Design of non-cytotoxic 6,7-dihydroxycoumarin-5-carboxylates with antibiofilm activity against Staphylococcus aureus and Candida albicans.

The 6,7-dihydroxycoumarin-5-carboxylates DHCou and 4-Me-DHCou have been synthesized via five-step route including a propargyl-Claisen rearrangement as key step. The compounds show antibiofilm activity against Stapylococcus aureus and Candida albicans but lack the cytotoxic activity of parent 6,7-dihydroxycoumarines such as esculetin and 4-methylesculetin.

Attitude and practice of regenerative endodontic procedures among endodontists and paediatric dentists: A multinational survey from 13 countries.

BACKGROUND: Regenerative endodontics (RET) refers to biologically based procedures that aim to restore damaged tooth structures and reinstate the pulp-dentine complex to its normal physiological state. AIM: The purpose of this study was to examine the attitudes and practices of endodontists and paediatric dentists regarding RET. DESIGN: A survey was conducted among endodontists and paediatric dentists from 13 countries. A number of factors were evaluated, including frequency of RET application, followed guidelines, disinfection techniques, intracanal medication type, scaffold type, preferred coronal seal material, and follow-up period. RESULTS: Among the 1394 respondents, 853 (61.2%) and 541 (38.8%) were endodontists and paediatric dentists, respectively. Almost half (43%) of participants have not performed RET yet. The American Association of Endodontics guideline (47.3%) was selected as the primary source for the clinical protocol. The most frequently selected irrigant solution was 1.5%-3% NaOCl at the first (26.1%) and second (13.6%) sessions. A blood clot (68.7%) and MTA (61.9%) were the most frequently selected scaffold type and coronal barrier. Most participants preferred a 6-month follow-up period. CONCLUSION: According to this survey, deviations exist from current RET guidelines regarding all aspects evaluated. Standardizing clinical protocols and adhering to available guidelines would help to ensure more predictable outcomes.

Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6.

Spinocerebellar ataxias are dominantly inherited disorders that are associated with progressive brain degeneration, mainly affecting the cerebellum and brainstem. As part of the multicentre European integrated project on spinocerebellar ataxias study, 37 patients with spinocerebellar ataxia-1, 19 with spinocerebellar ataxia-3 and seven with spinocerebellar ataxia-6 were clinically examined and underwent magnetic resonance imaging at baseline and after a 2-year follow-up. All patients were compared with age-matched and gender-matched healthy control subjects. Magnetic resonance imaging analysis included three-dimensional volumetry and observer-independent longitudinal voxel-based morphometry. Volumetry revealed loss of brainstem, cerebellar and basal ganglia volume in all genotypes. Most sensitive to change was the pontine volume in spinocerebellar ataxia-1, striatal volume in spinocerebellar ataxia-3 and caudate volume in spinocerebellar ataxia-6. Sensitivity to change, as measured by standard response mean, of the respective MRI measures was greater than that of the most sensitive clinical measure, the Scale for the Assessment and Rating of Ataxia. Longitudinal voxel-based morphometry revealed greatest grey matter loss in the cerebellum and brainstem in spinocerebellar ataxia-1, in the putamen and pallidum in spinocerebellar ataxia-3 and in the cerebellum, thalamus, putamen and pallidum in spinocerebellar ataxia-6. There was a mild correlation between CAG repeat length and volume loss of the bilateral cerebellum and the pons in spinocerebellar ataxia-1. Quantitative volumetry and voxel-based morphometry imaging demonstrated genotype-specific patterns of atrophy progression in spinocerebellar ataxias-1, 3 and 6, and they showed a high sensitivity to detect change that was superior to clinical scales. These structural magnetic resonance imaging findings have the potential to serve as surrogate markers, which might help to delineate quantifiable endpoints and non-invasive methods for rapid and reliable data acquisition, encouraging their use in clinical trials.

Awareness of possible complications associated with direct composite restorations: A multinational survey among dentists from 13 countries with meta-analysis.

