Development of an in chemico high-throughput screening method for the identification of skin sensitization potential.

It is well established that chemical-peptide conjugation represents the molecular initiating event (MIE) in skin sensitization. This MIE has been successfully exploited in the development of in chemico peptide reactivity assays, with the Direct Peptide Reactivity Assay (DPRA) being validated as a screening tool for skin sensitization hazard as well as an OECD test guideline. This test relies on the use of a high-performance liquid chromatography/ultraviolet detection method to quantify chemical-peptide conjugation through measurement of the depletion of two synthetic peptides containing lysine or cysteine residues, which is labor-intensive and time-consuming. To improve assay throughput, sensitivity, and accuracy, we have developed a spectrophotometric assay for skin sensitization potential based on MIE measurement-the ProtReact assay. ProtReact is also a cheaper, faster, simpler, and more accessible alternative for the DPRA, giving comparable results. A set of 106 chemicals was tested with ProtReact and the peptide depletion values compared with those reported for the DPRA. The predictive capacity of both assays was evaluated with human reference data. ProtReact and DPRA assays show similar predictive capacities for hazard identification (75% and 74%, respectively), although ProtReact showed a higher specificity (86% versus 74%, respectively) and lower sensitivity (69% versus 73%). Overall, the results show that ProtReact assay described here represents an efficient, economic, and accurate assay for the prediction of skin sensitization potential of chemical haptens.

Efficacy of different neoadjuvant treatment regimens in BRCA-mutated triple negative breast cancer: a systematic review and meta-analysis.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer strongly associated with BRCA mutation. Standard neoadjuvant chemotherapy remains the standard of care for early stage TNBC, the optimal chemotherapy regimen is still a matter of discussion. Other agents, such as poly-ADP-ribosyl polymerase inhibitors (PARPi) and anti-vascular endothelial growth factor (VEGF) antibodies were evaluated in the neoadjuvant setting. This systematic review and meta-analysis intend to evaluate the impact of neoadjuvant treatments in pCR rates in TNBC gBRCA mutation, beyond traditional standard chemotherapy. METHODS: PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase and key oncological meetings for trials were searched for studies reporting neoadjuvant chemo-immunotherapy in BRCA positive TNBC. RESULTS: Out of 1238 records reviewed, thirty-one trials were included, resulting in a total 619 BRCA-mutated TNBC patients. In BRCA mutated TNBC patients who received cisplatin in monotherapy the proportion of patients who achieved pCR was 0.53 (95%CI [0.30, 0.76]), and when treatment combined standard chemotherapy and platin derivatives the proportion of pCR increased to 0.62 (95% CI [0.48, 0.76]). The group of patients treated with platin derivatives, anthracyclines ± taxanes achieved the highest proportion of pCR, 0.66. Patients treated with PARPi alone show a pCR proportion of 0.55 (95% CI [0.30, 0.81]); and when standard chemotherapy and platin derivatives were combined with PARPi the proportion of pCR did not vary. CONCLUSIONS: Patients with BRCA mutated TNBC treated with cisplatin in monotherapy demonstrate inferior proportion in the pCR achievement when compared with standard chemotherapy plus platin derivates. The best pCR was achieved with platin derivates in association with anthracyclines ± taxanes. No difference in pCR was found between PARPi alone vs PARPi with standard chemotherapy.

Cold Atmospheric Plasma Apoptotic and Oxidative Effects on MCF7 and HCC1806 Human Breast Cancer Cells.

Breast cancer (BC) is a malignant neoplasia with the highest incidence and mortality rates in women worldwide. Currently, therapies include surgery, radiotherapy, and chemotherapy, including targeted therapies in some cases. However, treatments are often associated with serious adverse effects. Looking for new options in BC treatment, we evaluated the therapeutic potential of cold atmospheric plasma (CAP) in two cell lines (MCF7 and HCC1806) with distinct histological features. Apoptosis seemed to be the most prevalent type of death, as corroborated by several biochemical features, including phosphatidylserine exposure, the disruption of mitochondrial membrane potential, an increase in BAX/BCL2 ratio and procaspase 3 loss. Moreover, the accumulation of cells in the G2/M phase of the cell cycle points to the loss of replication ability and decreased survival. Despite reported toxic concentrations of peroxides in culture media exposed to plasma, intracellular peroxide concentration was overall decreased accompanying a reduction in GSH levels shortly after plasma exposure in both cell lines. In HCC1806, elevated nitric oxide (NO) concentration accompanied by reduced superoxide levels suggests that these cells are capable of converting plasma-derived nitrites into NO that competes with superoxide dismutase (SOD) for superoxide to form peroxinitrite. The concomitant inhibition of the antioxidative activity of cells during CAP treatment, particularly the inhibition of cytochrome c oxidase with sodium azide, synergistically increased plasma toxicity. Thus, this in vitro research enlightens the therapeutic potential of CAP in the treatment of breast cancer, elucidating its possible mechanisms of action.

Luting indirect restorations with resin cements versus composite resins: Effects of preheating and ultrasound energy on film thickness.

OBJECTIVE: This study aims to evaluate and compare the film thickness obtained with a resin cement and two composite resins, preheated and/or ultrasonically vibrated, as luting agents. MATERIALS AND METHODS: One hundred and twenty-six (126) pairs of resin discs were randomly assigned to six experimental groups (n = 21) according to luting agent (Variolink Esthetic LC, IPS Empress Direct or Estelite Omega) and cementation technique (preheating at 68°C and/or ultrasonic vibration). Specimens were luted by applying a controlled force. Following sectioning and film thickness measurement through field emission gun scanning electron microscopy, statistical analysis was carried out considering a 5% significance level. RESULTS: Statistically significant lower film thickness was observed in Variolink Esthetic LC group when compared to all composite resin groups (p < 0.001), except IPS Empress Direct preheated and ultrasonically vibrated group (p = 0.073). IPS Empress Direct with ultrasonic vibration yielded statistically lower film thickness values than Estelite Omega groups, regardless of luting technique (p < 0.05). Ultrasonically vibrated Estelite Omega groups showed statistically lower film thickness values than solely preheated groups (p < 0.05). CONCLUSIONS: Both Variolink Esthetic LC and IPS Empress Direct preheated and ultrasonically vibrated provided the lowest film thickness. The addition of ultrasonic vibration during cementation proved to be effective in reducing film thickness of both tested composite resins. CLINICAL SIGNIFICANCE: The cementation technique will have variable results depending on the luting material. Adhesive cementation protocols with composite resins should mainly consider ultrasonic vibration, but also preheating, as strategies for reducing film thickness. The tested resin cement, alongside with IPS Empress Direct composite resin preheated and ultrasonically vibrated, provided the lowest film thickness among the tested materials and techniques.

Implantoplasty Improves Clinical Parameters over a 2-Year Follow-Up: A Case Series.

Background and Objectives: Peri-implantitis treatment is still undefined. Regenerative treatment is expensive and technically demanding due to the need to handle biomaterials, membranes and different methodologies of decontamination. Resective treatment and implantoplasty might be a viable solution. This case series presents a 24 month retrospective observational study of 10 peri-implantitis patients treated with implantoplasty. Materials and Methods: In the present case series, 10 peri-implantitis patients (20 implants) were treated with a resective approach and implantoplasty. Previous to implantoplasty, all patients underwent non-surgical treatment. This surgery consisted in a full-thickness flap and implant surface exposure. The exposed non-osseointegrated implant body was submitted to implantoplasty. The flap was apically repositioned and sutured. Patients were accompanied for 24 months. Results: The mean initial probing depth (PD) (PD = 5.37 ± 0.86 mm), bleeding on probing (BoP = 0.12 ± 0.06%) and suppuration (Sup = 0.01 ± 0.01%) decreased significantly at the 12 month evaluation (PD = 2.90 ± 0.39 mm; BoP = 0.01 ± 0.01% and Sup = 0.00 ± 0.00%). Between the 12 and 24 month evaluations, there were no significant clinical changes (PD = 2.85 ± 0.45 mm; BoP = 0.01 ± 0.01% and Sup = 0.00 ± 0.00%). Mucosal recession (MR) had a significant increase between the baseline and the first 12 months (0.69 ± 0.99 mm vs. 1.96 ± 1.33 mm), but there were no significant changes between the 12th and 24th month (1.94 ± 1.48 mm). The success rate was 100% without implant fracture or loss. Conclusions: Resective surgery and implantoplasty might be a valid option in some specific peri-implantitis cases. Properly designed clinical trials are needed to confirm this possibility.

