Concrete damage analysis based on higher-order beam theories using fracture energy regularization.

This paper presents the numerical damage analysis of concrete structures using higher-order beam theories based on Carrera Unified Formulation (CUF). The concrete constitutive relation is modeled using continuum damage mechanics based on a modified Mazars concrete damage model, in which both the tensile and compressive softening behaviors are regularized with classical fracture energy methodology. An expression is proposed to estimate the characteristic length in higher-order beam theories, to prevent mesh dependency. Both softening constitutive laws and fracture energy calculations are obtained according to Model Code 2010. To assess the efficiency of the proposed model, three classical benchmark quasi-static experiments are taken for validation. From the comparison between numerical and experimental results, the proposed CUF model using continuum damage mechanics can present 3D accuracy with low computational costs and reduce the mesh dependency.

Flavonoids from the Amazon plant Brosimum acutifolium induce C6 glioma cell line apoptosis by disrupting mitochondrial membrane potential and reducing AKT phosphorylation.

Glioblastoma, which is highly invasive and has a poor patient prognosis, is the most common type of brain tumor. Flavonoids have known antiproliferative and antineoplastic effects, such as apoptosis induction and tumor growth inhibition. We investigated the effects of treatment with three flavonoids (BAS-1, BAS-4, and BAS-6) isolated from the Amazon plant Brosimum acutifolium on the proliferation and migration of the C6 glioma cell line. Cytotoxicity was evaluated by MTT assay, and morphological changes were evaluated by phase-contrast microscopy and by transmission electron microscopy. Apoptosis was determined using Annexin V-FITC-propidium iodide (PI) staining. A hemolysis assay was used to evaluate plasma membrane injury. Antiproliferative effects were assessed by wound migration and colony formation assays. Mitochondrial transmembrane potential (ΔΨm) was determined using JC-1 dye and flow cytometry. To identify the flavonoid targets, western blotting was performed. BAS-1 and BAS-4 reduced C6 cell proliferation in a dose-dependent manner. BAS-6 showed no effect. Due to its high toxicity toward primary glial cells and its high hemolytic index, BAS-1 was not used in the remaining experiments. BAS-4 treatment did not induce cytotoxicity in primary glial cells; however, in glioma cells, it suppressed migration and invasion and led to apoptosis through mitochondrial damage, ΔΨm loss, cell cycle arrest, and reduced AKT phosphorylation, which is a component of the main cell survival pathway. We conclude that BAS-4 showed potential activity against glioma by inducing apoptosis mediated by ΔΨm loss and AKT pathway disruption, and future studies should further evaluate BAS-4 as a promising antineoplastic agent against glioblastoma.

IDO, COX and iNOS have an important role in the proliferation of Neospora caninum in neuron/glia co-cultures.

Central nervous system (CNS) is the main site for encystment of Neospora caninum in different animal species. In this tissue, glial cells (astrocytes and microglia) modulate responses to aggression in order to preserve homeostasis and neuronal function. Previous data showed that when primary cultures of glial cells are infected with N. caninum, they develop gliosis and the immune response is characterized by the release of TNF and IL-10, followed by the control of parasite proliferation. In order to elucidate this control, three enzymatic systems involved in parasite-versus-host interactions were observed on a model of neuron/glia co/cultures obtained from rat brains. Indoleamine 2,3-dioxygenase (IDO), induced nitric oxide synthase (iNOS) responsible for the catabolism of tryptophan and arginine, respectively, and cycloxigenase (COX) were studied comparing their modulation by respective inhibitors with the number of tachyzoites or the immune response measured by the release of IL-10 and TNF. Cells were treated with the inhibitors of iNOS (1.5 mM L-NAME), IDO (1 mM 1-methyl tryptophan), COX-1 (1 µM indomethacin) and COX-2 (1 µM nimesulide) before infection with tachyzoites of N. caninum (1:1 cell: parasite). After 72 h of infection, immunocytochemistry showed astrogliosis and a significant increase in the number and length of neurites, compared with uninfected co-cultures, while an increase of IL-10 and TNF was verified. N. caninum did not change iNOS activity, but the inhibition of the basal levels of this enzyme stimulated parasite proliferation. Additionally, a significant increase of about 40% was verified in the IDO activity, whose inhibition caused 1.2-fold increase in parasitic growth. For COX-2 activity, infection of cultures stimulated a significant increase in release of PGE2 and its inhibition by nimesulide allowed the parasitic growth. These data indicate that iNOS, IDO and COX-2 control the proliferation of N. caninum in this in vitro model. On the other hand, the release of IL-10 by glia besides modulating the inflammation also allow the continuity of parasitism.