OBJECTIVES: Resin-based composites (RBCs) evolved into favoured materials for teeth restorations, marking a significant change in dental practice. Despite many advantages, RBCs exhibit various limitations in their physical and chemical properties. Therefore, we assessed the dentists' awareness of possible complications after direct composite restorations and their opinions about this material. METHODS: The online questionnaire was created in English in May 2023. A 16-item survey was dedicated to general dentists and specialists. The first section included four questions related to demographic characteristics. The second section comprised twelve questions and focused on awareness of potential side effects of composite restorations, the most crucial advantages and disadvantages of composite resins, and the frequency of experienced clinical complications after the application of composite materials. RESULTS: A total of 1830 dentists from 13 countries took part in the survey. Dentists most often declared awareness of low adhesion to the dentine (77.5 %) and, most rarely, solubility in oral fluids (42.6 %). Aesthetics was identified as the main advantage of composite fillings (79 %), followed by the possibility of repair (59 %) and adhesion to enamel (57 %). Polymerisation shrinkage was a major disadvantage for most countries (70 % overall). Analysing the declared potential clinical complications for all countries, statistically significant findings were obtained for marginal discolouration (OR=2.982, 95 % CI: 1.321-6.730, p-value=0.009) and borderline significance for secondary caries (OR=1.814, 95 % CI: 0.964-3.415, p-value=0.065). CONCLUSIONS: Dentists value aesthetics and repairability but are aware of shrinkage and experience discolouration. The issue of toxicity and solubility seems to be the least known to dentists. CLINICAL SIGNIFICANCE: Dentists should use RBCs with critical caution due to possible side effects. Despite the undoubted aesthetics of direct composite restorations, it is necessary to remember potential clinical complications such as marginal discolouration or secondary caries.

Repair versus replacement of defective direct dental restorations: A multinational cross-sectional study with meta-analysis.

OBJECTIVES: When dental practitioners encounter a defective restoration, they are faced with a crucial decision whether to repair or replace it. This study aims to explore international preferences for repair procedures and the clinical steps taken during the repair process. METHOD: An 11-question survey was distributed to dentists across 21 countries via different platforms. The survey comprised two sections: the first included five questions aimed at gathering demographic information, while the second consisted of six questions focusing on participants' practices related to the repair of composite or amalgam restorations A meta-analysis was employed to ascertain the pooled odds ratio of repairing versus replacement. The statistical analysis was carried out using the RevMan 5.3 program and forest plots were generated using the same program to visualize the results. RESULTS: The survey was completed by 3680 dental practitioners. The results indicated a strong tendency to repair defective composite restorations (OR: 14.23; 95 % CI: 7.40, 27.35, p < 0.001). In terms of amalgam, there was a significant tendency to replace the restorations (OR: 0.19; 95 % CI: 0.12, 0.30, p < 0.001). When repairing restorations, the most common protocols were etching with orthophosphoric acid and creating an enamel bevel, regardless of the restorative material used. CONCLUSION: The findings of this study indicate that there exists a knowledge gap among dental practitioners regarding restoration repair. It is imperative that dental practitioners receive proper education and training on restoration repair, to ensure the usage of adequate protocols and restoration survival. CLINICAL SIGNIFICANCE: A significant portion of dental practitioners lack the necessary knowledge and education required for the repair of restorations. Therefore, it is imperative to establish guidelines aimed at enhancing the management of defective restorations, along with protocols for clinical interventions. This includes the incorporation of proper courses in undergraduate, graduate, and continuing education programs.

Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disorders.

Imprinting disorders are associated with mutations and epimutations affecting imprinted genes, that is those whose expression is restricted by parent of origin. Their diagnosis is challenging for two reasons: firstly, their clinical features, particularly prenatal and postnatal growth disturbance, are heterogeneous and partially overlapping; secondly, their underlying molecular defects include mutation, epimutation, copy number variation, and chromosomal errors, and can be further complicated by somatic mosaicism and multi-locus methylation defects. It is currently unclear to what extent the observed phenotypic heterogeneity reflects the underlying molecular pathophysiology; in particular, the molecular and clinical diversity of multilocus methylation defects remains uncertain. To address these issues we performed comprehensive methylation analysis of imprinted genes in a research cohort of 285 patients with clinical features of imprinting disorders, with or without a positive molecular diagnosis. 20 of 91 patients (22%) with diagnosed epimutations had methylation defects of additional imprinted loci, and the frequency of developmental delay and congenital anomalies was higher among these patients than those with isolated epimutations, indicating that hypomethylation of multiple imprinted loci is associated with increased diversity of clinical presentation. Among 194 patients with clinical features of an imprinting disorder but no molecular diagnosis, we found 15 (8%) with methylation anomalies, including missed and unexpected molecular diagnoses. These observations broaden the phenotypic and epigenetic definitions of imprinting disorders, and show the importance of comprehensive molecular testing for patient diagnosis and management.

