Mechanism of molecular interaction of sitagliptin with human DPP4 enzyme - New Insights.

PURPOSE: Dipeptidyl peptidase 4 (DPP4) inactivates a range of bioactive peptides. The cleavage of insulinotropic peptides and glucagon-like peptide 1 (GLP1) by DPP4 directly influences glucose homeostasis. This study aimed to describe the mode of interaction between sitagliptin (an antidiabetic drug) and human DPP4 using in silico approaches. MATERIALS AND METHODS: Docking studies were conducted using AutoDock Vina, 2D and 3D schematic drawings were obtained using PoseView and PLIP servers, and the DPP4-sitagliptin complex was visualized with Pymol software. RESULTS: The best affinity energy to form the DPP4-sitagliptin complex was E-value â€‹= â€‹- 8.1 â€‹kcal â€‹mol-1, as indicated by docking simulations. This result suggests a strong interaction. According to our observations, hydrophobic interactions involving the amino acids residues Tyr663 and Val712, hydrogen bonds (Glu203, Glu204, Tyr663, and Tyr667), π-Stacking interactions (Phe355 and Tyr667), and halogenic bonds (Arg123, Glu204, and Arg356) were prevalent in the DPP4-sitagliptin complex. Root Mean Square Deviation prediction also demonstrated that the global structure of the human DPP4 did not have a significant change in its topology, even after the formation of the DPP4-sitagliptin complex. CONCLUSION: The stable interaction between the sitagliptin ligand and the DPP4 enzyme was demonstrated through molecular docking simulations. The findings presented in this work enhance the understanding of the physicochemical properties of the sitagliptin interaction site, supporting the design of more efficient gliptin-like iDPP4 inhibitors.

New insights about the EptA protein and its correlation with the pmrC gene in polymyxin resistance in Pseudomonas aeruginosa.

Nowadays, clinical and scientific interest in antibiotics, as polymyxin, has increased due to the large number of reports of multiresistant Gram-negative bacteria, as Pseudomonas aeruginosa. The aim of this study was to investigate a related group of proteins for resistance to polymyxins, encoded by P. aeruginosa genome, through in silico analysis. The mobilized colistin resistance 1 (MCR1) protein from Escherichia coli was used for comparison. Similar sequences to the protein MCR1 in P. aeruginosa were analysed for physicochemical properties. 31 protein isoforms in P. aeruginosa (EptA) were found able to confer resistance to polymyxin showing protein lengths between 551 and 572 amino acids, with molecular mass values between 61.36 - 62. 80 kDa, isoelectric point between 6.10 to 7.17, instability index between 33.76 to 41.87, aliphatic index between 98.67 to 102.63 and the hydropathyindex between - 0.008 to 0.094. These proteins belong to the DUF1705 superfamily with bit-score values between 559.81 and 629.78. A high degree of similarity between EpTAs in P. aeruginosa was observed in relation to other proteins that confer resistance to polymyxins, present in Gram-negative bacteria species of clinical interest. Although, further studies are needed to identify the actual contribution of EptAs in P. aeruginosa species.

Allergic Reactions in Orthodontic Patients: A Review

ABSTRACT: Allergic reactions are host immune responses to endogenous or exogenous antigens, which can result in local and systemic problems. Among the main allergens are the dental materials used in orthodontics, which faces some challenges with regard to biocompatibility with oral tissues.This study aimed to analyze in the literature which materials used in orthodontics are related to the appearance of oral and perioral allergic reactions, as well as to investigate the most prevalen t manifestations.An integrative review was carried out with articles published between 2010 and 2020 on the PubMed, Embase, and ScienceDirect on-line database. For this, MeSH descriptors and synonyms were used following two semantic fields: "Hypersensitivity" in association with "Orthodontic Appliances", the selection of studies counted with the stages of identifica tion, screening, eligibility and inclusion. Randomized clinical trials, cross-sectional or cohort clinical trials; Patients with alle rgic reactions affecting the oral or perioral region due to contact with orthodontic material, were included in the review.From a to tal of 549 articles only 04 were selected for the study. In accordance with what has been analyzed in the evidence of these studies, periodontal changes such as gingival inflammation as well as erythema, edema, papules and blisters were the main reactions described. Furthermore, in all articles there was an association with nickel and in only one with chromium. It is possible to i nfer that inflammatory lesions are frequent manifestations on the use of nickel in orthodontic patients.

