Clinical practice guideline of the spanish society of oral surgery for oral surgery in patients with coagulation disorders.

BACKGROUND: The number of patients treated with coagulation disorders, and more specifically with anticoagulant therapy, has increased worldwide in recent years due to increased life expectancy in developed countries. The protocols for managing this type of patient in oral surgery has varied over recent years, especially after the appearance of new direct-acting oral anticoagulants (DOACs). The assessment of risk of bleeding in this type of patient when undergoing a surgical procedure continues to be a controversial issue for patients, dentists and general practitioners. The objective of this document is to offer recommendations, based on evidence, for decision making for patients with coagulopathies who require dental surgical intervention. MATERIAL AND METHODS: Based on the indications of the "Preparation of Clinical Practice guidelines in the National Health System. Methodological manual", we gathered a group of experts who agreed on 15 PICO questions based on managing patients with coagulation disorders in dental surgical procedures, such as fitting of implants or dental extractions. RESULTS: The 15 PICO questions were answered based on the available evidence, being limited in most cases due to the lack of a control group. Two of the PICO questions were answered by the experts with a grade C recommendation, while the rest were answered with grade D. CONCLUSIONS: The results of this review highlight the need to undertake well designed clinical trials with control groups and with a representative sample size.

Mannose-coated polydiacetylene (PDA)-based nanomicelles: synthesis, interaction with concanavalin A and application in the water solubilization and delivery of hydrophobic molecules.

Carbohydrate-lectin interactions are involved in a number of relevant biological events including fertilization, immune response, cell adhesion, tumour cell metastasis, and pathogen infection. Lectins are also tissue specific, making carbohydrates not only promising drug candidates but also excellent low molecular weight ligands for active drug delivery system decorations. In order for these interactions to be effective multivalency is essential, as the interaction of a lectin with its cognate monovalent carbohydrate epitope usually takes place with low affinity. Unlike the covalent approach, supramolecular self-assembly of glyco-monomers mediated by non-covalent forces allows accessing multivalent systems with diverse topology, composition, and assembly dynamics in a single step. In order to fine-tune the size and sugar adaptability of spherical micelles at the nanoscale for an optimal glycoside cluster effect, herein we report the synthesis of mannose-coated static micelles from diacetylene-based mannopyranosyl glycolipids differing in the length of the poly(ethyleneglycol) (PEG) chains and the oxidation state of the anomeric sulfur atom. The reported shot-gun like synthetic approach for the synthesis of dilution-insensitive micelles is based on the ability of diacetylenic-based neoglycolipids to self-assemble into micelles in water and to undergo an easy photopolymerization by a simple irradiation at 254 nm. The affinity of the obtained 6 nanosystems was assessed by enzyme-linked lectin assay (ELLA) using the mannose-specific concanavalin A lectin as a model receptor. Relative binding potency enhancements, compared to methyl α-d-mannopyranoside used as control, from 20-, to 29- to 300-fold on a sugar molar basis were observed for micelles derived from sulfonyl-, sulfinyl- and thioglycoside monomers with a tatraethyleneglycol spacer, respectively, indicative of a significant cluster glycoside effect. Moreover, pMic1 micelles are able to solubilize and slowly liberate lipophilic clinically relevant drugs, and show the enhanced cytotoxic effect of docetaxel toward prostate cancer cells. These findings highlight the potential of mannose-coated photopolymerized micelles pMic1 as an efficient nanovector for active delivery of cytotoxic hydrophobic molecules.

Evaluation of scientific output in Dentistry in Spanish Universities.

BACKGROUND: The aim of this study was to assess the scientific output of Spanish universities that offer a bachelor's degree in dentistry through the use of various bibliometric indicators. MATERIAL AND METHODS: A total of 21 universities offered a bachelor's degree in dentistry in academic year 2016-2017. The search for papers published by authors associated with these institutions was carried out using the selection of journals listed in the Journal Citation Reports (JCR) and the Web of Knowledge database for the period 1986-2017. On the basis of these data, we determined the output, the h-, g- and hg-indexes, the most productive authors, international collaborations, and the most relevant journals. RESULTS: Public universities obtained better results than private universities. The University of Valencia was ranked first, followed by the Complutense University of Madrid and the University of Granada. The most productive author was José Vicente Bagán, but the author with the highest h-index was Mariano Sanz and Manuel Toledado. The universities with the greatest output and highest citation rates had more international collaborations. The most developed fields in Spanish universities were Oral surgery, Oral medicine and Dental materials. The universities had different models of production. At universities such as Barcelona or Valencia, the production was focused on very few departments and authors. At the other extreme, the University of Granada had various sources of research and authors, which meant that its output and citation rate could increase more. CONCLUSIONS: University faculties must provide suitable academic and research training, and therefore must be assessed using objective criteria and bibliometric tools. Although the number of university schools and faculties that teach dentistry has increased, and particularly the number of private universities, there is no correlation between their quality and output and the number of places offered on their courses.

