Efficiency of desensitizing materials in xerostomic patients with head and neck cancer: a comparative clinical study.

OBJECTIVES: To assess the clinical effectiveness of four desensitizing materials in patients who are xerostomic due to radiotherapy for head and neck cancer (HNC) in comparison to a healthy group with normal salivation. METHODS AND MATERIALS: The study was conducted as a split-mouth randomized clinical trial. Forty HNC patients (group A) and 46 healthy patients (group B) suffering from dentin hypersensitivity (DH) were included. Salivary flow was determined through a scialometric test. Hypersensitivity was assessed with air stimulus and tactile stimulus. The materials used as desensitizing agents were Vertise Flow, Universal Dentin Sealant, Clearfil Protect Bond, and Flor-Opal Varnish. The response was recorded before application of the materials, immediately after, and at 1 week, 4 weeks, and 12 weeks. RESULTS: Salivary flow rates in groups A/B were 0.15/0.53 mL/min (unstimulated) and 0.54/1.27 mL/min (stimulated), respectively. In group A, 100 hypersensitive teeth were included. Application of the desensitizing agents significantly decreased the hypersensitivity immediately and throughout the 4-week follow-up (p < 0.001). However, after the 12-week timepoint, a loss of efficacy was detected in all agents (p = 0.131). In group B, 116 hypersensitive teeth were included. The materials performed a more stable action, although a loss of effectiveness was detected at 12-week control (p = 0.297). CONCLUSION: The efficiency of the desensitizing agents after the first application was similar in both groups. In the radiated group, this effect lasted for shorter periods than in healthy controls. CLINICAL RELEVANCE: HNC patients with hyposalivation may be a new risk group for DH.

Factors influencing the relationship between fluoride in drinking water and dental fluorosis: a ten-year systematic review and meta-analysis.

The relationship between naturally fluoridated groundwater and dental fluorosis has received large attention from researchers around the world. Despite recognition that several factors influence this relationship, there is a lack of systematic studies analyzing the heterogeneity of these results. To fill such a gap, this study performs a systematic review and meta-analysis to understand which factors influence this relationship and how. Selected studies were sampled between 2007 and 2017 from Web of Science, PubMed, Google Scholar and Scopus using keywords and Boolean operators. Results of the systematic review show that dental fluorosis affects individuals of all ages, with the highest prevalence below 11, while the impact of other factors (gender, environmental conditions, diet and dental caries) was inconclusive. Meta-regression analysis, based on information collected through systematic review, indicates that both fluoride in drinking water and temperature influence dental fluorosis significantly and that these studies might be affected by publication bias. Findings show that fluoride negatively affects people's health in less developed countries. The conclusions discuss policy tools and technological innovations that could reduce fluoride levels below that of the World Health Organization (WHO) (<1.5 mg/L).

Dental pulp regeneration via cell homing.

The typical treatment for irreversibly inflamed/necrotic pulp tissue is root canal treatment. As an alternative approach, regenerative endodontics aims to regenerate dental pulp-like tissues using two possible strategies: cell transplantation and cell homing. The former requires exogenously transplanted stem cells, complex procedures and high costs; the latter employs the host's endogenous cells to achieve tissue repair/regeneration, which is more clinically translatable. This systematic review examines cell homing for dental pulp regeneration, selecting articles on in vitro experiments, in vivo ectopic transplantation models and in situ pulp revascularization. MEDLINE/PubMed and Scopus databases were electronically searched for articles without limits in publication date. Two reviewers independently screened and included papers according to the predefined selection criteria. The electronic searches identified 46 studies. After title, abstract and full-text examination, 10 articles met the inclusion criteria. In vitro data highlighted that multiple cytokines have the capacity to induce migration, proliferation and differentiation of dental pulp stem/progenitor cells. The majority of the in vivo studies obtained regenerated connective pulp-like tissues with neovascularization. In some cases, the samples showed new innervation and new dentine deposition. The in situ pulp revascularization regenerated intracanal pulp-like tissues with neovascularization, innervation and dentine formation. Cell homing strategies for pulp regeneration need further understanding and improvement if they are to become a reliable and effective approach in endodontics. Nevertheless, cell homing currently represents the most clinically viable pathway for dental pulp regeneration.

Clinical evaluation of the efficacy of one self-adhesive composite in dental hypersensitivity.

OBJECTIVES: The aim of the present study was to investigate the clinical effectiveness over 12 weeks of Vertise Flow(™), a self-adhering composite, in dental hypersensitivity (DH). MATERIAL AND METHODS: The study was conducted as a split-mouth randomized clinical trial. Vertise Flow™ was compared to the following: (1) Universal Dentine Sealant, (2) Clearfil Protect Bond, and (3) Flor-Opal® Varnish. A total of 46 patients with 116 hypersensitive teeth were studied. Pain experience was generated by a cold stimulus and assessed using the visual analog scale (VAS) of pain. The response was recorded before the application of the materials (pre-1), immediately after (post-1), at 1- (post-2), 2- (post-3), and 12-week controls (post-4). Statistical differences in VAS were performed using the Kruskal-Wallis analysis at the different time-points (P < 0.05), adjusting statistical significances for multiple comparisons (Bonferroni correction). RESULTS: All the materials showed any statistically significant differences at the baseline. After the application of each material, a VAS decrease was demonstrated at every post-control. VF showed significant hypersensitivity reduction in post-1. Statistically significant relief was also observed in post-2 while no significant differences were detected in post-3 and post-4. CONCLUSIONS: After 12-week controls, there was no statistically significant hypersensitivity reduction using VF in respect to the other materials. On the other hand, any significant differences were detected in the decrease of the VAS irrespective of the desensitizing agent employed at the 12-week controls. CLINICAL RELEVANCE: The significant increase in VAS scores within the 12-weeks of environment suggested there is instability of VF when used as desensitizing agent.

Recurrent aphthous stomatitis (RAS): guideline for differential diagnosis and management.

AIM: Recurrent aphthous stomatitis (RAS) is a painful and common ulcerative form that can pose a diagnostic challenge. In fact, similar oral ulcers can appear secondary to a variety of well-defined pathological conditions. Thus, the purpose of this work was to update the current knowledge about RAS METHODS: A narrative review is presented aiming to clarify the extensive differential diagnosis of RAS and its management. CONCLUSION: As a first aid in relieving the pain, topical applications of corticosteroids, antibiotics, and analgesics are highly recommended, while systemic therapy of RAS should be used in the case of multiple painful ulcerations compromising the quality of life of the patient. Also, natural anti-inflammatory substances from medicinal herbs, in the form of essential oils and extracts are promising agents in the management of RAS.

Pain perception in paediatric patients: evaluation of computerised anaesthesia delivery system vs conventional infiltration anaesthesia in paediatric patients.

Aim: The aim of the present study is to compare the effectiveness of a computerised system (QuickSleeper) compared to traditional syringe in injection of local anaesthetic focusing on the perception of anxiety and pain in paediatric patients. Methods: Study design: 100 children aged between 3 and 15 years in need of two dental treatments that required local anaesthesia were selected and treated randomly but alternately with computerised and traditional local anaesthesia. After each anaesthetic injection, patient's anxiety was measured using the Venham test. Results: Electronic anaesthesia showed statistically significant better results than traditional anaesthesia according to the Venham pain scale, in both mandibular and maxillary sites. Statistics: Data were analysed using the paired Wilcoxon test. Conclusion: The computer-assisted anaesthesia system resulted in a significantly lower pain perception score and yielded to helpful, cooperative behaviour. For this reason, it is an advantageous alternative to traditional injection anaesthesia and can avoid invasive treatments and trauma for young patients.

Paediatric endodontics Part 2: Pulp regeneration: current approaches.

Dental pulp regeneration: An overview of the current approaches. Regenerative Endodontic Procedures (REPs) are biologically based procedures aimed at restoring the damaged structures and physiological functions of the pulp-dentine complex. Clinically, two strategies have been proposed so far to induce REP: cell transplantation and cell homing. REPs success relies primarily on the clinical and biological conditions of the tooth; therefore, cell homing strategies will not be consistently successful in every condition. Root canal treatment remains the standard of care for mature teeth with necrotic pulps and closed apex.

A repertoire library that allows the selection of synthetic SH2s with altered binding specificities.