RESUMEN: Las reacciones alérgicas son respuestas inmunes del huésped a antígenos endógenos o exógenos, los cuales pueden provocar problemas locales y sistémicos. Entre los principales alérgenos se encuentran los materiales dentales utilizados en la ortodoncia, la cual se enfrenta a algunos desafíos respecto a la biocompatibilidad de los tejidos orales. Este estudio tuvo como objetivo analizar en la literatura que materiales utilizados en ortodoncia están relacionados con la aparición de reacciones alérgicas orales y periorales, así como investigar las manifestaciones más prevalentes. Se llevó a cabo una revisión con artículos publicados entre 2010 y 2020 en las bases de datos PubMed, Embase y ScienceDirect. Para ello, se utilizaron descriptores y sinónimos de MeSH siguiendo dos campos semánticos: "Hipersensibilidad" en asociación con "Aparatos de Ortodoncia", la selección de estudios contó con las etapas de identificación, cribado, elegibilidad e inclusión. Ensayos clínicos aleatorizados, ensayos clínicos transversales o de cohortes; en la revisión se incluyeron pacientes con reacciones alérgicas que afectaron a la regiones oral o perioral debido al contacto con material de ortodoncia. De un total de 549 artículos sólo cuatro fueron seleccionados para el estudio. De acuerdo con lo que se analizó en la evidencia, las principales reacciones descritas fueron cambios periodontales, como inflamación gingival, eritema, edema, pápulas y ampollas. Además, en todos los artículos hubo una asociación con níquel y solamente en uno con cromo. Es posible inferir que las lesiones inflamatorias son manifestaciones frecuentes sobre el uso de níquel en pacientes de ortodoncia.

Grape pectic polysaccharides stabilization of anthocyanins red colour: Mechanistic insights.

Grape pectic polysaccharides-malvidin-3-O- ß -d-glucoside binding was studied, aiming to unveil the impact of structural diversity of polysaccharides on anthocyanins-polysaccharides interactions. Polysaccharides were extracted with solutions of imidazole (ISP) and carbonate at 4 °C (CSP-4 °C) and room temperature (CSP-RT) and also recovered from the dialysis supernatant of the remaining cellulosic residue after the aqueous NAOH extraction of hemicellulosic polysaccharides (Sn-CR). Polysaccharides richer in homogalacturonan domains, like those present in the CSP-4 °C fraction had approximately 50-fold higher binding affinity to malvidin-3-O- ß-d-glucoside, than polysaccharides with side chains (as ISP and CSP-RT extractable polysaccharides). CSP-4 °C polysaccharides showed a positive effect on malvidin-3-O- ß-d-glucoside colour fading. Hydration equilibrium constant of malvidin-3-O- ß-d-glucoside in the presence of CSP-4 °C polysaccharides was higher, showing the preferential stabilization of the flavylium cation. The results showed that anthocyanins colour stabilization can be promoted by pectic polysaccharide structures such as those extracted by cold carbonate.

Hábitos associados à mordida aberta anterior em crianças: uma revisão integrativa / Habits associated to preceding open bite in children: an integrative revie

Objetivo: Analisar na literatura quais são os hábitos associados à mordida aberta anterior em crianças. Métodos: Realizou-se uma pesquisa bibliográfica referente aos artigos publicados de 2015 a 2020 nos bancos de dados on-line PubMed, Embase, SciELO, LILACS e BBO utilizando descritores e sinônimos MeSH, DeCS e Emtree com as seguintes etapas: identificação, triagem, elegibilidade e inclusão. Foram incluídos estudos observacionais, transversais ou de coorte, e artigos que demonstrassem hábitos associados à mordida aberta anterior em crianças de 2 a 12 anos de idade. Relatos de caso, revisões da literatura e outros tipos de estudos que não estavam de acordo com os critérios foram excluídos. Os artigos foram analisados por dois pesquisadores independentes e os estudos selecionados foram avaliados quanto à qualidade metodológica. Resultados: De um total de 462 artigos encontrados apenas 9 foram selecionados para o estudo. Desses, 8 (88,9%) apresentaram alta ou moderada qualidade metodológica, sendo apenas 1 (11,1%), dentre os artigos, de baixa qualidade. Mediante à análise dos estudos inclusos, observou-se que a manutenção de hábitos orais como sucção digital (66,6% dos artigos) e de chupeta (77,7%), bem como uso de mamadeira (33,3%) e duração do tempo de aleitamento materno (22,2%) pode ocasionar alterações na oclusão, fala, respiração, crescimento craniofacial, afetando diretamente a qualidade de vida da criança. Conclusão:Uma vez que a infância é a fase adequada para a implementação de novos hábitos saudáveis e tratamentos, é imprescindível que o cirurgião-dentista conheça essa associação, e adote medidas terapêuticas e preventivas.

Aim: To perform an analysis of in the literature regarding which habits are associated with anterior open bite in children. Methods:This was a bibliographic study conducted using articles published from 2015 to 2020 in the PubMed, Embase, SciELO, LILACS, and BBO online databases, using MeSH, DeCS, and Emtree descriptors and synonyms with the following steps: identification, screening, eligibility, and inclusion. Observational, cross-sectional, or cohort studies, as well as and articles demonstrating habits associated with anterior open bite in children aged 2 to 12 years, were included. Case reports, literature reviews, and other types of studies that were not in accordance with the criteria were excluded. The articles were evaluated by two independent researchers, and the selected studies were evaluated for methodological quality. Results:Of a total of 462 articles found, only nine were selected for the study. Of these, eight (88.9%) presented high or moderate methodological quality, with only 1 (11.1%) of the articles presenting a low quality. Through the analysis of the included studies, it was observed that the maintenance of oral habits, such as finger sucking (66.6% of the articles) and pacifiers (77.7%), as well as the use of a bottle (33.3%) and the duration of breastfeeding time (22.2%), may cause changes in occlusion, speech, breathing, and craniofacial growth, directly affecting the child's quality of life. Conclusion: Since childhood is the appropriate phase for the implementation of new healthy habits and treatments, it is essential for the dentist to understand this association and adopt therapeutic and preventive measures.

DIBMA nanodiscs keep α-synuclein folded.

α-Synuclein (αsyn) is a cytosolic intrinsically disordered protein (IDP) known to fold into an α-helical structure when binding to membrane lipids, decreasing protein aggregation. Model membrane enable elucidation of factors critically affecting protein folding/aggregation, mostly using either small unilamellar vesicles (SUVs) or nanodiscs surrounded by membrane scaffold proteins (MSPs). Yet SUVs are mechanically strained, while MSP nanodiscs are expensive. To test the impact of lipid particle size on α-syn structuring, while overcoming the limitations associated with the lipid particles used so far, we compared the effects of large unilamellar vesicles (LUVs) and lipid-bilayer nanodiscs encapsulated by diisobutylene/maleic acid copolymer (DIBMA) on αsyn secondary-structure formation, using human-, elephant- and whale -αsyn. Our results confirm that negatively charged lipids induce αsyn folding in h-αsyn and e-αsyn but not in w-αsyn. When a mixture of zwitterionic and negatively charged lipids was used, no increase in the secondary structure was detected at 45 °C. Further, our results show that DIBMA/lipid particles (DIBMALPs) are highly suitable nanoscale membrane mimics for studying αsyn secondary-structure formation and aggregation, as folding was essentially independent of the lipid/protein ratio, in contrast with what we observed for LUVs having the same lipid compositions. This study reveals a new and promising application of polymer-encapsulated lipid-bilayer nanodiscs, due to their excellent efficiency in structuring disordered proteins such as αsyn into nontoxic α-helical structures. This will contribute to the unravelling and modelling aspects concerning protein-lipid interactions and α-helix formation by αsyn, paramount to the proposal of new methods to avoid protein aggregation and disease.

Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site.

RCK domains regulate the activity of K+ channels and transporters in eukaryotic and prokaryotic organisms by responding to ions or nucleotides. The mechanisms of RCK activation by Ca2+ in the eukaryotic BK and bacterial MthK K+ channels are well understood. However, the molecular details of activation in nucleotide-dependent RCK domains are not clear. Through a functional and structural analysis of the mechanism of ATP activation in KtrA, a RCK domain from the B. subtilis KtrAB cation channel, we have found that activation by nucleotide requires binding of cations to an intra-dimer interface site in the RCK dimer. In particular, divalent cations are coordinated by the γ-phosphates of bound-ATP, tethering the two subunits and stabilizing the active state conformation. Strikingly, the binding site residues are highly conserved in many different nucleotide-dependent RCK domains, indicating that divalent cations are a general cofactor in the regulatory mechanism of many nucleotide-dependent RCK domains.

Interaction between Ellagitannins and Salivary Proline-Rich Proteins.

