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We lack knowledge about prognostic factors of resective epilepsy surgery (RES) in older adults (≥60 years), especially the role of comorbidities, which are a major consideration in managing the care of people with epilepsy (PWE). We analyzed a single-center cohort of 94 older adults (median age = 63.5 years, 52% females) who underwent RES between 2000 and 2021 with at least 6 months of postsurgical follow-up. Three fourths of the study cohort had lesional magnetic resonance imaging and underwent temporal lobectomy. Fifty-four (57%) PWE remained seizure-free during a median follow-up of 3.5 years. Cox proportional hazard multivariable analysis showed that aura (hazard ratio [HR] = .52, 95% confidence interval [CI] = .27-1.00), single ictal electroencephalographic pattern (HR = .33, 95% CI = .17-.660), and Elixhauser Comorbidity Index (HR = 1.05, 95% CI = 1.00-1.10) were independently associated with seizure recurrence at last follow-up. A sensitivity analysis using the Charlson Combined Score (HR = 1.38, 95% CI = 1.03-1.84, p = .027) confirmed the association of comorbidities with worse seizure outcome. Our findings provide a framework for a better informed discussion about RES prognosis in older adults. More extensive, multicenter cohort studies are needed to validate our findings and reduce hesitancy in pursuing RES in suitable older adults., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

This case report aimed to describe a rare benign mandibular tumour and assess the outcomes of the most recent reviews, between January 2017 and August 2023. Presenting a detailed clinical case, this study advances our understanding of the diagnostic and therapeutic aspects, ultimately improving the management of similar cases in clinical practice. Orthopantomogram (OPG) revealed a well-defined unilocular radiolucency extending from the midline of the ramus and teeth 47 and 48 were submerged at the base of the mandible. In the presented case, a PLANMECA ROMEXIS PROMAX® three-dimensional (3D) maximum (MAX) cone-beam computed tomography (CBCT) device was used for the 3D examination. An intraoral approach was preferred and the tumour was removed in toto by creating a bone window using a W&H® Dentalwerk Bürmoos GmbH Piezomed piezoelectric device, and the bone plates were fixed with 4 MEDARTIS® microplates, with a primary flap closure. A PANORAMIC 1000, 3DHISTECH Ltd® device was employed for the histological investigation. Odontogenic tumours are rare and typically asymptomatic, often discovered incidentally during routine radiographic examinations. Most of these benign lesions heal well after complete excision and require long-term follow-up. Once diagnosed, ameloblastic fibroma (AF) should be treated immediately to avoid malignant transformation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Statement of Problem: Minimally invasive treatments have gained popularity in recent years. However, research comparing the fracture resistance of lithium disilicate partial coverage veneer restorations with that of ceramic crowns is lacking., Purpose: The purpose of this in vitro study was to evaluate and compare the fracture resistance of lithium disilicate restorations fabricated for preparations of various designs. The designs included veneer preparations with finish lines in the upper, middle, and lower third of the facial surface and ceramic crown preparations with margins in the lower third of the facial surface. All restorations were designed and fabricated using a chairside digital workflow., Material and Methods: Four maxillary right central incisor typodont teeth were prepared for partial coverage veneer preparation with the margin in the upper middle third of the facial surface (PU1/3); partial coverage veneer preparation with margin in lower middle third of the facial surface (PL1/3); complete coverage veneer preparation (CV) with margin in the cervical region; and ceramic crown (CC) preparation. Each preparation was scanned, and 15 casts were 3D printed from each scan. A total of 60 lithium disilicate restorations were fabricated (n=15 per group) using a chairside computer-aided design and computer-aided manufacturing (CAD-CAM) system (Primescan and MCXL). The different restorations were cemented to the 3D printed testing dies with a photopolymerizable resin cement. The specimens were artificially aged with 10 000 thermal cycles between 5 and 55 °C with a dwell time of 30 seconds and were loaded to failure using a universal testing machine. The maximum load to fracture was analyzed using a 1-way ANOVA and post hoc Tukey honestly significant difference (HSD) test (α=.05). Additionally, the fracture patterns of the specimens were evaluated with a stereomicroscope for descriptive purposes., Results: The mean fracture resistance of the chairside CAD-CAM lithium disilicate veneers and ceramic crowns was statistically different depending on the design of the restoration (P<.05). Group CC demonstrated the highest fracture resistance values (1440.66 N), followed by CV (929.8 N) and PU1/3 (756.13 N). The lowest value was for PL1/3 (532.4 N)., Conclusions: The fracture resistance measured for the maxillary central incisor partial coverage veneers with margins in the middle third of the facial surface appear capable of resisting average occlusal forces. However, these veneers demonstrated lower fracture resistance values when compared with complete coverage veneers. Further, lithium disilicate crowns demonstrated higher fracture resistance than veneers, irrespective of their design., (Published by Elsevier Inc.)

The development of copper(II) thiosemicarbazone complexes as potential anticancer agents, possessing dual functionality as inhibitors of R2 ribonucleotide reductase (RNR) and tubulin polymerization by binding at the colchicine site, presents a promising avenue for enhancing therapeutic effectiveness. Herein, we describe the syntheses and physicochemical characterization of four isomeric proligands H 2 L 3 - H 2 L 6 , with the methylmorpholine substituent at pertinent positions of the pyridine ring, along with their corresponding Cu(II) complexes 3 - 6 . Evidently, the position of the morpholine moiety and the copper(II) complex formation have marked effects on the in vitro antiproliferative activity in human uterine sarcoma MES-SA cells and the multidrug-resistant derivative MES-SA/Dx5 cells. Activity correlated strongly with quenching of the tyrosyl radical (Y • ) of mouse R2 RNR protein, inhibition of RNR activity in the cancer cells, and inhibition of tubulin polymerization. Insights into the mechanism of antiproliferative activity, supported by experimental results and molecular modeling calculations, are presented.

