Absence of Interferon-γ–Inducible Gene IGTP Does Not Significantly Alter the Development of Chagasic Cardiomyopathy in Mice Infected with Trypanosoma cruzi (Brazil Strain)

Interferon-γ (IFN-γ) contributes to host resistance during acute infection with Trypanosoma cruzi, the causative agent of Chagas’ disease. Inducibly expressed guanosine triphosphatase (IGTP), a 48-kDa guanosine triphosphatase (GTPase), is a member of a family of GTPase proteins inducibly expressed by IFN-γ. The expression pattern of IGTP suggests that it may mediate IFN-γ–induced responses in a variety of cell types. IGTP has been demonstrated to be important for control of Toxoplasma gondii infection but not for resistance against Listeria monocytogenes. We evaluated the role of IGTP in development of chronic chagasic cardiomyopathy in IGTP null mice and C57X129sv (wild type [WT]) mice infected with the Brazil strain for 6 mo. There was no significant difference in parasitemia or cardiac histopathology between null and WT mice. Right ventricular remodeling was observed in infected IGTP null mice, suggesting that IGTP does not significantly alter the course of T. cruzi infection.

Nitric oxide is responsible for oxidative skin injury and modulation of cell proliferation after 24 hours of UVB exposures

Nitric oxide (NO) is produced by various mammalian cells and plays a variety of regulatory roles in normal physiology and in pathological processes. This article provides evidence regarding the participation of NO in UVB-induced skin lesions and in the modulation of skin cell proliferation following UVB skin irradiation. Hairless mice were subjected to UVB irradiation for 3 hours and the skin evaluated immediately, 6 and 24 hours postirradiation. The skin lipid peroxidation, and NO levels evaluated by chemiluminescence and inducible nitric oxide synthase (iNOS) and nitrotyrosine immunolabelling increased significantly 24 hours after irradiation and decreased under the treatment with aminoguanidine (AG). On the other hand, cell proliferation markers, PCNA and VEGF showed a strong labelling index when AG was used. The data indicate that NO mediates, at least in part, the lipid peroxidation and protein nitration and also promotes the down regulation of factors involved in cell proliferation. This work shows that the NO plays an important role in the oxidative stress damage and on modulation of cell proliferation pathways in UVB irradiated skin.

An algorithm for the strip packing problem using collision free region and exact fitting placement

The irregular shape packing problem is approached. The container has a fixed width and an open dimension to be minimized. The proposed algorithm constructively creates the solution using an ordered list of items and a placement heuristic. Simulated annealing is the adopted metaheuristic to solve the optimization problem. A two-level algorithm is used to minimize the open dimension of the container. To ensure feasible layouts, the concept of collision free region is used. A collision free region represents all possible translations for an item to be placed and may be degenerated. For a moving item, the proposed placement heuristic detects the presence of exact fits (when the item is fully constrained by its surroundings) and exact slides (when the item position is constrained in all but one direction). The relevance of these positions is analyzed and a new placement heuristic is proposed. Computational comparisons on benchmark problems show that the proposed algorithm generated highly competitive solutions. Moreover, our algorithm updated some best known results. (C) 2012 Elsevier Ltd. All rights reserved.

The presence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor on patients with rheumatoid arthritis (RA) does not interfere with the chance of clinical remission in a follow-up of 3 years

Autoantibodies in early rheumatoid arthritis (RA) have important diagnostic value. The association between the presence of autoantibodies against cyclic citrullinated peptide and the response to treatment is controversial. To prospectively evaluate a cohort of patients with early rheumatoid arthritis (< 12 months of symptoms) in order to determine the association between serological markers (rheumatoid factor (RF), anti-citrullinated protein antibodies) such as anti-cyclic citrullinated peptide antibodies (anti-CCP) and citrullinated anti-vimentin (anti-Sa) with the occurrence of clinical remission, forty patients diagnosed with early RA at the time of diagnosis were evaluated and followed for 3 years, in use of standardized therapeutic treatment. Demographic and clinical data were recorded, disease activity score 28 (DAS 28), as well as serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1) and anti-Sa in the initial evaluation and at 3, 6, 12, 18, 24, and 36 months of follow-up. The outcome evaluated was the percentage of patients with clinical remission, which was defined by DAS 28 lower than 2.6. Comparisons were made through the Student t test, mixed-effects regression analysis, and analysis of variance (significance level of 5%). The mean age was 45 years, and a female predominance was observed (90%). At the time of diagnosis, RF was observed in 50% of cases (RF IgA-42%, RF IgG-30%, and RF IgM-50%), anti-CCP in 50% (no difference between CCP2, CCP3, and CCP3.1) and anti-Sa in 10%. After 3 years, no change in the RF prevalence and anti-CCP was observed, but the anti-Sa increased to 17.5% (P = 0.001). The percentage of patients in remission, low, moderate, and intense disease activity, according to the DAS 28, was of 0, 0, 7.5, and 92.5% (initial evaluation) and 22.5, 7.5, 32.5, and 37.5% (after 3 years). There were no associations of the presence of autoantibodies in baseline evaluation and in serial analysis with the percentage of clinical remission during follow-up of 3 years The presence of autoantibodies in early RA has no predictive value for clinical remission in early RA.

The eagle and the starlings: Galileo's argument for the autonomy of science-how pertinent is it today?

After Galileo's argument for the autonomy of science is analysed and adapted to take into account later developments of scientific practices, we conclude that, in the final analysis, it is not compelling. Nevertheless, Galileo's argument still provides a useful point of reference, for aspects of it can be interpreted to anticipate central components of the often acclaimed ideal of science as value free, so that appraising it contributes to the larger purpose of exploring how well that ideal stands up today. Finally, we will argue that residue from Galileo's struggle with the Church remains with us, making it difficult to identify the conditions that would need to be put into place today for any robust sense of the autonomy of science to be defensible. (C) 2011 Elsevier Ltd. All rights reserved.

A marker-and-cell approach to free surface 2-D multiphase flows

This work describes a methodology to simulate free surface incompressible multiphase flows. This novel methodology allows the simulation of multiphase flows with an arbitrary number of phases, each of them having different densities and viscosities. Surface and interfacial tension effects are also included. The numerical technique is based on the GENSMAC front-tracking method. The velocity field is computed using a finite-difference discretization of a modification of the NavierStokes equations. These equations together with the continuity equation are solved for the two-dimensional multiphase flows, with different densities and viscosities in the different phases. The governing equations are solved on a regular Eulerian grid, and a Lagrangian mesh is employed to track free surfaces and interfaces. The method is validated by comparing numerical with analytic results for a number of simple problems; it was also employed to simulate complex problems for which no analytic solutions are available. The method presented in this paper has been shown to be robust and computationally efficient. Copyright (c) 2012 John Wiley & Sons, Ltd.

Is 2-mm Punch Biopsy Useful in the Diagnosis of Malignant Eyelid Tumors?

Purpose: Two-millimeter punch biopsy is a swift and practical diagnostic tool in the outpatient setting. However, few studies have evaluated the efficacy of the method for diagnosis of malignant eyelid tumors. Methods: This was an observational study of patients with suspicion of malignant eyelid tumor attending the Ocular Plastic Surgery Center at Hospital das Clinicas, University of Sao Paulo School of Medicine. Following standard procedures, preoperative biopsies were taken with a 2-mm trephine and surgical excision was performed with safety margins, followed by reconstruction. Anatomopathologic analysis of the surgical specimen was used as gold standard to evaluate the accuracy of diagnosis by punch biopsy. Results: The study included 50 periocular tumors with suspicion of malignancy. The indicators of efficacy in the identification of malignancy by 2-mm punch biopsy were: sensitivity 88%, specificity 100%, positive predictive value 100%, and negative predictive value 64%. Accuracy was 90% for malignancy and 80% for histologic type. The. index of agreement between the diagnostic methods was 0.722 (p < 0.001). Conclusion: A positive result with 2-mm punch biopsy is a safe indication for surgical excision of the tumor, whereas a negative result does not necessarily imply benignity. In cases of high clinical suspicion, a second biopsy should be taken from a different part of the tumor to rule out malignancy. (Ophthal Plast Reconstr Surg 2012;28:282-285)

Exogenous ornithine is an effective precursor and the delta-ornithine amino transferase pathway contributes to proline accumulation under high N recycling in salt-stressed cashew leaves

