Effect of ultrasonic agitation on marginal adaptation, intratubular penetration and bonding strength of calcium-silicate-based endodontic sealers: A laboratory study.

The effect of ultrasonic activation (UA) on marginal adaptation, intratubular penetration and bond strength provided by three calcium silicate-based sealers was evaluated. Ninety-six distobuccal root canals of maxillary molars were randomly divided into 8 groups (n = 12) according to the sealer and UA application: EndoSequence BC sealer (ESBC), Sealer Plus BC (SPBC) and Bio-C Sealer (BCS), using AH Plus (AH) as a control group. The specimens were sectioned at 2, 4 and 6 mm from the apex. The data were statistically analysed using Kruskall-Wallis, Dunn, Mann-Whitney and chi-squared tests. UA improved the marginal adaptation of ESBC (6 mm), SPBC (all levels), BCS (2/4 mm) and AH (4 mm) (p < 0.05); the bond strength of SBPC (2 mm) and BCS (6 mm) were also improved (p < 0.05). The UA of endodontic silicate-based sealers improved the marginal adaptation in all levels and the bond strength of SBPC and BCS sealer.

Developing a Card Game for Assessment and Intervention in the Person and the Family in Palliative Care: "Pallium Game".

Communication between the multidisciplinary team, the person, and the family in palliative and end-of-life situations implies, in most situations, a high negative emotional burden. Therefore, innovative strategies are needed to reduce it. The goal of this study is to describe the various stages of development and validation of a collaborative card game for people in palliative care and their families. Phase one is an exploratory study, Phase two is a Delphi study, and Phase three is a multiple case study. Participants for phases 2 and 3 were recruited using a convenience sampling method. The results demonstrate in an organized and structured way the different phases required to build a collaborative card game. The use of the game was found to be useful and effective. Four categories emerged from the content analysis of the open-ended responses: usability, evaluation tool, communication and therapeutic relationship, and meaning when using the game. A collaborative game in palliative care helps to create a space for individuals and families to express feelings and experiences, meeting the myriad of physical, psychosocial, and spiritual needs. The "Pallium game" is a useful and impactful approach to discussing sensitive topics in palliative care.

Serine-based surfactants as effective antimicrobial agents against multiresistant bacteria.

The antimicrobial activity of two serine derived gemini cationic surfactants, amide (12Ser)2CON12 and ester (12Ser)2COO12, was tested using sensitive, E. coli ATCC 25922 and S. aureus ATCC 6538, and resistant, E. coli CTX M2, E. coli TEM CTX M9 and S. aureus ATCC 6538 and S. aureus MRSA ATCC 43300 Gram-positive and Gram-negative bacteria strains. Very low MIC values (5 µM) were found for the two resistant strains E.coli TEM CTX M9 and S. aureus MRSA ATCC 43300, in the case of the amide derivative, and for S. aureus MRSA ATCC 43300, in the case of the ester derivative. The interaction of the serine amphiphiles with lipid-model membranes (DPPG and DPPC) was investigated using Langmuir monolayers. A more pronounced effect on the DPPG than on the DPPC monolayer was observed. The effect induced by the surfactants on bacteria membrane was explored by Atomic Force Microscopy. A clear disruption of the bacteria membrane was observed for E. coli TEM CTX M9 upon treatment with (12ser)2CON12, whereas for the S. aureus MRSA few observable changes in cell morphology were found after treatment with either of the two surfactants. The cytotoxicity of the two compounds was assessed by hemolysis assay on human red blood cells (RBC). The compounds were shown to be non-cytotoxic up to 10 µM. Overall, the results reveal a promising potential, in particular of the amide derivative, as antimicrobial agent for two strains of antibiotic resistant bacteria.

Formation of catanionic vesicles by threonine-derived surfactants and gemini surfactants based on conventional or serine-derived headgroups: designing versatile and cytocompatible nanocarriers.

In this work, we explore the ability of newly synthesized threonine-derived surfactants to form robust, versatile and cytocompatible catanionic vesicles when mixed with gemini surfactants, as potential effective nanocarriers for biomolecules. The threonine surfactants consist of single-tailed amphiphiles with carboxylate headgroups and varying alkyl tail length, CnThr, where n is the (even) number of tail C atoms, varying from 8 to 16. After an initial characterization of the micellization behavior of the neat CnThr surfactants (at pH = 7 and 12), the dodecyl derivative, C12Thr, was selected as the optimal surfactant to investigate regions of formation of spontaneous catanionic vesicles. Phase behavior studies and microstructural characterization of mixtures involving both conventional bis-quat n-s-n gemini (where n and s are the tail and spacer number of C atoms) and biocompatible serine-derived gemini surfactants were carried out. Light and electron microscopy, dynamic light scattering and zeta potential measurements show spontaneous vesicles indeed form and exhibit versatile features in terms of average size, morphology, polydispersity, surface charge and pH. The toxicological profile of the neat surfactants and C12Thr/gemini vesicles based on MTT assays with a L929 cell line was also evaluated, showing good levels of in vitro cytocompatibility. Overall, the assortment of developed catanionic vesicles offers very attractive physicochemical and biological features to be explored for delivery purposes.

Current Status of Amino Acid-Based Permeation Enhancers in Transdermal Drug Delivery.

Transdermal drug delivery (TDD) presents many advantages compared to other conventional routes of drug administration, yet its full potential has not been achieved. The administration of drugs through the skin is hampered by the natural barrier properties of the skin, which results in poor permeation of most drugs. Several methods have been developed to overcome this limitation. One of the approaches to increase drug permeation and thus to enable TDD for a wider range of drugs consists in the use of chemical permeation enhancers (CPEs), compounds that interact with skin to ultimately increase drug flux. Amino acid derivatives show great potential as permeation enhancers, as they exhibit high biodegradability and low toxicity. Here we present an overview of amino acid derivatives investigated so far as CPEs for the delivery of hydrophilic and lipophilic drugs across the skin, focusing on the structural features which promote their enhancement capacity.

Effective cytocompatible nanovectors based on serine-derived gemini surfactants and monoolein for small interfering RNA delivery.

Non-viral gene therapy based on gene silencing with small interfering RNA (siRNA) has attracted great interest over recent years. Among various types of cationic complexation agents, amino acid-based surfactants have been recently explored for nucleic acid delivery due to their low toxicity and high biocompatibility. Monoolein (MO), in turn, has been used as helper lipid in liposomal systems due to its ability to form inverted nonbilayer structures that enhance fusogenicity, thus contributing to higher transfection efficiency. In this work, we focused on the development of nanovectors for siRNA delivery based on three gemini amino acid-based surfactants derived from serine - (12Ser)2N12, amine derivative; (12Ser)2COO12, ester derivative; and (12Ser)2CON12, amide derivative - individually combined with MO as helper lipid. The inclusion of MO in the cationic surfactant system influences the morphology and size of the mixed aggregates. Furthermore, the gemini surfactant:MO systems showed the ability to efficiently complex siRNA, forming stable lipoplexes, in some cases clearly depending on the MO content, without inducing significant levels of cytotoxicity. High levels of gene silencing were achieved in comparison with a commercially available standard indicating that these gemini:MO systems are promising candidates as lipofection vectors for RNA interference (RNAi)-based therapies.

Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice.

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.

Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.

Investigation of different chemical modifiers based on the Pd/Mg mixture for the determination of sulfur in shale oil by high-resolution continuum source graphite furnace molecular absorption spectrometry.

This study investigated different combinations of Pd/Mg, as chemical modifier, for sulfur determination, via CS molecule, in shale oil samples by high-resolution continuum source graphite furnace molecular absorption spectrometry (HR-CS GF MAS). It was evaluated the mixture Pd/Mg in aqueous solution, Pd/Mg in propan-1-ol and the Pd/Mg in propan-1-ol plus Ru as a permanent modifier. The best sensitivity was achieved with Pd/Mg mixture in propan-1-ol. The high solubility of the samples in propan-1-ol promotes a better interaction with the modifier and, consequently, a more efficient thermal stability of the CS molecules. Due to the high sulfur content in the samples, the analytical line at 258.288 nm was used. Only a minimum sample preparation was required, i.e., a dilution in propan-1-ol by a factor of 1:10 (w/w). Temperatures of 800 °C and 2200 °C were the optimized conditions for pyrolysis and vaporization, respectively. The calibration curve was constructed with l-cysteine aqueous standard solutions. The characteristic mass was 27 ng; detection and quantification limits were 0.012% (w/w) and 0.039% (w/w), respectively. The accuracy of the proposed method was confirmed by the statistical agreement (Student's and Welch's t-test at 95% confidence level) using the certified reference material CRM NIST 1084a and an OTE oil sample whose sulfur content was previously determined by the standard method ASTM D4294. The method was successfully applied in three shale oil samples. The sulfur content in the investigated samples ranged from 1.0% (w/w) to 1.3% (w/w).

Surface charge tunable catanionic vesicles based on serine-derived surfactants as efficient nanocarriers for the delivery of the anticancer drug doxorubicin.

Self-assembled vesicles composed of amino acid-based cationic/anionic surfactant mixtures show promise as novel effective drug nanocarriers. Here, we report the in vitro performance of vesicles based on cationic (16Ser) and anionic (8-8Ser) serine-based surfactants using a cancer cell model for the delivery of the anticancer drug doxorubicin (DOX). This catanionic mixture yields both negatively (0.20 in the cationic surfactant molar fraction, x16Ser) and positively (x16Ser = 0.58) charged vesicles, hence providing a surface charge tunable system. Low toxicity is confirmed for concentration ranges below 32 µM in both formulations. DOX is successfully encapsulated in the vesicles, resulting in a surface charge switch to negative for the (0.58) system, making both (0.20) and (0.58) DOX-loaded vesicles highly interesting for systemic administration. High uptake by cells was demonstrated using flow cytometry and confocal microscopy. Drug accumulation results in an increase of cell uptake up to 250% and 200% for the (0.20) and (0.58) vesicles, respectively, compared to free DOX and with localizations near the nuclear regions in the cells. The in vitro cytotoxicity studies show that DOX-loaded vesicles induce cell death, confirming the therapeutic potential of the formulations. Furthermore, the efficient accumulation of the drug inside the cell compartments harbors the potential for optimization strategies including phased delivery for prolonged treatment periods or even on-demand release.

Dental caries are more likely to impact on children's quality of life than malocclusion or traumatic dental injuries.

AIM: To measure the impact of dental caries, malocclusion, and traumatic dental injuries (TDI) on the oral health-related quality of life (OHRQoL) of Brazilian children. STUDY DESIGN: population-based cross-sectional study. MATERIALS AND METHODS A representative sample of 1,204 8-to-10-year-old children randomly selected from 19 public and private schools in Belo Horizonte (Brazil) was evaluated. The Decayed, Missing and Filled Teeth Index (DMFT), the Dental Aesthetic Index (DAI), and Andreasen's classification were used by two calibrated examiners to diagnose dental caries, malocclusion, and TDI, respectively. Children were clinically examined at school. The Brazilian version of the Child Perceptions Questionnaire for ages 8 to 10 years (CPQ8-10) was used to assess the impact on OHRQoL. RESULTS: There were statistically significant differences (p<0.001) between groups (dental caries, malocclusion, and TDI) in all subscales and the CPQ8-10 total score. The presence of dental caries alone and its association with TDI and malocclusion were associated with all CPQ8-10 subscales (p<0.05). STATISTICS: the Poisson regression model with a robust variance estimator was utilised for the multivariate analysis. Adjusted prevalence ratios were obtained for the association between oral conditions and the total score on the CPQ8-10 and its subscales. CONCLUSION: Dental caries seems to be the oral condition most commonly associated with a higher impact on the OHRQoL of Brazilian 8-to-10-year-olds.

Influence of negative dental experiences in childhood on the development of dental fear in adulthood: a case-control study.

The aim of this study was to evaluate the factors associated with high dental fear among Brazilian university students, especially the effect of a negative dental experience in childhood. This paired case-control study was conducted at the Universidade Federal de Minas Gerais in Brazil. Dental, psychology and mathematics students were divided into cases (high fear) and controls (low fear), defined by cluster analysis, according to the items of the Dental Fear Survey (DFS). Cases (n = 65) and controls (n = 260) participants were paired (1:4) by gender, undergraduate course and social vulnerability. The students self-reported the DFS and a questionnaire about oral health. Descriptive analysis, bivariate and multivariate conditional logistic regression were used as statistical tests with a significance level of 5%. The multivariate model showed that students who reported negative dental experiences in childhood (OR = 2·97; 95% CI: 1·44-6·14), toothache in the last 12 months (OR = 11·31; 95% CI: 4·79-26·68), discomfort during dental treatment (OR = 5·36; 95% CI: 2·53-11·36) and poor self-evaluation of oral health (OR = 3·82; 95% CI: 1·61-8·11) were more likely to have high dental fear. Negative dental experiences in childhood influence dental fear in adulthood. Oral health education should be addressed among university students to reduce dental fear.

Evaluation of the impacts of climate change on disease vectors through ecological niche modelling.

Vector-borne diseases are exceptionally sensitive to climate change. Predicting vector occurrence in specific regions is a challenge that disease control programs must meet in order to plan and execute control interventions and climate change adaptation measures. Recently, an increasing number of scientific articles have applied ecological niche modelling (ENM) to study medically important insects and ticks. With a myriad of available methods, it is challenging to interpret their results. Here we review the future projections of disease vectors produced by ENM, and assess their trends and limitations. Tropical regions are currently occupied by many vector species; but future projections indicate poleward expansions of suitable climates for their occurrence and, therefore, entomological surveillance must be continuously done in areas projected to become suitable. The most commonly applied methods were the maximum entropy algorithm, generalized linear models, the genetic algorithm for rule set prediction, and discriminant analysis. Lack of consideration of the full-known current distribution of the target species on models with future projections has led to questionable predictions. We conclude that there is no ideal 'gold standard' method to model vector distributions; researchers are encouraged to test different methods for the same data. Such practice is becoming common in the field of ENM, but still lags behind in studies of disease vectors.

Land use and land cover changes in Zêzere watershed (Portugal)--Water quality implications.

To understand the relations between land use allocation and water quality preservation within a watershed is essential to assure sustainable development. The land use and land cover (LUC) within Zêzere River watershed registered relevant changes in the last decades. These land use and land cover changes (LUCCs) have impacts in water quality, mainly in surface water degradation caused by surface runoff from artificial and agricultural areas, forest fires and burnt areas, and caused by sewage discharges from agroindustry and urban sprawl. In this context, the impact of LUCCs in the quality of surface water of the Zêzere watershed is evaluated, considering the changes for different types of LUC and establishing their possible correlations to the most relevant water quality changes. The results indicate that the loss of coniferous forest and the increase of transitional woodland-shrub are related to increased water's pH; while the growth in artificial surfaces and pastures leads mainly to the increase of soluble salts and fecal coliform concentration. These particular findings within the Zêzere watershed, show the relevance of addressing water quality impact driven from land use and should therefore be taken into account within the planning process in order to prevent water stress, namely within watersheds integrating drinking water catchments.

Novel serine-based gemini surfactants as chemical permeation enhancers of local anesthetics: A comprehensive study on structure-activity relationships, molecular dynamics and dermal delivery.

This work aims at studying the efficacy of a series of novel biocompatible, serine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine, combining an experimental and computational approach. The surfactants consist of gemini molecules structurally related, but with variations in headgroup charge (nonionic vs. cationic) and in the hydrocarbon chain lengths (main and spacer chains). In vitro permeation and molecular dynamics studies combined with cytotoxicity profiles were performed to investigate the permeation of both drugs, probe skin integrity, and rationalize the interactions at molecular level. Results show that these enhancers do not have significant deleterious effects on the skin structure and do not cause relevant changes on cell viability. Permeation across the skin is clearly improved using some of the selected serine-based gemini surfactants, namely the cationic ones with long alkyl chains and shorter spacer. This is noteworthy in the case of ropivacaine hydrochloride, which is not easily administered through the stratum corneum. Molecular dynamics results provide a mechanistic view of the surfactant action on lipid membranes that essentially corroborate the experimental observations. Overall, this study suggests the viability of these serine-based surfactants as suitable and promising delivery agents in pharmaceutical formulations.

Size, charge, and stability of fully serine-based catanionic vesicles: towards versatile biocompatible nanocarriers.

Vesicles based on mixed cationic and anionic surfactants (catanionic vesicles) offer a number of advantageous colloidal features over conventional lipid-based vesicles, namely spontaneity in formation, long-term stability, and easy modulation of size and charge. If biocompatibility is added through rational design of the chemical components, the potential for biorelated applications further emerges. Here, we report for the first time on two catanionic vesicle systems in which both ionic amphiphiles are derivatized from the same amino acid--serine--with the goal of enhancing aggregate biocompatibility. Phase behavior maps for a mixture with chain length symmetry, 12Ser/12-12Ser, and another with asymmetry, 16Ser/8-8Ser, are presented, for which regions of vesicles, micelles, and coexisting aggregates are identified. For the asymmetric mixture, detailed phase behavior and microstructure characterization have been carried out based on surface tension, light microscopy, cryo-SEM, cryo-TEM, and dynamic light scattering analysis. Vesicles are found with tunable mean size, pH, and zeta potential. Changes in aggregate shape with varying composition and the effect of preparation methods and aging on vesicle features and stability have been investigated in detail. The results are discussed in the light of self-assembly models and related catanionic systems reported before. A versatile system of robust vesicles is thus presented for potential applications.

Gemini surfactants mediate efficient mitochondrial gene delivery and expression.

Gene delivery targeting mitochondria has the potential to transform the therapeutic landscape of mitochondrial genetic diseases. Taking advantage of the nonuniversal genetic code used by mitochondria, a plasmid DNA construct able to be specifically expressed in these organelles was designed by including a codon, which codes for an amino acid only if read by the mitochondrial ribosomes. In the present work, gemini surfactants were shown to successfully deliver plasmid DNA to mitochondria. Gemini surfactant-based DNA complexes were taken up by cells through a variety of routes, including endocytic pathways, and showed propensity for inducing membrane destabilization under acidic conditions, thus facilitating cytoplasmic release of DNA. Furthermore, the complexes interacted extensively with lipid membrane models mimicking the composition of the mitochondrial membrane, which predicts a favored interaction of the complexes with mitochondria in the intracellular environment. This work unravels new possibilities for gene therapy toward mitochondrial diseases.

New serine-derived gemini surfactants as gene delivery systems.

Gemini surfactants have been extensively used for in vitro gene delivery. Amino acid-derived gemini surfactants combine the special aggregation properties characteristic of the gemini surfactants with high biocompatibility and biodegradability. In this work, novel serine-derived gemini surfactants, differing in alkyl chain lengths and in the linker group bridging the spacer to the headgroups (amine, amide and ester), were evaluated for their ability to mediate gene delivery either per se or in combination with helper lipids. Gemini surfactant-based DNA complexes were characterized in terms of hydrodynamic diameter, surface charge, stability in aqueous buffer and ability to protect DNA. Efficient formulations, able to transfect up to 50% of the cells without causing toxicity, were found at very low surfactant/DNA charge ratios (1/1-2/1). The most efficient complexes presented sizes suitable for intravenous administration and negative surface charge, a feature known to preclude potentially adverse interactions with serum components. This work brings forward a new family of gemini surfactants with great potential as gene delivery systems.

Serine-based gemini surfactants with different spacer linkages: from self-assembly to DNA compaction.

Cationic gemini surfactants have strong potential as compaction agents of nucleic acids for efficient non-viral gene delivery. In this work, we present the aggregation behavior of three novel cationic serine-based gemini surfactants as well as their ability to compact DNA per se and mixed with a helper lipid, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). All the surfactants have a 12-12-12 configuration, i.e. two main 12-carbon alkyl chains linked to the nitrogen atom of the amino acid residue and a 12 methylene spacer, but they differ in the nature of the spacer linkage: for (12Ser)2N12, an amine bond; for (12Ser)2CON12, an amide bond; and for (12Ser)2COO12, an ester bond. Interestingly, while the amine-based gemini aggregates into micelles, the amide and ester ones spontaneously form vesicles, which denotes a strong influence of the type of linkage on the surfactant packing parameter. The size, ζ-potential and stability of the vesicles have been characterized by light microscopy, cryogenic scanning electron microscopy (cryo-SEM) and dynamic light scattering (DLS). The interaction of the gemini aggregates with DNA at different charge ratios and in the absence and presence of DOPE has been studied by DLS, fluorescence spectroscopy and cryo-SEM. All the compounds are found to efficiently compact DNA (complexation > 90%), but relevant differences are obtained in terms of the size, ζ-potential and stability of the lipoplexes formed. Results are rationalized in terms of headgroup differences and the type of aggregates present prior to DNA condensation.

Preheating impact on the degree of conversion and water sorption/solubility of selected single-bottle adhesive systems.

OBJECTIVE: This study evaluated the degree of conversion (DC) and the water sorption/solubility of preheated single-bottle adhesive systems. METHODS AND MATERIALS: Five adhesive systems were tested: Adper Easy One and Adper Single Bond 2 (3M ESPE), Excite and Tetric N-Bond (Ivoclar/Vivadent), and XP Bond (Dentsply/Caulk). After storage for two hours at 25°C or 60°C, 50 samples (n=5) were prepared for all adhesive systems and stored dry in lightproof containers at 37°C for 24 hours. Fourier transform infrared/attenuated total reflectance spectroscopy was used to evaluate the DC, and water sorption/solubility was measured by means of mass loss and gain after water storage. The data were analyzed by two-way analysis of variance followed by Tukey's test (p<0.05). RESULTS: Preheated adhesive systems showed statistically significantly higher DC than those kept at 25°C. Except for XP Bond, preheated adhesive systems presented statistically significantly lower water sorption/solubility means. CONCLUSIONS: Preheating improved the DC for all tested adhesive systems. Also, it promoted a decrease of water sorption/solubility, except for the XP Bond adhesive system.