Broad and Cross-Clade CD4(+) T-Cell Responses Elicited by a DNA Vaccine Encoding Highly Conserved and Promiscuous HIV-1 M-Group Consensus Peptides

T-cell based vaccine approaches have emerged to counteract HIV-1/AIDS. Broad, polyfunctional and cytotoxic CD4(+) T-cell responses have been associated with control of HIV-1 replication, which supports the inclusion of CD4(+) T-cell epitopes in vaccines. A successful HIV-1 vaccine should also be designed to overcome viral genetic diversity and be able to confer immunity in a high proportion of immunized individuals from a diverse HLA-bearing population. In this study, we rationally designed a multiepitopic DNA vaccine in order to elicit broad and cross-clade CD4(+) T-cell responses against highly conserved and promiscuous peptides from the HIV-1 M-group consensus sequence. We identified 27 conserved, multiple HLA-DR-binding peptides in the HIV-1 M-group consensus sequences of Gag, Pol, Nef, Vif, Vpr, Rev and Vpu using the TEPITOPE algorithm. The peptides bound in vitro to an average of 12 out of the 17 tested HLA-DR molecules and also to several molecules such as HLA-DP, -DQ and murine IA(b) and IA(d). Sixteen out of the 27 peptides were recognized by PBMC from patients infected with different HIV-1 variants and 72% of such patients recognized at least 1 peptide. Immunization with a DNA vaccine (HIVBr27) encoding the identified peptides elicited IFN-gamma secretion against 11 out of the 27 peptides in BALB/c mice; CD4(+) and CD8(+) T-cell proliferation was observed against 8 and 6 peptides, respectively. HIVBr27 immunization elicited cross-clade T-cell responses against several HIV-1 peptide variants. Polyfunctional CD4(+) and CD8(+) T cells, able to simultaneously proliferate and produce IFN-gamma and TNF-alpha, were also observed. This vaccine concept may cope with HIV-1 genetic diversity as well as provide increased population coverage, which are desirable features for an efficacious strategy against HIV-1/AIDS.

Push-out bond strength and SEM evaluation of a new bonding approach into the root canal

Objective: This study evaluated the performance of different adhesive systems in fiber post placement aiming to clarify the influence of different hydrophobic experimental blend adhesives, and of one commercially available adhesive on the frictional retention during a luting procedure. Material and Methods: One luting agent (70 Wt% BisGMA, 28.5% TEGDMA; 1.5% p-tolyldiethanolamine) to cement fiber posts into root canals was applied with 4 different adhesive combinations: Group 1: The etched roots were rinsed with water for 30 s to remove the phosphoric acid, then rinsed with 99.6% ethanol for 30 s, and blot-dried. A trial adhesive (base to catalyst on a 1: 1 ratio) was used with an experimental luting agent (35% Bis-GMA, 14.37% TEGDMA, 0.5% EDMAB, 0.13% CQ); Group 2: A trial adhesive (base to catalyst on a 1: 2 ratio) was luted as in Group 1; Group 3: One-Step Plus (OSP, Bisco Inc.) following the ethanol bonding technique in combination with the luting agent as in Group 1; Group 4: OSP strictly following the manufacturer's instructions using the luting agent as in Group 1. The groups were challenged with push-out tests. Posted root slices were loaded until post segment extrusion in the apical-coronal direction. Failure modes were analyzed under scanning electron microscopy. Results: Push-out strength was not significantly influenced by the luting agent (p>0.05). No statistically significant differences among the tested groups were found as Group 1 (Exp 1 - ethanol-wet bonding technique)=Group 2 (Exp 2 - ethanol-wet bonding technique)= Group 3 (OSP - ethanol-wet bonding technique)= Group 4 (control, OSP - water-wet bonding technique) (p>0.05). The dominating failure modes in all the groups were cohesive/adhesive failures, which were predominantly observed on the post/luting agent interface. Conclusions: The results of this study support the hypothesis that the proposal to replace water with ethanol to bond fiber posts to the root canal using highly hydrophobic resin is plausible, but this seems to be more the proof of a concept than a clinically applicable procedure.

Morphological Homogeneity of Neurons: Searching for Outlier Neuronal Cells

We report a morphology-based approach for the automatic identification of outlier neurons, as well as its application to the NeuroMorpho.org database, with more than 5,000 neurons. Each neuron in a given analysis is represented by a feature vector composed of 20 measurements, which are then projected into a two-dimensional space by applying principal component analysis. Bivariate kernel density estimation is then used to obtain the probability distribution for the group of cells, so that the cells with highest probabilities are understood as archetypes while those with the smallest probabilities are classified as outliers. The potential of the methodology is illustrated in several cases involving uniform cell types as well as cell types for specific animal species. The results provide insights regarding the distribution of cells, yielding single and multi-variate clusters, and they suggest that outlier cells tend to be more planar and tortuous. The proposed methodology can be used in several situations involving one or more categories of cells, as well as for detection of new categories and possible artifacts.