The role of the delta-ornithine amino transferase (OAT) pathway in proline synthesis is still controversial and was assessed in leaves of cashew plants subjected to salinity. The activities of enzymes and the concentrations of metabolites involved in proline synthesis were examined in parallel with the capacity of exogenous ornithine and glutamate to induce proline accumulation. Proline accumulation was best correlated with OAT activity, which increased 4-fold and was paralleled by NADH oxidation coupled to the activities of OAT and Delta(1)-pyrroline-5-carboxylate reductase (P5CR), demonstrating the potential of proline synthesis via OAT/P5C. Overall, the activities of GS. GOGAT and aminating GDH remained practically unchanged under salinity. The activity of P5CR did not respond to NaCl whereas Delta(1)-pyrroline-5-carboxylate dehydrogenase was sharply repressed by salinity. We suggest that if the export of P5C from the mitochondria to the cytosol is possible, its subsequent conversion to proline by P5CR may be important. In a time-course experiment, proline accumulation was associated with disturbances in amino acid metabolism as indicated by large increases in the concentrations of ammonia, free amino acids, glutamine, arginine and ornithine. Conversely, glutamate concentrations increased moderately and only within the first 24 h. Exogenous feeding of ornithine as a precursor was very effective in inducing proline accumulation in intact plants and leaf discs, in which proline concentrations were several times higher than glutamate-fed or salt-treated plants. Our data suggest that proline accumulation might be a consequence of salt-induced increase in N recycling, resulting in increased levels of ornithine and other metabolites involved with proline synthesis and OAT activity. Under these metabolic circumstances the OAT pathway might contribute significantly to proline accumulation in salt-stressed cashew leaves. (C) 2011 Elsevier GmbH. All rights reserved.

The ischial spine sign: does pelvic tilt and rotation matter?

Although the ischial spine sign (ISS) has been advocated to detect acetabular retroversion, it is unknown whether the sign is valid on anteroposterior (AP) pelvic radiographs with tilted or rotated pelves. We therefore evaluated reliability of the ISS as a tool for diagnosing acetabular retroversion in the presence of considerable pelvic tilt and/or malrotation. We obtained radiographs of 20 cadaver pelves in 19 different malorientations resulting in 380 pelvis images (760 hips) for evaluation. In addition, 129 clinical radiographs of patients' hips that had varying pelvis orientations were reviewed. We found an overall sensitivity of 81% (90%), specificity of 70% (71%), positive predictive value of 77% (80.7%), and negative predictive value of 75% (85%) in the cadaver (patient) hips. Our data suggest the ISS is a valid tool for diagnosing acetabular retroversion on plain radiographs taken using a standardized technique regardless of the degree of pelvic tilt and rotation.

Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses

The lower intestine of adult mammals is densely colonized with nonpathogenic (commensal) microbes. Gut bacteria induce protective immune responses, which ensure host-microbial mutualism. The continuous presence of commensal intestinal bacteria has made it difficult to study mucosal immune dynamics. Here, we report a reversible germ-free colonization system in mice that is independent of diet or antibiotic manipulation. A slow (more than 14 days) onset of a long-lived (half-life over 16 weeks), highly specific anticommensal immunoglobulin A (IgA) response in germ-free mice was observed. Ongoing commensal exposure in colonized mice rapidly abrogated this response. Sequential doses lacked a classical prime-boost effect seen in systemic vaccination, but specific IgA induction occurred as a stepwise response to current bacterial exposure, such that the antibody repertoire matched the existing commensal content.

Breastfeeding and lung function at school age: does maternal asthma modify the effect?

The evidence for an effect of breastfeeding on lung function is conflicting, in particular whether the effect is modified by maternal asthma.

Stress free configuration of the human eye

Numerical simulations of eye globes often rely on topographies that have been measured in vivo using devices such as the Pentacam or OCT. The topographies, which represent the form of the already stressed eye under the existing intraocular pressure, introduce approximations in the analysis. The accuracy of the simulations could be improved if either the stress state of the eye under the effect of intraocular pressure is determined, or the stress-free form of the eye estimated prior to conducting the analysis. This study reviews earlier attempts to address this problem and assesses the performance of an iterative technique proposed by Pandolfi and Holzapfel [1], which is both simple to implement and promises high accuracy in estimating the eye's stress-free form. A parametric study has been conducted and demonstrated reliance of the error level on the level of flexibility of the eye model, especially in the cornea region. However, in all cases considered 3-4 analysis iterations were sufficient to produce a stress-free form with average errors in node location <10(-6)mm and a maximal error <10(-4)mm. This error level, which is similar to what has been achieved with other methods and orders of magnitude lower than the accuracy of current clinical topography systems, justifies the use of the technique as a pre-processing step in ocular numerical simulations.

Why is 11beta-hydroxysteroid dehydrogenase type 1 facing the endoplasmic reticulum lumen? Physiological relevance of the membrane topology of 11beta-HSD1

11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is essential for the local activation of glucocorticoid receptors (GR). Unlike unliganded cytoplasmic GR, 11beta-HSD1 is an endoplasmic reticulum (ER)-membrane protein with lumenal orientation. Cortisone might gain direct access to 11beta-HSD1 by free diffusion across membranes, indirectly via intracellular binding proteins or, alternatively, by insertion into membranes. Membranous cortisol, formed by 11beta-HSD1 at the ER-lumenal side, might then activate cytoplasmic GR or bind to ER-lumenal secretory proteins. Compartmentalization of 11beta-HSD1 is important for its regulation by hexose-6-phosphate dehydrogenase (H6PDH), which regenerates cofactor NADPH in the ER lumen and stimulates oxoreductase activity. ER-lumenal orientation of 11beta-HSD1 is also essential for the metabolism of the alternative substrate 7-ketocholesterol (7KC), a major cholesterol oxidation product found in atherosclerotic plaques and taken up from processed cholesterol-rich food. An 11beta-HSD1 mutant adopting cytoplasmic orientation efficiently catalyzed the oxoreduction of cortisone but not 7KC, indicating access to cortisone from both sides of the ER-membrane but to 7KC only from the lumenal side. These aspects may be relevant for understanding the physiological role of 11beta-HSD1 and for developing therapeutic interventions to control glucocorticoid reactivation.

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

AIMS/HYPOTHESIS: Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance and the metabolic syndrome. This study tested the hypothesis that RBP4 is a marker of insulin resistance and the metabolic syndrome in patients with type 2 diabetes or coronary artery disease (CAD) or in non-diabetic control subjects without CAD. METHODS: Serum RBP4 was measured in 365 men (126 with type 2 diabetes, 143 with CAD and 96 control subjects) and correlated with the homeostasis model assessment of insulin resistance index (HOMA-IR), components of the metabolic syndrome and lipoprotein metabolism. RBP4 was detected by ELISA and validated by quantitative Western blotting. RESULTS: RBP4 concentrations detected by ELISA were shown to be strongly associated with the results gained in quantitative Western blots. There were no associations of RBP4 with HOMA-IR or HbA(1c) in any of the groups studied. In patients with type 2 diabetes there were significant positive correlations of RBP4 with total cholesterol, LDL-cholesterol, VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity. In patients with CAD, there were significant associations of RBP4 with VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity, while non-diabetic control subjects without CAD showed positive correlations of RBP4 with VLDL-cholesterol and plasma triacylglycerol. CONCLUSIONS/INTERPRETATION: RBP4 does not seem to be a valuable marker for identification of the metabolic syndrome or insulin resistance in male patients with type 2 diabetes or CAD. Independent associations of RBP4 with pro-atherogenic lipoproteins and enzymes of lipoprotein metabolism indicate a possible role of RBP4 in lipid metabolism.

[Does cataract surgery increase the risk of exudative age-related macular degeneration? Results from a large retrospective case-control study]

BACKGROUND: Many epidemiological studies indicate a positive correlation between cataract surgery and the subsequent progression of age-related macular degeneration (AMD). Such a correlation would have far-reaching consequences. However, in epidemiological studies it is difficult to determine the significance of a single risk factor, such as cataract surgery. PATIENTS AND METHODS: We performed a retrospective case-control study of patients with new onset exudative age-related macular degeneration to determine if cataract surgery was a predisposing factor. A total of 1496 eyes were included in the study: 984 cases with new onset of exudative AMD and 512 control eyes with early signs of age-related maculopathy. Lens status (phakic or pseudophakic) was determined for each eye. RESULTS: There was no significant difference in lens status between study and control group (227/984 [23.1 %] vs. 112/512 [21.8 %] pseudophakic, p = 0.6487; OR = 1.071; 95 % CI = 0.8284-1.384). In cases with bilateral pseudophakia (n = 64) no statistically significant difference of the interval between cataract surgery in either eye and the onset of exudative AMD in the study eye was found (225.9 +/- 170.4 vs. 209.9 +/- 158.2 weeks, p = 0.27). CONCLUSIONS: Our results provide evidence that cataract surgery is not a major risk factor for the development of exudative AMD.