Objective: There are 500 million patients living with diabetes mellitus worldwide and 50% of them remain undiagnosed. Routine periodontal probing provides gingival crevicular blood in patients with gingivitis. Gingival blood may be useful for diabetes screening without the need for any expensive, painful or time-consuming method by using convenient glucometers. Therefore, the objective of this systematic review and meta-analysis is to answer the question to "is there a difference in glucose or HbA1c levels (O) in patients with positive gingival bleeding (P) measured on gingival crevicular blood (GCB) (I) compared to finger prick capillary blood (CB) (C)., Materials and Methods: The authors performed an electronic search of six databases using identical MeSH phrases. Only human clinical studies without limitations on the year of publication were considered. Data extraction was done by using standardized data collection sheets. Risk of bias assessment were conducted using QUADAS-2 and QUADAS-C. Meta-analyses were carried out with the random effects model to aggregate the correlation coefficients and the difference between the means between gingival and capillary blood reading, using 95% confidence intervals., Results: The database and manual search yielded 268 articles, from which the selection procedure provided 36 articles for full-text screening, and the final pool of eligible articles composed of 23 studies with 1680 patients. Meta-analysis results on glycemic levels showed differences between the GCB and CB procedures in patients with and without diabetes with values of -6.80 [-17.35; 3.76] and - 4.36 [-9.89; 1.18], respectively. Statistically significant correlations were found (p = 0.001) between GCB and CB measurements in patients with (0.97 [0.927; 0.987]) and without diabetes (0.927 [0.873; 0.958])., Conclusion: Gingival blood could prove to be useful to identify patients with undiagnosed diabetes when the necessary amount of uncontaminated blood is present. However, this technique is limited by the possibility of contamination, prandial status and inaccuracies, so it is unsuited to address the patient's glycemic control accurately., (© 2024. The Author(s).)

Background: Coarctation of the aorta (CoA) is a congenital disease with an incidence of 4 out of 10,000 live births, therefore proper education of its treatment is essential. Understanding the disease and the wide array of treatment options is often difficult. Additive manufacturing technology can be used to produce 3D printed hands-on surgical training tools (HOSTT), which can be used for the education and practical training of CoA. This study aimed to investigate the effectiveness of a 3D printable HOSTT for the simulation of coarctation surgery, and it' possible role in practical education., Methods: Participants were medical students of Semmelweis University between the second and sixth academic year. A virtual 3D model of an aorta with CoA was generated from a computed tomography angiography scan. Each participant received a 3D-printed aorta phantom and performed either one of four surgical treatment modalities. The simulated surgeries included end-to-end anastomosis, end-to-side anastomosis, prosthetic patch, and subclavian flap aortoplasty. Participants provided feedback, evaluating their understanding of the disease and its treatment by the four surgical reconstruction modalities on a seven-point Likert scale before and after the sessions., Results: 21 medical students participated in this study. Participants' average rating of their understanding of CoA disease and it treatment options before practical training was 4.62 ± 1.07. After training, their average rating increased to 6.19 ± 1.08, showing statistically significant difference., Conclusions: Within this study's limitations, the applied HOSTT, manufactured using 3D printing, was effective for the practical training of CoA's surgical treatment methods for medical students., (© 2024. The Author(s).)

Objective: The aim of this research was to collate and analyse the data on the oral health knowledge and the related habits of a Hungarian cohort of monozygotic (MZ) and dizygotic (DZ) twins using the newly developed World Health Organisation Oral Health Questionnaire for Adults (Annex 7)., Method: A total of 15 sets of MZ twins and 14 sets of DZ twins (58 individuals) aged between 18 and 71 years were enrolled in the study. Each participant had to fill out a web-based questionnaire which comprised 23 questions (Google Forms). The data were collated and the oral health/hygiene habits of MZ and DZ twins were compared., Results: No significant differences were detected between MZ and DZ twins with regards to their daily tooth-cleaning habits or the tooth-cleaning products used by the 2 groups. For instance, when asked how often they clean their teeth, 80% of MZ twins and 71% of DZ twins responded similarly. Further, both groups provided similar responses when questioned about the use of fluoride toothpaste, frequency of dental visits, and dental counselling received as well as a number of other parameters such as snacking of sweets and fear of visiting dentists., Conclusions: Our pilot analysis of the questionnaire responses from MZ and DZ twins in Hungary did not indicate any significant differences in their oral care habits in general. Further studies with a large cohort are required to confirm or refute our findings., Competing Interests: Conflict of interest None disclosed., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the clinical performance of a two-piece zirconia implant system, with a focus on biologic complications., Materials and Methods: A total of 39 patients received 91 two-piece zirconia implants. The patients were recruited from two private clinics and were monitored for 5 to 12 years (median: 5.6 years). The primary outcomes were biologic complications, such as peri-implant infections (peri-implant mucositis and peri-implantitis), and the secondary outcome was radiographically evident marginal bone loss (MBL)., Results: Three patients (7.7%) with 9 total implants (9.9%) presented with peri-implant mucositis. MBL that did not exceed the first thread was evident at 32 mesial sites (35%) and 25 distal sites (27.4%). MBL exceeding the first thread but not the third thread was evident at 6 mesial and 5 distal sites (thread pitch: 0.7 mm). Only one peri-implant pocket deepened (4 mm) and showed bleeding; however, the estimated MBL did not exceed 1.65 mm. No peri-implantitis occurred, and no implant was lost., Conclusions: This prospective study shows high survival rates and a seemingly low prevalence of biologic and prosthetic complications for this two-piece zirconia implant system over an observation period of up to 12 years.

Rehabilitation of the edentulous maxilla with implant-supported fixed dental prostheses can represent a significant clinical challenge due to limited bone availability and surgical access, among other factors. This review addresses several treatment options to replace missing teeth in posterior maxillary segments, namely the placement of standard implants in conjunction with maxillary sinus floor augmentation, short implants, tilted implants, and distal cantilever extensions. Pertinent technical information and a concise summary of relevant evidence on the reported outcomes of these different therapeutic approaches are presented, along with a set of clinical guidelines to facilitate decision-making processes and optimize the outcomes of therapy., (© 2023 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd.)

