Durable bonds at the adhesive/dentin interface: an impossible mission or simply a moving target?

Composite restorations have higher failure rates, more recurrent caries and increased frequency of replacement as compared to dental amalgam. Penetration of bacterial enzymes, oral fluids, and bacteria into the crevices between the tooth and composite undermines the restoration and leads to recurrent decay and failure. The gingival margin of composite restora tions is particularly vulnerable to decay and at this margin, the adhesive and its seal to dentin provides the primary barrier between the prepared tooth and the environment. The intent of this article is to examine physico-chemical factors that affect the integrity and durability of the adhesive/dentin interfacial bond; and to explore how these factors act synergistically with mechanical forces to undermine the composite restoration. The article will examine the various avenues that have been pursued to address these problems and it will explore how alterations in material chemistry could address the detrimental impact of physico-chemical stresses on the bond formed at the adhesive/dentin interface.

Thyroid hormone status interferes with estrogen target gene expression in breast cancer samples in menopausal women

We investigated thyroid hormone levels in menopausal BrC patients and verified the action of triiodothyronine on genes regulated by estrogen and by triiodothyronine itself in BrC tissues. We selected 15 postmenopausal BrC patients and a control group of 18 postmenopausal women without BrC. We measured serum TPO-AB, TSH, FT4, and estradiol, before and after surgery, and used immunohistochemistry to examine estrogen and progesterone receptors. BrC primary tissue cultures received the following treatments: ethanol, triiodothyronine, triiodothyronine plus 4-hydroxytamoxifen, 4-hydroxytamoxifen, estrogen, or estrogen plus 4-hydroxytamoxifen. Genes regulated by estrogen (TGFA, TGFB1, and PGR) and by triiodothyronine (TNFRSF9, BMP-6, and THRA) in vitro were evaluated. TSH levels in BrC patients did not differ from those of the control group (1.34 ± 0.60 versus 2.41 ± 1.10  μ U/mL), but FT4 levels of BrC patients were statistically higher than controls (1.78 ± 0.20 versus 0.95 ± 0.16 ng/dL). TGFA was upregulated and downregulated after estrogen and triiodothyronine treatment, respectively. Triiodothyronine increased PGR expression; however 4-hydroxytamoxifen did not block triiodothyronine action on PGR expression. 4-Hydroxytamoxifen, alone or associated with triiodothyronine, modulated gene expression of TNFRSF9, BMP-6, and THRA, similar to triiodothyronine treatment. Thus, our work highlights the importance of thyroid hormone status evaluation and its ability to interfere with estrogen target gene expression in BrC samples in menopausal women.

Double-Observer Line Transect Methods: Levels of Independence

Double-observer line transect methods are becoming increasingly widespread, especially for the estimation of marine mammal abundance from aerial and shipboard surveys when detection of animals on the line is uncertain. The resulting data supplement conventional distance sampling data with two-sample mark–recapture data. Like conventional mark–recapture data, these have inherent problems for estimating abundance in the presence of heterogeneity. Unlike conventional mark–recapture methods, line transect methods use knowledge of the distribution of a covariate, which affects detection probability (namely, distance from the transect line) in inference. This knowledge can be used to diagnose unmodeled heterogeneity in the mark–recapture component of the data. By modeling the covariance in detection probabilities with distance, we show how the estimation problem can be formulated in terms of different levels of independence. At one extreme, full independence is assumed, as in the Petersen estimator (which does not use distance data); at the other extreme, independence only occurs in the limit as detection probability tends to one. Between the two extremes, there is a range of models, including those currently in common use, which have intermediate levels of independence. We show how this framework can be used to provide more reliable analysis of double-observer line transect data. We test the methods by simulation, and by analysis of a dataset for which true abundance is known. We illustrate the approach through analysis of minke whale sightings data from the North Sea and adjacent waters.

