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Abstract The aim of this study was to compare the effects of a single application of a new calcium mesoporous silica nanoparticle (Ca2+-MSN) versus other calcium and/or fluoride products against dental erosion. Enamel blocks were half-covered and assigned to six groups (n = 10): Ca2+-MSNs; casein phosphopeptide-amorphous calcium phosphate mousse (CPP-ACP); CPP-ACP/F− (900 ppm F−); titanium tetrafluoride (TiF4 1%); sodium fluoride (NaF 1.36%); and Milli-Q® water (negative control). A single application for each product was completed on the exposed areas of the blocks and were submitted to an erosive challenge. Differences in volumetric roughness (Sa), and tooth structure loss (TSL) by use of three-dimensional noncontact optical profilometry were evaluate. Scanning electron microscopy (SEM) was performed. Analysis of variance and Tukey’s test for Sa and the Kruskal-Wallis and Mann-Whitney U tests (p< 0.05) for TSL, respectively. Results: When evaluating Sa, all products presented differences in roughness when compared with the control group (p< 0.05) but not with each other (p > 0.05). However, when analyzing the TSL, it was observed that Ca2+-MSNs, TiF4, and NaF were more effective in preventing dental erosion versus CPP-ACP, CPP-ACP/F−, and Milli-Q® water (p< 0.05). In the SEM images, the negative control presented the worst loss of dental structure, with more porous enamel. Ca2+-MSNs were as effective as TiF4 and NaF to reduce the tooth structure loss.

The new fluoridated nanocomplexes did not induce critical cytotoxic effects during the experimental periods, whilst they did show bactericidal potential against S. mutans and inhibited enamel mineral loss.

Background: Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, although not yet recognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum in Bahia, Brazil and investigated the virological and immunological factors associated with co-infection. Methodology and Principal Findings: We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n=5,346 and CSC-II, n=317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected at the time of HIV-1 diagnosis between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house immunoassay (ELISA) with SLA (Soluble Leishmania Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46% and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10/IP-10 (p=0.0076) and a tendency of increased CXCL9/MIG (p =0.061) in individuals with DP serology for L. infantum, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. Conclusions/Significance: This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection.

The aim of this study was to check the in vitro accuracy of ICDAS criteria on digital images compared to visual examination for the diagnosis of occlusal caries against a micro-CT gold standard. ICDAS was scored in 40 extracted permanent molars by means of visual inspection and stereomicroscopic images. Visual examinations were performed in duplicate and at a one-week interval by three different calibrated examiners. The analysis of digital images by ICDAS criteria was also performed in duplicate, 1 month after visual examinations. The detection methods were compared by means of sensitivity, specificity, area under the curve, predictive positive and negative values, and accuracy for two different thresholds (1- sound vs. carious teeth; 2- tooth requiring operative vs. non-operative treatment). Sensitivity and accuracy values for threshold 1 in the visual ICDAS and image-based ICDAS methods were high for sensitivity (0.93 and 0.97) and for accuracy (0.83 and 0.85), but low for specificity (0.55 for both methods). Specificity values for threshold 2 were 0.77 and 0.82, while sensitivity was 0.33 and 0.28 for each method. Spearman's rank correlation coefficient was 0.53 and 0.43 (p<0.05) for visual and image-based ICDAS compared to the gold standard scores. Both visual and image-based ICDAS scores were similar to each other in terms of diagnostic accuracy when compared to the micro-CT gold standard. Low specificity for the presence of caries and sensitivity for the detection of caries requiring operative treatment were found.

Leishmania (L . ) amazonensis is one of the etiological agents of cutaneous leishmaniasis (CL) in Brazil. Currently, there is no vaccine approved for human use against leishmaniasis, although several vaccine preparations are in experimental stages. One of them is Leishvacin, or LaAg, a first-generation vaccine composed of total L . amazonensis antigens that has consistently shown an increase of mouse resistance against CL when administered intranasally (i.n.). Since Toll-like receptor 9 (TLR9) is highly expressed in the nasal mucosa and LaAg is composed of TLR9-binding DNA CpG motifs, in this study we proposed to investigate the role of TLR9 in both L . amazonensis infection and in LaAg vaccine efficacy in C57BL/6 (WT) mice and TLR9 -/- mice. First, we evaluated, the infection of macrophages by L . amazonensis in vitro , showing no significant difference between macrophages from WT and TLR9 -/- mice in terms of both infection percentage and total number of intracellular amastigotes, as well as NO production. In addition, neutrophils from WT and TLR9 -/- mice had similar capacity to produce neutrophil extracellular traps (NETs) in response to L . amazonensis . L . amazonensis did not activate dendritic cells from WT and TLR9 -/- mice, analysed by MHCII and CD86 expression. However, in vivo , TLR9 -/- mice were slightly more susceptible to L . amazonensis infection than WT mice, presenting a larger lesion and an increased parasite load at the peak of infection and in the chronic phase. The increased TLR9 -/- mice susceptibility was accompanied by an increased IgG and IgG1 production; a decrease of IFN-γ in infected tissue, but not IL-4 and IL-10; and a decreased number of IFN-γ producing CD8 + T cells, but not CD4 + T cells in the lesion-draining lymph nodes. Also, TLR9 -/- mice could not control parasite growth following i.n. LaAg vaccination unlike the WT mice. This protection failure was associated with a reduction of the hypersensitivity response induced by immunization. The TLR9 -/- vaccinated mice failed to respond to antigen stimulation and to produce IFN-γ by lymph node cells. Together, these results suggest that TLR9 contributes to C57BL/6 mouse resistance against L . amazonensis , and that the TLR9-binding LaAg comprising CpG motifs may be important for intranasal vaccine efficacy against CL.

Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp-) deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations.