Visual extended reality tools in image-guided surgery in urology: a systematic review.

PURPOSE: The aim of this systematic review is to assess the clinical implications of employing various Extended Reality (XR) tools for image guidance in urological surgery. METHODS: In June 2023, a systematic electronic literature search was conducted using the Medline database (via PubMed), Embase (via Ovid), Scopus, and Web of Science. The search strategy was designed based on the PICO (Patients, Intervention, Comparison, Outcome) criteria. Study protocol was registered on PROSPERO (registry number CRD42023449025). We incorporated retrospective and prospective comparative studies, along with single-arm studies, which provided information on the use of XR, Mixed Reality (MR), Augmented Reality (AR), and Virtual Reality (VR) in urological surgical procedures. Studies that were not written in English, non-original investigations, and those involving experimental research on animals or cadavers were excluded from our analysis. The quality assessment of comparative and cohort studies was conducted utilizing the Newcastle-Ottawa scale, whilst for randomized controlled trials (RCTs), the Jadad scale was adopted. The level of evidence for each study was determined based on the guidelines provided by the Oxford Centre for Evidence-Based Medicine. RESULTS: The initial electronic search yielded 1,803 papers after removing duplicates. Among these, 58 publications underwent a comprehensive review, leading to the inclusion of 40 studies that met the specified criteria for analysis. 11, 20 and 9 studies tested XR on prostate cancer, kidney cancer and miscellaneous, including bladder cancer and lithiasis surgeries, respectively. Focusing on the different technologies 20, 15 and 5 explored the potential of VR, AR and MR. The majority of the included studies (i.e., 22) were prospective non-randomized, whilst 7 and 11 were RCT and retrospective studies respectively. The included studies that revealed how these new tools can be useful both in preoperative and intraoperative setting for a tailored surgical approach. CONCLUSIONS: AR, VR and MR techniques have emerged as highly effective new tools for image-guided surgery, especially for urologic oncology. Nevertheless, the complete clinical advantages of these innovations are still in the process of evaluation.

Metaverse Surgical Planning with Three-dimensional Virtual Models for Minimally Invasive Partial Nephrectomy.

The recent integration of new virtual visualization modalities with artificial intelligence and high-speed internet connection has opened the door to the advent of the metaverse in medicine. In this totally virtual environment, three-dimensional virtual models (3DVMs) of the patient's anatomy can be visualized and discussed via digital avatars. Here we present for the first time a metaverse preoperative clinical case discussion before minimally invasive partial nephrectomy. The surgeons' digital avatars met in a virtual room and participated in a virtual consultation on the surgical strategy and clamping approach before the procedure. Robotic or laparoscopic procedures are then carried out according to the simulated surgical strategy. We demonstrate how this immersive virtual reality experience overcomes the barriers of distance and how the quality of surgical planning is enriched by a great sense of "being there", even if virtually. Further investigation will improve the quality of interaction with the models and among the avatars.

Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells.

S-adenosyl-homocysteine-hydrolase (AHCY) plays an important role in the methionine cycle regulating cellular methylation levels. AHCY has been reported to influence proliferation and differentiation processes in different cell types, e.g. in cancer cells and mouse embryonic stem cells. In the development of adipose tissue, both the proliferation and differentiation of adipocyte progenitor cells (APCs) are important processes, which in the context of obesity are often dysregulated. To assess whether AHCY might also be involved in cell proliferation and differentiation of APCs, we investigated the effect of reduced AHCY activity on human and mouse APCs in vitro. We show that the inhibition of AHCY using adenosine dialdehyde (AdOx) and the knockdown of AHCY using gene-specific siRNAs reduced APC proliferation and number. Inhibition of AHCY further reduced APC differentiation into mature adipocytes and the expression of adipogenic differentiation markers. Global DNA methylation profiling in human APCs revealed that inhibition of AHCY is associated with alterations in CpG methylation levels of genes involved in fat cell differentiation and pathways related to cellular growth. Our findings suggest that AHCY is necessary for the maintenance of APC proliferation and differentiation and inhibition of AHCY alters DNA methylation processes leading to a dysregulation of the expression of genes involved in the regulation of these processes.