Tyrosine phosphorylation is one of the major mechanisms involved in the intracellular propagation of external signals. Strategies aimed at interfering with this process might allow the control of several cellular phenotypes. SH2 domains mediate protein-protein interactions by recognizing phosphotyrosine (pY) residues in the context of specific phosphopeptides. We created an SH2-scaffolded repertoire library by randomly mutagenizing five critical amino acid positions in the specificity-determining region of the PLCgamma C-terminal SH2 domain. Synthetic SH2 domains were selected from the library using biotinylated phosphopeptides derived from a natural PLCgamma-SH2 ligand as well as unrelated SH2 ligands. The isolated SH2s displayed high binding affinity constants for the selecting peptides and were capable of interacting with the corresponding proteins.

Inhibition of CD4/p56lck signaling by a dominant negative mutant of the Shc adaptor protein.

T-cell antigen receptor stimulation results in phosphorylation of the SH2 containing Shc proteins and recruitment of the Grb2/mSos complex suggesting that Shc proteins are involved in transducing T-cell activating signals to Ras. We have measured the effects of the isolated Shc-SH2 domain and the dominant negative RasN17 protein on activation of the T-cell specific transcription factor NF-AT. The isolated Shc-SH2 domain was designed to compete with endogenous Shc binding to upstream tyrosine phosphorylated proteins and to interfere with coupling to regulators of Ras activation. We have demonstrated that both the Shc-SH2 domain and the RasN17 protein significantly inhibited NF-AT activation by the CD4 coreceptor and the CD4 associated tyrosine kinase p56lck. In contrast, only the RasN17 protein reduced NF-AT activation by the TCR/CD3 complex. Furthermore, tyrosine kinase activity and p56lck protein were found in complexes immunoprecipitated with Shc specific antisera after CD4 triggering but not after CD3 triggering. These results indicate that both CD4 and CD3 signal to Ras and that this signaling is mediated by independent pathways of activation of the Shc adaptor protein.

The aminoterminal phosphotyrosine binding domain of Shc associates with ZAP-70 and mediates TCR dependent gene activation.

T-cell antigen receptor stimulation results in recruitment to the zeta chain and phosphorylation both of the syk family protein tyrosine kinase ZAP-70 and of the Shc adaptor protein, which transduces activating signals to Ras. Both ZAP-70 and Ras are required for T-cell activation. We have investigated the functional link between these two molecules in TCR signaling. She was found to associate with ZAP-70 in response to TCR triggering. This association was dependent on the presence of the aminoterminal phosphotyrosine binding (PTB) domain of She. The analysis of She binding to a potential PTB domain binding site on ZAP-70 confirmed the interaction of the She PTB domain with ZAP-70 and identified the ZAP-70 phosphotyrosine residue involved in this interaction. To test the role of the She PTB domain in transducing TCR derived signals we measured the effects of the isolated She PTB domain on the activation of the T-cell specific transcription factor NF-AT. The isolated She PTB domain was designed to compete non productively with endogenous She for binding to up-stream tyrosine phosphorylated proteins and thus interfere with coupling to regulators of Ras activation. A significant inhibition of NF-AT activation by TCR triggering was observed, showing a functional involvement of She in TCR signaling through its PTB domain and suggesting an important role for She association with ZAP-70.

Gene activating and proapoptotic potential are independent properties of different CD4 epitopes.

CD4 engagement triggers an early signaling cascade which initiates late events such as transcription factor activation. The outcome of CD4 engagement is T-cell commitment to alternative, dramatically different fates, such as activation and apoptosis. We have tested a panel of anti-CD4 mAbs specific for different CD4 epitopes, as well as HIV-1 gp120, for the capacity to activate crucial early events such as enhancement of p56(lck) kinase activity and Shc phosphorylation. The same CD4 epitopes were characterized for their capacity both to deliver a gene activating signal and to program T-cells to activation dependent death. No correlation could be found between capacity of specific CD4 epitopes to deliver a gene activating signal and capacity to prime T-cells to apoptosis, suggesting that gene activating and proapoptotic potential are independent functions of CD4 epitopes. Furthermore, while triggering of the calcium pathway appears critical in NF-AT activation, optimal p56(lck) activation and Shc phosphorylation might be required for initiation of the apoptotic pathway.

Carious affected dentine: its behaviour in adhesive bonding.