Approximately 50% of individuals who undergo resective epilepsy surgery experience seizure recurrence. The heterogenous post-operative outcomes are not fully explained by clinical, imaging and electrophysiological variables. We hypothesized that molecular features may be useful in understanding surgical response, and that individuals with epilepsy can be classified into molecular subtypes that are associated with seizure freedom or recurrence after surgical resection. Pre-operative blood samples, brain tissue and post-operative seizure outcomes were collected from a cohort of 40 individuals with temporal lobe epilepsy, 23 of whom experienced post-operative seizure recurrence. Messenger RNA and microRNA extracted from the blood and tissue samples were sequenced. The messenger RNA and microRNA expression levels from the blood and brain were each subjected to a novel clustering approach combined with multiple logistic regression to separate individuals into genetic clusters that identify novel subtypes associated with post-operative seizure outcomes. We then compared the microRNAs and messenger RNAs from patient blood and brain tissue that were significantly associated with each subtype to identify signatures that are similarly over- or under-represented for an outcome and more likely to represent endophenotypes with common molecular aetiology. These target microRNAs and messenger RNAs were further characterized by pathway analysis to assess their functional role in epilepsy. Using blood-derived microRNA and messenger RNA expression levels, we identified two subtypes of epilepsy that were significantly associated with seizure recurrence (clusters A1 and B4) (adjusted P < 0.20). A total of 551 microRNAs and 2486 messenger RNAs were associated with clusters A1 and B4, respectively (adjusted P < 0.05). Clustering of brain-tissue messenger RNA expression levels revealed an additional subtype (C2) associated with seizure recurrence that had high overlap of dysregulated messenger RNA transcripts with cluster B4. Clusters A1, B4 and C2 also shared significant overlap of subjects, which altogether suggests a coordinated mechanism by which microRNA and messenger RNA transcripts may be related to seizure recurrence. Epileptic subtypes A1, B4 and C2 reveal both known and novel microRNA and messenger RNA targets in seizure recurrence. Furthermore, targets identified in A1 and B4 are quantifiable in pre-operative blood samples and could potentially serve as biomarkers for surgical resection outcomes., Competing Interests: D.M.R. holds an equity stake in Clarified Precision Medicine, LLC., and has received research support from Novo Nordisk and consulting honoraria from Interpares Biomedicine and Pharmazaam, LLC. C.E. is the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine at the Cleveland Clinic., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: Computer-aided design (CAD) and computer-aided manufacturing (CAM) technology in dentistry has become noticeably more significant in recent years. The further development of CAD/CAM systems has led to a broader range of applications, more user-friendly operation, and improved accessibility. The present online survey aimed to investigate CAD/CAM technology utilisation amongst Austrian dentists as the first social media pilot study from Europe on this specific topic., Materials and Methods: For this purpose, an online survey consisting of 27 questions was created using Google Forms. The questions were divided into 3 sections: general inquiries, questions for CAD/CAM users, and questions for nonusers. The questionnaire was randomly distributed to Austrian dentists via email and social media. A total of 115 responses were submitted., Results: The vast majority of respondents, 52.6% (n = 60), practised as general dentists. Furthermore, a significant proportion of participants specialised in oral surgery, 17.5% (n = 20), and orthodontics, 12.3% (n = 14). Approximately half of the respondents, 51.8% (n = 59), reported having a CAD/CAM device at their current workplace. Amongst the CAD/CAM users, 70.7% (n = 58) believed that CAD/CAM is important in increasing the number of patients visiting the dental practice. In total, 54.2% (n = 26) of nonusers indicated the high initial cost of purchasing a CAD/CAM device as the main reason for not utilising this technology., Conclusions: CAD/CAM technology appears to have infiltrated the workflow of Austrian dentists with predictions of growing implementation amongst dental practices in the future., Competing Interests: Conflict of interest None disclosed., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a type of jawbone necrosis caused by the use of drugs for some types of cancer and osteoporosis. The current study aimed to evaluate the associations between hyperglycemia and the development of medication-related osteonecrosis of the jaw., Methods: Our research group investigated data collected between 1 January 2019 and 31 December 2020. A total of 260 patients were selected from the Inpatient Care Unit, Department of Oromaxillofacial Surgery and Stomatology, Semmelweis University. Fasting glucose data were used and included in the study., Results: Approximately 40% of the necrosis group and 21% of the control group presented with hyperglycemia. There was a significant association between hyperglycemia and MRONJ ( p < 0.05, p = 0.003). Vascular anomaly and immune dysfunction caused by hyperglycemia can lead to necrosis after tooth extraction. Necrosis is more common in the mandible (75.0%) and in the case of parenteral antiresorptive treatment (intravenous Zoledronate and subcutaneous Denosumab). Hyperglycemia is a more relevant risk factor than bad oral habits (26.7%)., Conclusions: Ischemia is a complication of abnormal glucose levels, a possible risk factor for necrosis development. Hence, uncontrolled or poorly regulated plasma glucose levels can significantly increase the risk of jawbone necrosis after invasive dental or oral surgical interventions.