Evaluation of body composition using dual-energy X-ray absorptiometry in patients with non-functioning adrenal incidentalomas and an intermediate phenotype: Is there an association with metabolic syndrome?

PURPOSE: Metabolic syndrome (MS) and sarcopenia are associated with increased cardiovascular risk. No studies using dual-energy x-ray absorptiometry (DXA) have evaluated association between body composition (BC) changes and MS in adrenal incidentaloma (AI). Our aim was to analyse BC in non-functioning AI (NFAI) and intermediate phenotype (IP) relative to controls and to correlate with cortisol levels. METHODS: Cross-sectional study with 44 NFAI (serum cortisol ≤ 50 nmol/L after the overnight 1 mg dexamethasone suppression test), 27 IP (cortisol 51-138 nmol/L), and 41 controls (normal adrenal on imaging examination) using DXA. Autonomic cortisol secretion (cortisol > 138 nmol/L) was excluded from the study. BC data were compared using criteria for MS (World Health Organization, National Cholesterol Education Program-Adult Treatment Panel-III, American Association of Clinical Endocrinologists (AACE), and International Diabetes Federation). RESULTS: There was no significant difference in clinical data and body mass index (BMI) among the three groups. Waist circumference (WC) was larger in AI vs. controls (p < 0.01). Waist-to-hip ratio was higher in NFAI vs. controls and waist-to-height ratio was higher in IP vs. controls (p = 0.03 and p = 0.02, respectively). The frequency of MS was higher in AI vs. controls. BC was not different among the groups. Patients with AI there was a significant association of MS with both an increase in total fat and body fat index (all criteria), and a significant difference between MS and smaller BMI-adjusted lean mass (AACE, p = 0.036). No correlation of cortisol after 1 mg dexamethasone test with BC or MS. AI and WC were independently associated with MS. CONCLUSIONS: AI presented high frequency of MS and was independently associated with MS. Possible deleterious effects of cortisol secretion seem to initially affect the muscular system.

Fragmentation of Valence and Carbon Core Excited and Ionized CH2FCF3 Molecule.

The photofragmentation dynamics of 1,1,1,2-tetrafluoroethane (R134a) with photon energies from 12 eV up to 320 eV, surrounding the C 1s edge is discussed. The ionic moieties were measured in coincidence with the ejected electrons (PEPICO mode), and detected as a function of the photon energy. Around the C K core edge, the fragmentation profiles are examined regarding the site specific excitation of the CH2FCF3 molecule. In the present case, site-selectivity is favored by the distinct chemical environments surrounding both C atoms. NEXAFS spectrum at the C 1s edge simulation has been obtained at the TDDFT level and excited state geometry optimization calculations have been performed at the inner-shell multiconfigurational self-consistent field level. Our observations indicate that the C(H2F) 1s excitation to a highly repulsive potential expels a fluorine atom leaving the heavier radical fragment C2F3H2* which relaxes to the fundamental state of the ion C2F3H2+. On the other hand, the excitation from the C(F3) 1s carbon to a repulsive state in the C-C bond, leads to a C-C bond cleavage, explaining the observed site specific fragmentation.

Association between impacted third molars and position of the mandibular canal: a morphological analysis using cone-beam computed tomography.

