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.

Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs.

Background: Fasting indices of glucose-insulin-metabolism are an easy and affordable tool to assess insulin resistance. We aimed to establish reference ranges for fasting insulin indices that reflect age-dependent variation over the entire life span and subsequently test their clinical application regarding the prediction of glycemic deterioration in children. Methods: We calculated age- and puberty-dependent reference values for HOMA-IR, HOMA2-IR, HOMA-ß, McAuley index, fasting insulin, and fasting glucose from 6994 observations of 5512 non-obese healthy subjects aged 5-80 years. Applying those references, we determined the prevalence of insulin resistance among 2538 subjects with obesity. Furthermore, we investigated the intraindividual stability and the predictive values for future dysglycemia of these fasting indices in 516 children and adolescents with obesity up to 19 years of follow-up. We validated the results in three independent cohorts. Findings: There was a strong age-dependent variation of all indices throughout the life span, including prolonged recovery of pubertal insulin resistance and a subsequent continuous increase throughout adulthood. Already from age 5 years onwards, >40% of children with obesity presented with elevated parameters of insulin resistance. Applying newly developed reference ranges, insulin resistance among children with obesity doubled the risk for future glycemic deterioration (HOMA-IR HR 1.88 (95% CI 1.1-3.21)), fasting insulin HR 1.89 (95% CI 1.11-3.23). In contrast, fasting glucose alone was not predictive for emerging dysglycemia in children with obesity (HR 1.03 (95% CI 0.62-1.71)). The new insulin-based thresholds were superior to fasting glucose and HbA1c in detecting children eventually manifesting with dysglycemia in prospective analyses. Interpretation: The variation of fasting glucose-insulin-metabolism across the life span necessitates age-specific reference ranges. The improved prediction of future glycemic deterioration by indices based on fasting insulin beyond simple glucose measures alone could help to stratify risk characteristics of children with obesity in order to guide patient-tailored prevention and intervention approaches. Funding: German Research Foundation (DFG)-through SFB 1052, project number 209933838, subproject C5; Federal Ministry of Education and Research, Germany; European Union-European Regional Development Fund; Free State of Saxony. The German Diabetes Association, the CarbHealth consortium (01EA1908B). EU-IMI2-Consortium SOPHIA (grant agreement No 875534), German Center for Diabetes Research (DZD), grant number 82DZD14E03.

Genome-wide aggregated trans-effects on risk of type 1 diabetes: A test of the "omnigenic" sparse effector hypothesis of complex trait genetics.

The "omnigenic" hypothesis postulates that the polygenic effects of common SNPs on a typical complex trait are mediated through trans-effects on expression of a relatively sparse set of effector ("core") genes. We tested this hypothesis in a study of 4,964 cases of type 1 diabetes (T1D) and 7,497 controls by using summary statistics to calculate aggregated (excluding the HLA region) trans-scores for gene expression in blood. From associations of T1D with aggregated trans-scores, nine putative core genes were identified, of which three-STAT1, CTLA4 and FOXP3-are genes in which variants cause monogenic forms of autoimmune diabetes. Seven of these genes affect the activity of regulatory T cells, and two are involved in immune responses to microbial lipids. Four T1D-associated genomic regions could be identified as master regulators via trans-effects on gene expression. These results support the sparse effector hypothesis and reshape our understanding of the genetic architecture of T1D.

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.

SARS-CoV-2-related bronchiolitis: a multicentre international study.

BACKGROUND: Bronchiolitis is the main acute lower respiratory tract infection in infants. Data regarding SARS-CoV-2-related bronchiolitis are limited. OBJECTIVE: To describe the main clinical characteristics of infants with SARS-CoV-2-related bronchiolitis in comparison with infants with bronchiolitis associated with other viruses. SETTING, PATIENTS, INTERVENTIONS: A multicentre retrospective study was conducted in 22 paediatric emergency departments (PED) in Europe and Israel. Infants diagnosed with bronchiolitis, who had a test for SARS-CoV-2 and were kept in clinical observation in the PED or admitted to hospital from 1 May 2021 to 28 February 2022 were considered eligible for participation. Demographic and clinical data, diagnostic tests, treatments and outcomes were collected. MAIN OUTCOME MEASURES: The main outcome was the need for respiratory support in infants testing positive for SARS-CoV-2 compared with infants testing negative. RESULTS: 2004 infants with bronchiolitis were enrolled. Of these, 95 (4.7%) tested positive for SARS-CoV-2. Median age, gender, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative infants. Human metapneumovirus and respiratory syncytial virus were the viruses most frequently detected in the group of infants negative for SARS-CoV-2.Infants testing positive for SARS-CoV-2 received oxygen supplementation less frequently compared with SARS-CoV-2-negative patients, 37 (39%) vs 1076 (56.4%), p=0.001, OR 0.49 (95% CI 0.32 to 0.75). They received less ventilatory support: 12 (12.6%) high flow nasal cannulae vs 468 (24.5%), p=0.01; 1 (1.0%) continuous positive airway pressure vs 125 (6.6%), p=0.03, OR 0.48 (95% CI 0.27 to 0.85). CONCLUSIONS: SARS-CoV-2 rarely causes bronchiolitis in infants. SARS-CoV-2-related bronchiolitis mostly has a mild clinical course.

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.

Single Point Insulin Sensitivity Estimator (SPISE) As a Prognostic Marker for Emerging Dysglycemia in Children with Overweight or Obesity.

The single point insulin sensitivity estimator (SPISE) is a recently developed fasting index for insulin sensitivity based on triglycerides, high density lipoprotein cholesterol, and body mass index. SPISE has been validated in juveniles and adults; still, its role during childhood remains unclear. To evaluate the age- and sex-specific distribution of SPISE, its correlation with established fasting indexes and its application as a prognostic marker for future dysglycemia during childhood and adolescence were assessed. We performed linear modeling and correlation analyses on a cross-sectional cohort of 2107 children and adolescents (age 5 to 18.4 years) with overweight or obesity. Furthermore, survival analyses were conducted upon a longitudinal cohort of 591 children with overweight/obesity (1712 observations) with a maximum follow-up time of nearly 20 years, targeting prediabetes/dysglycemia as the end point. The SPISE index decreased significantly with age (−0.34 units per year, p < 0.001) among children and adolescents with overweight and obesity. Sex did not have an influence on SPISE. There was a modest correlation between SPISE and established fasting markers of insulin resistance (R = −0.49 for HOMA-IR, R = −0.55 for QUICKI-IR). SPISE is a better prognostic marker for future dysglycemia (hazard ratio (HR) 3.47, 95% confidence interval (CI) 1.60−7.51, p < 0.01) than HOMA-IR and QUICKI-IR (HR 2.44, 95% CI 1.24−4.81, p < 0.05). The SPISE index is a surrogate marker for insulin resistance predicting emerging dysglycemia in children with overweight or obesity, and could, therefore, be applied to pediatric cohorts that lack direct insulin assessment.

Prevalence of SARS-CoV-2 positivity in infants with bronchiolitis: a multicentre international study.

BACKGROUND: Bronchiolitis is the leading acute respiratory tract infection in infants during the winter season. Since the beginning of the SARS-CoV-2 pandemic, a reduction in the number of bronchiolitis diagnoses has been registered. OBJECTIVE: The present study aimed to describe the incidence and clinical features of bronchiolitis during the 2020-2021 winter season in a large cohort of children in Europe and Israel, and to clarify the role of SARS-CoV-2. SETTING, PATIENTS, INTERVENTIONS: We conducted a multicentre observational cross-sectional study in 23 paediatric emergency departments in Europe and Israel. Clinical and demographic data about all the cases of infants diagnosed with bronchiolitis from 1 October 2020 to 30 April 2021 were collected. For each enrolled patient, diagnostic tests, treatments and outcomes were reported. MAIN OUTCOME MEASURES: The main outcome was the prevalence of SARS-CoV-2-positive bronchiolitis. RESULTS: Three hundred and fourteen infants received a diagnosis of bronchiolitis during the study period. Among 535 infants who tested positive for SARS-CoV-2, 16 (3%) had bronchiolitis. Median age, male sex predominance, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative groups. Rhinovirus was the most common involved pathogen, while respiratory syncytial virus (RSV) was detected in one case. SARS-CoV-2 bronchiolitis had a mild clinical course, with one patient receiving oxygen supplementation and none requiring paediatric or neonatal intensive care unit admission. CONCLUSIONS: During the SARS-CoV-2 pandemic, a marked decrease in the number of bronchiolitis diagnoses and the disappearance of the RSV winter epidemic were observed. SARS-CoV-2-related bronchiolitis was rare and mostly displayed a mild clinical course.

Maternal Dietary Glycemic Index and Glycemic Load in Pregnancy and Offspring Cord Blood DNA Methylation.