Objective: This study was undertaken to better understand the long-term palliative and disease-modifying effects of surgical resection beyond seizure freedom, including frequency reduction and both late recurrence and remission, in patients with drug-resistant epilepsy., Methods: This retrospective database-driven cohort study included all patients with >9 years of follow-up at a single high-volume epilepsy center. We included patients who underwent lobectomy, multilobar resection, or lesionectomies for drug-resistant epilepsy; we excluded patients who underwent hemispherectomies. Our main outcomes were (1) reduction in frequency of disabling seizures (at 6 months, each year up to 9 years postoperatively, and at last follow-up), (2) achievement of seizure remission (>6 months, >1 year, and longest duration), and (3) seizure freedom at last follow-up., Results: We included 251 patients; 234 (93.2%) achieved 6 months and 232 (92.4%) experienced 1 year of seizure freedom. Of these, the average period of seizure freedom was 10.3 years. A total of 182 (72.5%) patients were seizure-free at last follow-up (defined as >1 year without seizures), with a median 11.9 years since remission. For patients not completely seizure-free, the mean seizure frequency reduction at each time point was 76.2%, and ranged from 66.6% to 85.0%. Patients decreased their number of antiseizure medications on average by .58, and 53 (21.2%) patients were on no antiseizure medication at last follow-up. Nearly half (47.1%) of those seizure-free at last follow-up were not seizure-free immediately postoperatively., Significance: Patients who continue to have seizures after resection often have considerable reductions in seizure frequency, and many are able to achieve seizure freedom in a delayed manner., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: The application of blood concentrates has gained popularity in dentistry in recent years. Platelet-rich fibrin (PRF) has been discussed frequently due to a high content of growth factors and the option of chair-side manufacturing in a simple centrifugation process. PRF is free from adjuvants and inexpensive to produce. The number of studies reporting beneficial effects of PRF in various clinical applications such as alveolar ridge preservation, sinus floor elevation, management and prevention of medical-related osteonecrosis of the jaw, third molar extractions, and guided bone regeneration in dentistry has increased recently. However, to date, neither clinical recommendations nor guidelines are available. The present narrative review aims to summarize the level of evidence on the clinical application of PRF within the field of oral surgery and implantology., Summary: A literature search in Pubmed and Medline has identified 34 articles as a basis for this narrative review. The effectiveness of the clinical application of PRF has been analyzed for five indications within dentistry: medical-related osteonecrosis of the jaw, wisdom tooth extraction, guided bone regeneration, sinus floor elevation, and alveolar ridge preservation. The amount of data for third molar extractions, socket preservation, and guided bone regeneration is extensive. Less data were available for the use of PRF in combination with sinus floor elevations. There is a lack of studies with scientific evidence on PRF and medical-related osteonecrosis of the jaw; however, studies positively impact patient-related outcome measures. Most studies report on beneficial effects when PRF is additionally applied in intrabony defects. There is no evidence of the positive effects of PRF combined with bone graft materials during sinus floor elevation. However, some benefits are reported with PRF as a sole filling material., Key Messages: Many recently published studies show the positive clinical impact of PRF. Yet, further research is needed to ensure the validity of the evidence., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Objective: Seizure outcomes after brain surgery for drug-resistant epilepsy (DRE) are very heterogeneous and difficult to predict with models utilizing the current clinical, imaging, and electrophysiological variables. In this pilot study, we investigated whether genetic and molecular biomarkers (e.g., genomic, transcriptomic) can provide additional insight into differential response to surgery., Methods: Post-operative seizure-outcomes were collected at last follow-up (>6 months) for 201 adult patients with DRE who underwent surgery between 2004 and 2020. Resected tissue was sent for miRNA sequencing ( n = 132) and mRNA sequencing ( n = 135). Following the selection of 10 genes ( SCN1A, NBEA, PTEN, GABRA1, LGL1, DEPDC5, IL1A, ABCB1, C3, CALHM1 ), we investigated SNPs in those 10 genes from previously acquired exome sequencing data ( n = 106). Logistic regression was performed to test for associations between individual features (mRNAs, miRNAs, and SNPs) and post-operative seizure-outcome with an exploratory FDR P < 0.25 as the threshold for significance. Post-operative time-to-seizure analyses were performed for each SNP using a Cox proportional hazards model., Results: The majority of patients (83%) had temporal lobe epilepsy. Mean age at surgery was 38.3 years, and 56% were female. Three SNPs (rs10276036, rs11975994, rs1128503) in multi-drug resistance gene, ABCB1 , were associated with post-operative seizure outcomes. Patients with alternate alleles in ABCB1 were more likely to be seizure-free at last follow-up (52-56% reduction in seizure recurrence; FDR P = 0.24). All three SNPs were in linkage disequilibrium and highly correlated with each other. Median post-operative time-to-seizure was 63 months for patients with 2 alternate alleles, 24-33 months with 1 alternate allele, and 10-11 months with 0 alternate alleles. These SNPs improved outcome prediction beyond MRI and sex alone. No independent miRNAs or mRNAs were significantly associated with seizure-outcome ( P > 0.05). However, pathway analysis identified "cancer drug resistance by drug efflux" (mir-154 and mir-379) as enriched ( P = 0.02), supporting the role of drug response genes in post-operative seizure recurrence., Significance: ABCB1 may have a role in epileptogenesis and surgery outcomes independent of its drug efflux activity necessitating further investigation. SNPs in ABCB1 may serve as independent predictors of post-operative outcome., Competing Interests: Author DR has an equity stake in Clarified Precision Medicine, LLC. DR has received research support from Novo Nordisk, consulting honoraria from Interpares Biomedicine and Pharmazaam, LLC. Author CE is the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine at the Cleveland Clinic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Louis, Busch, Lal, Hockings, Hogue, Morita-Sherman, Vegh, Najm, Ghosh, Bazeley, Eng, Jehi and Rotroff.)

Background/aim: This study aimed to investigate the link between preoperative glycated hemoglobin (HbA1c) levels and oral cancer patients and diabetes mellitus (DM). We aimed to highlight the importance of point-of-care HbA1c measurements in oral cancer patients., Patients and Methods: A total of 214 patients were admitted to the Department of Inpatient Care at Semmelweis University's Department of Oromaxillofacial Surgery and Stomatology between 1 September 2020 and 21 May 2021; individuals, who had undergone maxillofacial surgery under general anesthesia, were included in the study., Results: There was a significant difference between the oral cancer group and the control group in terms of smoking (p=0.009) and alcohol intake (p=0.003). There was no statistically significant difference regarding sex (p=0.132) and DM (p=0.147) between the two groups. The tumor group had an 8.52% greater prevalence of DM, which was not significant. In the oral cancer group, twenty individuals (17.69%) had a higher HbA1c level than the upper level of the optimal metabolic value (6.9%). Nine participants (8.91%) in the control group had an HbA1c value greater than 6.9%, which means that their metabolic level was poor. The oral cancer group did not have higher blood glucose levels than those of the control group., Conclusion: No direct connection between high blood glucose levels and oral cancer was found. However, point-of-care HbA1c measurement can be a diagnostic tool to detect DM in the dental office., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Although titanium has been traditionally used as the gold standard for dental implants, recent years have seen the widespread application of zirconia implants given their superiority with regards to reduced bacterial adhesion, inflammation and cellular-interaction in terms of bio-compatibility. The JAK-STAT signaling pathway plays an important role in bone remodeling and formation. The aim of the study was to investigate the activation of the JAK-STAT pathway through different cytokines in osteoblast-like cells (MG-63) on zirconia in comparison to titanium discs. IFN-γ induced the very strong activation of STAT1 protein, IFN-α activated both STAT1 and STAT3 molecules, IL-6 activated STAT3 and IL-4 induced the activation of STAT6 on both surfaces. The activation of STAT proteins was confirmed by western blot, immunofluorescence and flow cytometry using phospho-specific anti-STAT antibodies, which recognize only phosphorylated STAT proteins. The incubation of MG-63 cells with IFN-γ caused the upregulation of MHC class I and class II proteins when MG-63 cells were grown on zirconia and titanium discs. In sum, the present study shows that the JAK-STAT pathway is activated in MG-63 cells when they are incubated on titanium or zirconia surfaces.