Our aim was to assess the association between the angle of impaction of the third molar and the position of the mandibular canal on cone-beam computed tomography (CT). We designed a retrospective study of 100 cone-beam CT images of 173 mandibular third molars that were obtained between January 2012 and December 2015, and recorded the angle of impaction of the third molar, the position of the mandibular canal in relation to the impacted tooth, and the potential contact between the roots of the tooth and the mandibular canal. Most third molars tilted mesially (n=33), while the mandibular canal was positioned below the roots of the third molar in most cases (n=73). Contact between the two was most likely when the mandibular canal was between (RR=1.49; 95% CI 1.27 to 1.75, p<0.001), or to the lingual side (RR=1.49; 95% CI 1.27 to 1.75, p<0.001) of the roots of the tooth. These outcomes indicate a greater likelihood of contact between the canal and the roots when the canal is between, and to the lingual side, of the roots. We found no association between the angle of impaction and the position of the canal. These findings illustrate the importance of surgical planning using complementary imaging tests such as cone-beam CT.

Genomic and epidemiological monitoring of yellow fever virus transmission potential.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

Primary Headaches and School Performance-Is There a Connection?

PURPOSE OF REVIEW: Headache is a common complaint among children and adolescents. School functioning is one of the most important life domains impacted by chronic pain in children. This review discusses the epidemiological and pathophysiological connections between headaches and school functioning including a suggested clinical approach. RECENT FINDINGS: The connection between recurrent and chronic headache and learning disabilities might be psychosocial (fear of failure) or anatomical (malfunctioning of the frontal and prefrontal areas). Only few population-based and clinical studies were done and good studies are still needed in order to understand the complex relationship better. However, relating to our patients' learning and school performance, history is crucial when a child with primary headaches is evaluated. Learning disabilities seem to have a high prevalence among children with primary headache syndromes especially migraine. The connection between the two is complex and might be either part of a common brain pathophysiology and/or a consequence of poor quality of life.

Non-Markovianity induced by a single-photon wave packet in a one-dimensional waveguide.

The concept of non-Markovianity (NM) in quantum dynamics is still an open debate. Understanding how to generate and measure NM in specific models may aid in this quest. In quantum optics, an engineered electromagnetic environment coupled to a single atom can induce NM. The most common scenario of structured electromagnetic environment is an optical cavity, composed by a pair of mirrors. Here, we show how to generate and measure NM on a two-level system coupled to a one-dimensional waveguide with no mirrors required. The origin of the non-Markovian behavior lies in the initial state of the field, prepared as a single-photon packet. NM is shown to depend on two experimentally controllable parameters, namely, the linewidth of the packet and its central frequency. We relate the presence of NM to quantum interference. We also show how the two output channels of the waveguide provide distinct signatures of NM, both experimentally accessible.

Acute selenium selenite exposure effects on oxidative stress biomarkers and essential metals and trace-elements in the model organism zebrafish (Danio rerio).

Selenium (Se) is an essential trace-element that becomes toxic when present at high concentrations. Little is known regarding Se effects on parameters such as oxidative stress biomarkers. The aim of the present study was to investigate the effects of acute selenium exposure on oxidative stress biomarkers in a model organism, zebrafish (Danio rerio). Fish were exposed to selenium selenite at 1mgL(-1). Reduced glutathione (GSH), and metallothionein (MT) concentrations were determined in liver, kidney and brain, with MT also being determined in bile. Essential metals and trace-elements were also determined by inductively coupled mass spectrometry (ICP-MS) in order to verify possible metal homeostasis alterations. GSH concentrations in liver, kidney and brain increased significantly (1.05±0.03µmolg(-1) ww, 1.42±0.03µmolg(-1) ww and 1.64±0.03µmolg(-1) ww, respectively) in the Se-exposed group when compared to the controls (0.88±0.05µmolg(-1) ww, 0.80±0.04µmolg(-1) ww and 0.89±0.03µmolg(-1) ww for liver, kidney and brain, respectively). MT levels in Se-exposed liver (0.52±0.03µmolg(-1) ww) decreased significantly in comparison to the control group (0.64±0.02µmolg(-1) ww), while levels in bile increased, albeit non-significantly. This is in accordance with previous studies that indicate efficient biliary MT action, leading to a rapid metabolism and elimination of contaminants from the body. Levels in the brain increased significantly after Se-exposure (0.57±0.01µmolg(-1) ww) when compared to the control group (0.35±0.03µmolg(-1) ww) since this organ does not present a detoxification route as quick as the liver-gallbladder route. Several metal and trace-elements were altered with Se-exposure, indicating that excess of selenium results in metal dyshomeostasis. This is the first report on metal dyshomeostasis due to Se-exposure, which may be the first step in the mechanism of action of selenium toxicity, as is postulated to occur in certain major human pathophysiologies.

Ipilimumab-induced hypophysitis: review of the literature.

PURPOSE: Ipilimumab is a human monoclonal antibody against cytotoxic T-lymphocyte antigen 4 available as an immunotherapy mainly for advanced melanoma. It induces an activation of T cells, resulting in an immune-mediated anti-tumor response and also immune-related adverse events, including hypophysitis. The aim of this review is to identify and discuss features concerning ipilimumab-induced hypophysitis (IIH). DESIGN: A MEDLINE research of all years of publication of IIH was conducted. We gathered information regarding clinical, radiologic and laboratory features of 71 cases recorded in the literature. RESULTS: In our review, IIH was more frequent among older and male patients. Fatigue and headache were the most frequent initial clinical manifestations of IIH and enlargement of the pituitary gland at MRI was present in the majority of patients. Those who received more than 3 cycles of ipilimumab had more fatigue (p = 0.04) and arthritis (p = 0.04). Adrenal insufficiency was more prevalent in men (p = 0.007). Glucocorticoid therapy and hormone replacement were required in most patients and pituitary function recovery was uncommon. Low prolactin at diagnosis tended to predict permanent pituitary dysfunction (p = 0.07). CONCLUSION: Hypopituitarism as a consequence of IIH, if not promptly recognized, can lead to potentially fatal events, such as adrenal insufficiency. IIH can be easily managed with glucocorticoids and hormonal replacement; therefore, physicians should be familiar with the key aspects of this condition. More studies to develop screening protocols and therapeutic intervention algorithms should be performed to decrease morbidity related to IIH.

Spectroscopic, luminescence and in vitro biological studies of solid ketoprofen of heavier trivalent lanthanides and yttrium(III).

Solid-state compounds of the general formulae [ML3] (M=Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y; L=ketoprofen) were synthesized and characterized using infrared, diffuse reflectance and luminescence spectroscopies. IR data suggested that the carboxylate group in ketoprofen is coordinated to the metals as a bidentate ligand. The triplet state energy level was determined using the Gd(3+) complex, which exhibited a ketoprofen blue luminescence when excited in the UV region. The compound containing Tb(3+) ion was sensitized by the ligand and emitted in the green region of the visible spectrum. On the other hand, for the analogous species containing the dysprosium ion, a competition for luminescence between the Dy(3+) and the ligand levels was observed. Finally, Tm(3+) complex exhibits only ligand luminescence. These optical behaviors are discussed based on rare earth energy diagrams. In addition, the compounds were evaluated for their anti-inflammatory activities. All the compounds showed a higher production of H2O2 and IL-10 than the ketoprofen, suggesting that the compounds exhibited an immunomodulatory effect and this opens up new perspectives for immunotherapeutic approaches.

Electrophoresis and spectrometric analyses of adaptation-related proteins in thermally stressed Chromobacterium violaceum.

Chromobacterium violaceum is a Gram-negative proteobacteria found in water and soil; it is widely distributed in tropical and subtropical regions, such as the Amazon rainforest. We examined protein expression changes that occur in C. violaceum at different growth temperatures using electrophoresis and mass spectrometry. The total number of spots detected was 1985; the number ranged from 99 to 380 in each assay. The proteins that were identified spectrometrically were categorized as chaperones, proteins expressed exclusively under heat stress, enzymes involved in the respiratory and fermentation cycles, ribosomal proteins, and proteins related to transport and secretion. Controlling inverted repeat of chaperone expression and inverted repeat DNA binding sequences, as well as regions recognized by sigma factor 32, elements involved in the genetic regulation of the bacterial stress response, were identified in the promoter regions of several of the genes coding proteins, involved in the C. violaceum stress response. We found that 30 °C is the optimal growth temperature for C. violaceum, whereas 25, 35, and 40 °C are stressful temperatures that trigger the expression of chaperones, superoxide dismutase, a probable small heat shock protein, a probable phasing, ferrichrome-iron receptor protein, elongation factor P, and an ornithine carbamoyltransferase catabolite. This information improves our comprehension of the mechanisms involved in stress adaptation by C. violaceum.

Hydride generation using a metallic atomizer after microwave-assisted extraction for inorganic arsenic speciation in biological samples.

The present speciation method reports the determination of inorganic arsenic forms, using metallic furnace hydride generation atomic absorption spectrometry. The inorganic As speciation is carried out using mild conditions for hydride formation, such as slightly acid pH media (4.50) and low tetrahydridoborate(1-) concentration (0.1% (w/v)). Limits of detection and quantification of 2.0 and 6.6 µg L(-1) of iAs(III) are obtained using optimized conditions. Additionally, microwave-assisted extraction using water as solvent is carried out to provide the appropriate environment for As species extraction as well as impeding inter-conversion between species. With these analytical strategies, As was accurately determined (at 99.9% confidence level) in water and plankton samples.

Diabetes mellitus and inflammatory pulpal and periapical disease: a review.

Diabetes mellitus (DM) is one of the most common metabolic disorders. DM is characterized by hyperglycaemia, resulting in wound healing difficulties and systemic and oral manifestations, which have a direct effect on dental pulp integrity. Experimental and clinical studies have demonstrated a higher prevalence of periapical lesions in patients with uncontrolled diabetes. The influence of DM on periapical bone resorption and its impact on dental intervention of such patients are reviewed, and its aetiology and pathogenesis are analysed at molecular level. Pulps from patients with diabetes have the tendency to present limited dental collateral circulation, impaired immune response, increased risk of acquiring pulp infection (especially anaerobic ones) or necrosis, besides toothache and occasional tendency towards pulp necrosis caused by ischaemia. In regard to molecular pathology, hyperglycaemia is a stimulus for bone resorption, inhibiting osteoblastic differentiation and reducing bone recovery. The relationship between poorly controlled diabetes and bone metabolism is not clearly understood. Molecular knowledge about pulp alterations in patients with diabetes could offer new therapeutic directions. Knowledge about how diabetes affects systemic and oral health has an enduring importance, because it may imply not only systemic complications but also a higher risk of oral diseases with a significant effect on pulp and periapical tissue.

Caracterização físico-química e análises por espectrofotometria e cromatografia de Peperomia pellucida L. (H. B. K. ) / Physical chemical characterization and spectrophotometric analysis and chromatography (TLC) of the Peperomia pellucida L. (H. B. K. )

O objetivo deste trabalho foi realizar a caracterização físico-química do pó e da tintura, e análise por espectrofotometria e cromatografia do extrato seco de Peperomia pellucida L. (H. B. K.). As metodologias seguiram a Farmacopéia Brasileira IV ed., com exceção da prospecção química, da espectrofotometria, da obtenção do perfil cromatográfico do extrato seco, e determinação do resíduo seco. A prospecção química revelou a presença de saponinas espumídicas; açúcares redutores; proteínas e aminoácidos; fenóis; taninos; flavonóides; esteróides e triterpenóides. Na análise por CCD, o melhor perfil da fração flavonoídica foi obtido com MeOH/CHOOH (90:10). Foi confirmada, através de CLAE, a presença de 3',4',7-tri-O-metoxiflavona no extrato seco deste material vegetal. Os resultados obtidos contribuem para a determinação de especificações de uma futura monografia em Farmacopéias da Peperomia pellucida L. (H.B.K.).

The aim of this study was the physical chemical characterization of the powder and the tincture, and the chromatographic and spectrophotometric analysis of the Peperomiapellucida L. (H. B. K.) dry extract. The methodology followed the Farmacopeia Brasileira IV ed., except for the chemical prospection, the chromatographic profile obtained and the spectrophotometry of the dry extract, and determination of dried residues. The chemical prospection revealed the presence of foaming saponins; reducing sugars; proteins and amino acids; phenols; tannins; flavonoids; steroids and triterpenoids; depsideos and depsidones. The best profile from TLC for flavonoidic fraction was obtained with methanol/formic acid (90:10 v/v). HPLC confirmed the presence of 3 ',4',7-tri-methoxyflavone in the dry extract of the plant material. The results obtained in this work should contribute for the determination of specifications for a future monograph on Peperomia pellucida L. (H.B.K.).

