Alcohol Myopia and Risk Taking

The aim of this paper is to develop a model that explains how the consumption of some additive substances a¤ects an individual?s choice between risky alternatives. We do this by assuming that some additives substances, speci?cally alcohol, increase individual?s present bias. As individuals that consume alcohol show greater preference for the present and less for the future, they would ?nd risky choices with rewards in the present and costs in the future more attractive. Theferore, an individual that wouldn´t have accepted a lottery may do so after consuming alcohol and he regret his decision after the alcohol in his blood is eliminated. We analyze the e¤ect of two taxes in discouraging a risky activity: a tax on the consumption of alcohol and a tax (or penalty) if the future costs of the lottery are realized.habit-formation, risk taking, alcohol consumption

THE INFLUENCE of MATERNAL DIABETES ON the EXPRESSION of INFLAMMATORY MARKERS in the OFFSPRING

Universidade Federal de São Paulo, Diadema, SP, BrazilUniv São Paulo, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Diadema, SP, BrazilWeb of Scienc

REDUCTION in INFLAMMATORY MARKERS EXPRESSION in SERUM IS RELATED TO IMPROVEMENT in RENAL FUNCTIONS in INTRAUTERINE UNDERNOURISHED RATS

Univ São Paulo, Inst Biomed Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Nephrol, São Paulo, BrazilWeb of Scienc

CYLD Proteolysis Protects Macrophages from TNF-Mediated Auto-necroptosis Induced by LPS and Licensed by Type I IFN

SummaryTumor necrosis factor (TNF) induces necroptosis, a RIPK3/MLKL-dependent form of inflammatory cell death. In response to infection by Gram-negative bacteria, multiple receptors on macrophages, including TLR4, TNF, and type I IFN receptors, are concurrently activated, but it is unclear how they crosstalk to regulate necroptosis. We report that TLR4 activates CASPASE-8 to cleave and remove the deubiquitinase cylindromatosis (CYLD) in a TRIF- and RIPK1-dependent manner to disable necroptosis in macrophages. Inhibiting CASPASE-8 leads to CYLD-dependent necroptosis caused by the TNF produced in response to TLR4 ligation. While lipopolysaccharides (LPS)-induced necroptosis was abrogated in Tnf−/− macrophages, a soluble TNF antagonist was not able to do so in Tnf+/+ macrophages, indicating that necroptosis occurs in a cell-autonomous manner. Surprisingly, TNF-mediated auto-necroptosis of macrophages requires type I IFN, which primes the expression of key necroptosis-signaling molecules, including TNFR2 and MLKL. Thus, the TNF necroptosis pathway is regulated by both negative and positive crosstalk

CD73-generated adenosine restricts lymphocyte migration into draining lymph nodes.

After an inflammatory stimulus, lymphocyte migration into draining lymph nodes increases dramatically to facilitate the encounter of naive T cells with Ag-loaded dendritic cells. In this study, we show that CD73 (ecto-5\u27-nucleotidase) plays an important role in regulating this process. CD73 produces adenosine from AMP and is expressed on high endothelial venules (HEV) and subsets of lymphocytes. Cd73(-/-) mice have normal sized lymphoid organs in the steady state, but approximately 1.5-fold larger draining lymph nodes and 2.5-fold increased rates of L-selectin-dependent lymphocyte migration from the blood through HEV compared with wild-type mice 24 h after LPS administration. Migration rates of cd73(+/+) and cd73(-/-) lymphocytes into lymph nodes of wild-type mice are equal, suggesting that it is CD73 on HEV that regulates lymphocyte migration into draining lymph nodes. The A(2B) receptor is a likely target of CD73-generated adenosine, because it is the only adenosine receptor expressed on the HEV-like cell line KOP2.16 and it is up-regulated by TNF-alpha. Furthermore, increased lymphocyte migration into draining lymph nodes of cd73(-/-) mice is largely normalized by pretreatment with the selective A(2B) receptor agonist BAY 60-6583. Adenosine receptor signaling to restrict lymphocyte migration across HEV may be an important mechanism to control the magnitude of an inflammatory response

Screening for Developmental Neurotoxicity Using PC12 Cells: Comparisons of Organophosphates with a Carbamate, an Organochlorine, and Divalent Nickel