Salivary counts of Streptococcus mutans and Lactobacillus in patients with and without cleft lip and/or palate undergoing orthodontic treatment: A meta-analysis.

OBJECTIVE: To conduct a systematic review with meta-analysis to assess if cleft lip and palate (CLP) patients undergoing orthodontic treatment have a higher colonization of Streptococcus mutans and Lactobacillus than patients without this condition. METHODS: Five electronic databases were searched systematically. The inclusion criteria were as follows: randomized clinical trials, non-randomized, or quasi-randomized controlled trials, prospective and retrospective studies published until March, 2021; articles that evaluated S. mutans and Lactobacillus profile in patients with and without cleft lip and palate undergoing orthodontic treatment. The random-effect model was used to perform the analysis of all the data collected. Statistic heterogeneity was evaluated with I2 test. RESULTS: In this systematic review, 2 cohort studies were included. The data analysis from 160 patients revealed that patients without cleft lip and palate had 4.5 times more predisposition to oral colonization with S. mutans than CLP patients. No statistical significant difference was found between these patients for colonization with Lactobacillus. CONCLUSIONS: Despite the limitations in the included studies, this systematic review suggested that CLP patients have a lower predisposition to oral colonization with S. mutans when compared to healthy patients.

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis in childhood: A genetic and epigenetic study with comparison with basal cell carcinomas evolving in chronically sun-exposed areas.

BACKGROUND: Basal cell carcinoma (BCC) has been mostly associated with sun exposure, but ionizing radiation is also a known risk factor. It is not clear if the pathogenesis of BCC, namely at a genomic and epigenetic level, differs according to the underlying triggering factors. OBJECTIVE: The present study aims to compare genetic and epigenetic changes in BCCs related to ionizing radiation and chronic sun exposure. METHODS: Tumor samples from BCCs of the scalp in patients submitted to radiotherapy to treat tinea capitis in childhood and BCCs from sun-exposed areas were analysed through array comparative genomic hybridization (array-CGH) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to detect copy number alterations and methylation status of specific genes. RESULTS: Genomic characterization of tumor samples revealed several copy number gains and losses in all chromosomes, with the most frequent gains observed at 2p, 6p, 12p, 14q, 15q, 18q, Xp and Yp, and the most frequent losses observed at 3q, 14q, 16p, 17q, 22q, Xp, Yp and Yq. We developed a statistical model, encompassing gains in 3p and 16p and losses in 14q and 20p, with potential to discriminate BCC samples with sporadic aetiology from BCC samples that evolve after radiotherapy in childhood for the treatment of tinea capitis, which presented statistical significance (P = 0.003). Few methylated genes were detected through MS-MLPA, most frequently RARB and CD44. CONCLUSIONS: Our study represents a step forward in the understanding of the genetic mechanisms underlying the pathogenesis of BCC and suggests potential differences according to the underlying ris k factors.

Multiple Basal Cell Carcinomas of the Scalp After Radiotherapy: Genomic Study in a Case With Latency Period Over 80 Years.