The Role of Cellular Metabolism in Maintaining the Function of the Dentine-Pulp Complex: A Narrative Review.

The cellular metabolic processes ensure the physiological integrity of the dentine-pulp complex. Odontoblasts and odontoblast-like cells are responsible for the defence mechanisms in the form of tertiary dentine formation. In turn, the main defence reaction of the pulp is the development of inflammation, during which the metabolic and signalling pathways of the cells are significantly altered. The selected dental procedures, such as orthodontic treatment, resin infiltration, resin restorations or dental bleaching, can impact the cellular metabolism in the dental pulp. Among systemic metabolic diseases, diabetes mellitus causes the most consequences for the cellular metabolism of the dentine-pulp complex. Similarly, ageing processes present a proven effect on the metabolic functioning of the odontoblasts and the pulp cells. In the literature, several potential metabolic mediators demonstrating anti-inflammatory properties on inflamed dental pulp are mentioned. Moreover, the pulp stem cells exhibit the regenerative potential essential for maintaining the function of the dentine-pulp complex.

Increased Myeloperoxidase Concentrations in Saliva could Reflect Increased Body Mass and Oral Microinflammation.

BACKGROUND: Increased myeloperoxidase (MPO) levels in saliva are thought to reflect ongoing periodontal inflammation. Less clear is whether and to what extent salivary MPO is increased as a result of systemic inflammation. METHODS: In the present study, we aimed to determine which demographic, anthropometric, biochemical, and dental parameters affect the level of MPO in whole mixed saliva in healthy adults with no apparent inflammatory lesions in the oral cavity. Thus, 113 individuals, aged 20-61 years (including 30.1% men and 23.9% smokers), were examined. RESULTS: In the univariate analysis, higher levels of MPO in saliva were found to be associated with age, an increased body mass index (BMI), higher levels of cytokines tumour necrosis factor-α and interleukin-6, as well as poorer oral hygiene, gingival status, and lower saliva flow. Multivariate logistic regression analysis determined that the main predictors of MPO concentration in saliva were BMI and stimulated saliva flow rate. CONCLUSIONS: Overall, an increase in MPO in saliva could be related to an increase in BMI, possibly as a result of subclinical chronic microinflammation, which also involves the gingiva.

Concentrations and kinetics of renal biomarkers in dogs with gastric dilatation-volvulus with and without 24-h intravenous lidocaine.

Background: Gastric dilatation volvulus (GDV) can lead to organ failure including acute kidney injury (AKI). Due to its cytoprotective, antioxidant and anti-inflammatory effects, lidocaine has a potential to prevent AKI in dogs with GDV. Design and setting: Prospective, observational cohort study in client-owned dogs with GDV. Objective: To determine concentrations of renal biomarkers for AKI in dogs with GDV with and without intravenous (IV) lidocaine therapy. Methods: Thirty-two dogs were randomized to receive either IV lidocaine (2 mg/kg, followed by a lidocaine constant rate infusion at a dose of 50 µg/kg/min over 24 h; n = 17) or no lidocaine (n = 15). Blood and urine samples were taken at admission (T 0) (only blood), during or immediately after surgery (T 1), and 24 (T 24) and 48 (T 48) h after surgery. Plasma creatinine (pCr), plasma neutrophil gelatinase-associated lipocalin (pNGAL), urinary NGAL (uNGAL), uNGAL to creatinine ratio (UNCR), and urinary gamma-glutamyl transferase to creatinine ratio (uGGT/uCr) were evaluated. Biomarker concentrations were compared between dogs with and without IV lidocaine and the course of each marker was determined in comparison to its admission value. Results: In the entire population, a significantly higher pCr at T 0 (median, 95 µmol/L, interquartile range, 82-105) compared with T 1 (69 µmol/L, 60-78), T 24 (63 µmol/L, 52-78), and T 48 (78 µmol/L, 65-87) (P < 0.001) was found. Plasma NGAL increased significantly between T 0 (5.66 ng/mL, 3.58-7.43) and T 24 (7.50 ng/mL, 4.01-11.89) (P = 0.006) and T 48 (9.86 ng/mL, 5.52-13.92) (P < 0.001), respectively. Urinary NGAL increased significantly between T 1 (0.61 ng/mL, 0.30-2.59) and T 24 (2.62 ng/mL, 1.86-10.92) (P = 0.001) and T 48 (4.79 ng/mL, 1.96-34.97 (P < 0.001), respectively. UNCR increased significantly between T 1 (0.15 µg/mmol, 0.09-0.54) and T 24 (1.14 µg/mmol, 0.41-3.58) (P = 0.0015) and T 48 (1.34 µg/mmol, 0.30-7.42) (P < 0.001), respectively. Concentrations of uGGT/uCr increased significantly from T 0 highest at T 24 (6.20 U/mmol, 3.90-9.90) and significantly decreased at T 48 (3.76 U/mmol, 2.84-6.22) (P < 0.001). No significant differences in any renal biomarker concentration were found between dogs with and without IV lidocaine therapy. Conclusion and clinical relevance: Plasma NGAL, uNGAL and UNCR remained increased up to 48 h post-surgery. No evidence of lidocaine-associated renoprotection was found.

Salivary Alterations in Autoimmune Thyroid Diseases: A Systematic Review.

Autoimmune thyroid disease (AITD) is a dysregulation of the immune system that causes an attack on the thyroid gland. Two major clinical manifestations are Hashimoto's thyroiditis and Graves' disease. Saliva performs many functions and, importantly, has the potential for easy, non-invasive diagnostics of several systemic disorders. This systematic review was designed to answer the question whether salivary alterations are reliable for the diagnosis of autoimmune thyroid diseases. Following the inclusion and exclusion criteria, fifteen studies were included. Due to their heterogeneity, saliva analysis was divided into two subgroups: quantitative assessment analysing salivation and qualitative assessment concerning potential salivary biomarkers for AITD. In addition to detecting altered levels of thyroid hormones and antibodies, salivary changes were also observed in the concentrations of total protein, cytokines and chemokines, as well as markers of oxidative status. According to the saliva flow rate values, significantly reduced saliva secretion was observed in patients with HT. In conclusion, it is not possible to unequivocally state if salivary biomarkers can potentially be used in autoimmune thyroid disease diagnosis. Therefore, further investigations, including salivation disorders, are necessary to validate these findings.

Inflammatory biomarker concentrations in dogs with gastric dilatation volvulus with and without 24-h intravenous lidocaine.

Background: Canine gastric dilatation volvulus (GDV) is characterized by tissue ischemia, reperfusion, and systemic inflammation. Evidence exists that lidocaine exerts anti-inflammatory properties and potentially improves outcome. Design and setting: Prospective, randomized observational cohort study in client-owned dogs with GDV. Objective: The primary objective of the study was the determination of pro- and anti-inflammatory biomarker concentrations in dogs with GDV with and without intravenous (IV) lidocaine therapy. The second objective was the evaluation of side effects of lidocaine. Methods: Of 35 dogs included in the study, 20 dogs were assigned to receive lidocaine (LIDO) (2 mg/kg initially, followed by a continuous infusion at a rate of 50 µg/kg/min over 24 h) and 15 dogs not to receive lidocaine (NO-LIDO). Plasma concentrations of cytokines interleukin (IL)-6, IL-7, IL-8, IL-10, IL-15, IL-18, interferon gamma, keratinocyte chemotactic-like, monocyte chemotactic protein, and C-reactive protein (CRP) were measured at admission (prior any therapeutic intervention, T0), immediately after surgery (T1), at 24 h (T24), and at 48 h (T48) post-surgery. Results: No significant differences in concentrations of any cytokines were found between the LIDO- and the NO-LIDO group. Significant lower CRP concentrations (median [range]) were found in dogs with lidocaine compared to dogs without at T24 (97.5 pg/mL [46.3-161.7] vs. 127.9 pg/mL [26.9-182.0]; p = 0.046) and T48 (73.7 pg/mL [18.4-169.4] vs. 116.3 pg/mL [71.4-176.8]; p = 0.002). Dogs receiving lidocaine exhibited significantly impaired mentation, a prolonged period of anorexia, and longer hospitalization compared to dogs without lidocaine. Conclusion: Lidocaine administration had no impact on the plasma levels of cytokines during the 48-h study period, but significantly lower CRP concentrations were found at T24 and T48. Lidocaine's potential side effects require careful decision making regarding its use.

Assessment of the Prevalence of Middle Mesial Canal in Mandibular First Molar: A Multinational Cross-sectional Study with Meta-analysis.

BACKGROUND: An additional canal found in the mandibular first molar (M1M) is the middle mesial canal (MMC), which is often missed during root canal treatment. In this study, the prevalence of MMC in M1M on cone-beam computed tomography (CBCT) images was evaluated in 15 countries, along with the effect of some demographic factors on its prevalence. METHODS: Deidentified CBCT images were scanned retrospectively, and the ones including bilateral M1Ms were included in the study. A written and video instruction program explaining the protocol to be followed step-by-step was provided to all observers to calibrate them. The CBCT imaging screening procedure consisted of evaluating three planes (coronal, sagittal, and axial) after a 3-dimensional alignment of the long axis of the root(s). The presence of an MMC in M1Ms (yes/no) was identified and recorded. RESULTS: In total, 6304 CBCTs, representing 12,608 M1Ms, were evaluated. A significant difference was found between countries (P < .05). MMC prevalence ranged from 1% to 23%, and the overall prevalence was 7% (95% confidence interval [CI]: 5%-9%). No significant differences were found between the left and right M1M (odds ratio = 1.09, 95% CI: 0.93, 1.27; P > .05) or between genders (odds ratio= 1.07, 95% CI: 0.91, 1.27; P > .05). As for the age groups, no significant differences were found (P > .05). CONCLUSIONS: The prevalence of MMC varies by ethnicity, but it is generally estimated at 7% worldwide. Physicians must pay close attention to the presence of MMC in M1M, especially for opposite M1Ms, due to the prevalence of MMC being significantly bilateral.

Influence of the Polymerization Modes on the Methacrylic Acid Release from Dental Light-Cured Materials-In Vitro Study.

The study focuses on the problem of lowering the pH around a composite filling concerning the polymerization modes and methacrylic acid release, which may affect not only the oral health but also the whole organism. A total of 90 specimens (30 of each: Filtek Bulk Fill, Evetric and Riva LC) were placed in 90 sterile hermetic polyethene containers with saline and incubated at 37 °C. Ten samples of each material were light-cured for 40 s with one of the three curing modes: full power mode (FPM), ramping mode (RM) and pulse mode (PM). The pH and methacrylic acid release evaluation were performed at the following time points: after 2 h and after 3, 7, 21 and 42 days from the specimen preparation. Regardless of light-curing mode, all used materials were characterized by a gradual elevation in methacrylic acid concentration. Only for Filtek Bulk Fill, increased methacrylic acid release was closely associated with lower pH. The choice of the polymerization mode has no significant influence on the methacrylic acid release. However, further research about composite light-curing is necessary to create the procedure algorithm, reducing the local and systemic complications associated with composite fillings.

Extended family impact of genetic testing: the experiences of X-linked carrier grandmothers.

In many cases, X-linked conditions are transmitted through families "silently" until the first affected individual is diagnosed. Grandmothers are often then tested to help determine the risk to other family members. To date, psychosocial research on carriers of X-linked conditions has focused primarily on mothers and sisters of affected males. In the wider social science literature, studies on grandparents of children with disabilities have centered on their role within the family and relationship with the grandchild. We therefore know little about the impact of carrier testing for a genetic condition on grandparents. This qualitative study aims to contribute towards filling that gap. This study included thirteen grandmothers in families with Fragile X or Duchenne muscular dystrophy; ten had living affected grandsons and three had daughters who chose not to continue with affected male pregnancies after prenatal diagnosis. All thirteen took part in semi-structured interviews and provided a rich and varied data source for conducting thematic analysis. Most of the grandmothers expressed recurring feelings of guilt and a strong sense of responsibility for what had occurred in the family. Other themes included feelings of shock after receiving their test result, changes in family relationships and searching to make sense of the inheritance within the context of the family's experience. This study provides evidence that X-linked carrier testing can have a profound and lasting impact on grandmothers. Although genetic counseling for X-linked conditions is often focused on the potential reproductive implications for carriers, these findings suggest that grandmothers should also be offered genetic counseling when tests are carried out, because of the likely psychosocial impact of a positive test result.

The Effectiveness of the Blended Learning in Conservative Dentistry with Endodontics on the Basis of the Survey among 4th-Year Students during the COVID-19 Pandemic.

The COVID-19 pandemic has undoubtedly affected education at all levels, including medical and dental education. Our study aimed to assess the effectiveness of the blended learning in conservative dentistry with endodontics. The students had theoretical classes in a remote form (using the e-learning portal and Teams communicator) and practical classes with the participation of patients in the appropriate sanitary regime. The author's survey was conducted among fourth-year dental students. The online questionnaire consisted of 5 parts: self-evaluation, evaluation of theoretical e-learning classes, evaluation of practical clinical classes, evaluation of safety, and evaluation of performed blended learning. The majority of respondents declared that their learning effectiveness increased during the pandemic. Most surveyed students preferred remote learning in asynchronous form (e-learning portals) to synchronous form (virtual meetings in real-time). All respondents described the provided personal protective equipment as sufficient or even as excessive. Our students were very satisfied with the proposed blended-learning model and would like to continue it even after the pandemic has ended. Among the advantages, they particularly mentioned the increase in efficiency and the individualised pace of learning, while the disadvantage was the limitation of social contacts. The appropriate use of modern technology can effectively revolutionise dental education.

Kinetics of Plasma Cytokines, Angiopoietin-2, and C-Reactive Protein in Dogs With Gastric Dilatation Volvulus.

Background: The degree of systemic inflammation, reperfusion injury and endothelial activation are potentially important determinants of clinical outcomes in dogs with gastric dilatation volvulus (GDV). Objective: To evaluate plasma concentrations and kinetics of inflammatory markers in dogs with GDV over a time frame of 48 h, and to compare to healthy dogs. Design and Setting: Prospective, observational cohort study in client-owned dogs with GDV. Materials and Methods: Fifteen dogs with GDV and 9 healthy control dogs were enrolled. Plasma concentrations of interleukin (IL)-6, IL-7, IL-8, IL-10, IL-15, IL-18, interferon gamma (IFN-γ), keratinocyte chemotactic-like, monocyte chemotactic protein (MCP)-1, Angiopoietin (Ang)-2, and C-reactive protein (CRP) were measured at admission (prior any therapeutic intervention, (T0), immediately after surgery (T1), 24 ± 4 h (T24), and 48 ± 4 h (T48) post-surgery. Cytokines were measured using multiplex magnetic bead assay. Plasma Ang-2 was measured with a commercial human ELISA test kit validated for dogs. Results: Dogs with GDV had significantly higher plasma concentrations of IFN-γ and IL-10 compared to healthy control dogs at all time points. Concentrations of IL-6 were significantly higher at T1 and T24, concentrations of MCP-1 at T24, and concentrations of CRP at T24 and T48. A significant increase between T0 and T1 was found for IL-6, IL-10, and CRP, between T1 and T24 for IL-8, IFN-γ, MCP-1, and CRP, and between T24 and T48 for IL-15, Ang-2, and CRP. A significant decrease between T0 and T1 was found for IL-7, IL-8, IL-15, IL-18, and Ang-2; between T1 and T24 for IL-6 and KC-like; and between T24 and T48 for IL-6. Conclusion: In GDV dogs, a mild pro-inflammatory reaction was present at admission, which peaked immediately after and up to 24 h post-surgery, mainly represented by IL-6, IFN-γ, MCP-1, and CRP, and which decreased at T48. In addition, the anti-inflammatory IL-10 was increased in GDV dogs at all time points.