OBJECTIVE: Suboptimal nutrition in pregnancy is associated with worse offspring cardiometabolic health. DNA methylation may be an underlying mechanism. We meta-analyzed epigenome-wide association studies (EWAS) of maternal dietary glycemic index and load with cord blood DNA methylation. RESEARCH DESIGN AND METHODS: We calculated maternal glycemic index and load from food frequency questionnaires and ran EWAS on cord blood DNA methylation in 2,003 mother-offspring pairs from three cohorts. Analyses were additionally stratified by maternal BMI categories. We looked-up the findings in EWAS of maternal glycemic traits and BMI as well as in EWAS of birth weight and child BMI. We examined associations with gene expression in child blood in the online Human Early Life Exposome eQTM catalog and in 223 adipose tissue samples. RESULTS: Maternal glycemic index and load were associated with cord blood DNA methylation at 41 cytosine-phosphate-guanine sites (CpGs, P < 1.17 × 10-7), mostly in mothers with overweight/obesity. We did not observe overlap with CpGs associated with maternal glycemic traits, BMI, or child birth weight or BMI. Only DNA methylation at cg24458009 and cg23347399 was associated with expression of PCED1B and PCDHG, respectively, in child blood, and DNA methylation at cg27193519 was associated with expression of TFAP4, ZNF500, PPL, and ANKS3 in child subcutaneous adipose tissue. CONCLUSIONS: We observed multiple associations of maternal glycemic index and load during pregnancy with cord blood DNA methylation, mostly in mothers with overweight/obesity; some of these CpGs were associated with gene expression. Additional studies are required to further explore functionality, uncover causality, and study pathways to offspring health.

Severe lactic acidosis and persistent diastolic hypotension following standard dose of intermittent nebulized salbutamol in a child: a case report.

BACKGROUND: Salbutamol is a selective ß2-receptor agonist widely used to treat asthma in both emergency and outpatient settings. However, it has been associated with a broad spectrum of side effects. Lactic acidosis and diastolic hypotension are rarely reported together following intermittent salbutamol nebulization in children, even less so at standard therapeutic doses. CASE PRESENTATION: We present the case of a 12-year-old Italian boy, 34 kg body weight, who experienced a serious drug reaction during a moderate asthma exacerbation with associated dehydration (blood urea nitrogen/creatinine 0.25), following intermittent inhaled (0.2 mg at 3-hour intervals-overall 1.4 mg in 24 hours before arrival) and nebulized treatment (3.25 mg at 20-minute intervals in 60 minutes, overall 11.25 mg in our emergency department). The patient developed hyperglycemia (peak concentration 222 mg/dL), hypokalemia (lowest concentration 2.6 mEq/L), electrocardiogram alterations (corrected QT interval 467 ms), long-lasting arterial hypotension despite fluid boluses (lowest value 87/33 mmHg), and elevated blood lactate levels (peak concentration 8.1 mmol/L), following the third nebulized dose. Infections, liver dysfunction, and toxicity following other medications were ruled out. The aforementioned alterations improved within 24 hours after discontinuation of salbutamol. CONCLUSIONS: We reinforce the message that even the use of intermittent nebulized salbutamol for acute moderate asthma can lead to severe transient complications in children. Then, healthcare providers should pay attention not only in emergency settings, to achieve prompt recognition and proper management of this adverse reaction. Careful reassessment could prevent similar reactions.

Restorative Materials Exposed to Acid Challenge: Influence of Temperature on In Vitro Weight Loss.

Consumption of acidic beverages and foods could provoke erosive damage, both for teeth and for restorative materials. Temperatures of consumption could influence the erosive effects of these products. The aim of this in vitro study is to assess the influence of an acidic challenge on the weight loss of different restorative materials. Resin composites and glass-ionomer cements (GIC) were tested. The medium of storage was Coca-Cola (Coca-Cola, Coca-Cola Company, Milano, Italy) at two different temperatures, 4 and 37 °C, respectively for Group A and Group B. For each group, nine specimens were prepared for each material tested. After 7 days, weight was assessed for each sample, and the percentage weight loss was calculated. For all the resin composites (Groups 1−13), no significant weight losses were noticed. (<1%). Conversely, GICs (Groups 14 and 15) showed significant weight loss during the acidic challenge, which was reduced in the case of these materials that included a protective layer applied above. Significant differences were registered with intra-group analysis; weight loss for specimens immersed in Coca Cola at 37 °C was significantly higher for almost all materials tested when compared to specimens exposed to a cooler medium. In conclusion, all the resin composites showed reliable behaviour when exposed to acidic erosion, whereas glass-ionomer cements generally tended to solubilize.