Home blood pressure monitoring and control in a group of hypertensive patients

This qualitative study was performed with 71 hypertensive patients, with the objectives to compare outpatient and home blood pressure monitoring (HBPM), to assess blood pressure control, and characterize white-coat hypertension. A nurse performed the outpatient blood pressure measurement. The home blood pressure monitoring was carried out over seven days. White-coat hypertension was quantified as a difference between the outpatient measurement and home blood pressure monitoring in the ranges from 1 to 5, 6 to 10 and > 10 mmHg. The outpatient blood pressure measurement was significantly higher (p<0.05) than the home blood pressure measurement. Pressure control corresponded to 9.9% in the outpatient measurement and 23.9% in the home blood pressure measurement. The white-coat effect > 10 mmHg was 57.7% for systolic and 32.4% for diastolic pressure, in the range from 6 to 10 mmHg. Home blood pressure measurement provided a better assessment of hypertensive patients' control.

Low fatness, reduced fat intake and adequate plasmatic concentrations of LDL-cholesterol are associated with high bone mineral density in women: a cross-sectional study with control group

Background: Several parameters are associated with high bone mineral density (BMD), such as overweight, black background, intense physical activity (PA), greater calcium intake and some medications. The objectives are to evaluate the prevalence and the main aspects associated with high BMD in healthy women. Methods: After reviewing the database of approximately 21,500 BMD scans performed in the metropolitan area of Sao Paulo, Brazil, from June 2005 to October 2010, high BMD (over 1400 g/cm(2) at lumbar spine and/or above 1200 g/cm2 at femoral neck) was found in 421 exams. Exclusion criteria were age below 30 or above 60 years, black ethnicity, pregnant or obese women, disease and/or medications known to interfere with bone metabolism. A total of 40 women with high BMD were included and matched with 40 healthy women with normal BMD, paired to weight, age, skin color and menopausal status. Medical history, food intake and PA were assessed through validated questionnaires. Body composition was evaluated through a GE-Lunar DPX MD + bone densitometer. Radiography of the thoracic and lumbar spine was carried out to exclude degenerative alterations or fractures. Biochemical parameters included both lipid and hormonal profiles, along with mineral and bone metabolism. Statistical analysis included parametric and nonparametric tests and linear regression models. P < 0.05 was considered significant. Results: The mean age was 50.9 (8.3) years. There was no significant difference between groups in relation to PA, smoking, intake of calcium and vitamin D, as well as laboratory tests, except serum C-telopeptide of type I collagen (s-CTX), which was lower in the high BMD group (p = 0.04). In the final model of multivariate regression, a lower fat intake and body fatness as well a better profile of LDL-cholesterol predicted almost 35% of high BMD in women. (adjusted R2 = 0.347; p < 0.001). In addition, greater amounts of lean mass and higher IGF-1 serum concentrations played a protective role, regardless age and weight. Conclusion: Our results demonstrate the potential deleterious effect of lipid metabolism-related components, including fat intake and body fatness and worse lipid profile, on bone mass and metabolism in healthy women.

Sedimentological and provenance response to Cambrian closure of the Clymene ocean: The upper Alto Paraguai Group, Paraguay belt, Brazil

Final Gondwana amalgamation was marked by the closure of the Neoproterozoic Clymene ocean between the Amazonia craton and central Gondwana. The events which occurred in the last stage of this closure were recorded in the upper Alto Paraguai Group in the foreland of the Paraguay orogen. Outcrop-based fades analysis of the siliciclastic rocks of upper Alto Paraguai Group, composed of the Sepotuba and Diamantino Formations, was carried out in the Diamantino region, within the eastern part of the Barra dos Bugres basin, Mato Grosso state, central-western Brazil. The Sepotuba Formation is composed of sandy shales with planar to wave lamination interbedded with fine-grained sandstone with climbing ripple cross-lamination, planar lamination, swaley cross-stratification and tangential to sigmoidal cross-bedding with mud drapes, related to marine offshore deposits. The lower Diamantino Formation is composed of a monotonous, laterally continuous for hundreds of metres, interbedded siltstone and fine-grained sandstone succession with regular parallel lamination, climbing ripple cross-lamination and ripple-bedding interpreted as distal turbidites. The upper part of this formation consists of fine to medium-grained sandstones with sigmoidal cross-bedding, planar lamination, climbing ripple cross-lamination, symmetrical to asymmetrical and linguoid ripple marks arranged in lobate sand bodies. These fades are interbedded with thick siltstone in coarsening upward large-scale cycles related to a delta system. The Sepotuba Formation characterises the last transgressive deposits of the Paraguay basin representing the final stage of a marine incursion of the Clymene ocean. The progression of orogenesis in the hinterland resulted in the confinement of the Sepotuba sea as a foredeep sub-basin against the edge of the Amazon craton. Turbidites were generated during the deepening of the basin. The successive filling of the basin was associated with progradation of deltaic lobes from the southeast, in a wide lake or a restricted sea that formed after 541 +/- 7 Ma. Southeastern to east dominant Neoproterozoic source regions were confirmed by zircon grains that yielded ages around 600 to 540 Ma, that are interpreted to be from granites in the Paraguay orogen. This overall regressive succession recorded in the Alto Paraguai Group represents the filling up of a foredeep basin after the final amalgamation of westem Gondwana in the earliest Phanerozoic. (C) 2011 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