Objective: Anterior temporal lobectomy (ATL) is a widely performed and successful intervention for drug-resistant temporal lobe epilepsy (TLE). However, up to one third of patients experience seizure recurrence within 1 year after ATL. Despite the extensive literature on presurgical electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities to prognosticate seizure freedom following ATL, the value of quantitative analysis of visually reviewed normal interictal EEG in such prognostication remains unclear. In this retrospective multicenter study, we investigate whether machine learning analysis of normal interictal scalp EEG studies can inform the prediction of postoperative seizure freedom outcomes in patients who have undergone ATL., Methods: We analyzed normal presurgical scalp EEG recordings from 41 Mayo Clinic (MC) and 23 Cleveland Clinic (CC) patients. We used an unbiased automated algorithm to extract eyes closed awake epochs from scalp EEG studies that were free of any epileptiform activity and then extracted spectral EEG features representing (a) spectral power and (b) interhemispheric spectral coherence in frequencies between 1 and 25 Hz across several brain regions. We analyzed the differences between the seizure-free and non-seizure-free patients and employed a Naïve Bayes classifier using multiple spectral features to predict surgery outcomes. We trained the classifier using a leave-one-patient-out cross-validation scheme within the MC data set and then tested using the out-of-sample CC data set. Finally, we compared the predictive performance of normal scalp EEG-derived features against MRI abnormalities., Results: We found that several spectral power and coherence features showed significant differences correlated with surgical outcomes and that they were most pronounced in the 10-25 Hz range. The Naïve Bayes classification based on those features predicted 1-year seizure freedom following ATL with area under the curve (AUC) values of 0.78 and 0.76 for the MC and CC data sets, respectively. Subsequent analyses revealed that (a) interhemispheric spectral coherence features in the 10-25 Hz range provided better predictability than other combinations and (b) normal scalp EEG-derived features provided superior and potentially distinct predictive value when compared with MRI abnormalities (>10% higher F1 score)., Significance: These results support that quantitative analysis of even a normal presurgical scalp EEG may help prognosticate seizure freedom following ATL in patients with drug-resistant TLE. Although the mechanism for this result is not known, the scalp EEG spectral and coherence properties predicting seizure freedom may represent activity arising from the neocortex or the networks responsible for temporal lobe seizure generation within vs outside the margins of an ATL., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Rasmussen encephalitis (RE) is a rare inflammatory disease affecting one hemisphere, causing progressive neurological deficits and intractable seizures., Objective: To report long-term seizure outcomes, reoperations, and functional outcomes in patients with RE who underwent hemispherectomy at our institution., Methods: Retrospective review was performed for all patients with RE who had surgery between 1998 and 2020. We collected seizure history, postoperative outcomes, and functional data. Imaging was independently reviewed in a blinded fashion by 2 neurosurgeons and a neuroradiologist., Results: We analyzed 30 patients with RE who underwent 35 hemispherectomies (5 reoperations). Using Kaplan-Meier analysis, seizure-freedom rate was 81.5%, 63.6%, and 55.6% at 1, 5, and 10 years after surgery, respectively. Patients with shorter duration of hemiparesis preoperatively were less likely to be seizure-free at follow-up (P = .011) and more likely to undergo reoperation (P = .004). Shorter duration of epilepsy (P = .026) and preoperative bilateral MRI abnormalities (P = .011) were associated with increased risk of reoperation. Complete disconnection of diseased hemisphere on postoperative MRI after the first operation improved seizure-freedom (P = .021) and resulted in fewer reoperations (P = .034), and reoperation resulted in seizure freedom in every case., Conclusion: Obtaining complete disconnection is critical for favorable seizure outcomes from hemispherectomy, and neurosurgeons should have a low threshold to reoperate in patients with RE with recurrent seizures. Rapid progression of motor deficits and bilateral MRI abnormalities may indicate a subpopulation of patients with RE with increased risk of needing reoperation. Overall, we believe that hemispherectomy is a curative surgery for the majority of patients with RE, with excellent long-term seizure outcome., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objectives: This study aimed to collect information about oral health knowledge and the habits of people living with diabetes (PwD), primarily type 1 diabetes, using the newly developed World Health Organisation Oral Health Questionnaire for Adults (Annex 7)., Materials and Methods: Comparable and reliable questionnaires, comprising 23 questions for PwD, were sent to diabetes social media groups, mailing lists, and associations. The survey explored the relationships amongst demographic factors, age, dental education, eating habits, and other factors., Results: The 23-question survey was answered by 307 individuals from 60 different countries. Alcohol and tobacco use, dental anxiety, and bad habits were often reported. Of the participants, 61.2% (n = 188) had at least 1 drink during the past 30 days. Of the participants, 22.8% (n = 70) were smokers. In total, 80.8% (n = 248) of the participants consumed biscuits, 76.2% (n = 234) consumed sweets, and 63.2% (n = 194) consumed soft drinks regularly. A total of 26.4% (n = 81) of the participants reported being afraid of dental treatment. Of the participants, 48.5% (n = 149) reported dry mouth and other oral complications. The frequency of visits to the dentist was satisfactory. A total of 71.3% (n = 219) of the participants reported visiting a dentist during the past 12 months., Conclusions: There is a need for proper oral health education for PwD. Trained diabetes advocates could be core messengers. However, interdisciplinary cooperation is mandatory for both education and the clinical aspect of diabetes care. For example, diabetes nurses need to be educated with the help of dentists or oral hygienists., Competing Interests: Conflict of interest None disclosed., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Epilepsy surgery is an effective treatment option for drug-resistant focal epilepsy patients with associated structural brain lesions. However, little epidemiological data are available regarding the number of patients with these lesions. We reviewed data regarding (1) the prevalence and incidence of epilepsy; (2) the proportion of epilepsy patients with focal epilepsy, drug-resistant epilepsy, and drug-resistant focal epilepsies; and (3) the number of epilepsy presurgical evaluations and surgical resections. We also assessed the relative proportion of brain lesions using post-surgical histopathological findings from 541 surgical patients from the Cleveland Clinic and 9,523 patients from a European multi-center cohort. Data were combined to generate surgical candidate incidence and prevalence estimates and the first lesion-specific estimates for hippocampal sclerosis (HS), low-grade epilepsy-associated brain tumors (LEAT), malformations of cortical development (MCD), glial scars, vascular malformations, and encephalitis. The most frequently diagnosed brain lesions were HS (incidence = 2.32 ± 0.26 in 100,000, prevalence = 19.40 ± 2.16 in 100,000) for adults and MCD (incidence = 1.15 ± 0.34 in 100,000, prevalence = 6.52 ± 1.89 in 100,000) for children. Our estimates can guide patient advocacy groups, clinicians, researchers, policymakers in education, development of health care strategy, resource allocation, and reimbursement schedules., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: 3D printing is a rapidly developing technology in the healthcare industry and in dentistry. Its application clearly shows that this area of digital dentistry has potential for everyday usage across all fields, including prosthodontics, orthodontics, maxillofacial surgery, and oral implantology. However, despite gaining ground, there is a lack of information about how specialists (dentists and dental technicians) use additive technology. Our research group aimed to investigate the impact of social media on additive manufacturing technology among dental specialists and their everyday usage of 3D printing., Methods: This paper investigated specialists' everyday usage of 3D printers via an online survey (Google Forms). The survey questions aimed to discover the number of 3D printers used, the accessibility of the devices, the annual cost, and the design programs. Since specialists tend to build online communities on social media, we circulated our study questionnaire using our profiles on LinkedIn, Facebook, and Instagram platforms during our research., Results: A total of 120 responses were received from 20 countries, with the most significant numbers being from Hungary 23.7% ( n = 27), the United States 18.4% ( n = 21), and the United Kingdom 7.9% ( n = 9). Most of the participants were dentists ( n = 68) or dental technicians ( n = 29), but some CAD/CAM specialists ( n = 23) also completed our survey. The participants had an average of 3.8 years (±0.7) of experience in the 3D printing field, and owned a total of 405 printing devices (3.6 on average/person)., Conclusions: The impact of social media on this research field is growing increasingly. Hence, we support specialists in joining virtual communities on professional platforms. This article intended to provide a practical overview, feedback, and direction for dentists interested in 3D printing technology. From our survey, we can conclude that additive technology is broadening dental applications and the services that we can provide for our patients.

Paullone isomers are known as inhibitors of tubulin polymerase and cyclin dependent kinases (Cdks), which are potential targets for cancer chemotherapy. Herein we report an efficient and clean pathway to the fourth isomer, which remained elusive so far, namely 7,8-dihydroindolo[2,3- d ][1]benzazepin-6(5 H )-one. Moreover, we demonstrate the generality of our pathway by synthesizing two closely related analogues, one containing a bromo substituent and the other one incorporating an 8-membered instead of a 7-membered ring. The key transformation in this four-step synthesis, with an overall yield of 29%, is the Fischer indole reaction of 2-nitrophenylacetyl acetoacetate with 1-benzyl-1-phenylhydrazine in acetic acid that delivers methyl 2-(1-benzyl-3-(2-nitrophenyl)-1 H -indol-2-yl)acetate in 55% yield., (Copyright © 2022, Kuznetcova et al.)

Background: Diabetes is a well-known predisposing factor for oral diseases, so prevention in an early age is mandatory., Objective: To provide oral screening for children living with type 1 diabetes. We aimed to investigate the oral and general health indexes of T1DM children and compare these data to healthy siblings and controls., Methods: In this cross-sectional study, 120 DM patients and 78 siblings, thereafter 80 DM children and 95 controls, took part. A detailed questionnaire, panoramic radiographs, and lateral cephalograms were obtained in every orthodontic consultation. We used Pearson's chi-square test for statistical analysis and compared the data of the study and control groups., Results: The oral health values of DM children were significantly better (DMF-T 0.83-1.3) than the national average (3.8-4.5). A total of 75% ( n = 60) of the children needed orthodontic treatment for orthodontic or skeletal anomalies. The prevalence of skeletal anomalies was significantly ( p < 0.05) higher among patients with diabetes mellitus (DM) than in the control group. The frequency of coeliac disease was significantly elevated compared to any literature data (1-3.5%) in the study (15%) and in the control sibling group (13%)., Conclusions: Co-morbidities such as CD should get more attention as a prognostic factor for a future higher incidence of diabetes. T1DM children can be motivated and health-conscious patients with excellent oral hygiene and dental status. Orthodontic treatment can help eliminate the oral complications of DM. Special diabetes ambulances may help provide oral care for patients with DM.

Background/aim: Diabetes mellitus (DM) is one of the most common chronic metabolic disorders. Our research aimed to demonstrate the relationship between DM and oral cancer., Patients and Methods: We pursued a retrospective research study in Hungary between January 2019 and December 2020. We investigated 597 inpatient records and compared them to the results of our previous studies (1998-2002 and 2012-2015)., Results: The frequency of patients with DM in the oral cancer group is 2.45 times higher today than 20 years ago. The prevalence rate of DM and oral malignancies increased from 14.6% to 35.8%. In the oral cancer group, 54.4% of the patients had elevated blood glucose levels and of these, 61.1% of them had type 2 diabetes, 34.2% had impaired fasting glycemia, and only 4.7% had type 1 diabetes. We observed that 45.3% of them were smokers. Of those whose blood sugar levels were under 6.1 mmol/l, the mean body mass index was 25.33 [standard deviation (SD)=±4.5; range=15.57-39.84], while among patients with DM, it was 26.92 (SD=±5.8; range=18.36-44.08)., Conclusion: It may be necessary to continuously monitor the patient's blood sugar level to maintain euglycemic levels when managing patients with malignant oral lesions., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: This study aims to evaluate the role of scalp electroencephalography (EEG; ictal and interictal patterns) in predicting resective epilepsy surgery outcomes. We use the data to further develop a nomogram to predict seizure freedom., Methods: We retrospectively reviewed the scalp EEG findings and clinical data of patients who underwent surgical resection at three epilepsy centers. Using both EEG and clinical variables categorized into 13 isolated candidate predictors and 6 interaction terms, we built a multivariable Cox proportional hazards model to predict seizure freedom 2 years after surgery. Harrell's step-down procedure was used to sequentially eliminate the least-informative variables from the model until the change in the concordance index (c-index) with variable removal was less than 0.01. We created a separate model using only clinical variables. Discrimination of the two models was compared to evaluate the role of scalp EEG in seizure-freedom prediction., Results: Four hundred seventy patient records were analyzed. Following internal validation, the full Clinical + EEG model achieved an optimism-corrected c-index of 0.65, whereas the c-index of the model without EEG data was 0.59. The presence of focal to bilateral tonic-clonic seizures (FBTCS), high preoperative seizure frequency, absence of hippocampal sclerosis, and presence of nonlocalizable seizures predicted worse outcome. The presence of FBTCS had the largest impact for predicting outcome. The analysis of the models' interactions showed that in patients with unilateral interictal epileptiform discharges (IEDs), temporal lobe surgery cases had a better outcome. In cases with bilateral IEDs, abnormal magnetic resonance imaging (MRI) predicted worse outcomes, and in cases without IEDs, patients with extratemporal epilepsy and abnormal MRI had better outcomes., Significance: This study highlights the value of scalp EEG, particularly the significance of IEDs, in predicting surgical outcome. The nomogram delivers an individualized prediction of postoperative outcome, and provides a unique assessment of the relationship between the outcome and preoperative findings., (© 2021 International League Against Epilepsy.)

Quantitative volumetric brain MRI measurement is important in research applications, but translating it into patient care is challenging. We explore the incorporation of clinical automated quantitative MRI measurements in statistical models predicting outcomes of surgery for temporal lobe epilepsy. Four hundred and thirty-five patients with drug-resistant epilepsy who underwent temporal lobe surgery at Cleveland Clinic, Mayo Clinic and University of Campinas were studied. We obtained volumetric measurements from the pre-operative T1-weighted MRI using NeuroQuant, a Food and Drug Administration approved software package. We created sets of statistical models to predict the probability of complete seizure-freedom or an Engel score of I at the last follow-up. The cohort was randomly split into training and testing sets, with a ratio of 7:3. Model discrimination was assessed using the concordance statistic (C-statistic). We compared four sets of models and selected the one with the highest concordance index. Volumetric differences in pre-surgical MRI located predominantly in the frontocentral and temporal regions were associated with poorer outcomes. The addition of volumetric measurements to the model with clinical variables alone increased the model's C-statistic from 0.58 to 0.70 (right-sided surgery) and from 0.61 to 0.66 (left-sided surgery) for complete seizure freedom and from 0.62 to 0.67 (right-sided surgery) and from 0.68 to 0.73 (left-sided surgery) for an Engel I outcome score. 57% of patients with extra-temporal abnormalities were seizure-free at last follow-up, compared to 68% of those with no such abnormalities ( P -value = 0.02). Adding quantitative MRI data increases the performance of a model developed to predict post-operative seizure outcomes. The distribution of the regions of interest included in the final model supports the notion that focal epilepsies are network disorders and that subtle cortical volume loss outside the surgical site influences seizure outcome., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: Patients undergoing frontal lobectomy demonstrate lower seizure-freedom rates than patients undergoing temporal lobectomy and several other resective interventions. We attempted to utilize automated preoperative quantitative analysis of focal and global cortical volume loss to develop predictive volumetric indicators of seizure outcome after frontal lobectomy., Methods: Ninety patients who underwent frontal lobectomy were stratified based on seizure freedom at a mean follow-up time of 3.5 (standard deviation [SD] 2.5) years. Automated quantitative analysis of cortical volume loss organized by distinct brain region and laterality was performed on preoperative T1-weighted magnetic resonance imaging (MRI) studies. Univariate statistical analysis was used to select potential predictors of seizure freedom. Backward variable selection and multivariate logistical regression were used to develop models to predict seizure freedom., Results: Forty-eight of 90 (53.3%) patients were seizure-free at the last follow-up. Several frontal and extrafrontal brain regions demonstrated statistically significant differences in both volumetric cortical volume loss and volumetric asymmetry between the left and right sides in the seizure-free and non-seizure-free cohorts. A final multivariate logistic model utilizing only preoperative quantitative MRI data to predict seizure outcome was developed with a c-statistic of 0.846. Using both preoperative quantitative MRI data and previously validated clinical predictors of seizure outcomes, we developed a model with a c-statistic of 0.897., Significance: This study demonstrates that preoperative cortical volume loss in both frontal and extrafrontal regions can be predictive of seizure outcome after frontal lobectomy, and models can be developed with excellent predictive capabilities using preoperative MRI data. Automated quantitative MRI analysis can be quickly and reliably performed in patients with frontal lobe epilepsy, and further studies may be developed for integration into preoperative risk stratification., (© 2021 International League Against Epilepsy.)

Objective: To characterize seizure and cognitive outcomes of sparing vs removing an magnetic resonance imaging (MRI)-normal hippocampus in patients with temporal lobe epilepsy., Methods: In this retrospective cohort study, we reviewed clinical, imaging, surgical, and histopathological data on 152 individuals with temporal lobe epilepsy and nonlesional hippocampi categorized into hippocampus-spared (n = 74) or hippocampus-resected (n = 78). Extra-hippocampal lesions were allowed. Pre- and postoperative cognitive data were available on 86 patients. Predictors of seizure and cognitive outcomes were identified using Cox-proportional hazard modeling followed by treatment-specific model reduction according to Akaike information criterion, and built into an online risk calculator., Results: Seizures recurred in 40% within one postoperative year, and in 63% within six postoperative years. Male gender (P = .03), longer epilepsy duration (P < .01), normal MRI (P = .04), invasive evaluation (P = .02), and acute postoperative seizures (P < .01) were associated with a higher risk of recurrence. We found no significant difference in postoperative seizure freedom rates at 5 years between those whose hippocampus was spared and those whose hippocampus was resected (P = .17). Seizure outcome models built with pre- and postoperative data had bootstrap validated concordance indices of 0.65 and 0.72. The dominant hippocampus-spared group had lower rates of decline in verbal memory (39% vs 70%; P = .03) and naming (41% vs 79%; P = .01) compared to the hippocampus-resected group. Partial hippocampus sparing had the same risk of verbal memory decline as for complete removal., Significance: Sparing or removing an MRI-normal hippocampus yielded similar long-term seizure outcome. A more conservative approach, sparing the hippocampus, only partially shields patients from postoperative cognitive deficits. Risk calculators are provided to facilitate clinical counseling., (© 2020 International League Against Epilepsy.)