Effect of serum sample storage temperature on metabolomic and proteomic biomarkers.

Prospective biomarker studies can be used to identify biomarkers predictive of disease onset. However, if serum biomarkers are measured years after their collection, the storage conditions might affect analyte concentrations. Few data exists concerning which metabolites and proteins are affected by storage at - 20 °C vs - 80 °C. Our objectives were to document analytes affected by storage of serum samples at - 20 °C vs - 80 °C, and to identify those indicative of the storage temperature. We utilized liquid chromatography tandem mass spectrometry and Luminex to quantify 300 analytes from serum samples of 16 Finnish individuals with type 1 diabetes, with split-aliquot samples stored at - 80 °C and - 20 °C for a median of 4.2 years. Results were validated in 315 Finnish and 916 Scottish individuals with type 1 diabetes, stored at - 20 °C and at - 80 °C, respectively. After quality control, we analysed 193 metabolites and proteins of which 120 were apparently unaffected and 15 clearly susceptible to storage at - 20 °C vs - 80 °C. Further, we identified serum glutamate/glutamine ratio greater than 0.20 as a biomarker of storage at - 20 °C vs - 80 °C. The results provide a catalogue of analytes unaffected and affected by storage at - 20 °C vs - 80 °C and biomarkers indicative of sub-optimal storage.

Influence of Enamel Exposure to Acidic Drink on Shear Bond Strength of Different Fissure Sealants.

In the present study, we evaluated the influence of bovine enamel exposure to acidic drinks (Coca-Cola, Coca-Cola Company, Milano, Italy, pH = 2.37) on shear bond strength of three sealants (Fissurit; Grandio Seal and Admira Fusion-Voco Gmbh, Cuxhaven, Germany). For each sealant, two adhesive techniques were tested to investigate the impact of the adhesive application on shear bond strength of sealants after immersion in acidic drink and in the control: Group 1-Control: enamel surface was not in contact with acid drinks, acid etching application and self-adhesive technique for fissure sealant; Group 2-enamel surface was not in contact with acid drinks, acid etching, and adhesive applications, an etch-and-rinse technique for fissure sealant; Group 3-enamel surface was immersed in acid drink, acid etching application and self-adhesive technique for fissure sealant; Group 4-enamel surface was immersed in acid drink, acid etching, and adhesive applications, an etch-and-rinse technique for fissure sealant. For each specimen, the sealant composite resin was applied to the enamel surface and tested with a universal testing machine. Shear bond strength was measured in MPa and with an optical microscope to determine failure modes, quantified with adhesive remnant index (ARI). Enamel acidification variably influenced bond strength values of the different sealants. When no enamel pretreatment was applied, no significant differences were found among the sealants (p > 0.05). However, the mere application of acid etching without adhesive procedures resulted in lower bond strength (p < 0.001). The acid pretreatment affected significantly the bond strength of all sealants tested (p < 0.001), but no significant differences were recorded between the subgroups.

Trueness of Intraoral Scanners in Implant-Supported Rehabilitations: An In Vitro Analysis on the Effect of Operators' Experience and Implant Number.

(1) Background: Intraoral scanners (IOS) are widely used in prosthodontics. However, a good trueness is mandatory to achieve optimal clinical results. The aim of the present in vitro study was to compare two IOS considering the operator's experience and different implant clinical scenarios. (2) Methods: Two IOS (IT-Itero, Align Technology; and OP-Opera MC, Opera System, Monaco) were compared simulating three different clinical scenarios: single implant, two implants, and full-arch rehabilitation. Ten scans were taken for each configuration by two different operators (one expert, one inexperienced); influence of operator experience and the type of scanner used was investigated. (3) Results: Trueness of the scans differed between the experienced and non-experienced operator and this difference was statistically significant in all the three scenarios (p = 0.000-0.001, 0.037). A significant difference was present between the scanners (p = 0.000), in the two-implant and full-arch scenarios (p = 0.00). (4) Conclusions: Experience of the operator significantly affect trueness of IT and OP scanners. A statistically significant difference was present among IOS in the two-implant and full-arch scenarios.

Ozone Gel in Chronic Periodontal Disease: A Randomized Clinical Trial on the Anti-Inflammatory Effects of Ozone Application.