BACKGROUND: Carious affected dentine (CAD) represents a very common substrate in adhesive dentistry. Despite its ability to interact with adhesive systems, the intrinsic character of CAD leads to lower bonding compared with sound dentine, regardless of the adhesive systems used. This low bonding may be more susceptible to leakage and hydrolysis of the interface by matrix metalloproteinases (MMPs). This systematic review aimed to determine current knowledge of CAD bonding, together with bond strength and MMP inhibitors' ability to prevent hybrid layer instability. METHODS: MEDLINE/Pubmed, Scopus and The Cochrane Library databases were electronically searched for articles published from 1 January 1960 to 31 August 2014. Two reviewers independently screened and included papers according to predefined selection criteria. RESULTS: The electronic searches identified 320 studies. After title, abstract and full-text examinations, 139 articles met the inclusion criteria. Data highlighted that a poor resin saturation of the already demineralized collagen matrix in CAD is strictly related to nanoleakage in interdiffusion and is the basis of the progressive decrease in strength with hydrolysis by MMPs. The use of mild self-etching systems seems to be the more accredited method to establish bonding in CAD. Inhibitors of MMPs may ensure better performance of CAD bonding, allowing undisturbed remineralization of the affected matrix. CONCLUSIONS: CAD bonding needs further understanding and improvement, particularly to enhance the strength and durability of the hybrid layer.

Cell vacuolization induced by Helicobacter pylori: inhibition by bafilomycins A1, B1, C1 and D.

All available bafilomycins (A1, B1, C1 and D) inhibit and revert macroscopic vacuolization induced by Helicobacter pylori cell-free extracts. Bafilomycin A1 displays the highest activity, followed by bafilomycin B1, C1 and D. The different potency of bafilomycins correlates with their ability to inhibit the vacuolar-type ATPase (V-ATPase) and to dissipate the membrane pH gradient of intracellular acidic organelles. These results suggest that bafilomycins should be considered as possible therapeutic agents in the treatment of gastritis.

Periodontal status in an Italian young adult population. Prevalence and relationship with periodontopathic bacteria.

To determine the prevalence of periodontitis in an Italian young adult population and the relationship with Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in subgingival plaque. A full-mouth periodontal and oral examination was performed in 70 subjects. Dental and behaviour habits were assessed with a standardised questionnaire. Subgingival plaque samples were collected from the deepest pocket of the first molars in each quadrant with a sterile curette. A. actinomycetemcomitans, P. gingivalis and P. intermedia were detected using a multiplex polymerase chain reaction. At subject level, the prevalence of bleeding on probing, calculus, normal pocket depth (PD), PD > 5mm and bacterial positivity were 44.8%, 43.3%, 22.9%, 11.4% and 95.7%, respectively. At quadrant level bacterial prevalence was 79.4%; P. intermedia was the most common bacteria (79.0%); A. actinomycetemcomitans had a prevalence of 40.8%. A significant linear trend across categories of gingival conditions (healthy, bleeding on probing, calculus presence) was detected for P. intermedia (p = 0.0038) and A. actinomycetemcomitans (p = 0.00005) proportions. No significant association was observed between pathogenic bacteria and PD, nor with behavioural attitudes. Gingival conditions are found to be a good predictors (VPP = 85%) for periodontopathic bacteria. For the Italian population, as no data are present, prospective longitudinal studies are needed to examine the relationship between PD and bacteria presence with periodontal disease onset and/or progression.

In vivo effect of a self-etching primer on dentin.

PURPOSE: To determine the ultrastructural aspects of the dentin collagen area in the cavity preparation floor produced in vivo after phosphoric acid acid-etching or after using Clearfil Liner Bond 2 self-etching primer (LB2 Primer). MATERIALS AND METHODS: Twenty-four non-carious third molars scheduled for extraction from young adult patients (16-30 years old) were used. Conventional Class I cavities (+/- 2 mm deep) were prepared on the occlusal surfaces of all teeth using a cylindrical diamond bur on a high-speed handpiece with copious water spray. To avoid dehydration of the dentin, the smear layer-covered dentin was briefly air-dried for 2 seconds. Cavities were assigned at random to the following groups: Group A: Dentin etched for 15 seconds with 34% phosphoric acid, rinsed for 20 seconds and then briefly air-dried for 2 seconds with oil-free compressed air leaving the surfaces slightly moist. Group B: LB2 Primer was applied to the cavity surfaces for 30 seconds and then briefly air-dried to remove the solvent. Group C: The untreated dentin smear layer was used as a control. In all three groups, the cavities were filled incrementally with a resin-based composite (APX), light curing every increment for 40 seconds. After 30 minutes, the teeth were extracted atraumatically and the samples immediately prepared for evaluation with the transmission electron microscope. RESULTS: The use of a self-etching primer did not produce significant morphological changes in the moist dentin substrate. Adverse morphological conditions where observed when there was an excess water on the dentin surface. Phosphoric acid altered the collagen more severely than the self-etching primer.

