Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients.

Optimal vaccine strategies must be identified for improving T-cell vaccination against infectious and malignant diseases. MelQbG10 is a virus-like nano-particle loaded with A-type CpG-oligonucleotides (CpG-ODN) and coupled to peptide(16-35) derived from Melan-A/MART-1. In this phase IIa clinical study, four groups of stage III-IV melanoma patients were vaccinated with MelQbG10, given (i) with IFA (Montanide) s.c.; (ii) with IFA s.c. and topical Imiquimod; (iii) i.d. with topical Imiquimod; or (iv) as intralymph node injection. In total, 16/21 (76%) patients generated ex vivo detectable Melan-A/MART-1-specific T-cell responses. T-cell frequencies were significantly higher when IFA was used as adjuvant, resulting in detectable T-cell responses in all (11/11) patients, with predominant generation of effector-memory-phenotype cells. In turn, Imiquimod induced higher proportions of central-memory-phenotype cells and increased percentages of CD127(+) (IL-7R) T cells. Direct injection of MelQbG10 into lymph nodes resulted in lower T-cell frequencies, associated with lower proportions of memory and effector-phenotype T cells. Swelling of vaccine site draining lymph nodes, and increased glucose uptake at PET/CT was observed in 13/15 (87%) of evaluable patients, reflecting vaccine triggered immune reactions in lymph nodes. We conclude that the simultaneous use of both Imiquimod and CpG-ODN induced combined memory and effector CD8(+) T-cell responses.

Problems of allometric scaling analysis: examples from mammalian reproductive biology.

Biological scaling analyses employing the widely used bivariate allometric model are beset by at least four interacting problems: (1) choice of an appropriate best-fit line with due attention to the influence of outliers; (2) objective recognition of divergent subsets in the data (allometric grades); (3) potential restrictions on statistical independence resulting from phylogenetic inertia; and (4) the need for extreme caution in inferring causation from correlation. A new non-parametric line-fitting technique has been developed that eliminates requirements for normality of distribution, greatly reduces the influence of outliers and permits objective recognition of grade shifts in substantial datasets. This technique is applied in scaling analyses of mammalian gestation periods and of neonatal body mass in primates. These analyses feed into a re-examination, conducted with partial correlation analysis, of the maternal energy hypothesis relating to mammalian brain evolution, which suggests links between body size and brain size in neonates and adults, gestation period and basal metabolic rate. Much has been made of the potential problem of phylogenetic inertia as a confounding factor in scaling analyses. However, this problem may be less severe than suspected earlier because nested analyses of variance conducted on residual variation (rather than on raw values) reveals that there is considerable variance at low taxonomic levels. In fact, limited divergence in body size between closely related species is one of the prime examples of phylogenetic inertia. One common approach to eliminating perceived problems of phylogenetic inertia in allometric analyses has been calculation of 'independent contrast values'. It is demonstrated that the reasoning behind this approach is flawed in several ways. Calculation of contrast values for closely related species of similar body size is, in fact, highly questionable, particularly when there are major deviations from the best-fit line for the scaling relationship under scrutiny.

Evaluation of serum myostatin and sclerostin levels in chronic spinal cord injured patients.

STUDY DESIGN: Case-control study. OBJECTIVES: To assess serum myostatin levels, bone mineral density (BMD), appendicular skeletal muscle mass (ASMM) and serum sclerostin levels in chronic spinal cord injured (SCI) patients and healthy controls. SETTING: SCI centre in Italy. METHODS: Blood samples, whole-body bioelectrical impedance analysis and BMD measurement with the ultrasound technique at the calcaneus level were taken from patients suffering from chronic SCI (both motor complete and incomplete) and healthy control subjects. RESULTS: A total of 28 SCI patients and 15 healthy controls were enrolled. Serum myostatin levels were statistically higher (P<0.01) in SCI patients compared with healthy controls. Similar results were found comparing both the motor complete and the motor incomplete SCI subgroups to healthy controls. Serum sclerostin was significantly higher in patients with SCI compared with healthy controls (P<0.01). BMD, stiffness and mean T-score values in SCI patients were significantly lower than those in healthy controls. Serum myostatin concentrations in the motor complete SCI subgroups correlated only with serum sclerostin levels (r(2)=0.42; P=0.001) and ASMM (r(2)=0.70; P=0.002) but not in healthy controls. DISCUSSION: Serum myostatin and serum sclerostin are significantly higher in chronic SCI patients compared with healthy controls. They are potential biomarkers of muscle and bone modifications after SCI. This is the first study reporting an increase in serum myostatin in patients suffering from chronic SCI and a correlation with ASMM.

Experimental enhancement of corticosterone levels positively affects subsequent male survival.

Corticosterone is an important hormone of the stress response that regulates physiological processes and modifies animal behavior. While it positively acts on locomotor activity, it may negatively affect reproduction and social activity. This suggests that corticosterone may promote behaviors that increase survival at the cost of reproduction. In this study, we experimentally investigate the link between corticosterone levels and survival in adult common lizards (Lacerta vivipara) by comparing corticosterone-treated with placebo-treated lizards. We experimentally show that corticosterone enhances energy expenditure, daily activity, food intake, and it modifies the behavioral time budget. Enhanced appetite of corticosterone-treated individuals compensated for increased energy expenditure and corticosterone-treated males showed increased survival. This suggests that corticosterone may promote behaviors that reduce stress and it shows that corticosterone per se does not reduce but directly or indirectly increases longer-term survival. This suggests that the production of corticosterone as a response to a stressor may be an adaptive mechanism that even controls survival.

Cómo aplicar las pruebas paramétricas bivariadas t de Student y ANOVA en SPSS.

Las pruebas paramétricas son un tipo de pruebas de significación estadística que cuantifican la asociación o independencia entre una variable cuantitativa y una categórica. Las pruebas paramétricas exigen ciertos requisitos previos para su aplicación: la distribución Normal de la variable cuantitativa en los grupos que se comparan, la homogeneidad de varianzas en las poblaciones de las que proceden los grupos y una n muestral no inferior a 30. Su incumplimiento conlleva la necesidad de recurrir a pruebas estadísticas no paramétricas. Las pruebas paramétricas se clasifican en dos: prueba t (para una muestra o para dos muestras relacionadas o independientes) y prueba ANOVA (para más de dos muestras independientes).

Efeito do lisinopril sobre parametros cardiacos e mortalidade no infarto experimental em ratos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Microleakage evaluation of pit and fissure sealants done with different procedures, materials, and laser after invasive technique

This study evaluated the microleakage of pit and fissure sealants after different surface preparation (invasive technique and laser irradiation) and the use of different materials (fluoride resin-filled sealant, resin-modified glass ionomer cement and adhesive system). Eighty-four pre molars were used in this study, which were divided into seven groups. After the accomplishment of the different treatments, these were submitted to thermocycling process and assess for microleakage by examination under an epifluorescent microscope and scored zero to seven. Two specimens of each group were observed under scanning electron microscope (SEM). The results showed that laser irradiation did not lessen microleakage in pit and fissures when using a filled-resin sealant with fluoride or a resin-modified glass ionomer cement. The use of laser irradiation and adhesive system, followed by a resin-filled sealant with fluoride, showed the lowest microleakage scores in pit and fissures. Comparing this group to the resin-modified glass ionomer cement group, there was statistical significance. The use of a adhesive system decreased microleakage when using a fluoride resin-filled sealant with or without previous laser irradiation; although it was not statistically significant.

Role of ticlopidine on adriamycin-induced nephropathy

The effect of ticlopidine on rats with adriamycin nephropathy was observed during 26 weeks. In the ticlopidine-treated nephrotic animals (TNG), proteinuria was less than in the untreated nephrotic animals (NG), but this difference was significant only at week 6 (TNG = 47.27 ± 16.52 versus NG = 100.08 ± 13.83 mg/24h, p < 0.01) and week 26 (TNG = 157.00 ± 28.73 versus NG = 217.00 ± 21.73 mg/24h, p< 0.01) after ADR injection. NG presented severe tubulointerstitial abnormalities with a tubulointerstitial lesion index of 3+. No difference in glomerular lesions was observed among the groups (NG median = 6%, TNG median = 4% and TCG median = 2%). The tubulointerstitial lesion index of TNG was less intense (median = 2+) but not different from those of the control groups (CG median = 1+; TCG median = 0+) nor NG (median = 3+). We concluded that the treatment with ticlopidine produced some partially beneficial effects but did not prevent the development of adriamycin-induced nephropathy.

A comparison of molar root canal preparation using stainless-steel and nickel-titanium instruments

Fifty-four extracted human mandibular molars were embedded and sectioned at two levels. The reassembled mesial root canals were prepared with stainless-steel hand K-files (Flexofiles) and either Nitiflex or Mity nickel-titanium hand K-files using a push-pull anticurvature filing technique. Each of the three experimental groups contained 36 mesial canals randomly distributed. Superimposed pre- and postinstrumentation cross-sectional root images were magnified using a stereomicroscope and transferred to a computer for measurement and statistical analysis. The direction and extent of canal center movement were evaluated. At the apical level, the groups produced no significant difference of direction of canal center movement. In cervical sections, all groups tended to move in a distolingual direction. The three groups, however, produced no significant difference in the cervical sections in the extent of canal center movement. In apical sections, Nitiflex produced the least canal center movement. Copyright © 1999 by The American Association of Endodontists.

Evaluation of cell culture cytotoxicity of five root canal sealers

The cytotoxicity of four calcium hydroxide-based root canal sealers (Sealapex, CRCS, Apexit, and Sealer 26) and one zinc oxide-eugenol-based sealer (Fill Canal) was evaluated microscopically for morphological changes in rat peritoneal macrophages. The least cytotoxic sealer was Fill Canal, followed in increasing order of cytotoxicity by CRCS, Sealer 26, Apexit, and Sealapex. Copyright © 2000 by The American Association of Endodontists.

Caries and its association with infant feeding and oral health-related behaviours in 3-4-year-old Brazilian children

Objectives: To investigate the relationships between socio-demographic factors, infant feeding habits, oral hygiene and the prevalence and patterns of caries in Brazilian 3-4-year-olds. Methods: Systematic random sampling was used to select children enrolled in municipal nurseries in Araraquara, Brazil, in 1998. Clinical examinations were carried out by one examiner using dmft and dmfs indices and WHO criteria. Questionnaires for information related to the socio-demographic background, oral hygiene and dietary history of the children were completed by their mothers. Results: Caries was seen in 46% of the children; 17% of them had the more extensive pattern involving molars and incisors. Social class, mother's education, and age at which breast-feeding terminated showed statistically significant associations with caries. Feeding bottles with added sugars were still being given to 80% of the children. When the significant variables were taken into account only age at which breast-feeding terminated showed a significant relationship to the pattern of disease. Children who were never breast-fed or were breast-fed beyond the age of 24 months had a higher prevalence of the more extensive pattern of caries. Conclusions: The association between the length of time a mother breast-feeds and extensive caries should be a consideration in any local infant feeding policies or health promotion strategies. The duration for appropriate breast- or bottle-feeding should be emphasised.

Effect of whitening agents on dentin bonding

Background: Several studies have shown a reduction in enamel bond strengths when the bonding procedure is carried out immediately after vital bleaching with peroxides. This reduction in bond strengths has become a concern in cosmetic dentistry with the introduction of new in-office and waiting-room bleaching techniques. The aim of this in vitro study was to evaluate the effect of three bleaching regimens: 35% hydrogen peroxide (HP), 35% carbamide peroxide (CP), and 10% CP, on dentin bond strengths. Materials and Methods: One hundred and twenty fresh bovine incisors were used in this study. The labial surface of each tooth was ground flat to expose dentin and was subsequently polished with 600-grit wet silicon carbide paper. The remaining dentin thickness was monitored and kept at an average of 2 mm. The teeth were randomly assigned to four bleaching regimens (n = 30): (A) control, no bleaching treatment; (B) 35% HP for 30 minutes; (C) 35% CP for 30 minutes; and (D) 10% CP for 6 hours. For each group, half of the specimens (n = 15) were bonded with Single Bond/Z100 immediately after the bleaching treatment, whereas the other half was bonded after the specimens were stored for 1 week in artificial saliva at 37°C. The specimens were fractured in shear using an Instron machine. Results: For the groups bonded immediately after bleaching, one-way analysis of variance (ANOVA) followed by the Duncan's post hoc test revealed a statistically significant reduction in bond strengths in a range from 71% to 76%. For the groups bonded at 1 week, one-way ANOVA showed that group B (35% HP for 30 min) resulted in the highest bond strengths, whereas 10% CP resulted in the lowest bond strengths. Student's t-test showed that delayed bonding resulted in a significant increase in bond strengths for groups B (35% HP) and C (35% CP); whereas the group bleached with 10% CP (group D) remained in the same range obtained for immediate bonding. Storage in artificial saliva also affected the control group, reducing its bond strengths to 53% of the original. ©2000 BC Decker Inc.

Effect of Surface Treatments on the Bond Strength between Composite Resin and Acrylic Resin Denture Teeth

Purpose: This investigation studied the effects of 3 surface treatments on the shear bond strength of a light-activated composite resin bonded to acrylic resin denture teeth. Materials and Methods: The occlusal surfaces of 30 acrylic resin denture teeth were ground flat with up to 400-grit silicon carbide paper. Three different surface treatments were evaluated: (1) the flat ground surfaces were primed with methyl methacrylate (MMA) monomer for 180 seconds; (2) light-cured adhesive resin was applied and light polymerized according to the manufacturer's instructions; and (3) treatment 1 followed by treatment 2. The composite resin was packed on the prepared surfaces using a split mold. The interface between tooth and composite was loaded at a cross-head speed of 0.5 mm/min until failure. Results: Analysis of variance indicated significant differences between the surface treatments. Results of mean comparisons using Tukey's test showed that significantly higher shear bond strengths were developed by bonding composite resin to the surfaces that were previously treated with MMA and then with the bonding agent when compared to the other treatments. Conclusion: Combined surface treatment of MMA monomer followed by application of light-cured adhesive resin provided the highest shear bond strength between composite resin and acrylic resin denture teeth.