Poor Oral Hygiene and High Levels of Inflammatory Cytokines in Saliva Predict the Risk of Overweight and Obesity.

The study aimed to determine if oral hygiene influences not only oral health but also potentially metabolic disorders such as overweight or obesity. Participants were 94 patients: 40 with increased body mass and 54 with normal body mass. The methods included dental examination, a questionnaire concerning hygienic habits and an assessment of selected salivary inflammatory markers. The new parameter named "cleaning index" (describing the interaction between average time of tooth brushing in minutes and its frequency per day) significantly correlated with Body Mass Index (RSpearman = 0.300). The multivariate regression model incorporating cleaning index, approximal plaque index, receptor 1 for tumor necrosis factor-alpha (TNFα-R1) and interleukin-15 (IL-15) had a high power to predict overweight or obesity (AUC = 0.894). Patients with poor oral hygiene (approximal plaque index >40%) were more than eight times more likely to suffer from obesity than patients with good oral hygiene. Cleaning index higher than 4 decreased the odds by about 85%. Oral hygiene habits, adjusted by salivary concentrations of selected inflammatory markers may allow predicting effectively overweight or obesity risk. Early proper dental prophylaxis and treatment could lead to the better prevention of metabolic disorders.

Characteristics of salivary inflammation in obesity.

INTRODUCTION: The discovery of the secretory function of adipose tissue has led to a new direction in research on obesity­ related health problems. Adipokines are present not only in blood but also in saliva. Numerous studies have indicated that obesity affects salivary concentrations of adipokines. OBJECTIVES: The aim of this study was to evaluate the levels of selected inflammatory markers in saliva and to determine their discriminatory value in obese individuals. PATIENTS AND METHODS: The study included 125 patients (82 women and 43 men), aged from 20 to 65 years. There were 59 patients with obesity (body mass index [BMI] >30 kg/m2) and 66 controls with normal body weight (BMI <25 kg/m2). Mixed saliva samples were collected from all participants to determine the concentrations of the following inflammatory markers: tumor necrosis factor­ α receptors 1 and 2, pentraxin 3, interleukin 15, monocyte chemoattractant protein 1, soluble intercellular adhesion molecule 1, and soluble CD40 ligand (sCD40L). RESULTS: Compared with controls, individuals with obesity had significantly higher levels of all inflammatory markers except sCD40L levels, which were lower. The salivary marker sCD40L seems to have the best discriminatory value in obesity regardless of sex, with the optimal cutoff point of 3.28 pg/ml and the area under the curve of 0.8. CONCLUSIONS: Obesity may be associated with altered levels of selected inflammatory markers in saliva. The discriminatory values determined in this study may facilitate the diagnosis of metabolic diseases.

Fission yeast F-box protein Pof3 is required for genome integrity and telomere function.

The Skp1-Cullin-1/Cdc53-F-box protein (SCF) ubiquitin ligase plays an important role in various biological processes. In this enzyme complex, a variety of F-box proteins act as receptors that recruit substrates. We have identified a fission yeast gene encoding a novel F-box protein Pof3, which contains, in addition to the F-box, a tetratricopeptide repeat motif in its N terminus and a leucine-rich-repeat motif in the C terminus, two ubiquitous protein-protein interaction domains. Pof3 forms a complex with Skp1 and Pcu1 (fission yeast cullin-1), suggesting that Pof3 functions as an adaptor for specific substrates. In the absence of Pof3, cells exhibit a number of phenotypes reminiscent of genome integrity defects. These include G2 cell cycle delay, hypersensitivity to UV, appearance of lagging chromosomes, and a high rate of chromosome loss. pof3 deletion strains are viable because the DNA damage checkpoint is continuously activated in the mutant, and this leads to G2 cell cycle delay, thereby preventing the mutant from committing lethal mitosis. Pof3 localizes to the nucleus during the cell cycle. Molecular analysis reveals that in this mutant the telomere is substantially shortened and furthermore transcriptional silencing at the telomere is alleviated. The results highlight a role of the SCF(Pof3) ubiquitin ligase in genome integrity via maintaining chromatin structures.