and sandblasting were 16.76 ± 5.79 MPa and 12.01 ± 2.49 MPa, respectively, and no statistically significant difference was found. These results were in agreement with those reported in the study of Jain et al. , in whicIt seems that short- or long-pulsed Er,Cr:YSGG laser application is a more effective surface treatment procedure for ceramic surfaces than zirconia surfaces, because no statistically significant differences were determined between laser treatment and other methods in Group III which consists specimens comprising only ceramic surfaces. For Group II, comprising ceramic and zirconia surfaces, even though the mean bond strength value found for grinding with diamond bur was the highest, the difference between short-pulsed laser and grinding was not statistically significant.Surface conditioning using grinding with diamond bur provided better repair bond strength for each level of fractured zirconia ceramicsSandblasting and Er,Cr:YSGG laser applications obtained appropriate bond strength for 50% veneering ceramic-50% zirconia surface, due to no significant differences observed among the applied surface conditioning methods in this groupThe recommendations of manufacturer should be followed to acquire adequate bond strength between the composite resin and the cracked zirconia ceramicsThe veneering ceramic included surfaces illustrated dominantly cohesive or mix failure modes. Intact veneering ceramic surfaces may be included into the repairing zone, in order to enhance bonding strength.Within the limitations of the current study, the following conclusions could be reported: