; Indianapolis, IN, USA) [11]. Data are expressed as the mean ± SEM. The statistical significance of difference in mean values between TGR

and SD rats was assessed by unpaired Student’s t-test or two-way ANOVA (glucagon and pyruvate challenge tests). Significance level was set at p < 0.05. Twelve weeks old TGR rats (0.0269 ± 0.00067 g/g BW) showed no difference in liver weight corrected by body weight when compared with SD rats. (0.0265 ± 0.00047 g/g BW) as illustrated in Fig. 1. Glucagon stimulation test also not demonstrate statistical difference between fasted Akt signaling pathway TGR rats and SD rats (Fig. 2). Analysis of basal hepatic glycogen measurement showed no variation between TGR (0.4005 ± 0.1562 mg/g) and SD rats (0.5825 ± 0.1778 mg/g) as demonstrated in Fig. 2. In order to evaluate the gluconeogenesis pathway we performed the pyruvate challenge test (Fig. 1). Pyruvate administration in fasting TGR showed a decrease in the synthesis of glucose in these rats compared this website to the SD with the minimum peak for glycemic values of the curve in TGR rats at 30 min (106.8 in SD vs. 85.73 in TGR; P < 0.01) and 45 min (117.0 in SD vs. 98.00 in TGR; P < 0.01). To understand the molecular mechanisms underlying changes in gluconeogenesis and glycogenolysis

we analyzed the levels of glycongen phosphorylase enzyme, PYGB/L/M by Western blotting method (Fig. 2). The total of PYG enzyme level was not altered (4.148 ± 0.6282 in TGR vs. 5.893 ± 0.4164 in SD rats). In addition, real-time PCR analysis revealed a marked decrease in PEPCK expression in TGR hepatic tissue (1.403 ± 0.1441 in SD vs. 0.4598 ± 0.2391 in TGR), without difference in G6Pase expression in TGR and SD rats (0.7363 ± 0.09964

in SD vs. 1.133 ± 0.2475 in TGR) as showed in Fig. 1. In order to confirm the downregulation in gluconeogenesis we evaluated the mRNA expression of HNF-4α, responsible for the regulation of transcription enzymes on gluconeogenesis pathway (Fig. 1), and we observed an important decrease in TGR rats (0.7214 ± 0.1196 in TGR vs. 1.307 ± 0.2023 in SD). It is well documented that Ang-(1-7) presents several effects opposite to those produced by Ang II [13], [15], [20], [22] and [23], however, this is the first study evaluating the role of Ang-(1-7) on liver gluconeogenesis and glycogenolysis. The main result of the present study was Suplatast tosilate to show that transgenic rats with increased circulating Ang-(1-7) presents a decreased activation of the gluconeogenesis pathway, demonstrated by the pyruvate challenge test accompanied by a significantly reduction in PEPCK and HNF4α. The role of Ang II in glucose metabolism is well established. Coimbra et al. [4] demonstrated that administration of Ang II increases hepatic glucose output, mostly by activation of gluconeogenesis pathway in comparison to the glycogenolysis pathway. The present results point to a counterregulatory action of Angiotensin-(1-7) on gluconeogenesis, which opposes the effect of Ang II.

Stable isotopes were determined in each sample by continuous-flow isotope mass spectrometer (Isoprime100, Isoprime Limited, Cheadle Hulme, UK) coupled with an elemental analyzer (Elementar vario MICRO CUBE, Elementar, Hanau, D). Each fragment (2.0–2.5 mg dry-weight) was analyzed individually. Isotopic ratios were expressed in ‘δ’ units as the relative difference (in parts per thousand)

between the sample and conventional standards (atmospheric N2 (Air) for 15N; PD-belemnite [PDB] carbonate for 13C) in accordance with the formula δR   (‰) = [(R  sample − R  standard)/R  standard] ∗∗ 103 ( Ponsard and Arditi, 2000), where R is the heavy-to-light isotope ratio of the element (R = 13C/12C or 15N/14N). learn more Results were monitored with reference to an internal standard calibrated to International Atomic Energy Agency reference materials (Caffeine: IAEA-CH6). Differences in δ15N values between T0 and T1 and among sites, and in isotopic enrichment between bathymetries and among sites, were tested by

t-test or Wilcoxon rank-sum test. The assumption of homogeneity of variances was checked using Cochran’s C-test, and data transformations were used where necessary. Spearman Statistical significance was evaluated at α = 0.05. The δ15N values of the macroalgae after 48 h of exposure were analyzed for spatial autocorrelation by Moran’s test with uniform spatial weights ( Cliff and Ord, 1981) and PD98059 price by distance-based nearest neighbour. Spatial analyses were performed using R software 2.15.2 (geoR and spdep package). In the reference area (Circeo), the initial N and C isotopic signatures (mean ± S.D.) of macroalgae were δ15N = 5.96 ± 0.54‰ and δ13C = −22.53‰ ± 2.04‰ in U. lactuca, and δ15N = 7.69 ± 0.39‰ and δ13C = −19.73‰ ± 2.43‰ in C. amentacea. After 48 h (T1), δ15N and δ13C values were not significantly different in U. lactuca ADP ribosylation factor ( Table 1; t-test, n.s.) whereas δ13C was greater in C. amentacea (t-test, p-value < 0.001). In the Gulf of

Gaeta, the isotopic signature of U. lactuca was δ15N = 5.71 ± 1.25‰ and δ13C = −22.26 ± 2.23‰ at start (T0) and δ15N = 8.15 ± 1.03‰ and δ13C = −22.42 ± 2.10‰ at T1. There was thus a statistically significant increase in δ15N ( Fig. 2 and Table 1; t-test, p < 0.001) and no significant change in δ13C (t-test, n.s.). The high 15N enrichment of U. lactuca was also evident in comparison with the reference area (Circeo) ( Fig. 2; t-test, p < 0.001). During 48 h of submersion in the Gulf, the coefficient of variation of N15 among replicate fronds of U. lactuca fell considerably, from 12.37% at T0 to 1.85% at T1 in the Vendicio area, from 23.73% to 6.76% in Formia, from 26.40% to 16.00% in Scauri, and from 14.70% to 6.03% in Garigliano. C. amentacea, which had higher starting values, was much less enriched in δ15N than U. lactuca after 48 h in the Gulf ( Table 1; Fig. 2).

This is in line with the constructivist basis of the adopted risk perspective of Section

2.3, where the elements in the framework serve to assess the strength of the argumentation. Considering what validity means for the adopted risk perspective, important elements in this context are the completeness of the uncertainty assessment (Aven and Heide, 2009) and the completeness of the bias assessment (Rosqvist and Tuominen, 2004). Thus, the validity framework serves not only to assess how well the model describes the system it intends to describe, but also to systematically reflect on uncertainties and biases underlying its construction. While the various validity concepts can act as sources of model confidence, the extent to which the validity tests fail can be indicated by providing a qualitative uncertainty and bias assessment. This uncertainty and bias assessment www.selleckchem.com/products/3-deazaneplanocin-a-dznep.html highlights which parts of the

model would benefit most from a more accurate or comprehensive modeling approach. In the framework application, we focus on face, content and predictive validity. Concurrent validity cannot be established as no other BN models for accidental oil outflow are known to exist. Convergent and discriminant validity require an in-depth comparison of the BN with models of similar, respectively different systems. These are in-principle options but are considered beyond the scope of the current work. In terms of face validity, the presented BN can be considered an appropriate model Methamphetamine for oil outflow Olaparib in ship–ship collision, conditional to impact conditions. This is clear from its construction, which is based on the tank arrangement model by Smailys and Česnauskis (2006) and the collision damage extent model by van de Wiel and van Dorp (2011). The model by Smailys and Česnauskis (2006) has been validated for a number of cases and the analysis in Section 4.2.2 shows that the model leads to a reasonable, conservative estimate of the ship deadweight. The regression model by van de Wiel and van

Dorp (2011) shows a reasonable fit with the cases reported in NRC (2001), see also Section 5.2, and the underlying ship collision mechanics model by Brown and Chen (2002) has been validated for some accident scenarios by Chen (2000). Thus, the BN can be expected to provide reasonable estimates of oil outflows for the intended application in risk assessment for maritime transportation, even when only very limited data about the vessels is available. The oil outflow model includes many, but not all relevant variables for determining the oil outflow. Impact speeds, angle and location and ship masses are important variables in determining the collision damage extent. However, the yaw and sway velocities at the moment of impact also have a certain influence on the collision energy (Ståhlberg, 2010) and damage extent (Wiśniewski and Kołakowski, 2003).