The first contact of tannins with the human body occurs in the mouth, where some of these tannins are known to interact with salivary proteins, in particular with proline-rich proteins (PRPs). These interactions are important at a sensory level, especially for astringency development, but could also affect the biological activities of the tannins. This study gathers information on the relative affinity of the interaction, complex stoichiometry, and tannin molecular epitopes of binding for the interactions between the families of PRPs (bPRPs, gPRPs, and aPRPs) and three representative ellagitannins (castalagin, vescalagin, and punicalagin). These interactions were studied by saturation-tranfer difference NMR and microcalorimetry. The effect of the PRP-ellagitannin interaction on their antioxidant ability was also assessed by ferric reduction antioxidant power (FRAP) assays. The results support a significant interaction between the studied tannins and PRPs with binding affinities in the micromolar range. Punicalagin was always the ellagitannin with higher affinity. aPRPs were the salivary PRPs with higher affinity. Moreover, it was observed that when ellagitannins are present in low concentrations (5-50 µM), as occurs in food, the antioxidant ability of these tannins when complexed with salivary PRPs could be significantly impaired.

Effect of malvidin-3-glucoside and epicatechin interaction on their ability to interact with salivary proline-rich proteins.

At red wine pH, malvidin-3-glucoside (mv-3-glc), the major anthocyanin of red wine, is expected to be present mainly in its non-colored hemiketal form. However, due to copigmentation with flavanols (e.g. epicatechin), the stabilization of the colored forms of mv-3-glc occurs. Some flavanols have been linked to astringency, due to their ability to interact/precipitate salivary proteins, namely proline-rich proteins (PRPs). So, a major question is if this copigmentation interaction could affect the ability of flavanols to interact with SP. To answer this, the effect of the interaction between mv-3-glc and epicatechin with basic and acidic PRPs, was investigated by saturation-tranfer difference (STD)-NMR and isothermal titration calorimetry (ITC). The most relevant result was that epicatechin:mv-3-glc mixture presents a synergic effect toward the interaction with both PRPs when compared to individual polyphenols. Furthermore, was observed that epicatechin interaction was driven by hydrophobic and hydrophilic interactions while mv-3-glc interaction was driven by electrostatic interactions.

The Interaction between the Drosophila EAG Potassium Channel and the Protein Kinase CaMKII Involves an Extensive Interface at the Active Site of the Kinase.

The Drosophila EAG (dEAG) potassium channel is the founding member of the superfamily of KNCH channels, which are involved in cardiac repolarization, neuronal excitability and cellular proliferation. In flies, dEAG is involved in regulation of neuron firing and assembles with CaMKII to form a complex implicated in memory formation. We have characterized the interaction between the kinase domain of CaMKII and a 53-residue fragment of the dEAG channel that includes a canonical CaMKII recognition sequence. Crystal structures together with biochemical/biophysical analysis show a substrate-kinase complex with an unusually tight and extensive interface that appears to be strengthened by phosphorylation of the channel fragment. Electrophysiological recordings show that catalytically active CaMKII is required to observe active dEAG channels. A previously identified phosphorylation site in the recognition sequence is not the substrate for this crucial kinase activity, but rather contributes importantly to the tight interaction of the kinase with the channel. The available data suggest that the dEAG channel is a docking platform for the kinase and that phosphorylation of the channel's kinase recognition sequence modulates the strength of the interaction between the channel and the kinase.

Arabidopsis thaliana SPF1 and SPF2 are nuclear-located ULP2-like SUMO proteases that act downstream of SIZ1 in plant development.

Post-translational modifiers such as the small ubiquitin-like modifier (SUMO) peptide act as fast and reversible protein regulators. Functional characterization of the sumoylation machinery has determined the key regulatory role that SUMO plays in plant development. Unlike components of the SUMO conjugation pathway, SUMO proteases (ULPs) are encoded by a relatively large gene family and are potential sources of specificity within the pathway. This study reports a thorough comparative genomics and phylogenetic characterization of plant ULPs, revealing the presence of one ULP1-like and three ULP2-like SUMO protease subgroups within plant genomes. As representatives of an under-studied subgroup, Arabidopsis SPF1 and SPF2 were subjected to functional characterization. Loss-of-function mutants implicated both proteins with vegetative growth, flowering time, and seed size and yield. Mutants constitutively accumulated SUMO conjugates, and yeast complementation assays associated these proteins with the function of ScUlp2 but not ScUlp1. Fluorescence imaging placed both proteins in the plant cell nucleoplasm. Transcriptomics analysis indicated strong regulatory involvement in secondary metabolism, cell wall remodelling, and nitrate assimilation. Furthermore, developmental defects of the spf1-1 spf2-2 (spf1/2) double-mutant opposed those of the major E3 ligase siz1 mutant and, most significantly, developmental and transcriptomic characterization of the siz1 spf1/2 triple-mutant placed SIZ1 as epistatic to SPF1 and SPF2.