[Activation of the immune system in periapical infection. 1. Lympho-monocytoid and plasma cellular elements of reactive soft tissue cells]. / Attivazione del sistema immunocompetente nella patologia del periapice infetto. Nota 1: elementi cellulari della serie linfomonocitoide, plasmacellulare e propri dei tessuti molli reattivi.

The authors have carried out a study on the immunitary mechanisms which stimulate and avoid eventual alterations of infected periapex. Above all the aim of this first study has been the microscopic and ultrastructural valuation of the cellular components that characterize the process of chronic phlogosis of periradicular tissue, lymphocytes T and B, plasmacells and macrophages, and of those even more typical of the soft reactive tissues, fibroblasts and epithelial cells. It's just the interaction among these immunocompetent cells which determines the structural change of the periapical bone whose most common image of radiotransparence make it possible to diagnose the sufference of the pulpo-periapical system.

[Phenolic derivatives in intermediate medications in endodontics. 1. A review of the literature]. / I derivati fenolici nelle medicazioni intermedie in endodonzia. Nota 1: Revisione della letteratura.

The authors review the literature on phenolic derivatives, a widely used compound antiseptic for intermediate endodontic medication. There is interest in these substances owing to the frequency of their clinical application in order to maintain the antiseptic conditions obtained during the course of the chemico-mechanical preparation of the radicular canal.

¿Nos formamos los pediatras para publicar artículos médicos? Encuesta piloto / How are pediatricians trained to write biomedical articles? A pilot study

Introducción: Redactar y publicar requiere una metodología, una organización y una sistemática que los pediatras deben conocer. Objetivo: Evaluar la formación en publicaciones biomédicas entre los pediatras y especialistas médicos que trabajan en nuestra área de pediatría, así como su experiencia personal respecto a la publicación de artículos. Material y métodos: Se realizó una encuesta de oportunidad con 13 preguntas cerradas y una mixta sobre formación, experiencia y motivación para publicar. La muestra estuvo constituida por los asistentes a una sesión sobre «Cómo publicar artículos » de un curso dirigido a pediatras, médicos de familia, residentes de pediatría (MIR-pediatría) y residentes de medicina familiar. La estadística descriptiva se llevó a cabo con el programa SPSS versión 15. Resultados: La población diana estuvo formada por 53 médicos; cumplimentaron el cuestionario 34 (64,1%). Sólo 13 de los 34 respondedores (38%) refirieron haber asistido a cursos o seminarios sobre cómo realizar una publicación: 9 de 21 pediatras (42,8%), 2 de 6 MIR-pediatría (33,3%) y 2 de 7 MIR-medicina de familia (28,6%). Respecto a la experiencia, 18 pediatras (85,7%) publicaron al menos 1 artículo en los últimos 5 años; publicaron más de 5 artículos 5 pediatras (23,8%), 2 MIR-pediatría (ambos menos de 6 artículos) y 5 MIR-medicina de familia. Respecto a la motivación, publicar les resultó «demasiado difícil» a 5 (un 20% de los que publicaron). El motivo principal para publicar fue el currículum personal (un 94,1% de 34). Discusión: Este estudio piloto nos sirvió para conocer la realidad y la necesidad formativa para escribir artículos biomédicos en nuestra muestra local. Es una propuesta para extender este tipo de estudios a otros distritos o áreas sanitarias. Un porcentaje importante señaló que no le resultó emocionalmente positivo publicar, antes al contrario, que tuvo «demasiadas dificultades». Conclusiones: En nuestra muestra se observa una falta de formación percibida en escritura científica. Para conocer, promover y orientar las necesidades de formación en docencia sobre escritura biomédica, creemos recomendable potenciar herramientas como este tipo de encuestas (AU)

Title: How are pediatricians trained to write biomedical articles? A pilot study Introduction: Writing and publishing require a methodology, organization, and systematics that all pediatricians should know. Objective: To evaluate the level of training on biomedical publications among pediatricians and other medical specialists who work in pediatrics in our area, as well as their personal experience in publishing. Material and methods: An opportunity survey with 13 closed questions and another mixed question on training, experience, and motivation to publish. Sample: physicians attending to a lecture about «How to publish articles» from a course aimed to pediatricians, family physicians, pediatrics residents (MIR-pediatrics), and residents in family medicine (MIR-family physicians). Descriptive statistics: SPSS version 15. Results: The target population was 53 physicians. Thirty four (64.1%) fulfilled the questionnaire. Only 13 (38.2%) from the people who answered were trained in publication techniques (through courses and seminars): pediatricians 9 out of 21 (42.8%), MIR-pediatrics 2 out of 6 (33.3%), MIR-family physicians 2 out of 7 (28.6%). Experience: a) published at least one article in the last 5 years: pediatricians 18 (85.7%); b) more than 5 articles: pediatricians 5 (23.8%), MIR-pediatrics 2 (33%, both <6 articles), MIR-family physicians 5. Motivation: publishing was experienced as «too difficult» for 5 (20% of those who had published). The main reason for publishing was personal curriculum (94.1% of 34). Discussion: This pilot study offers a glance at reality and let us know the necessity to train on how to write biomedical article. This work is a proposal to extend this kind of studies to other districts or sanitary areas. A considerable percentage of people didn't remark publishing as emotionally positive, instead, they found it «too difficult». Conclusions: In our sample, a lack of training in scientific writing has been proven. We recommend enhancing tools such as these surveys, in order to discover, promote, and guide through training skills to teach biomedical writing (AU)

Interactions between the tyrosine kinases p56lck, p59fyn and p50csk in CD4 signaling in T cells.

Interaction of the CD4 co-receptor with major histocompatibility complex (MHC) class II molecules during antigen presentation results in enhancement of antigen receptor signaling. The synergism between the two receptors is believed to result from the juxtaposition of the CD4-associated tyrosine kinase p56lck with the cytoplasmic domains of CD3 complex components. Here, we report that cross-linking of CD4 on the surface of Jurkat cells using monoclonal antibodies results in activation of the CD3-associated kinase p59fyn. Co-cross-linking of CD4 and CD3 results in synergistic activation of p59fyn. The p59fyn kinase is also hyperactive in a Jurkat cell line stably transfected with a constitutively active p56lck mutant, indicating that p56lck mediates CD4 activation of p59fyn. In support of this hypothesis, expression of a dominant inhibitory mutant of p59fyn blocks CD4 signals involved in gene activation. In addition, the p59fyn dominant inhibitor mutant blocks gene-activating signals induced by expression of a constitutively active mutant of p56lck. Overexpression of the regulatory kinase p50csk, which attenuates TcR signaling by inactivation of p59fyn, inhibits signaling from the constitutively active form of p56lck. Taken together, these data suggest that CD4/p56lck enhancement of TcR signaling is, at least in part, mediated by activation of p59fyn, and may be regulated by p50csk.

A motif within the T cell receptor alpha chain constant region connecting peptide domain controls antigen responsiveness.

Mutant alphabeta TCRs were generated by replacing domains of the alpha and beta chain constant regions with homologous domains from TCR delta and gamma chains, respectively. Chimeric TCRs in which the alpha chain contains TCR delta chain sequences within the connecting peptide domain are unresponsive to alloantigens and superantigens, and have defective interactions with the CD3/zeta complex. Although these antigen-unresponsive TCRs undergo zeta chain phosphorylation upon stimulation with superantigen, they do not generate a full signal capable of producing IL-2. Mutant TCRs acquire signaling activity with a combination of superantigen and calcium ionophore, indicating a defect in calcium-mediated signaling. Finally, a conserved motif, FETDxNLN, present in the alpha chain connecting peptide domain, is disrupted in all signaling-defective TCRs. This conserved alpha chain connecting peptide motif might mediate the transfer of signals from the alphabeta heterodimer to the CD3/zeta complex.