The search for new topical treatments able to display not only antimicrobial properties but also a multiplicity of other beneficial effects while expressing safe cytocompatibility toward host tissues is being progressively developed. Antiseptics represent an aid to the gold standard nonsurgical treatment Scaling-and-Root-Planing (SRP) for periodontal disease. This split-mouth study aims to assess the efficacy of the ozonized gel GeliO3 (Bioemmei Srl, Vicenza, Italy) plus SRP (experimental treatment), with respect to SRP + chlorhexidine gel. Ten participants were treated with SRP + chlorhexidine gel (control sites) and with SRP + ozone gel (trial sites). After 1 (T1) and 3 months (T2) from baseline (T0), patients were revisited. At each time-point, the following indexes were assessed: probing pocket depth (PPD), clinical attachment level (CAL), gingival index (GI), plaque index (PI), and bleeding on probing (BoP). It has been assessed that the use of the ozonized gel in addition to SRP did not show significant differences if compared to conventional SRP + chlorhexidine. Chlorhexidine was found to be more effective than ozone in reducing CAL and GI at T2. Ozone deserves consideration for its wide applicability in several clinical fields. In this connection, we also glance at the latest research on ozone therapy.

Development and validation of a cardiovascular risk prediction model in type 1 diabetes.

AIMS/HYPOTHESIS: We aimed to report current rates of CVD in type 1 diabetes and to develop a CVD risk prediction tool for type 1 diabetes. METHODS: A cohort of 27,527 people with type 1 diabetes without prior CVD was derived from the national register in Scotland. Incident CVD events during 199,552 person-years of follow-up were ascertained using hospital admissions and death registers. A Poisson regression model of CVD was developed and then validated in the Swedish National Diabetes Register (n = 33,183). We compared the percentage with a high 10 year CVD risk (i.e., ≥10%) using the model with the percentage eligible for statins using current guidelines by age. RESULTS: The age-standardised rate of CVD per 100,000 person-years was 4070 and 3429 in men and women, respectively, with type 1 diabetes in Scotland, and 4014 and 3956 in men and women in Sweden. The final model was well calibrated (Hosmer-Lemeshow test p > 0.05) and included a further 22 terms over a base model of age, sex and diabetes duration (C statistic 0.82; 95% CI 0.81, 0.83). The model increased the base model C statistic from 0.66 to 0.80, from 0.60 to 0.75 and from 0.62 to 0.68 in those aged <40, 40-59 and ≥ 60 years, respectively (all p values <0.005). The model required minimal calibration in Sweden and had a C statistic of 0.85. Under current guidelines, >90% of those aged 20-39 years and 100% of those ≥40 years with type 1 diabetes were eligible for statins, but it was not until age 65 upwards that 100% had a modelled risk of CVD ≥10% in 10 years. CONCLUSIONS/INTERPRETATION: A prediction tool such as that developed here can provide individualised risk predictions. This 10 year CVD risk prediction tool could facilitate patient discussions regarding appropriate statin prescribing. Apart from 10 year risk, such discussions may also consider longer-term CVD risk, the potential for greater benefits from early vs later statin intervention, the potential impact on quality of life of an early CVD event and evidence on safety, all of which could influence treatment decisions, particularly in younger people with type 1 diabetes.

Cytotoxicity of Different Composite Resins on Human Gingival Fibroblast Cell Lines.

The aim of the present study was to evaluate and compare the cytotoxic effects of eight composite resins on immortalized human gingival fibroblasts. Composite resins were eluted in cell culture medium for 48 or 72 h at 37 °C. Immortalized human gingival fibroblast-1 (HGF-1) cell lines were seeded in 96-well (1 × 104) plates and incubated for 24 h at 37 °C with the obtained extraction medium. The percentage of viable cells in each well (MTT test) was calculated relative to control cells, which were set to 100%. Data observed were not normally distributed, and nonparametric statistical methods were used for statistical analysis. The Wilcoxon test was used for intragroup comparison, and the Kruskal-Wallis test was used for intergroup multiple comparisons. Significance value was set as p < 0.05. All materials tested showed cytotoxic effects on gingival fibroblasts, recordable as noncytotoxic, mildly cytotoxic or severely cytotoxic, depending on the percentage of cell viability. The Wilcoxon test for intragroup comparison showed that the percentage of viable cells decreased significantly for extracts, for all composite resins tested. The composite resins contained monomers that displayed cytotoxic properties. BisGMA, TEGDMA and UDMA had inhibitory effects and induced apoptotic proteins in pulp fibroblast. Composite resins that contained lower percentages of unbound free monomers-and that released less ions-possessed superior biocompatibility in vitro.