Study of human salivary proline-rich proteins interaction with food tannins.

In this work, saturation transfer difference-NMR, isothermal microcalorimetry and molecular dynamics simulations have been used to study the individual interactions between basic, glycosylated and acidic proline-rich proteins (bPRPS, gPRPs, aPRPs) and P-B peptide with some representative food tannins [procyanidin B2, procyanidin B2 3'-O-gallate (B2g) and procyanidin trimer (catechin-4-8-catechin-4-8-catechin)]. Results showed that P-B peptide was in general the salivary protein (SP) with higher affinity whereas aPRPs showed lower affinity to the studied procyanidins. Moreover, B2g was the procyanidin with higher affinity for all SP. Hydrophobic and hydrogen bonds were present in all interactions but the major driving force depended on the procyanidin-SP pair. Furthermore, proline clusters or residues in their vicinity were identified as the probable sites of proteins for interaction with procyanidins. For bPRP and aPRP a significant change to less extended conformations was observed, while P-B peptide did not display any structural rearrangement upon procyanidins binding.

Relationship Between Occlusal Features and Enzyme Replacement Therapy in Patients With Mucopolysaccharidoses.

PURPOSE: The aim of this study was to describe the relation between occlusal features and enzyme replacement therapy in patients with mucopolysaccharidoses. MATERIALS AND METHODS: A cross-sectional study was conducted. The sample consisted of 20 patients with mucopolysaccharidoses, 10 of whom were undergoing treatment at a hospital in northeast Brazil. Occlusal features were evaluated by clinical examination and panoramic radiography. A structured questionnaire was administered to evaluate the dental care of each patient. Pearson χ2, Fisher exact, and Mann-Whitney tests were used for data analysis, with a level of significance of 5%. RESULTS: Marked overjet (75%) and anterior open bite (70%) were the most frequent occlusal alterations, and 15% had Class III disorders. Radiography visualized the presence of impacted teeth (75%) and prolonged retention of deciduous teeth (65%). Patients with enzyme replacement therapy had a lower average maximum protrusion (P = .033). A total of 75% of mothers said they had not been advised to take their children to the dentist and 10% of children had never been to the dentist. CONCLUSION: Patients with mucopolysaccharidoses exhibited notable occlusal alterations, especially marked overjet and anterior open bite. Enzyme replacement therapy seems to influence the maximum protrusion of patients.

Avaliação in vitro de bactérias e fungos na superfície de aparelhos ortodônticos removíveis / Evaluation in vitro of bacteria and fungi in surface removable orthodontic appliances

O acometimento do indivíduo por patologias, como a cárie e doenças periodontais, pode ser traumático e extremamente devastador, podendo levá-lo a situações de grande comprometimento da saúde bucal e sistêmica. A introdução dos aparelhos removíveis pode predispor o desenvolvimento destas de modo que, além de aumentar o número populacional destes microrganismos, induz uma grande queda do pH intrabucal, favorecendo o processo de desmineralização dos tecidos duros e agredindo concomitantemente os tecidos moles. Logo, é necessário pesquisar e entender a fixação destes na superfície de aparelhos ortodônticos. A coleta foi realizada antes e 15 dias após a instalação dos aparelhos ortodônticos removíveis na cavidade bucal, mediante um esfregaço com swab estéril, aplicando movimentos anteroposteriores sob pressão manual na região do acrílico e na região dos parafusos expansores, quando houvesse. Na coleta inicial, houve crescimento de microrganismos em 15% dos casos para o Agar Mitis Salivarius, e 5% para o Ágar Sabouraud. Já na coleta após os 15 dias de instalação, verificou-se aumento para 100% de contaminação nas placas de Agar Mitis Salivarius, e as placas de Ágar Sabouraud permaneceram com os 5% de contaminação. Um padrão de limpeza mais bem elaborado desses aparelhos deve ser praticado pelos que o utilizam, além de estar indicada a substituição do aparato após algum tempo de uso, pois a inserção do aparelho modifica o ambiente da cavidade bucal.

The involvement of the individual by diseases such as caries and periodontal disease can be traumatic and extremely devastating and can lead one to situations of great commitment of oral and systemic health. Also, the introduction of removable appliances may predispose the development of these so that in addition to increasing the population of these microorganisms, it induces a large drop in the intraoral pH value, favoring the process of demineralization of hard tissues and simultaneously attacking the soft tissue, thus it is important to research and understand the fixation of these on the surface of orthodontic appliances. Data collection was conducted prior to installation of removable orthodontic appliances and 15 days after by a swipe with a sterile swab, applying movements from front to back under manual pressure in acrylic region and the region of expander bolts. At the first exam, 15% of cases had Agar Mitis Salivarius and 5% Agar Sabouraud. Fifteen days later, all appliances were contaminated with Agar Mitis Salivarius, while only 5% of devices were contaminated with Agar Sabouraud. A detailed cleaning must be exercised over these devices, along with replacement of the orthodontic device after some period because it can change the oral environment.

Epidemiological Profile of Facial Fractures and Their Relationship With Clinical-Epidemiological Variables.

The objective of this study was to identify the epidemiological profile of facial fractures and to associate with clinical-epidemiological variables. An epidemiological survey was conducted in which data retrieved from the records of patients with facial fractures were analyzed. Pearson χ(2) test, Student t-test, one-way analysis of variance, Bonferroni post-hoc test, and logistic regression were used for statistical analysis, adopting a level of significance of 5%. The sample consisted of 718 patients ranging in age from 21 to 30 years (56.4%), including 480 (66.9%) men. Traffic accidents were the main etiological agent (62.7%) and the nasal bones were the most affected (41.8%). An association was observed between age and etiology (P < 0.001), fractured bone (P < 0.001), type of treatment (P < 0.001), hospital length of stay (P < 0.001), and complications (P = 0.001). Patients with traffic accident [odds ratio (OR) = 3.08, P < 0.001] and fall (OR = 2.50, P = 0.049) as etiology had more risk of complications. The type of fractured bone was associated with etiology (P < 0.001), type of treatment (P < 0.001), hospital length of stay (P < 0.001), and complications (maxilla--OR = 1.90, P = 0.004). In conclusion, facial fractures predominantly affect men aged 21 to 30 years. Traffic accidents are the main etiology and the nasal bone is the site most affected. It was observed that the older the patient, the greater the susceptibility to falls, surgical treatment, hospital stay, and complications. Patients with maxillary or mandibular fractures remain hospitalized for longer periods of time. Fractures by traffic accident and fall had more risk of complications. The risk of complications was also higher in patients with maxilla fracture.

Mucopolysaccharidosis: radiographic findings in a series of 16 cases.

OBJECTIVES: To investigate the radiographic findings of mucopolysaccharidoses (MPS) on panoramic radiographs in a series of 16 patients. STUDY DESIGN: This retrospective cross-sectional study included panoramic radiographs of 16 patients with cytogenetically diagnosed MPS. Two blinded, previously calibrated observers evaluate the presence or absence of the following features: type of dentition; stage of dental age in comparison with chronologic age; delayed exfoliation of deciduous teeth; supernumerary teeth; teeth impaction; enlarged, cyst-like dental crypt; hypercementosis; taurodontism; generalized enamel hypoplasia; enlargement of the bone marrow spaces; thinning of cortical bone; unusual morphology of condyles; and flattening of the condylar head. RESULTS: The final sample was composed of 8 MPS IV, 7 MPS VI, and 1 MPS I cases. All patients presented unusual morphology of condyles. Cyst-like dental crypt (75%), taurodontism, and teeth impaction (68.75% each) were also overall common findings. Generalized enamel hypoplasia was exclusively identified in patients with MPS IV (75% of those patients). CONCLUSIONS: Radiographic features of oral and maxillofacial manifestations in patients with MPS frequently encountered by dentists may help recognize the disorder. However, because of sample size limitations, it was not possible to infer any statistical relationship between the radiographic features and the types of MPS.

Patients with mucopolysaccharidosis have tendencies towards vertical facial growth.

PURPOSE: Studies addressing the changes in craniofacial morphology of patients with mucopolysaccharidosis (MPS) are important for a better understanding of the progression of this disease. The present objective was to identify major cephalometric abnormalities in these patients. MATERIALS AND METHODS: This was a cross-sectional case-and-control study. The sample was composed of 2 types of study subjects (patients with MPS and normal subjects). The outcome variables were numerous cephalometric elements that measure facial height, dental positioning, facial growth pattern, and mandibular and maxillary positioning. The Student t test was used to compare the mean angular and linear measurements of the case and control groups and the level of significance was set at a P value less than .05. The Bonferroni method was used for adjustment of the P value (P<.003 was deemed significant). RESULTS: The control group consisted of randomly selected subjects matched to the patients with MPS for the demographic variables of gender and age. Seventeen patients with MPS were evaluated (64.7% female). The mean age of the sample was 13.29 years. One patient had MPS I, 8 had MPS IV, and 8 had MPS VI. The results showed important differences between groups in angular measurements (angle formed by the line between the sella and nasion [SN] and the plane of the gonion and gnathion, angle formed by the intersection of the gnathion point and the SN line, angle formed by the intersection of the long axis of the lower incisor with the line between the nasion and the B point, angle formed by the intersection of the long axes of the upper and lower incisors, and angle formed by the Frankfort horizontal plane with the mandibular plane) and linear measurements (condyle to A point, condyle to gnathion, pro-nasal ( Pn) point to the line between the pogonion and upper incisor, and the nearest point of the anterior half of the soft palate to the posterior pharyngeal wall). The angle formed by the SN line with the plane between the gonion and the gnathion and the distance from the condyle to the A point showed meaningful differences after Bonferroni adjustment. CONCLUSION: Patients with MPS present a tendency toward vertical growth that results in a dolichocephalic facial pattern. In addition, a smaller nasopharyngeal space was observed, a factor that might be responsible for the mouth breathing observed in these patients.

Determinants of ligand selectivity in a cyclic nucleotide-regulated potassium channel.

Cyclic nucleotide-binding (CNB) domains regulate the activity of channels, kinases, exchange factors, and transcription factors. These proteins are highly variable in their ligand selectivity; some are highly selective for either cAMP or cGMP, whereas others are not. Several molecular determinants of ligand selectivity in CNB domains have been defined, but these do not provide a complete view of the selectivity mechanism. We performed a thorough analysis of the ligand-binding properties of mutants of the CNB domain from the MlotiK1 potassium channel. In particular, we defined which residues specifically favor cGMP or cAMP. Inversion of ligand selectivity, from favoring cAMP to favoring cGMP, was only achieved through a combination of three mutations in the ligand-binding pocket. We determined the x-ray structure of the triple mutant bound to cGMP and performed molecular dynamics simulations and a biochemical analysis of the effect of the mutations. We concluded that the increase in cGMP affinity and selectivity does not result simply from direct interactions between the nucleotide base and the amino acids introduced in the ligand-binding pocket residues. Rather, tighter cGMP binding over cAMP results from the polar chemical character of the mutations, from greater accessibility of water molecules to the ligand in the bound state, and from an increase in the structural flexibility of the mutated binding pocket.

Influência da saúde bucal sobre a qualidade de vida de crianças pré-escolares / Influence of oral health on the lifequality of preschool children / Influencia de la salud oral en la calidad de vida de los niños de preescolar

O objetivo deste estudo foi investigar o impacto da saúde bucalem relação à qualidade de vida de crianças pré-escolares, associando-o àscondições sociodemográficas. Para avaliar o impacto foi utilizada a escala ECOHIS.A amostra foi composta por 122 crianças de 2 a 5 anos, matriculadas em umacreche pública pertencente a um município de pequeno porte do sertão depernambucano. Com relação à seção “impacto na criança”, foram verificados maiorespercentuais de repostas “nunca” ou “quase nunca” em todos os domínios do formulário.Referindo-se ao segmento “impacto na família”, a questão relativa à evasão no trabalhopor parte dos pais ou outros membros da família em decorrência de transtornosdentários sofridos pela criança representou 26,2 por cento das respostas que traduziram algumafrequência. Foi observado que 14,8 por cento dos pré-escolares não apresentaram impacto,59 por cento apresentaram impacto fraco e 26,2 por cento, impacto médio. Constatou-se a inexistênciade impacto geral forte influenciando negativamente a qualidade de vida das criançase de seus familiares. Dentre os fatores sociodemográficos pesquisados, apenas a variável“tempo de trabalho materno” mostrou associação estatisticamente significativa como impacto (p=0,011). Faz-se necessária a realização de mais estudos dessa natureza,os quais sejam direcionados não só à localidade pesquisada, mas que se estendam àslocalidades com as mesmas condições sociais...