Heme modulates smooth muscle cell proliferation and migration via NADPH oxidase: a counter-regulatory role for heme oxygenase system.

Accumulation of vascular smooth muscle cells (VSMC) in response to inflammatory stimuli is a key event in atherogenesis, which commonly occurs in sinuous vessels with turbulent blood flow what leads to hemolysis and consequent free heme accumulation, a known pro-oxidant and pro-inflammatory molecule. In this work, we investigated the effects of free heme on VSMC, and the molecular mechanisms underlying this process. Free heme induces a concentration-dependent migration and proliferation of VSMC which depends on the production of reactive oxygen species (ROS) derived from NADPH oxidase (NADPHox) activity. Additionally, heme activates redox-sensitive proliferation-related signaling routes, such as mitogen activated protein kinase (MAPK) and NF-κB, and induces heme oxygenase-1 (HO-1) expression. NADPHox-dependent proliferative effect of heme seems to be endogenously modulated by HO since the pretreatment of VSMC with HO inhibitors potentiates heme-induced proliferation and, in parallel, increases ROS production. These effects were no longer observed in the presence of heme metabolites, carbon monoxide and biliverdin. The data indicate that VSMC proliferation induced by heme is endogenously modulated by a critical counter-regulatory crosstalk between NADPHox and HO systems.

Evidence of DNA damage in humans inhabiting a volcanically active environment: a useful tool for biomonitoring.

The present study was designed to evaluate whether chronic exposure to a volcanically active environment might result in genotoxic and cytotoxic effects in human oral epithelial cells. A study group of 120 individuals inhabiting a volcanically active environment (exposed group; Furnas village) and a reference group of 122 individuals inhabiting a village without manifestations of volcanic activity (Santo António village) were examined in this study. Individuals from Furnas village inhabit a volcanically active environment marked by several degassing manifestations, including fumarolic fields, thermal and cold CO2 springs and soil diffuse degassing areas. For each individual, 1000 buccal epithelial cells were analyzed for the frequency of micronucleated cells (MNC) and the frequency of cells with other nuclear anomalies (ONA: pyknosis, karyolysis and karyorrhexis), by using the micronucleus assay. Information on life-style factors and an informed consent were obtained from each participant. The frequencies of MNC and of ONA per 1000 cells in the exposed group (4.3‰ and 23.5‰, respectively) were significantly higher than in the reference group (1.7‰ and 7.7‰, respectively). The risk of having a high frequency of MNC or ONA was 2.4 and 3.1-fold higher in exposed individuals compared to reference group. The analyzed confounding factors (age, gender, smoking status, alcohol consumption, and mouthwash use) did not show any significant association with the frequency of MNC or ONA. The higher risk of DNA damage in individuals inhabiting a volcanically active environment is for the first time clearly highlighted with this biomonitoring study. Given that MNC in oral epithelia are recognized as a predictive biomarker of cancer risk within a population of healthy subjects, these findings could contribute to explain the high incidence rates of lip, oral cavity and pharynx cancers previously referred for Furnas village inhabitants.

On the use of classic epidemiological formulae for estimating the intensity of endemic malaria transmission by vectors in the Amazon.

Although various reports have described entomological inoculation rates of malaria vector species, most were limited to providing descriptive field data. Here, we report biting rates and survival data for two important malaria vectors in the Amazon, Anopheles darlingi (Root) and Anopheles albitarsis E (Lynch-Arribalzaga) (Diptera: Culicidae), in the state of Roraima, Brazil. We calculated theoretical sporozoite infection rates and critical vector biting rates for these species during 1 year, comprising six bimestrial collections. Anopheles darlingi had higher sporozoite rates and lower critical biting rates, indicating that it would be the more efficient vector at the beginning of epidemic malaria transmission. Our data, together with compiled information from the literature in the Amazon, suggest that epidemic malaria transmission may be initiated by the primary vector, such as A. darlingi, while secondary vectors, such as A. albitarsis E, may only become epidemiologically important when there is an increase in the prevalence of human malaria. We propose that mathematical modeling may be able to quantify the relative importance of secondary vector species in malaria epidemiology.