Conformationally-locked C-glycosides: tuning aglycone interactions for optimal chaperone behaviour in Gaucher fibroblasts.

A series of conformationally locked C-glycosides based on the 3-aminopyrano[3,2-b]pyrrol-2(1H)-one (APP) scaffold has been synthesized. The key step involved a totally stereocontrolled C-Michael addition of a serine-equivalent C-nucleophile to tri-O-benzyl-2-nitro-D-galactal, previously published by the authors. Stereoselective transformations of the Michael adduct allowed us the synthesis of compounds with mono- or diantennated aglycone moieties and different topologies. In vitro screening showed highly selective inhibition of bovine liver ß-glucosidase/ß-galactosidase and specific inhibition of human ß-glucocerebrosidase among lysosomal glycosidases for compounds bearing palmitoyl chains in the aglycone, with a marked dependence of the inhibition potency upon their number and location. Molecular dynamics simulations highlighted the paramount importance of an optimal orientation of the hydrophobic substituent to warrant efficient non-glycone interactions, which are critical for the binding affinity. The results provide a rationale for the strong decrease of the inhibition potency of APP compounds on going from neutral to acidic pH. The best candidate was found to behave as pharmacological chaperone in Gaucher fibroblasts with homozygous N370S and F213I mutations, with enzyme activity enhancements similar to those encountered for the reference compound Ambroxol.

Tuning of glyconanomaterial shape and size for selective bacterial cell agglutination.

Multivalent glycosystems are potential candidates for anti-adhesive therapy, a non-lethal approach against the ever increasing antibiotic resistance of pathogenic bacteria. In order to fine-tune the glyconanomaterial size and shape for selective bacterial cell agglutination, herein we report the synthesis of sugar-coated dynamic and polymeric 3D-micelles and 1D-carbon nanotubes. The reported shot-gun like synthetic approach is based on the ability of diacetylenic-based neoglycolipids to self-assemble into micelles in water and hierarchically self-assemble into hemimicelles on a single-walled carbon nanotube surface. The affinity of the nanosystems was preliminarily assessed by enzyme-linked lectin assay (ELLA) using the mannose-specific Concanavalin A lectin as a model receptor. Relative binding potency enhancements, compared to methyl α-d-mannopyranoside used as control, from 10- to 25- to 2340-folds in sugar molar basis were observed when passing from 3D dynamic micelles to static micelles, to 1D-mannose coated carbon nanotubes, respectively, indicative of a significant cluster glycoside effect. Importantly, these results were confirmed in vivo showing that the 1D-glyconanoring-coated carbon nanotubes efficiently and selectively regulate the agglutination and proliferation of the enterobacteria Escherichia coli type 1 fimbriae. These findings highlight the potential of sugar coated nano-materials as novel and effective tools in the control of bacterial pathogenesis.

Flow cytometric and morphological characterization of platelet-rich plasma gel.

UNLABELLED: BACKGROUND OF PROBLEMS: Platelet-rich plasma (PRP) gel is derived from an autogenous preparation of concentrated platelets and is widely used in implant dentistry as a vector for cell growth factors. However, limited data are available on its structure and composition. The present study was aimed at providing a flow cytometric and ultrastructural characterization of PRP gel. MATERIALS AND METHODS: Twenty PRP gel samples were obtained from healthy volunteers. These PRP gel specimens were prepared for transmission (TEM) and scanning electron microscopy (SEM) examination of their morphological ultrastructure. Flow cytometry with CD41-PE monoclonal antibody was used to detect platelet cells, as this antibody recognizes human-platelet-specific antigen CD41. RESULTS: Both SEM and TEM showed that PRP gel contains two components: a fibrillar material with striated band similar to fibrin filaments, and a cellular component that contains human platelet cells. Both techniques indicated that no morphological elements were bound between the cellular component and the fibrillar material. The cells were confirmed as platelet cells by flow cytometric study after incubation with specific monoclonal antibody CD41-PE. CONCLUSION: PRP gel contains a fibrillar and a cellular (largely human platelet cell) component. This unique structure may be capable of acting as a vehicle for carrying of cells that are essential for soft/hard tissue regeneration.