Epigenome-Wide Meta-analysis Reveals Associations Between Dietary Glycemic Index and Glycemic Load and DNA Methylation in Children and Adolescents of Different Body Sizes.

OBJECTIVE: Dietary glycemic index (GI) and glycemic load (GL) are associated with cardiometabolic health in children and adolescents, with potential distinct effects in people with increased BMI. DNA methylation (DNAm) may mediate these effects. Thus, we conducted meta-analyses of epigenome-wide association studies (EWAS) between dietary GI and GL and blood DNAm of children and adolescents. RESEARCH DESIGN AND METHODS: We calculated dietary GI and GL and performed EWAS in children and adolescents (age range: 4.5-17 years) from six cohorts (N = 1,187). We performed stratified analyses of participants with normal weight (n = 801) or overweight or obesity (n = 386). We performed look-ups for the identified cytosine-phosphate-guanine (CpG) sites (false discovery rate [FDR] <0.05) with tissue-specific gene expression of 832 blood and 223 subcutaneous adipose tissue samples from children and adolescents. RESULTS: Dietary GL was positively associated with DNAm of cg20274553 (FDR <0.05), annotated to WDR27. Several CpGs were identified in the normal-weight (GI: 85; GL: 17) and overweight or obese (GI: 136; GL: 298; FDR <0.05) strata, and none overlapped between strata. In participants with overweight or obesity, identified CpGs were related to RNA expression of genes associated with impaired metabolism (e.g., FRAT1, CSF3). CONCLUSIONS: We identified 537 associations between dietary GI and GL and blood DNAm, mainly in children and adolescents with overweight or obesity. High-GI and/or -GL diets may influence epigenetic gene regulation and thereby promote metabolic derangements in young people with increased BMI.

New Generation of 3D Virtual Models with Perfusional Zones: Perioperative Assistance for the Best Pedicle Management during Robotic Partial Nephrectomy.

Selective clamping during robot-assisted partial nephrectomy (RAPN) may reduce ischemia-related functional impairment. The intraoperative use of 3D-virtual models (3DVMs) can improve surgical planning, resulting in a greater success rate for selective clamping. Our goal is to introduce a new generation of 3DVMs, which consider the perfusion volumes of the kidney. Patients listed for RAPN from 2021 to 2022 were recruited. A selective clamping strategy was designed and intraoperatively performed based on the specifically generated 3DVMs. The effectiveness of selective clamping was evaluated using near-infrared-fluorescence imaging (NIRF) and 3DVM. Perfusion areas extensions were compared, and relevant preoperative characteristics were analyzed. In 61 of 80 (76.25%) cases, selective clamping was performed. The concordance between the 3DVM areas and the NIRF-enhanced areas was verified (k = 0.91). According to the distribution of perfused areas crossing the tumor, there were one, two, three, four, and five crossing areas, with relative perfusion rates of 13.75%, 35%, 32.5%, 13.75%, and 5%, respectively. Lesion diameter and mesorenal location were the only factors related to a higher number (>3) of perfusion volumes crossing the lesion. The implementation of mathematical algorithms to 3DVMs allows for precise estimation of the perfusion zone of each arterial branch feeding the organ, leading to the performance of safe and effective pedicle management planning.

Three-dimensional Virtual Models of the Kidney with Colored Perfusion Regions: A New Algorithm-based Tool for Optimizing the Clamping Strategy During Robot-assisted Partial Nephrectomy.