Simultaneous optical signal-to-noise ratio and differential group delay monitoring based on degree of polarization measurements in optical communications systems

We present a simultaneous optical signal-to-noise ratio (OSNR) and differential group delay (DGD) monitoring method based on degree of polarization (DOP) measurements in optical communications systems. For the first time in the literature (to our best knowledge), the proposed scheme is demonstrated to be able to independently and simultaneously extract OSNR and DGD values from the DOP measurements. This is possible because the OSNR is related to maximum DOP, while DGD is related to the ratio between the maximum and minimum values of DOP. We experimentally measured OSNR and DGD in the ranges from 10 to 30 dB and 0 to 90 ps for a 10 Gb/s non-return-to-zero signal. A theoretical analysis of DOP accuracy needed to measure low values of DGD and high OSNRs is carried out, showing that current polarimeter technology is capable of yielding an OSNR measurement within 1 dB accuracy, for OSNR values up to 34 dB, while DGD error is limited to 1.5% for DGD values above 10 ps. For the first time to our knowledge, the technique was demonstrated to accurately measure first-order polarization mode dispersion (PMD) in the presence of a high value of second-order PMD (as high as 2071 ps(2)). (C) 2012 Optical Society of America

Effect of the root canal final rinse protocols on the debris and smear layer removal and on the push-out strength of an epoxy-based sealer

The aim of the present study was to evaluate the efficacy of QMiX, SmearClear, and 17% EDTA for the debris and smear layer removal from the root canal and its effects on the push-out bond strength of an epoxy-based sealer by scanning electron microscopy (SEM). Forty extracted human canines (n = 10) were assigned to the following final rinse protocols: G1-distilled water (control), G2–17% EDTA, G3-SmearClear, and G4-QMiX. The specimens were submitted to a SEM analysis to evaluate the presence of debris and smear layer, respectively, in the apical or cervical segments. In sequence, forty extracted human maxillary canines with the root canals instrumented were divided into four groups (n = 10) similar to the SEM analysis study. After the filling with AH Plus, the roots were transversally sectioned to obtain dentinal slices. The specimens were submitted to a push-out bond strength test using an electromechanical testing machine. The statistical analysis for the SEM and push-out bond strength studies were performed using the Kruskal–Wallis and Dunn tests (α = 5%). There was no difference among the G2, G3, and G4 efficacy in removing the debris and smear layer (P > 0.05). The efficacy of these groups was superior to the control group. The push-out bond strength values of G2, G3, and G4 were superior to the control group. The ability to remove the debris and smear layer by SmearClear and QMiX was as effective as the 17% EDTA. The final rinse with these solutions promoted similar push-out bond strength values.

SEM analysis and push-out bond strength of fiberglass posts luted with different cements of glass-ionomer in humid environment: pilot test

The objective of this study was to evaluate the push-out bond strength of fiberglass resin reinforced bonded with five ionomer cements. Also, the interface between cement and dentin was inspected by means of SEM. Fifty human canines were chose after rigorous scrutiny process, endodontically treated and divided randomly into five groups (n = 3) according to cement tested: Group I – Ionoseal (VOCO), Group II – Fugi I (GC), Group III – Fugi II Improved (GC), Group IV – Rely X Luting 2 (3M ESPE), Group V – Ketac Cem (3M ESPE). The post-space was prepared to receive a fiberglass post, which was tried before cementation process. No dentin or post surface pretreatment was carried out. After post bonding, all roots were cross-sectioned to acquire 3 thin-slices (1 mm) from three specific regions of tooth (cervical, medium and apical). A Universal test machine was used to carry out the push-out test with cross-head speed set to 0.5mm/mim. All failed specimens were observed under optical microscope to identify the failure mode. Representative specimens from each group was inspected under SEM. The data were analyzed by Kolmogorov-Smirnov and Levene’s tests and by two-way ANOVA, and Tukey’s port hoc test at a significance level of 5%. It was compared the images obtained for determination of types of failures more occurred in different levels. SEM inspection displayed that all cements filled the space between post and dentin, however, some imperfections such bubles and voids were noticed in all groups in some degree of extension. The push-out bond strength showed that cement Ketac Cem presented significant higher results when compared to the Ionoseal (P = 0.02). There were no statistical significant differences among other cements.