Thiosemicarbazones continue to attract the interest of researchers as potential anticancer drugs. For example, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, or triapine, is the most well-known representative of this class of compounds that has entered multiple phase I and II clinical trials. Two new triapine derivatives HL 1 and HL 2 were prepared by condensation reactions of 2-pyridinamidrazone and S-methylisothiosemicarbazidium chloride with 3- N -( tert -butyloxycarbonyl) amino-pyridine-2-carboxaldehyde, followed by a Boc-deprotection procedure. Subsequent reaction of HL 1 and HL 2 with CuCl 2 ·2H 2 O in 1:1 molar ratio in methanol produced the complexes [Cu II (HL 1 )Cl 2 ]·H 2 O ( 1·H 2 O ) and [Cu II (HL 2 )Cl 2 ] ( 2 ). The reaction of HL 2 with Fe(NO 3 ) 3 ∙9H 2 O in 2:1 molar ratio in the presence of triethylamine afforded the complex [Fe III (L 2 ) 2 ]NO 3 ∙0.75H 2 O ( 3∙0.75H 2 O ), in which the isothiosemicarbazone acts as a tridentate monoanionic ligand. The crystal structures of HL 1 , HL 2 and metal complexes 1 and 2 were determined by single crystal X-ray diffraction. The UV-Vis and EPR spectroelectrochemical measurements revealed that complexes 1 and 2 underwent irreversible reduction of Cu(II) with subsequent ligand release, while 3 showed an almost reversible electrochemical reduction in dimethyl sulfoxide (DMSO). Aqueous solution behaviour of HL 1 and 1, as well as of HL 2 and its complex 2 , was monitored as well. Complexes 1 - 3 were tested against ovarian carcinoma cells, as well as noncancerous embryonic kidney cells, in comparison to respective free ligands, triapine and cisplatin. While the free ligands HL 1 and HL 2 were devoid of antiproliferative activity, their respective metal complexes showed remarkable antiproliferative activity in a micromolar concentration range. The activity was not related to the inhibition of ribonucleotide reductase (RNR) R2 protein, but rather to cancer cell homeostasis disturbance-leading to the disruption of cancer cell signalling.

Background and Purpose: NeuroQuant is an FDA-approved software that performs automated MR imaging quantitative volumetric analysis. This study aimed to compare the accuracy of NeuroQuant analysis with visual MR imaging analysis by neuroradiologists with expertise in epilepsy in identifying hippocampal sclerosis., Materials and Methods: We reviewed 144 adult patients who underwent presurgical evaluation for temporal lobe epilepsy. The reference standard for hippocampal sclerosis was defined by having hippocampal sclerosis on pathology ( n = 61) or not having hippocampal sclerosis on pathology ( n = 83). Sensitivities, specificities, positive predictive values, and negative predictive values were compared between NeuroQuant analysis and visual MR imaging analysis by using a McNemar paired test of proportions and the Bayes theorem., Results: NeuroQuant analysis had a similar specificity to neuroradiologist visual MR imaging analysis (90.4% versus 91.6%; P = .99) but a lower sensitivity (69.0% versus 93.0%, P < .001). The positive predictive value of NeuroQuant analysis was comparable with visual MR imaging analysis (84.0% versus 89.1%), whereas the negative predictive value was not comparable (79.8% versus 95.0%)., Conclusions: Visual MR imaging analysis by a neuroradiologist with expertise in epilepsy had a higher sensitivity than did NeuroQuant analysis, likely due to the inability of NeuroQuant to evaluate changes in hippocampal T2 signal or architecture. Given that there was no significant difference in specificity between NeuroQuant analysis and visual MR imaging analysis, NeuroQuant can be a valuable tool when the results are positive, particularly in centers that lack neuroradiologists with expertise in epilepsy, to help identify and refer candidates for temporal lobe epilepsy resection. In contrast, a negative test could justify a case referral for further evaluation to ensure that false-negatives are detected., (© 2020 by American Journal of Neuroradiology.)

Holographic theories with classical gravity duals are maximally chaotic; i.e., they saturate the universal bound on the rate of growth of chaos [J. Maldacena, S. H. Shenker, and D. Stanford, J. High Energy Phys. 08 (2016) 106JHEPFG1029-847910.1007/JHEP08(2016)106]. It is interesting to ask whether this property is true only for leading large N correlators or if it can show up elsewhere. In this Letter, we consider the simplest setup to tackle this question: a Brownian particle coupled to a thermal ensemble. We find that the four-point out-of-time-order correlator that diagnoses chaos initially grows at an exponential rate that saturates the chaos bound, i.e., with a Lyapunov exponent λ&#95;{L}=2π/β. However, the scrambling time is parametrically smaller than for plasma excitations, t&#95;{*}∼βlogsqrt[λ] instead of t&#95;{*}∼βlogN^{2}. Our result shows that, at least in certain cases, maximal chaos can be attained in the probe sector without the explicit need of gravitational degrees of freedom.

Background: Diabetes and periodontitis are chronic non-communicable diseases independently associated with mortality and have a bidirectional relationship., Aims: To update the evidence for their epidemiological and mechanistic associations and re-examine the impact of effective periodontal therapy upon metabolic control (glycated haemoglobin, HbA1C)., Epidemiology: There is strong evidence that people with periodontitis have elevated risk for dysglycaemia and insulin resistance. Cohort studies among people with diabetes demonstrate significantly higher HbA1C levels in patients with periodontitis (versus periodontally healthy patients), but there are insufficient data among people with type 1 diabetes. Periodontitis is also associated with an increased risk of incident type 2 diabetes., Mechanisms: Mechanistic links between periodontitis and diabetes involve elevations in interleukin (IL)-1-β, tumour necrosis factor-α, IL-6, receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio, oxidative stress and Toll-like receptor (TLR) 2/4 expression., Interventions: Periodontal therapy is safe and effective in people with diabetes, and it is associated with reductions in HbA1C of 0.27-0.48% after 3 months, although studies involving longer-term follow-up are inconclusive., Conclusions: The European Federation of Periodontology (EFP) and the International Diabetes Federation (IDF) report consensus guidelines for physicians, oral healthcare professionals and patients to improve early diagnosis, prevention and comanagement of diabetes and periodontitis., (Copyright © 2017 John Wiley & Sons A/S, Elsevier B.V. Published by Elsevier B.V. All rights reserved.)