BACKGROUND: An empirical selective clamping strategy based on the direction of the arterial branches can lead to failures during partial nephrectomy, even when assisted by three-dimensional virtual models (3DVMs). OBJECTIVE: To develop and test new 3DVMs that include kidney perfusion regions and evaluate their intraoperative accuracy in guiding selective clamping and their impact on postoperative renal function. DESIGN, SETTING, AND PARTICIPANTS: For patients with a kidney suitable for nephron-sparing surgery, 3DVMs were supplemented with a Voronoi diagram, a Euclidean distance-based mathematical tool, to calculate vascular-dominant regions the kidney. SURGICAL PROCEDURE: Robot-assisted partial nephrectomy guided by perfusion-region (PR)-3DVMs. MEASUREMENTS: All anatomic information given by the PR-3DVMs was collected. Selective or superselective clamping was planned and performed intraoperatively when feasible under 3DVM assistance. Changes in split renal function (SRF) and estimated renal plasmatic flow (ERPF) were evaluated for 51 patients who underwent baseline and 3-mo postoperative renal scintigraphy. RESULTS AND LIMITATIONS: A total of 103 patients were prospectively enrolled. The median number of kidney and tumor perfusion regions were 8 (interquartile range [IQR] 7-10) and 3 (IQR 2-3), respectively. A clampless, selective clamping, and global clamping strategy was applied in eight (7.8%), 79 (76.6%), and 16 (15.5%) cases, respectively, with no differences between planning and surgery in terms of the number or order of arteries clamped or the perfusion regions that underwent ischemia. Among the 51 patients who underwent renal scintigraphy, the mean SRF decreased by 11.3%, 7.7%, and 1.7% after global, selective, and superselective clamping, respectively (p = 0.004). Similar results were obtained for ERPF (18.9%, 9.9%, and 6.0%; p = 0.02). The main limitation is the need for a bioengineer to manually refine the 3DVMs. CONCLUSIONS: Use of mathematical algorithms for 3DVMs allows precise estimation of kidney perfusion regions to maximize the efficacy of selective clamping and minimize renal function impairment. PATIENT SUMMARY: Three-dimensional models that include regions of blood flow to the kidney can be used to guide clamping of blood vessels when part of the kidney is being surgically removed. More limited clamping can reduce damage to the remaining portion of the kidney and result in better recovery of kidney function after surgery.

Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes.

OBJECTIVES: To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D. METHODS: Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes <-3 and > 3 mL/min/1.73m2 /year, respectively), and albumin-creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource. RESULTS: In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor-3, cystatin C, and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19 [-0.27, -0.12], P = 7.0 × 10-7 ; -0.18 [-0.26, -0.11], P = 5.1 × 10-6 ; -0.12 [-0.20, -0.05], P = 1.6 × 10-3 ), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21 [-0.28, -0.14], P = 2.3 × 10-8 ) and cystatin C (-0.16 [-0.22, -0.09], P = 1.6 × 10-6 ). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10-6 ), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59 [1.23, 2.04], P = 2.6 × 10-4 ). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR. CONCLUSIONS: In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF-23 was associated with eGFR increases, whereas trefoil factor-3, cystatin C, and B2M were associated with baseline eGFR.

Custom-made 3D printed subperiosteal titanium implants for the prosthetic restoration of the atrophic posterior mandible of elderly patients: a case series.

PURPOSE: To present the application of custom-made 3D-printed subperiosteal implants for fixed prosthetic restoration of the atrophic posterior mandible of elderly patients. METHODS: Between January 2017 and June 2018, all partially edentulous patients aged over 65 years, with two or more missing teeth in the posterior atrophic mandible, and who did not want to undergo bone regenerative procedures, were included in this study. These patients were rehabilitated with custom-made subperiosteal implants, designed from cone beam computed tomography (CBCT) and fabricated in titanium by means of direct metal laser sintering (DMLS). The outcome measures were fit and stability of the implants at placement, duration of the intervention, implant survival, and early and late complications. All patients were followed for 1 year after surgery. RESULTS: Ten patients (four males, six females; mean age 69.6, SD ± 2.8, median 69, 95% CI 67.9-71.6) were included in the study. The fit of the implants was satisfactory, with a mean rating of 7 out of 10 (SD ± 1.6, median 7, 95% CI 6-8). Only two implants had insufficient fit, because of the presence of scattering in the CBCT; however, they were adapted to the sites during the interventions. The mean duration of the intervention was 44.3 min (SD ± 19.4, median 37, 95% CI 32.3-56.3). At the one-year follow-up, no implants were lost (survival rate 100%). One implant presented immediate postoperative complications with pain, discomfort and swelling, and two patients experienced late complications, having their provisional restorations fractured during the temporisation phase. All these complications were minor in nature, but the final complication rate amounted to 30% (three of ten patients). CONCLUSIONS: Although this study has limits (small patient sample and short follow-up), DMLS has proven to be an effective method for fabricating accurate subperiosteal implants, with high survival rates. This may represent an alternative treatment procedure in elderly patients with a severely atrophic posterior mandible, since it allows avoidance of regenerative bone therapies. Further studies are needed to confirm these outcomes.

Association of response to TNF inhibitors in rheumatoid arthritis with quantitative trait loci for CD40 and CD39.

OBJECTIVES: We sought to investigate whether genetic effects on response to TNF inhibitors (TNFi) in rheumatoid arthritis (RA) could be localised by considering known genetic susceptibility loci for relevant traits and to evaluate the usefulness of these genetic loci for stratifying drug response. METHODS: We studied the relation of TNFi response, quantified by change in swollen joint counts ( Δ SJC) and erythrocyte sedimentation rate ( Δ ESR) with locus-specific scores constructed from genome-wide assocation study summary statistics in 2938 genotyped individuals: 37 scores for RA; scores for 19 immune cell traits; scores for expression or methylation of 93 genes with previously reported associations between transcript level and drug response. Multivariate associations were evaluated in penalised regression models by cross-validation. RESULTS: We detected a statistically significant association between Δ SJC and the RA score at the CD40 locus (p=0.0004) and an inverse association between Δ SJC and the score for expression of CD39 on CD4 T cells (p=0.00005). A previously reported association between CD39 expression on regulatory T cells and response to methotrexate was in the opposite direction. In stratified analysis by concomitant methotrexate treatment, the inverse association was stronger in the combination therapy group and dissipated in the TNFi monotherapy group. Overall, ability to predict TNFi response from genotypic scores was limited, with models explaining less than 1% of phenotypic variance. CONCLUSIONS: The association with the CD39 trait is difficult to interpret because patients with RA are often prescribed TNFi after failing to respond to methotrexate. The CD39 and CD40 pathways could be relevant for targeting drug therapy.

Cytotoxicity evaluation of a new ozonized olive oil.

OBJECTIVE: The cytocompatibility of a new ozonized olive oil toward immortalized human gingival fibroblasts (HGFs) was evaluated and compared with two common antimicrobial agents based on chlorhexidine digluconate (CHX). MATERIALS AND METHODS: The cytocompatibility of the samples was tested on immortalized HGF-1 cells by 3-(4, 5-dimethyl thiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were incubated for 2 or 24 h with increasing dilution of ozonized olive oil or CHX agents. The percentage of viable cells was calculated relative to control cells set to 100%. RESULTS: The ozonized olive oil is cytocompatible, and the viability values of the cells treated for 2 or 24 h with increasing concentrations of ozonized olive oil were significantly higher (P < 0.01) compared with the values obtained using CHX. CONCLUSIONS: The present data demonstrate that due to its cytocompatibility, the new ozonized olive oil could be considered an alternative antibacterial agent.

Genome-wide association study of response to tumour necrosis factor inhibitor therapy in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterised by chronic synovial joint inflammation. Treatment has been revolutionised by tumour necrosis factor alpha inhibitors (TNFi) but each available drug shows a significant non-response rate. We conducted a genome-wide association study of 1752 UK RA TNFi-treated patients to identify predictors of change in the Disease Activity Score 28 (DAS28) and subcomponents over 3-6 months. The rs7195994 variant at the FTO gene locus was associated with infliximab response when looking at a change in the swollen joint count (SJC28) subcomponent (p = 9.74 × 10-9). Capture Hi-C data show chromatin interactions in GM12878 cells between rs2540767, in high linkage disequilibrium with rs7195994 (R2 = 0.9) and IRX3, a neighbouring gene of FTO. IRX3 encodes a transcription factor involved in adipocyte remodelling and is regarded as the obesity gene at the FTO locus. Importantly, the rs7195994 association remained significantly associated following adjustment for BMI. In addition, using capture Hi-C data we showed interactions between TNFi-response associated variants and 16 RA susceptibility variants.

Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes.

BACKGROUND AND AIMS: Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded. METHODS: Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2-77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5-year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction. RESULTS: Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95% Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95% CI 1.12, 1.60) and hsTnT (1.40, 95% CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745. CONCLUSIONS: The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score.

Evaluation of the antibacterial activity of a new ozonized olive oil against oral and periodontal pathogens.

BACKGROUND: In the present study, the antimicrobial properties of a new ozonized olive oil (O-zone gel) against oral and periodontal pathogens will be evaluated and compared with that of common CHX-based agents. MATERIAL AND METHODS: O-zone gel was compared with two agents based on chlorhexidine digluconate (CHX): Corsodyl Dental Gel and Plak Gel. A. actinomycetemcomitans, P. intermedia and S. mutans, were selected and the antibacterial capability of the compounds was tested by using direct contact agar diffusion test (DCT) and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) evaluations. Differences between specific means were analyzed by a one-way analysis of variance (ANOVA). Group means were compared using a one-way ANOVA and Tukey's test (P<0.05). RESULTS: O-zone gel reported inhibition zones which correspond to 33% and 43% of that achieved by the CHX agents. No inhibition of bacterial growth (MIC) on the Gram-positive strain by using O-zone gel was found and no antimicrobial effect (MBC) was observed by using O-zone gel on both Gram-negative and -positive strains. CONCLUSIONS: The new ozonated oil was a relatively moderate antiseptic. Gram-negative bacteria proved to be more sensitive to ozonized olive oil than Gram-positive ones. The ozonized olive oil demonstrated a lower antibacterial activity if compared to the CHX-based agents tested. Key words:Agar diffusion test, antibacterial activity, direct contact test, ozone, ozonized olive oil.

Clinical applications and effectiveness of guided implant surgery: a critical review based on randomized controlled trials.

BACKGROUND: Nowadays implant placement protocols are widespread among clinicians all over the world. However, available literature, only partially analyses what can be potential benefits for the clinicians and patients, often focusing just on specific aspects, such as accuracy. The purpose of this review is to compare computer guided implant placement with conventional treatment protocols. METHODS: A search strategy according to the P-I-C-O format was developed and executed using an electronic MEDLINE plus manual search from 2000 up to December 2016. This review included only randomized controlled trials (RCTs) focusing on subjects treated with digital workflow for oral implant placement compared to conventional procedures. Data were extracted from eligible papers and analysed. All kinds of outcomes were considered, even patient-related and economical outcomes. RESULTS: The search strategy revealed 16 articles; additional manual searches selected further 21 publications. Afterwards the evaluation of articles, only two studies could be selected for subsequent data extraction. The two identified RCTs analysed primary outcomes as prosthesis failure, implant failure, biological or prosthetic complications, and secondary outcomes as periimplant marginal bone loss. One RCT evaluated also the duration of treatment, post-surgical progress, additional treatment costs and patient satisfaction. The other RCT focused instead on evaluating eventual improvement of patient's quality of life. In both selected studies, were not observed by the authors statistically significant differences between clinical cases treated with digital protocols and those treated with conventional ones. In one RCT, however post-surgical progress evaluation showed more patients' self-reported pain and swelling in conventional group. CONCLUSIONS: Within the limitation of this review, based on only two RCTs, the only evidence was that implant survival rate and effectiveness are similar for conventional and digital implant placement procedures. This is also confirmed by many other studies with however minor scientific evidence levels. Reduction of post-operative pain, surgical time and overall costs are discussed. Authors believe that scientific research should focus more in identifying which clinical situations can get greatest benefits from implant guided surgery. This should be done with research protocols such as RCT that assess comprehensively the advantages and disadvantages of fully digital surgical protocols.

GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.

Male pattern baldness (MPB) or androgenetic alopecia is one of the most common conditions affecting men, reaching a prevalence of ~50% by the age of 50; however, the known genes explain little of the heritability. Here, we present the results of a genome-wide association study including more than 70,000 men, identifying 71 independently replicated loci, of which 30 are novel. These loci explain 38% of the risk, suggesting that MPB is less genetically complex than other complex traits. We show that many of these loci contain genes that are relevant to the pathology and highlight pathways and functions underlying baldness. Finally, despite only showing genome-wide genetic correlation with height, pathway-specific genetic correlations are significant for traits including lifespan and cancer. Our study not only greatly increases the number of MPB loci, illuminating the genetic architecture, but also provides a new approach to disentangling the shared biological pathways underlying complex diseases.

From Guided Surgery to Final Prosthesis with a Fully Digital Procedure: A Prospective Clinical Study on 15 Partially Edentulous Patients.

Scope. To demonstrate guided implant placement and the application of fixed, implant-supported prosthetic restorations with a fully digital workflow. Methods. Over a 2-year period, all patients with partial edentulism of the posterior maxilla, in need of fixed implant-supported prostheses, were considered for inclusion in this study. The protocol required intraoral scanning and cone beam computed tomography (CBCT), the superimposition of dental-gingival information on bone anatomy, surgical planning, 3D-printed teeth-supported surgical templates, and modelling and milling of polymethylmethacrylate (PMMA) temporaries for immediate loading. After 3 months, final optical impression was taken and milled zirconia frameworks and 3D-printed models were fabricated. The frameworks were veneered with ceramic and delivered to the patients. Results. Fifteen patients were selected for this study. The surgical templates were stable. Thirty implants were placed (BTK Safe®, BTK, Vicenza, Italy) and immediately loaded with PMMA temporaries. After 3 months, the temporaries were replaced by the final restorations in zirconia-ceramic, fabricated with a fully digital process. At 6 months, none of the patients reported any biological or functional problems with the implant-supported prostheses. Conclusions. The present procedure for fully digital planning of implants and short-span fixed implant-supported restorations has been shown to be reliable. Further studies are needed to validate these results.

Effect of self-assembling peptide P11 -4 on enamel erosion: AFM and SEM studies.

The aim of the present in vitro study was to evaluate the protective effect of self-assembling peptide P11 -4 (Curodont™ Protect/Credentis) on enamel erosion produced by a soft-drink, by using Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). Thirty human incisors were equally and randomly assigned to 6 groups. Group 1: intact enamel, group 2: soft drink, group 3: Curodont(™) Protect applied, group 4: Curodont(™) Protect applied + soft drink, group 5: soft drink + Curodont(™) Protect applied, group 6: soft drink + Curodont(™) Protect applied + soft drink. Specimens were observed through atomic force microscopy (AFM). The root mean-square roughness (Rrms) was obtained from the AFM images and the differences in the averaged values among the groups were analyzed by Shapiro-Wilk test in order to assess the normality of the distribution. Parametric ANOVA and post hoc Tuckey test were performed to assess the differences between the different groups. After demineralization process, enamel demonstrated a high degree of surface porosity. This morphological aspect was reflected in the increase of Rrms values. No significant differences (p > 0.05) were reported between intact enamel and enamel only treated with P11 -4 and between eroded enamel and enamel treated with P11 -4 and then demineralized. However significant differences (p < 0.05) were recorded when comparing softened enamel with softened enamel further remineralized with biomimetic self-assembling peptides and enamel treated with the protective paste between two acid attacks. The use of P11 -4 remineralizing may offer a degree of protection from enamel erosion. SCANNING 38:344-351, 2016. © 2015 Wiley Periodicals, Inc.

Protein biomarkers for the prediction of cardiovascular disease in type 2 diabetes.