ABSTRACT: Basal cell carcinoma (BCC) has been linked mostly to ultraviolet radiation exposure, but ionizing radiation has also been implicated in the genesis of a subset of BCCs occurring after radiotherapy. We present a 93-year-old woman with 4 BCCs of the scalp after radiotherapy for tinea capitis, diagnosed after a latency period of over 80 years. The largest lesion was located on the right temporal region and corresponded to a BCC of mixed type, with nodular, infiltrative, and micronodular components. We performed genomic study with array comparative genomic hybridization in samples from each BCC, which revealed more imbalances in the largest lesion than in the remaining ones, correlating with its higher histological complexity. Furthermore, this was the only lesion presenting loss at 2p22.3, where is mapped the BIRC6 gene associated with regulation of apoptosis, and loss at 16q24.3, where is mapped FANCA gene, responsible for DNA repair and maintenance of chromosome stability. Despite these differences, there were aberrations shared by all tumor samples, suggesting a common genetic signature. Our report describes, to the best of our knowledge, the longest latency period between exposure to radiotherapy and the diagnosis of BCC. The genomic study showed imbalances common to all tumor samples but also differences that could explain their heterogeneity in terms of histological subtype and biological potential. In addition, these differences could also be a consequence of different times in the evolution of the lesions at the moment of presentation, thus having a diverse combination of accumulated genomic imbalances.

Collagenated Porcine Heterologous Bone Grafts: Histomorphometric Evaluation of Bone Formation Using Different Physical Forms in a Rabbit Cancellous Bone Model.

Collagenated porcine-derived bone graft materials exhibit osteoconductive properties and the development of different formulations intends to enhance bone regeneration. This study aims to evaluate bone healing in a rabbit cancellous bone defect in response to grafting with different physicochemical forms of heterologous porcine bone. Twenty-six adult male New Zealand White rabbits received two critical size femoral bone defects per animal (n = 52), each randomly assigned to one of the five tested materials (Apatos, Gen-Os, mp3, Putty, and Gel 40). Animals were sacrificed at 15- and 30-days post-surgery. Qualitative and quantitative (new bone, particle and connective tissue percentages) histological analyses were performed. Histomorphometry showed statistically significant differences in all evaluated parameters between mp3 and both Putty and Gel 40 groups, regardless of the timepoint (p < 0.05). Moreover, statistical differences were observed between Apatos and both Putty (p = 0.014) and Gel 40 (p = 0.007) groups, at 30 days, in regard to particle percentage. Within each group, regarding new bone formation, mp3 showed significant differences (p = 0.028) between 15 (40.93 ± 3.49%) and 30 (52.49 ± 11.04%) days. Additionally, intragroup analysis concerning the percentage of particles revealed a significant reduction in particle occupied area from 15 to 30 days in mp3 and Gen-Os groups (p = 0.009). All mp3, Gen-Os and Apatos exhibited promising results in terms of new bone formation, thus presenting suitable alternatives to be used in bone regeneration.

A retrospective and tridimensional study of the maxillary sinus in patients with cleft lip and palate.

INTRODUCTION: Structural or anatomic differences may arise during the development of the maxillary sinus and the process of fusion of the palate in the presence of cleft lip and palate. The present study aimed to compare the maxillary sinus volume of patients with unilateral cleft lip and palate and a control group (noncleft patients). METHODS: In this retrospective case-control study, 160 cone-beam computed tomography images of 80 unilateral cleft lip and palate patients (41 males and 39 females; mean age, 12.7 ± 6.03 years) and 80 control patients (43 males and 37 females; mean age, 13.1 ± 6.27 years) were evaluated through the ITK-SNAP software (Cognitica, Philadelphia, Pa) to access the maxillary sinus volume. Analysis of covariance and regression analysis were used to assess the differences between the groups while considering the relationship between maxillary sinus volume, age, and sex. RESULTS: No statistically significant differences were found in the maxillary sinus volume analyzing a unilateral cleft lip and palate and a control group (P = 0.677). Considering the cleft group, there is a tendency for the maxillary sinus volume of the cleft side to be smaller than its contralateral (P < 0.001). Statistically significant differences were found in the maxillary sinus volume, regarding the age and sex of cleft and noncleft patients (P < 0.001 for age; P = 0.001 for sex). CONCLUSIONS: According to these results, the presence of unilateral cleft lip and palate did not affect the maxillary sinus volume, comparing cleft and noncleft patients. A biphasic growth pattern of the maxillary sinus and a presence of sexual dimorphism were found.