BACKGROUND: In light of the large number of chemicals that are potential developmental neurotoxicants, there is a need to develop rapid screening techniques. OBJECTIVES: We exposed undifferentiated and differentiating neuronotypic PC12 cells to different organophosphates (chlorpyrifos, diazinon, parathion), a carbamate (physostigmine), an organochlorine (dieldrin), and a metal (divalent nickel; Ni(2+)) and examined indices of cell replication and differentiation for both short- and long-term exposures. RESULTS: In undifferentiated cells, all the agents inhibited DNA synthesis, with the greatest effect for diazinon, but physostigmine eventually produced the largest deficits in the total number of cells after prolonged exposure. The onset of differentiation intensified the adverse effects on DNA synthesis and changed the rank order in keeping with a shift away from noncholinergic mechanisms and toward cholinergic mechanisms. Differentiation also worsened the effects of each agent on cell number after prolonged exposure, whereas cell growth was not suppressed, nor were there any effects on viability as assessed with trypan blue. Nevertheless, differentiating cells displayed signs of oxidative stress from all of the test compounds except Ni(2+), as evidenced by measurements of lipid peroxidation. Finally, all of the toxicants shifted the transmitter fate of the cells away from the cholinergic phenotype and toward the catecholaminergic phenotype. CONCLUSIONS: These studies point out the feasibility of developing cell-based screening methods that enable the detection of multiple end points that may relate to mechanisms associated with developmental neurotoxicity, revealing some common targets for disparate agents

Diffusion-weighted MRI for differentiation between sialadenitis and pleomorphic adenoma

Objectives: The aim of this study was to compare apparent diffusion coefficient (ADC) values from diffusion-weighted MRI (DWI) among normal salivary glands, cases with sialadenitis and cases with pleomorphic adenoma of major salivary glands.Methods: 22 patients (totalling 44 major salivary glands) diagnosed with either unilateral sialadenitis (on either parotid or submandibular gland) or parotid gland pleomorphic adenoma were selected. Contralateral non-affected glands (normal) were also analyzed. DW images were achieved using a spin-echo pulse sequence with a 1.5-T MRI device. Mean ADC values were compared among the three groups analyzed (contralateral normal glands, sialadenitis and pleomorphic adenoma).Results: The mean ADC values were significantly higher in cases of parotid sialadenitis (p = 0.001), but not in cases of submandibular sialadenitis (p = 0.466), as compared with the contralateral non-affected glands. Cases of pleomorphic adenoma presented the highest ADC values of the study. In addition, one-way ANOVA test revealed a significant difference among the three groups of parotid glands analyzed.Conclusions: Within the limitations of this study, the present results suggest that DWI allows for differentiation between parotid sialadenitis and pleomorphic adenoma.peer-reviewe

Inter-rater agreement in the assessment of abnormal chest X-ray findings for tuberculosis between two Asian countries

<p>Abstract</p> <p>Background</p> <p>Inter-rater agreement in the interpretation of chest X-ray (CXR) films is crucial for clinical and epidemiological studies of tuberculosis. We compared the readings of CXR films used for a survey of tuberculosis between raters from two Asian countries.</p> <p>Methods</p> <p>Of the 11,624 people enrolled in a prevalence survey in Hanoi, Viet Nam, in 2003, we studied 258 individuals whose CXR films did not exclude the possibility of active tuberculosis. Follow-up films obtained from accessible individuals in 2006 were also analyzed. Two Japanese and two Vietnamese raters read the CXR films based on a coding system proposed by Den Boon et al. and another system newly developed in this study. Inter-rater agreement was evaluated by kappa statistics. Marginal homogeneity was evaluated by the generalized estimating equation (GEE).</p> <p>Results</p> <p>CXR findings suspected of tuberculosis differed between the four raters. The frequencies of infiltrates and fibrosis/scarring detected on the films significantly differed between the raters from the two countries (<it>P </it>< 0.0001 and <it>P </it>= 0.0082, respectively, by GEE). The definition of findings such as primary cavity, used in the coding systems also affected the degree of agreement.</p> <p>Conclusions</p> <p>CXR findings were inconsistent between the raters with different backgrounds. High inter-rater agreement is a component necessary for an optimal CXR coding system, particularly in international studies. An analysis of reading results and a thorough discussion to achieve a consensus would be necessary to achieve further consistency and high quality of reading.</p