As shown in Fig. 4A, all concentrations from 6.2 up to 100 μg/mL of BbV induced a significant release of IL-6 by human neutrophils compared to control. Fig. 4B shows that after 4 h incubation of neutrophils with concentrations from 12.5 up to 100 μg/mL

of BbV induced a significant release of IL-8 by human neutrophils. Our results demonstrate that BbV activated human neutrophils and induced the release of IL-6 and IL-8. In order to investigate the ability of BbV to induce the liberation of NETs by human neutrophils, the cells were incubated with non-cytotoxic concentrations of BbV or RPMI (control) or PMA (positive control). As shown in Fig. 5A and B, 4 and 15 h of incubation of human neutrophils Saracatinib datasheet with different non-cytotoxic concentrations of BbV induced an increase in NETs liberation compared to the negative control (RPMI) and the positive control (PMA). These findings demonstrate the ability of BbV to stimulate human neutrophils to induce NETs liberation. The literature shows that leukocytes, and particularly neutrophils, play a critical role in skeletal muscle regeneration following myonecrosis induced by Bothrops asper venom

( Teixeira et al., 2003). In addition, PLX4032 a marked inflammatory cell response with a pronounced neutrophil infiltration associated with bothropic envenomation has been reported ( Gutiérrez et al., 1986, Flores et al., 1993, Farsky et al., 1997, Arruda et al., 2003, Zamunér Resveratrol et al., 2005 and Porto et al., 2007), but the state of activation of these cells is unknown. Besides this, it is quite possible that neutrophils – as the first cells at the site of an infection – might be able to clear a minor infection before monocytes even arrive. It therefore suggests the clearance of an infection by neutrophils without the classical symptoms of inflammation. Symptoms like

reddening, swelling, pain and potential tissue damage are all induced by pro-inflammatory cytokines that are secreted by the later arriving monocytes (Schröder et al., 2006). Taking this into account, we designed a study to investigate the ability of B. bilineata crude venom (BbV) to activate isolated human neutrophils since it has been shown that this venom causes inflammation and induces neutrophil recruitment into the peritoneal cavity of mice 4 h after its injection ( Porto et al., 2007). First, the effect of BbV on human neutrophil viability was evaluated. The results showed that BbV did not affect neutrophil viability indicating its low toxicity on this cell type. The effect of BbV on human neutrophil viability was not demonstrated until now, but literature shows that B. asper venom decreases the viability of neutrophils isolated from mice ( Moreira et al., 2009).

The bone was clamped at a 9° angle lateral to the vertical axis of the bone as described previously [32]. Load was applied to the femoral head until fracture occurred. Stiffness was obtained from the slope

of the force-displacement curve and the ultimate load obtained was from the maximum force that the bone was able to resist. Proximal parts of the femurs were decalcified in 11% EDTA (pH 8.0, 5 N NaOH) for 14 days. Samples were embedded in paraffin wax and 5 μm longitudinal sections were cut on a microtome (Leica RM2035, Milton Keynes, Selleck Selumetinib UK). Alternate sections were stained with sirius red staining for collagen content and Tartrate-resistant acid phosphatase (TRAP) staining for osteoclasts. The sirius red staining was completed using the picro-sirius red method as described [33] followed by counterstaining with haematoxylin. To standardize staining, all sections were stained in a single batch. To assess the collagen content, sections from the proximal femur shaft were stained with sirius red and bright field images collected (n = 5 for each mouse) using an Axioskop50 microscope with a 40× objective

(Zeiss, Cambridge, UK) and Carl Zeiss AxioCam MRc camera (Zeiss, Cambridge, UK). Five regions of interest (approximately 219 μm × 164 μm), were selected for quantification, and averages per section were taken as the final measures for each genotype. The % area of red pixels corresponding to collagen fibres, relative to total tissue area, was estimated using a colour segmentation

plugin in ImageJ (Biomedical Imaging Alectinib in vivo Group, EPFL, Switzerland: http://bigwww.epfl.ch/sage/soft/colorsegmentation/) using independent colour channels and the K-means algorithm. Distal femurs were sectioned transversely just above the condyles and stored in 2.5% paraformaldehyde in 0.1 M sodium phosphate buffer (pH 7.4) at 4 °C for 48 h. Adherent soft tissue was removed by immersion in 3% hydrogen peroxide solution for 48 h. After rinsing with distilled water, specimens were defatted in 50:50 methanol/chloroform for 24 h at room temperature and transferred to a 5% trypsin solution (0.1 M PB, pH 7.4) at room temperature for 48 h. After cleaning with distilled water, specimens were desiccated prior to preparing on a sputter coater (Polaron E5000, East Sussex, UK). Images were obtained using a scanning electron Etomidate microscope (Stereoscan 250 MK3, Cambridge, UK). Small Angle X-ray Scattering (SAXS) was used to assess the nano-scale bone mineral structure of the cortical bone in the humerus of the female mice. Five right humeri from each group of the female mice were formalin fixed, dehydrated in a series of increasing concentration alcohol solutions and embedded in methylmethacrylate resin. A transverse slice was cut from the mid shaft and polished down to 100 μm thickness. The I911-SAXS beamline of the MAX II ring (1.5 GeV) at the MAX IV Laboratory (Lund University, Lund) was used [34]. A monochromatic beam of wavelength 0.

5% (two-sided 95% CI should not exceed 5.5% to each direction from a point value), the sample size of 317 children would be sufficient to perform the tasks of the study protocol. Taking into account the possibility of patient or data loss of about

Apoptosis inhibitor 10–15% it was planned to enroll 350 children into the main study group. The data of all 350 children were used in the final analysis. To reach the power of at least 80% with α-error of 0.05 the sample size for the laboratory part of the study was calculated based on the reference laboratory values for all the parameters and estimated minimal group values difference of 13.0 mcg/l for ferritin and 3.0 g/l for hemoglobin. To meet such estimations, the sample should include at least 92 persons. Taking into account the possibility that about 5% of the data AZD4547 nmr could be lost, we included into the study 105 children randomly selected from the main study group. At the time of enrollment into the study 12 (19.05%) infants, 18 (11.69%)

children of the second and 2 (1.5%) children in the third year of life were breastfed. Thirty-five (55.56%), 63 (40.91%) and 24 (18.05%) children respectively in the three age groups were fed with infant (special) formula (Fig. 1). The diet composition was mostly adequate for age at the time of enrollment into the study (Tab. I). Thirty-two (9.14%) babies were breastfed and 122 (34.86%) children received infant formula. Two hundred and fifty-seven

(78.83%) children consumed infant cereals, 315 (93.47%) – beef, 191 (60.06%) – pork, 315 (91.3%) – poultry, 301 (87.76%) – fish, 314 (91.81%) – eggs, 322 (94.15%) – cheese, 342 (99.71%) – fruit and 343 (99.71%) – vegetables. However, the consumption of unmodified cow’s milk ranged from 60% in infants to 8% of children in the third year of life. The proportions of children who ate sweets or candy (48%), chocolate (33%), nuts (72%), as well as hot dogs and sausages (34%) were also significant (Tab. I). The average frequency of weekly formula consumption decreased with age, while the number of cow’s milk intakes increased. Infant cereals, vegetables and fruits remained most commonly used food to all ages. The daily diet of the majority of children contained these products. Older children Oxymatrine consumed more meat of all kinds, and the corresponding positive trend was particularly evident for pork. The amount of fish intake per week remained mostly unchanged. A similar conclusion could be drawn regarding the consumption of eggs and cheese. The frequency of use of “adult” products (ketchup, sauces, mayonnaise, etc.) increased with age. According to history data 59 (93.65%) infants, 149 (93.65%) children of the second and 125 (93.98%) children in the third year of life were breastfed at the study point or in the past. The average duration of breastfeeding was 10.

Patients hospitalized in Asia,4 in Europe and the United Kingdom,1 and 43 and in North44 and South America45 were at higher risk of dying if malnourished. Costs were also higher when extra care and longer stays were needed to treat health complications, as supported by studies from Singapore,