Evaluation of a novel dog animal model for peri-implant disease: clinical, radiographic, microbiological and histological assessment.

OBJECTIVE: To assess longitudinal peri-implant tissue evaluation in a plaque compromised ligature free dog model, clinically, radiographically, microbiologically and histologically. MATERIALS AND METHODS: Six beagle mandibular premolars and first molars were extracted. Plaque accumulated for 16 weeks. Two implants were placed per hemi-mandible. For 17 weeks, control implants (CI) in one hemi-mandible were brushed daily; test implants (TI) in the other were not. These parameters were then assessed: clinically, probing depth (PD), bleeding-on-probing (BOP), presence of plaque (PP) and clinical attachment level (CAL); radiographically, marginal bone level; microbiologically, counts for Streptococcus spp., Fusobacterium spp., Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia and total bacterial load. At week 17, histomorphometric analysis was performed (MM-ISH (mucosal margin-implant shoulder); ISH-fBIC (implant shoulder-first bone-to-implant contact); MM-aJE (mucosal margin-apical area junctional epithelium); MM-aINF (mucosal margin-apical limit of the inflammatory infiltrate); %INF (percentage of inflammatory infiltrate)). RESULTS: At week 17, TI had significant increased PD, BOP, PP and CAL versus baseline. All clinical variables presented intergroup differences. There was no intergroup difference for radiographic bone loss (p > 0.05). Total bacteria, Fusobacterium spp., A. actinomycetemcomitans and P. gingivalis had intergroup differences. There was no statistically significant intergroup difference for ISH-fBIC. CONCLUSIONS: Longitudinal microbiology evaluation detected a shift period. Final intergroup microbiological differences were the basis of W17 clinical intergroup differences, with higher values in TI. Microbiological and clinical changes detected in peri-implant tissues were compatible with onset of peri-implant disease. Despite histological inflammatory intergroup difference, no histological or radiographic intergroup bone loss was detected. CLINICAL RELEVANCE: This study set-up describes a valuable method for generating "true" early peri-implant defects without mechanical trauma.

Cytotoxic effects of a chlorhexidine mouthwash and of an enzymatic mouthwash on human gingival fibroblasts.

The aim of this study was to evaluate the cytotoxic effects of an enzymatic mouthwash and of a chlorhexidine mouthwash on human gingival fibroblasts. The metabolic activity of the fibroblasts exposed to each mouthwash was assessed by the MTT assay and the protein content was assessed by the SRB assay. The flow cytometry was used to evaluate the cell cycle and the types of cell death. The oxidative status was evaluated through the DCF and the DHE probes and the intracellular GSH concentration and the mitochondrial membrane potential through JC-1. The cytotoxicity of both mouthwashes was found to be dependent on the exposure time and on the concentration. However, the cytotoxicity of the enzymatic mouthwash was found to be lower than that of the chlorhexidine mouthwash. A trend towards increased oxidative stress was observed for both mouthwashes. After exposing the fibroblasts to the mouthwashes, a G2/M phase block was observed and cell death occurred predominantly by necrosis. The effects of chlorhexidine on fibroblasts were identified at lower concentrations than those used in clinical practice. Therefore, the use of chlorhexidine as an antiseptic in surgical and postoperative situations should be limited. In order to clarify the clinical significance of the enzymatic mouthwash cytotoxicity new clinical studies will be necessary.

Dental caries, diabetes mellitus, metabolic control and diabetes duration: A systematic review and meta-analysis.