The aim of this study was to investigate the impact of oral health on the lifequality of preschool children associated with socio-demographic conditions. To assessthe impact the ECOHIS scale was used. The sample consisted of 122 children from2 to 5 years old, enrolled in a public kindergarten from a small town in the interior ofPernambuco, Brazil. Regarding the impact section on the child, there were higherpercentages of answers “never” or “almost never” in all fields of the form. Referring tothe impact on the family section, the question of evasion at work by their parents orother family members due to dental disorders suffered by the child represented 26.2 percentof the responses that translated some frequency. It was observed that 14.8 percent of preschoolchildren had no impact, 59 percent had low impact and 26.2 percent had medium impact. There is nostrong overall impact negatively influencing the life quality of children and their families.Among the socio-demographic factors studied, only the variable “time of maternalemployment” was associated with statistically significant impact (p=0.011). Furtherstudies are necessary, which should be directed not only to the studied area, but extendedto the towns with the same social conditions...

El objetivo de este estudio fue investigar el impacto de la salud bucal en la calidadde vida de los niños en edad preescolar asociándose a las condiciones sociodemográficas.Para evaluar el impacto se utilizó la escala ECOHIS. La muestra estuvo conformada por122 niños de dos a cinco años, inscriptos en un jardín de infantes público, que pertenece auna pequeña ciudad del interior de Pernambuco. En relación con la sesión “impacto sobre elniño”, hubo un mayor porcentaje de respuestas “nunca” o “casi nunca” en todos los camposdel formulario. Refiriéndose al segmento “impacto sobre la familia”, la cuestión de la evasiónen el trabajo por parte de sus padres u otros miembros de la familia debido a los trastornosdentales sufridas por el niño, representó el porcentaje de 26,2 por ciento de respuestas que tradujeron cierta frecuencia. Se observó que en el 14,8 por ciento de los niños en edad preescolar no hubo ningúnimpacto, 59 por ciento débil impacto y 26,2 por ciento medio impacto. Se encontró que no hay un fuerteimpacto global influyendo negativamente en la calidad de vida de los niños y sus familias. Entrelos factores sociodemográficos estudiados, sólo la variable “tiempo de trabajo de la madre”se asoció con el impacto estadísticamente significativa (p = 0,011). Es necesario realizar másestudios de esta naturaleza, que estén dirigidos no sólo para el local investigado, sino quetambién se extiendan a las ciudades de las mismas condiciones sociales...

Conhecimento e práticas em saúde bucal nas escolas de ensino fundamental de um município de pequeno porte do sertão paraibano / Knowledge and practices in oral health of elementary school teachers from a small city in the savanna region of the state of Paraíba, Brazil

Objetivo: Este estudo objetivou avaliar o conhecimento dos professores e práticas de saúde bucal nas escolas de ensino fundamental em um município de pequeno porte pertencente ao Sertão Paraibano. Materiais e Métodos: Utilizou-se um questionário composto por questões relativas às condições sociodemográficas, ao conhecimento das principais medidas preventivas e agravos de saúde bucal, como também questões relacionadas à existência de atividades educativas em saúde bucal nas unidades públicas de ensino. A amostra correspondeu ao censo de professores cadastrados na rede de ensino fundamental de Desterro-PB, totalizando 61 educadores. Os dados foram analisados por meio da estatística descritiva. Resultados: Comprovou-sepercentual considerado de professores graduados ou pós-graduados (81,9%). Quando avaliados a respeito dosprincipais agravos de saúde bucal; 54,3% dos entrevistados mencionaram cárie dentária como uma patologiae apresentam conhecimento satisfatório em relação à etiologia da doença. Ao serem questionados em relaçãoàs medidas preventivas em saúde bucal; 95,1% dos educadores afirmaram que a técnica utilizada é o fatormais importante durante a escovação dentária, porém, apenas 16,4% relataram inserir a quantidade correta de dentifrício na escova. Um percentual expressivo da amostra já recebeu informações a respeito dos cuidadosem saúde bucal (95,1%). Porém, do total de pesquisados, um pouco mais da metade afirmou transmitir essasinformações aos alunos. Entre aqueles que relataram não realizar tal tarefa, 41% mencionaram a falta de materialde apoio como maior obstáculo para abordar os conteúdos dentro das instituições de ensino. A existência deatividades educativas em saúde bucal, realizada por odontólogos, foi presenciada por 85,2 % dos educadores.Conclusão: Embora existam práticas preventivas nas escolas pesquisadas, há necessidade da implementaçãode programas de educação continuada sobre saúde bucal...