Brazil, and The Netherlands (Table 1). The traditional recommendations of nutrition screening, assessment, and intervention are sometimes overlooked or inadequate. In a European-wide survey of hospital nutrition care (1217 units, 325 www.selleckchem.com/HDAC.html hospitals, 25 countries, >21,000 patients), only half of the units reported routine use of nutrition screening.51 Even when energy intake was assessed and an energy goal was specified, about half of the patients consumed less than their energy goal; or they self-reported inadequate food intake.8 and 51 According to the British Nutrition Foundation, more than 60% of hospital patients experienced a decline in nutritional status during their stay in the hospital.12 Nutrition guidelines worldwide advise nutritional intervention for patients who cannot meet nutrient needs with a diet of regular food. Nutrition interventions, including oral nutrition supplements click here (ONS) and enteral and parenteral nutrition, had significant clinical and economic

benefits across patient groups and in different settings, as shown by results of randomized, AZD9291 controlled trials (RCTs), prospective studies, and meta-analyses. Health benefits of nutrition intervention include improved nutrition status, muscle mass, strength, or performance; fewer health complications; improved quality of life; and reduced risk of mortality (Table 2).23, 24, 25, 52, 53, 54, 55, 56 and 57 Economic benefits include reduced length of stay, fewer hospital readmissions,

and lowered cost of care (Table 3).24, 26, 55, 58, 59 and 60 To provide best-practice nutrition care, it is essential that caregivers appreciate the current definition of malnutrition. Malnutrition has been newly defined as 3 clinical syndromes, which are characterized by underlying illness or injury and varying degrees of inflammation.61 The three syndromes are (1) starvation-related malnutrition, a form of malnutrition without inflammation; (2) chronic disease-related malnutrition, which is nutritional inadequacy associated with chronic conditions that impose sustained inflammation of a mild-to-moderate degree; and (3) acute disease- or injury-related malnutrition, which is undernutrition related to conditions that elicit marked inflammatory responses. Many chronic conditions (such as kidney disease, cancer, heart failure, or rheumatoid arthritis) have inflammation as a disease component, thus increasing the risk of malnutrition, 62 and 63 even among patients who are overweight or obese.

Conviria detalhar que complicação ocorreu (Estenose preexistente? Abcesso após utilização de IFX? Outra?)

e respetiva interpretação, em função do status prévio do doente. De facto, a cirurgia eletiva poderá ter um papel relevante na DC em idade pediátrica, tanto na doença fistulizante como na estenosante, tendo sido preconizada como alternativa ao LGK-974 cell line IFX nas formas localizadas 3. Por outro lado, teria interesse a menção a eventual intervenção nutricional, dado constituir reconhecidamente uma componente fundamental da abordagem terapêutica neste grupo etário3 and 4. De facto, na DC pediátrica, a nutrição entérica exclusiva e a corticoterapia são igualmente eficazes na indução da remissão, independentemente da atividade ou localização da doença, embora com significativas vantagens da nutrição entérica devido ao impacto positivo no crescimento e menor frequência de efeitos adversos3 and 4. Os autores tiveram o cuidado de avaliar o impacto do tratamento

no IMC (variabilidade na resposta); apesar do curto período de seguimento, teria sido igualmente interssante a inclusão do Z score da velocidade de crescimento (importante end point terapêutico) e do estadio pubertário (Tanner), quando aplicáveis. A anemia é uma complicação frequente no decurso da evolução da DII em idade pediátrica e que justifica uma abordagem eletiva, tendo merecido a atenção dos autores. É mencionada melhoria dos valores médios de hemoglobina aos 6 meses pós-tratamento em 5/6 casos

em concordância find more com outras séries (sendo no entanto omissa a referência a eventual instituição concomitante de terapêutica marcial, nomeadamente por via parentérica). Constituindo um dos objetivos do estudo a avaliação dos efeitos adversos, teria sido interessante mencionar como foi efetuada a sua monitorização ao longo do periodo de seguimento (registo sistemático – checklist ou apenas os constatados / reportados ?). A reduzida duração do periodo de seguimento, poderá ter contribuído parcialmente para a baixa frequência de efeitos adversos observados neste grupo etário Glutathione peroxidase (adolescência). Em estudos futuros desta natureza, será também relevante a menção ao impacto da doença e da intervenção terapêutica na qualidade de vida. De acordo com as recomendações da ECCO3, preconiza-se que o seguimento e tratamento da DII em idade pediátrica (≤18 anos) sejam da responsabilidade de Unidades de Gastrenterologia Pediátrica, numa perspetiva interdisciplinar, incluindo idealmente consultas de transição para a Gastrenterologia de Adultos. Neste contexto e atendendo à idade dos doentes do presente estudo (2 com 16 anos, 2 com 17 anos, no início do tratamento com IFX), seria interessante conhecer o modelo específico de organização e articulação adotado com o Serviço de Gastrenterologia de Adultos.