OBJECTIVE: To analyze articles aimed at evaluating the association between diabetes, metabolic control, diabetes duration, and dental caries. OVERVIEW: A systematic search in PubMed, Cochrane Library, Embase, and Web of Science was conducted to retrieve papers in English, Portuguese, and Spanish, up to April 2019. The research strategy was constructed considering the "PECO" strategy. Only quantitative observational studies were analyzed. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. The meta-analyses were performed based on random-effects models using the statistical platform R. A total of 69 articles was included in the systematic review and 40 in the meta-analysis. Type 1 diabetics have a significantly higher DMFT compared to controls. No significant differences were found between type 2 diabetics and controls and between well-controlled and poorly controlled diabetics. Concerning diabetes duration, all authors failed to find differences between groups. CONCLUSION: Although there is still a need for longitudinal studies, the meta-analysis proved that type 1 diabetics have a high dental caries risk. CLINICAL SIGNIFICANCE: It is necessary to be aware of all risk factors for dental caries that may be associated with these patients, making it possible to include them into an individualized prevention program.

Different Treatments in Patients with Temporomandibular Joint Disorders: A Comparative Randomized Study.

BACKGROUND AND OBJECTIVES: Temporomandibular joint disorders (TMJDs) are associated with pain and reduced jaw mobility. The aim of this study was to compare the outcome of patients with TMJ arthralgia when submitted to four different treatment modalities, in some cases using intra-articular injections of substances with anti-inflammatory properties and in others, a more conservative approach consisting only of a bite splint. Materials and Methods: The sample was made up of 80 patients, randomly distributed into 4 groups of 20 patients each. Each patient was given a nocturnal bite splint. One of the groups was treated with the bite splint only, while each patient in the other 3 was injected with betamethasone, sodium hyaluronate, or platelet-rich plasma in addition to using the bite splint. Two variables were assessed, namely pain intensity between 0 to 10 according to the visual analogue scale and maximum pain-free mouth opening in mm. The patients were evaluated at four different points: at the beginning of the treatment, as well as one week, one month and six months after initiation. RESULTS: The results showed that maximum pain-free mouth opening improved in all the groups that made up the sample, with either a reduction in pain severity or with no pain. However, the group injected with platelet-rich plasma yielded the best results after six months, while patients treated with sodium hyaluronate or betamethasone obtained the best results at the end of the first week. CONCLUSIONS: We concluded that all the treatments used caused a reduction in pain and increased pain-free mouth opening. The splint combined with the platelet-rich plasma injection achieved long-term success.

Short-term pharyngeal airway space changes after mandibular advancement surgery in Class II patients-a two-dimensional retrospective study.

INTRODUCTION: Planning successful treatment for the correction of anatomic abnormalities of the upper airways, by surgical advancement of the mandible, depends on extensive knowledge of the pharyngeal airway space (PAS). However, there is limited scientific evidence about changes in PAS after mandibular advancement surgery. AIM: To evaluate the immediate changes in superior posterior airway space (SPAS) in Class II patients, after mandibular advancement surgery. MATERIALS AND METHODS: A cephalometric evaluation of 37 patients with skeletal Class II deformity was performed at 2 distinct time intervals: Pre-operative (T0) and immediate post-operative (T1), using Dolphin Image & Management Solutions, version 11.9, according to the method of Arnett/Gunson FAB Surgery. The differences due to the surgical intervention were assessed with Student's t test, and a Principal Component Analysis was used to evaluate the relationship between mandibular advancement and SPAS variables. Anticlockwise and clockwise rotation groups were also evaluated with Mann-Whitney tests. The statistical analysis was conducted in SPSS and R assuming a 0.05 level of significance. RESULTS: As an effect of mandibular advancement, an anteroposterior statistically significant increase in SPAS (P < 0.001) was perceived at all points measured. CONCLUSION: Our findings indicate that mandibular advancement surgery is a viable option to achieve widening of the SPAS in patients with Class II skeletal morphology.

The effect of neoadjuvant platinum-based chemotherapy in BRCA mutated triple negative breast cancers -systematic review and meta-analysis.