Parental Ethnotheories of Child Development: Looking Beyond Independence and Individualism in American Belief Systems

Over the past several decades, the topic of child development in a cultural context has received a great deal of theoretical and empirical investigation. Investigators from the fields of indigenous and cultural psychology have argued that childhood is socially and historically constructed, rather than a universal process with a standard sequence of developmental stages or descriptions. As a result, many psychologists have become doubtful that any stage theory of cognitive or socialemotional development can be found to be valid for all times and places. In placing more theoretical emphasis on contextual processes, they define culture as a complex system of common symbolic action patterns (or scripts) built up through everyday human social interaction by means of which individuals create common meanings and in terms of which they organize experience. Researchers understand culture to be organized and coherent, but not homogenous or static, and realize that the complex dynamic system of culture constantly undergoes transformation as participants (adults and children) negotiate and re-negotiate meanings through social interaction. These negotiations and transactions give rise to unceasing heterogeneity and variability in how different individuals and groups of individuals interpret values and meanings. However, while many psychologists—both inside and outside the fields of indigenous and cultural psychology–are now willing to give up the idea of a universal path of child development and a universal story of parenting, they have not necessarily foreclosed on the possibility of discovering and describing some universal processes that underlie socialization and development-in-context. The roots of such universalities would lie in the biological aspects of child development, in the evolutionary processes of adaptation, and in the unique symbolic and problem-solving capacities of the human organism as a culture-bearing species. For instance, according to functionalist psychological anthropologists, shared (cultural) processes surround the developing child and promote in the long view the survival of families and groups if they are to demonstrate continuity in the face of ecological change and resource competition, (e.g. Edwards & Whiting, 2004; Gallimore, Goldenberg, & Weisner, 1993; LeVine, Dixon, LeVine, Richman, Leiderman, Keefer, & Brazelton, 1994; LeVine, Miller, & West, 1988; Weisner, 1996, 2002; Whiting & Edwards, 1988; Whiting & Whiting, 1980). As LeVine and colleagues (1994) state: A population tends to share an environment, symbol systems for encoding it, and organizations and codes of conduct for adapting to it (emphasis added). It is through the enactment of these population-specific codes of conduct in locally organized practices that human adaptation occurs. Human adaptation, in other words, is largely attributable to the operation of specific social organizations (e.g. families, communities, empires) following culturally prescribed scripts (normative models) in subsistence, reproduction, and other domains [communication and social regulation]. (p. 12) It follows, then, that in seeking to understand child development in a cultural context, psychologists need to support collaborative and interdisciplinary developmental science that crosses international borders. Such research can advance cross-cultural psychology, cultural psychology, and indigenous psychology, understood as three sub-disciplines composed of scientists who frequently communicate and debate with one another and mutually inform one another’s research programs. For example, to turn to parental belief systems, the particular topic of this chapter, it is clear that collaborative international studies are needed to support the goal of crosscultural psychologists for findings that go beyond simply describing cultural differences in parental beliefs. Comparative researchers need to shed light on whether parental beliefs are (or are not) systematically related to differences in child outcomes; and they need meta-analyses and reviews to explore between- and within-culture variations in parental beliefs, with a focus on issues of social change (Saraswathi, 2000). Likewise, collaborative research programs can foster the goals of indigenous psychology and cultural psychology and lay out valid descriptions of individual development in their particular cultural contexts and the processes, principles, and critical concepts needed for defining, analyzing, and predicting outcomes of child development-in-context. The project described in this chapter is based on an approach that integrates elements of comparative methodology to serve the aim of describing particular scenarios of child development in unique contexts. The research team of cultural insiders and outsiders allows for a look at American belief systems based on a dialogue of multiple perspectives.

Synthesis and Photodynamic Effect of New Highly Photostable Decacationically Armed [60]- and [70]Fullerene Decaiodide Monoadducts To Target Pathogenic Bacteria and Cancer Cells

Novel water-soluble decacationically armed C-60 and C-70 decaiodide monoadducts, C-60- and C-70[>M(C3N6+C3)(2)], were synthesized, characterized, and applied as photosensitizers and potential nano-PDT agents against pathogenic bacteria and cancer cells. A high number of cationic charges per fullerene cage and H-bonding moieties were designed for rapid binding to the anionic residues displayed on the outer parts of bacterial cell walls. In the presence of a high number of electron-donating iodide anions as parts of quaternary ammonium salts in the arm region, we found that C-70[>M(C3N6+C3)(2)] produced more HO center dot than C-60[>M(C3N6+C3)(2)], in addition to O-1(2). This finding offers an explanation of the preferential killing of Gram-positive and Gram-negative bacteria by C-60[>M(C3N6+C3)(2)] and C-70[>M(C3N6+C3)(2)], respectively. The hypothesis is that O-1(2) can diffuse more easily into porous cell walls of Gram-positive bacteria to reach sensitive sites, while the less permeable Gram-negative bacterial cell wall needs the more reactive HO center dot to cause real damage.

The remarkable solar twin HIP 56948: a prime target in the quest for other Earths

Context. The Sun shows abundance anomalies relative to most solar twins. If the abundance peculiarities are due to the formation of inner rocky planets, that would mean that only a small fraction of solar type stars may host terrestrial planets. Aims. In this work we study HIP 56948, the best solar twin known to date, to determine with an unparalleled precision how similar it is to the Sun in its physical properties, chemical composition and planet architecture. We explore whether the abundances anomalies may be due to pollution from stellar ejecta or to terrestrial planet formation. Methods. We perform a differential abundance analysis (both in LTE and NLTE) using high resolution (R similar to 100 000) high S/N (600-650) Keck HIRES spectra of the Sun (as reflected from the asteroid Ceres) and HIP 56948. We use precise radial velocity data from the McDonald and Keck observatories to search for planets around this star. Results. We achieve a precision of sigma less than or similar to 0.003 dex for several elements. Including errors in stellar parameters the total uncertainty is as low as sigma similar or equal to 0.005 dex (1%), which is unprecedented in elemental abundance studies. The similarities between HIP 56948 and the Sun are astonishing. HIP 56948 is only 17 +/- 7 K hotter than the Sun, and log g, [Fe/H] and microturbulence velocity are only +0.02 +/- 0.02 dex, +0.02 +/- 0.01 dex and +0.01 +/- 0.01 km s(-1) higher than solar, respectively. Our precise stellar parameters and a differential isochrone analysis shows that HIP 56948 has a mass of 1.02 +/- 0.02 M-circle dot and that it is similar to 1 Gyr younger than the Sun, as constrained by isochrones, chromospheric activity, Li and rotation. Both stars show a chemical abundance pattern that differs from most solar twins, but the refractory elements (those with condensation temperature T-cond greater than or similar to 1000 K) are slightly (similar to 0.01 dex) more depleted in the Sun than in HIP 56948. The trend with T-cond in differential abundances (twins -HIP 56948) can be reproduced very well by adding similar to 3 M-circle plus of a mix of Earth and meteoritic material, to the convection zone of HIP 56948. The element-to-element scatter of the Earth/meteoritic mix for the case of hypothetical rocky planets around HIP 56948 is only 0.0047 dex. From our radial velocity monitoring we find no indications of giant planets interior to or within the habitable zone of HIP 56948. Conclusions. We conclude that HIP 56948 is an excellent candidate to host a planetary system like our own, including the possible presence of inner terrestrial planets. Its striking similarity to the Sun and its mature age makes HIP 56948 a prime target in the quest for other Earths and SETI endeavors.

The Role of Target Therapies in Schistosomiasis-Associated Pulmonary Arterial Hypertension

Background: Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) may be one of the most prevalent forms of pulmonary arterial hypertension (PAH) worldwide. However, the clinical and hemodynamical response to specific PAH therapy in Sch-PAH is not known. Methods: We retrospectively analyzed the charts of all patients with Sch-PAH who initiated specific PAH treatment between June 2003 and June 2010 in a single PAH reference center in Sao Paulo, Brazil. Clinical and hemodynamical data were retrospectively collected and evaluated in two periods: baseline and posttreatment. Results: The study population consisted of 12 patients with Sch-PAH. They were treated with phosphodiseterase-5 inhibitors (seven patients), endothelin receptor antagonists (four patients), or combination therapy (one patient). Mean treatment period was 34.9 +/- 15.5 months. Patients with Sch-PAH presented significant improvements in terms of functional class, 6-min walk test distance (439 +/- 85 to 492 +/- 79 m, P = .032), cardiac index (2.66 +/- 0.59 to 3.08 +/- 0.68 L/min/m(2), P = .028), and indexed pulmonary vascular resistance (20.7 +/- 11.6 to 15.9 +/- 9 W/m(2), P = .038) with the introduction of specific PAH treatment. Conclusions: We conclude that specific PAH therapy may be of benefit to patients with Sch-PAH, considering clinical, functional, and hemodynamic parameters. CHEST 2012; 141(4):923-928

Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma

Melanoma cells express the platelet-activating factor receptor (PAFR) and, thus, respond to PAF, a bioactive lipid produced by both tumour cells and those in the tumour microenvironment such as macrophages. Here, we show that treatment of a human melanoma SKmel37 cell line with cisplatin led to increased expression of PAFR and its accumulation. In the presence of exogenous PAF, melanoma cells were significantly more resistant to cisplatin-induced cell death. Inhibition of PAFR-dependent signalling pathways by a PAFR antagonist (WEB2086) showed chemosensitisation of melanoma cells in vitro. Nude mice were inoculated with SKmel37 cells and treated with cisplatin and WEB2086. Animals treated with both agents showed significantly decreased tumour growth compared to the control group and groups treated with only one agent. PAFR accumulation and signalling are part of a prosurvival program of melanoma cells, therefore constituting a promising target for combination therapy for melanomas.

BIOCIVILIZACAO: OVERVIEW AND BACKGROUND TO COMPLETE OUR independence

Latin American countries have a privileged position to tackle the environmental crisis, producing a new framework of relations and interdependencies: a biocivilizacao. Inspired by the ideas and Gourou Sachs, founded in centralities other than those of the "global market", and fed by other "sources" than those of high-carbon, embodied in examples like those provided by the Amazons, that teach us how the interaction between cultural and natural elements can produce the main source of biodiversity on the planet and your invaluable environmental service. Countries that share, if you can settle in other conditions (have) dependencies, guided references and values different from those that have chaired the hegemonic order. But for that, the paths that lead only to "cooperate" with the construction of "common markets", which will be replaced by others, eg, dialogues between the Organization of the Amazon Cooperation Treaty and Pan Amazonian Social Forum.

Sets of probability distributions, independence, and convexity

This paper analyzes concepts of independence and assumptions of convexity in the theory of sets of probability distributions. The starting point is Kyburg and Pittarelli's discussion of "convex Bayesianism" (in particular their proposals concerning E-admissibility, independence, and convexity). The paper offers an organized review of the literature on independence for sets of probability distributions; new results on graphoid properties and on the justification of "strong independence" (using exchangeability) are presented. Finally, the connection between Kyburg and Pittarelli's results and recent developments on the axiomatization of non-binary preferences, and its impact on "complete" independence, are described.

The leishmanicidal flavonols quercetin and quercitrin target Leishmania (Leishmania) amazonensis arginase

Polyamine biosynthesis enzymes are promising drug targets for the treatment of leishmaniasis, Chagas' disease and African sleeping sickness. Arginase, which is a metallohydrolase, is the first enzyme involved in polyamine biosynthesis and converts arginine into ornithine and urea. Ornithine is used in the polyamine pathway that is essential for cell proliferation and ROS detoxification by trypanothione. The flavonols quercetin and quercitrin have been described as antitrypanosomal and antileishmanial compounds, and their ability to inhibit arginase was tested in this work. We characterized the inhibition of recombinant arginase from Leishmania (Leishmania) amazonensis by quercetin, quercitrin and isoquercitrin. The IC50 values for quercetin, quercitrin and isoquercitrin were estimated to be 3.8, 10 and 4.3 mu M, respectively. Quercetin is a mixed inhibitor, whereas quercitrin and isoquercitrin are uncompetitive inhibitors of L. (L.) amazonensis arginase. Quercetin interacts with the substrate L-arginine and the cofactor Mn2+ at pH 9.6, whereas quercitrin and isoquercitrin do not interact with the enzyme's cofactor or substrate. Docking analysis of these flavonols suggests that the cathecol group of the three compounds interact with Asp129, which is involved in metal bridge formation for the cofactors Mn-A(2+) and Mn-B(2+) in the active site of arginase. These results help to elucidate the mechanism of action of leishmanicidal flavonols and offer new perspectives for drug design against Leishmania infection based on interactions between arginase and flavones. (C) 2012 Elsevier Inc. All rights reserved.

Functional independence in patients with chronic kidney disease being treated with haemodialysis

Purpose: This study has described and analysed the functional independence of the patients served in the haemodialysis services of a countryside town in the State of Sao Paulo, Brazil, using the Functional Independence Measure (FIM). Method: The population considered was that of 214 patients being treated with haemodialysis, assessed in 2011, by means of a social, demographic and clinical report, a Mini-Mental State Examination (MMSE) and also the FIM. Results: The mean age of the population under study was 58.01 years, while the mean FIM point score was 118.38 points, showing a level of complete or modified independence within this population. Even though the level of dependence found has been low, this can be highlighted, within the locomotion domain, in the activity of going up and down stairs (10.28%). Age, complications arising from haemodialysis, and comorbidities show a negative correlation with FIM. Conclusion: Awareness of the level of functional independence of the patients being subjected to treatment with haemodialysis is essential in order to back up intervention for the improvement of nursing assistance provided to this population.

Different approaches, one target: understanding cellular mechanisms of Parkinson's and Alzheimer's diseases

Neurodegenerative disorders are undoubtedly an increasing problem in the health sciences, given the increase of life expectancy and occasional vicious life style. Despite the fact that the mechanisms of such diseases are far from being completely understood, a large number of studies; that derive from both the basic science and clinical approaches have contributed substantial data in that direction. In this review, it is discussed several frontiers of basic research on Parkinson's and Alzheimer's diseases, in which research groups from three departments of the Institute of Biomedical Sciences of the University of Sao Paulo have been involved in a multidisciplinary effort. The main focus of the review involves the animal models that have been developed to study cellular and molecular aspects of those neurodegenerative diseases, including oxidative stress, insulin signaling and proteomic analyses, among others. We anticipate that this review will help the group determine future directions of joint research in the field and, more importantly, set the level of cooperation we plan to develop in collaboration with colleagues of the Nucleus for Applied Neuroscience Research that are mostly involved with clinical research in the same field.

Mönckeberg's sclerosis – is the artery the only target of calcification?

Abstract Background Since its first description, Mönckeberg's sclerosis has only been related to arterial media calcification, being listed among the primary diseases of the vessels. Case presentation We report here a clinically and histologically confirmed case of Mönckeberg's sclerosis in which the patient presented with massive areas of soft tissue calcifications in the pharynx and larynx. Polysomnographic parameters showed severe obstructive apnea refractory to nasal continuous positive airway pressure. Clinical and laboratory findings excluded concomitant endocrine or rheumatological diseases. Conclusion Our data provide a new insight about Mönckeberg's sclerosis, i.e., the fact that the etiopathogenic process involved in the phenomenon of calcification may not be restricted only to the arteries, but may occur in the entire organism. Further studies of the etiopathogenesis of this disease are needed.

Differential cellular FGF-2 upregulation in the rat facial nucleus following axotomy, functional electrical stimulation and corticosterone: a possible therapeutic target to Bell's palsy

Abstract Background The etiology of Bell's palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically addressed in the resistant cases are not known. Fibroblast growth factor-2 (FGF-2) pathway signaling is a potential candidate for therapeutic development because its role on wound repair and autocrine/paracrine trophic mechanisms in the lesioned nervous system. Methods Adult rats received unilateral facial nerve crush, transection with amputation of nerve branches, or sham operation. Other group of unlesioned rats received a daily functional electrical stimulation in the levator labii superioris muscle (1 mA, 30 Hz, square wave) or systemic corticosterone (10 mgkg-1). Animals were sacrificed seven days later. Results Crush and transection lesions promoted no changes in the number of neurons but increased the neurofilament in the neuronal neuropil of axotomized facial nuclei. Axotomy also elevated the number of GFAP astrocytes (143% after crush; 277% after transection) and nuclear FGF-2 (57% after transection) in astrocytes (confirmed by two-color immunoperoxidase) in the ipsilateral facial nucleus. Image analysis reveled that a seven days functional electrical stimulation or corticosterone led to elevations of FGF-2 in the cytoplasm of neurons and in the nucleus of reactive astrocytes, respectively, without astrocytic reaction. Conclusion FGF-2 may exert paracrine/autocrine trophic actions in the facial nucleus and may be relevant as a therapeutic target to Bell's palsy.