He is former Chair of the Association for Paediatric Immunology and current Chair of the advisory board of the ‘Preventive Medicine in Paediatrics’ Foundation. Professor Zepp is also a member of the scientific advisory board of the German Medical Association and last

year was mTOR inhibitor appointed President of the German Society of Paediatric and Adolescent Medicine. He has published more than 100 original papers and reviews. Figure options Download full-size image Download as PowerPoint slide “
“Key concepts ■ Vaccines have made the second most major contribution to the control and eradication of infectious diseases after the distribution of clean water Vaccines have dramatically improved human health. The steady decline in deaths in children under Selleck PD 332991 5 years of age is attributable to the increasing

availability of vaccines in the developing world. A growing knowledge of immunology has increasingly influenced vaccine design in the past century, leading to the production of new types of vaccines (whole cell, live or inactivated, subunit, recombinant proteins etc) with associated advantages and challenges. In addition, public health priorities have evolved over time. The first vaccines were developed against diseases with high morbidity and mortality rates, such as smallpox, diphtheria and tetanus. In addition, ‘battlefield diseases’ – particularly in the era of trench warfare – including typhoid fever, plague and cholera, drove the development of early vaccines. More recently, the drivers for vaccine development Pyruvate dehydrogenase have changed, reflecting changes in global society. Although highly pathogenic infectious diseases remain the principal targets for effective vaccination, assessments of benefit versus risk and consideration of health economics

are now an obligatory part of the development process. Better understanding of immunology and pathogenesis of the targeted diseases facilitates identification of the type and quality of immune responses that are desirable for each new prophylactic or therapeutic vaccine. In December 1979, the World Health Organization (WHO) announced the eradication of smallpox following successful vaccination campaigns throughout the previous two centuries. Another disease presently close to eradication is polio (Figure 1.1). The WHO declared that the Americas were polio-free in 1994, followed by the Western Pacific region in 2000 and the European region in 2002. In the past 20 years, polio cases have decreased from an estimated 350,000 annual cases to 1640 cases in 23 countries in 2009, the majority of which (69%) occurred in Nigeria and India. In the ancient world, it was common knowledge that a person was rarely infected twice with the same disease and the term ‘immunity’ was first used in reference to plague in the 14th century.

In general, amplitude and latency of the component are considered to be influenced by (unconscious) expectancy,4 task relevance, novelty, contextual constraints,

and motivational significance (see e.g., Nieuwenhuis et al., 2005). Of most interest to our study, the P300 has been assumed to be related to domain-general context-updating processes and to reflect PI3K inhibitors ic50 the revision of a mental model or the “conditions of the environment” (Donchin and Coles (1988, p. 367); but see Verleger (1988) and the following commentaries). Our design strictly followed a simple pattern of lead-in–context-question–target-sentence, revealing all referents given in the lead-in. The reduced late positivity in response to the sentence-initial object following the topic context could index a reduced need for general context updating, BGB324 because the listener is less “surprised” about the object if previously announced as the topic of the scene compared to the neutral context. Thus, in line with Cowles (2003) who also reported a contextually modulated late

positivity (i.e., the Late Positive Component (LPC)) during sentence comprehension, the late positivity in our study could reflect context-updating processes in terms of the P300. Notably, a number of authors argue against the context-updating interpretation of the P300 in favor of a general reflection of simple attentional, evaluative, or memory mechanisms (for a review, see Nieuwenhuis et al., 2005). Hence, it remains almost a matter of debate if late positivities/P600 responses elicited by sentences really belong to the P300 family or whether they should be considered an independent component (e.g., Coulson et al., 1998 and Roehm et al., 2007; see Brouwer, Fitz,

& Hoeks, 2012 for a related discussion of the P600 in response to semantic violations or illusions). The N400 has been described as another ERP component sensitive to discourse level information. It is thought to reflect processing costs for linking an entity to the current mental model (Burkhardt, 2006, Burkhardt and Roehm, 2007 and Wang and Schumacher, 2013). The SDM assumes that discourse linking processes are driven by expectancy as indexed by a modulation of the N400 (see Sections 1.2 and 1.3). In these studies, the degree of inferability, expectancy, or accessibility of an entity in the mental model modulated the N400: The N400 for previously given, expected, or repeated noun phrases was reduced because those entities were easier to link to the current discourse. Importantly, due to the preceding lead-in context in our study which was identical for the neutral and the topic condition, both characters of the scene were discourse-given (Prince, 1981).