BACKGROUND: Triple negative breast cancers (TNBC) are associated with an aggressive clinical course, earlier recurrence and short survival. BRCA - mutated tumours represent up to 25% of all TNBC. BRCA status is being studied as a predictive biomarker of response to platinum agents. However, the predictive role of BRCA status is still uncertain in this setting. Since TNBC is a very heterogeneous group of diseases, it is important to identify subsets of TNBC patients that may benefit from platinum-based therapy. This study aims to establish if the presence of a germline BRCA mutation in women with TNBC improves the pathologic complete response (pCR) after neoadjuvant chemotherapy with platinum compounds. METHODS: An extensive literature search was performed in MEDLINE, EMBASE and LILACS databases, WHO (WHO International Clinical Trials Registry Platform) and the Cochrane Controlled Trials Register Database, for online trial registries and conference proceedings. The measurement of pCR was assessed by pathology review of breast specimen and lymph nodes. RESULTS: The overall OR was computed using random effects models.Seven studies were included, comprising a total of 808 TNBC patients, among which 159 were BRCA mutated. Among mutated TNBC patients, 93 (93/159; 58.4%) achieved pCR, while 410 wildtype patients (410/808; 50.7%) showed pCR (OR 1.459 CI 95% [0.953-2.34] p = 0.082) although this result did not reach statistical significance. CONCLUSIONS: This meta-analysis shows that the addition of platinum to chemotherapy regimens in the neoadjuvant setting increases pCR rate in BRCA - mutated as compared to wild-type TNBC patients. However, this trend did not achieve statistical significance. TRIAL REGISTRATION: CRD42018092341.

Cyclic fatigue resistance of three rotary file systems in a dynamic model after immersion in sodium hypochlorite.

To evaluate the effect of immersion in 3% sodium hypochlorite solution in the resistance to cyclic fatigue of three nickel-titanium (NiTi) rotary file systems, ProTaper Next (PTN), Hyflex CM (CM), and Hyflex EDM (EDM), in a mechanical model featuring axial movement. Ninety instruments of three different NiTi rotary file systems, PTN (size 25, 0.06 taper), CM (25, 0.06), and EDM (25/~, variable taper), were randomly divided according to a 3 × 3 factorial design and tested under dynamic immersion in a 3% NaOCl solution (1 or 5 min) or without immersion, making a total of 9 groups (n = 10). Files were tested in an artificial root canal with 45° angle and 5 mm radius apical curvature being submitted to back-and-forth movements until fracture. Statistical analysis was performed using two-way factorial ANOVA with Bonferroni post-hoc tests, at a significance level of 5%. Instruments were evaluated for reliability using a Weilbull approach. Regardless of the immersion treatment, PTN had on average 1200 ± 178 cycles to fracture, CM had 1949 ± 362, and EDM had 5573 ± 853, which was a significantly different (P < 0.01). The NaOCl immersion promoted a significant reduction in the mean number of cycles to fracture (P = 0.01), and was reflected in a significant reduction of the characteristic life of the instruments of the CM end EDM groups. Within this study conditions, EDM instruments performed better to cyclic fatigue followed by CM and then PTN. Immersion in NaOCl decreased the resistance to cyclic fatigue of all tested instruments, but affected more those manufactured from CM wire.

Using Resistin, glucose, age and BMI to predict the presence of breast cancer.

BACKGROUND: The goal of this exploratory study was to develop and assess a prediction model which can potentially be used as a biomarker of breast cancer, based on anthropometric data and parameters which can be gathered in routine blood analysis. METHODS: For each of the 166 participants several clinical features were observed or measured, including age, BMI, Glucose, Insulin, HOMA, Leptin, Adiponectin, Resistin and MCP-1. Machine learning algorithms (logistic regression, random forests, support vector machines) were implemented taking in as predictors different numbers of variables. The resulting models were assessed with a Monte Carlo Cross-Validation approach to determine 95% confidence intervals for the sensitivity, specificity and AUC of the models. RESULTS: Support vector machines models using Glucose, Resistin, Age and BMI as predictors allowed predicting the presence of breast cancer in women with sensitivity ranging between 82 and 88% and specificity ranging between 85 and 90%. The 95% confidence interval for the AUC was [0.87, 0.91]. CONCLUSIONS: These findings provide promising evidence that models combining age, BMI and metabolic parameters may be a powerful tool for a cheap and effective biomarker of breast cancer.

Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause.

BACKGROUND: The association that exists between livedo reticularis (LR) and stroke is known as Sneddon's syndrome (SnS). The disorder is classified as primary SnS (PSnS), if the cause remains unknown and secondary SnS. The condition is rare and it occurs mainly sporadically. In 2014, 2 independent teams described a new genetic disorder with childhood-onset, which was called deficiency of adenosine deaminase 2 (DADA2), characterized by recurrent fevers and vascular pathologic features that included LR and stroke. All the patients carried recessively inherited mutations in cat eye syndrome chromosome region candidate 1 gene (CECR1), encoding the adenosine deaminase 2 (ADA2) protein. Genetic testing is the standard for the diagnosis of DADA2. However, the diagnostic accuracy of more affordable laboratorial analysis in CECR1-mutated individuals remains to be established. We aim to determine whether plasma ADA2 activity and serum immunoglobulin M (IgM) levels can distinguish (1) DADA2 from other adult patients within the SnS spectrum, and (2) healthy CECR1 heterozygous (HHZ) from healthy controls (HC). METHODS: ADA2 activity in plasma and serum IgM concentrations was measured in adult patients within the SnS spectrum, healthy first-degree relatives and HC. Genetic results were used as the reference standard. The primary outcome measures were sensitivity and specificity derived from receiver operating curve analysis. RESULTS: A total of 73 participants were included in the study: 26 patients with PSnS with no CECR1 mutation (PSnS), 6 bi-allelic (DADA2 patients) and 7 HHZ CECR1 mutations and 34 HC. Plasma ADA2 activity and serum IgM levels were significantly lower in DADA2 patients than in PSnS. With the use of the best indexes, plasma ADA2 activity differentiated PSnS from DADA2 with a sensitivity and specificity of 100.0% and HHZ from HC with a sensitivity of 97.1% and specificity of 85.7%. Serum IgM levels also differentiated PSnS from DADA2 with a sensitivity of 85.2% and specificity of 83.3%. CONCLUSION: Serum IgM levels might be used as a triage tool and plasma ADA2 activity performs perfectly as a diagnostic test for DADA2 in adult patients within the SnS spectrum. ADA2 activity in plasma also reliably distinguishes HHZ from HC.

Type 1 diabetes in children is not a predisposing factor for oral yeast colonization.

Type 1 diabetes mellitus (T1D) is considered a risk factor associated with oral yeast infections. The aim of this study was to evaluate the yeast oral carriage (in saliva and mucosal surface) of children with T1D and potential relation with host factors, particularly the subset of CD4+ T cells. Yeasts were quantified and identified in stimulated saliva and in cheek mucosal swabs of 133 diabetic T1D and 72 healthy control subjects. Salivary lymphocytes were quantified using flow cytometry. The presence of yeasts in the oral cavity (60% of total patients) was not affected by diabetes, metabolic control, duration of the disease, salivary flow rate or saliva buffer capacity, by age, sex, place of residence, number of daily meals, consumption of sweets or frequency of tooth brushing. Candida albicans was the most prevalent yeast species, but a higher number of yeast species was isolated in nondiabetics. T1D children with HbA1c ≤ 7.5 (metabolically controlled) presented higher number of CD4+ T salivary subsets when compared with the other groups of children (non-diabetic and nonmetabolically controlled) and also presented the highest number of individuals without oral yeast colonization. In conclusion, T1D does not predisposes for increased oral yeast colonization and a higher number of salivary CD4+T cells seems to result in the absence of oral colonization by yeasts.