AIMS/HYPOTHESIS: We selected the most informative protein biomarkers for the prediction of incident cardiovascular disease (CVD) in people with type 2 diabetes. METHODS: In this nested case-control study we measured 42 candidate CVD biomarkers in 1,123 incident CVD cases and 1,187 controls with type 2 diabetes selected from five European centres. Combinations of biomarkers were selected using cross-validated logistic regression models. Model prediction was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: Sixteen biomarkers showed univariate associations with incident CVD. The most predictive subset selected by forward selection methods contained six biomarkers: N-terminal pro-B-type natriuretic peptide (OR 1.69 per 1 SD, 95% CI 1.47, 1.95), high-sensitivity troponin T (OR 1.29, 95% CI 1.11, 1.51), IL-6 (OR 1.13, 95% CI 1.02, 1.25), IL-15 (OR 1.15, 95% CI 1.01, 1.31), apolipoprotein C-III (OR 0.79, 95% CI 0.70, 0.88) and soluble receptor for AGE (OR 0.84, 95% CI 0.76, 0.94). The prediction of CVD beyond clinical covariates improved from an AUROC of 0.66 to 0.72 (AUROC for Framingham Risk Score covariates 0.59). In addition to the biomarkers, the most important clinical covariates for improving prediction beyond the Framingham covariates were estimated GFR, insulin therapy and HbA1c. CONCLUSIONS/INTERPRETATION: We identified six protein biomarkers that in combination with clinical covariates improved the prediction of our model beyond the Framingham Score covariates. Biomarkers can contribute to improved prediction of CVD in diabetes but clinical data including measures of renal function and diabetes-specific factors not included in the Framingham Risk Score are also needed.

Ultrastructural analysis of the root canal walls after preparation with two rotary nickel-titanium endodontic instruments.

BACKGROUND: Root canal preparation may produce a large quantity of smear layer that covers canal walls. AIMS: The aim of this study was to evaluate by Scanning Electron Microscope (SEM) the root canal dentine after instrumentation with nickel-titanium rotary files, in order to evaluate the presence/absence of smear layer and the presence/absence of open tubules on the root canal walls at the coronal, middle, and apical third of each sample. MATERIALS AND METHODS: A total of 20 single-rooted freshly extracted teeth were selected and divided into two groups. For each group, root canals were shaped with Mtwo and Revo-S instruments under irrigation with Sodium hypochlorite and 17% ethylenediaminetetraacetic acid. Specimens were fractured longitudinally and SEM analyzed at standard magnification of ×1000 and ×5000. The presence/absence of smear layer and the presence/absence of open tubules at the coronal, middle, and apical third of each canal were evaluated using a three-step scale for scores. STATISTICAL ANALYSIS USED: Numeric data were analyzed using the Kruskall-Wallis and Mann-Whitney U-Statistical tests and significance was pre-determined at P < 0.05. RESULTS AND CONCLUSIONS: This study did not reveal differences among the two groups. Mtwo and Revo-S showed no significant difference between them and both presented very low smear layer scores and open tubules scores, with no significant difference among coronal, middle, and apical third. Mtwo and Revo-S rotary instruments seem to be effective in removing smear layer from canal walls.

Ecomorphological disparity in an adaptive radiation: opercular bone shape and stable isotopes in Antarctic icefishes.

To assess how ecological and morphological disparity is interrelated in the adaptive radiation of Antarctic notothenioid fish we used patterns of opercle bone evolution as a model to quantify shape disparity, phylogenetic patterns of shape evolution, and ecological correlates in the form of stable isotope values. Using a sample of 25 species including representatives from four major notothenioid clades, we show that opercle shape disparity is higher in the modern fauna than would be expected under the neutral evolution Brownian motion model. Phylogenetic comparative methods indicate that opercle shape data best fit a model of directional selection (Ornstein-Uhlenbeck) and are least supported by the "early burst" model of adaptive radiation. The main evolutionary axis of opercle shape change reflects movement from a broad and more symmetrically tapered opercle to one that narrows along the distal margin, but with only slight shape change on the proximal margin. We find a trend in opercle shape change along the benthic-pelagic axis, underlining the importance of this axis for diversification in the notothenioid radiation. A major impetus for the study of adaptive radiations is to uncover generalized patterns among different groups, and the evolutionary patterns in opercle shape among notothenioids are similar to those found among other adaptive radiations (three-spined sticklebacks) promoting the utility of this approach for assessing ecomorphological interactions on a broad scale.