Modeling the effect of substitution on the Pb(OAc)4 mediated oxidative cleavage of steroidal 1,2-diols.

[reaction: see text] We comment on the effects of angular substitution on the outcome of a Pb(OAc)4 (LTA) mediated heterodomino reaction, with selected bicyclic unsaturated 1,2-diols, which is considered to proceed through a series of transformations in a single vessel. The first two, oxidative and pericyclic, are followed by the key step, an electrophilic addition of LTA to the olefin, responsible for the course of the domino process. In this study, the electrophilic addition of LTA to the double bond has been modeled with B3LYP, where the 6-31G* basis set is used for C, O, and H atoms and the LANL2DZ method is used for Pb. The modeling in the gaseous phase and in solution has revealed the concerted nature of the addition of LTA to the double bond of the intermediate. The fact that LTA adds from the same side as the substituent R, for R=H and from the opposite side when R=CH3 has been attributed to steric hindrance, which causes deformation of the olefinic intermediate.

P53 protein expression in oral squamous cell carcinoma. survival analysis.

BACKGROUND: The present study aimed to analyze the pattern of p53 expression and its influence on survival in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: An immunohistochemical technique with BP53-12 antibody was performed on stored tissue from 78 patients with OSCC (intraoral cancer n=40; lip cancer n=38). The nuclear and cytoplasmic extension of p53 staining was assessed. Clinical and histopathological data were gathered and the patient survival was analyzed. RESULTS: 57.7% (n=45) of the OSCCs expressed p53, with nuclear expression in 52.6% (n=41) of cases and cytoplasmic expression in 24.4% (n=19). The OSCCs with extensive nuclear expression of p53 showed dissociated patterns of invasion of adjacent tissues (p<0.05). A greater extension of cytoplasmic expression of p53 most commonly appeared in tumors that were better-differentiated (p<0.005), more keratinized (p<0.01) and with less nuclear atypia (p<0.05). The parameters that significantly influenced survival of patients were tumor localization (p<0.01), size (p<0.0001), lymph node invasion (p<0.0001), clinical stage (p<0.0001), differentiation degree (p<0.01) and nucleargrade (p<0.01). CONCLUSION: The expression of p53 protein did not behave as a marker of prognostic value in patients with OSCC.

Expression of the p53 protein in oral squamous cell carcinomas associated with Epstein-Barr virus.

The behaviour of the p53 protein has been investigated in some human carcinomas associated with Epstein-Barr virus (EBV) but not in EBV-positive oral squamous cell carcinomas (OSCC). The present study aimed to compare the p53 protein expression in EBV-positive OSCC with that in EBV-negative OSCC. The cases had been gathered in a study previously published. An immunohistochemical technique with BP53-12 monoclonal antibody was applied on 74 of the 107 OSCC from the earlier work. The nuclear or cytoplasmic expression of the p53 protein was classified as, absent (0% of neoplastic cells positive), mild (<25% positive), moderate (25-30% positive), or extensive (>50% positive). The p53 protein was expressed by 60.8% of the OSCC. Out of the fourteen EBV-positive OSCC, 57.1% (8 cases) expressed p53, always in the nucleus and never in the cytoplasm. Of the 60 EBV-negative OSCC, 61.6% (37 cases) expressed the p53 protein. Of 37 cases 33 (89.1%) showed nuclear expression of p53 and nineteen cases (51.3%) revealed cytoplasmic expression. There was a statistically significant inverse correlation between cytoplasmic expression of the p53 protein and the presence of EBV DNA (p <0.01). Thus, the EBV-positive tumours less frequently expressed p53 in the cytoplasm. No evidence of an accumulation of the p53 protein in OSCC associated with EBV was recorded.