Exposure to Environmental Tobacco Smoke and Cognitive Abilities among U.S. Children and Adolescents

We used the Third National Health and Nutrition Examination Survey (NHANES III), conducted from 1988 to 1994, to investigate the relationship between environmental tobacco smoke (ETS) exposure and cognitive abilities among U.S. children and adolescents 6–16 years of age. Serum cotinine was used as a biomarker of ETS exposure. Children were included in the sample if their serum cotinine levels were ≤15 ng/mL, a level consistent with ETS exposure, and if they denied using any tobacco products in the previous 5 days. Cognitive and academic abilities were assessed using the reading and math subtests of the Wide Range Achievement Test–Revised and the block design and digit span subtests of the Wechsler Intelligence Scale for Children–III. Analyses were conducted using SUDAAN software. Of the 5,365 6- to 16-year-olds included in NHANES III, 4,399 (82%) were included in this analysis. The geometric mean serum cotinine level was 0.23 ng/mL (range, 0.035–15 ng/mL); 80% of subjects had levels < 1 ng/mL. After adjustment for sex, race, region, poverty, parent education and marital status, ferritin, and blood lead concentration, there was a significant inverse relationship between serum cotinine and scores on reading (β= −2.69, p = 0.001), math (β= −1.93, p = 0.01), and block design (β= −0.55, p < 0.001) but not digit span (β= −0.08, p = 0.52). The estimated ETS-associated decrement in cognitive test scores was greater at lower cotinine levels. A log-linear analysis was selected as the best fit to characterize the increased slope in cognitive deficits at lower levels of exposure. These data, which indicate an inverse association between ETS exposure and cognitive deficits among children even at extremely low levels of exposure, support policy to further restrict children’s exposure

Time-trend of melanoma screening practice by primary care physicians: A meta-regression analysis

Objective. To assess whether the proportion of primary care physicians implementing full body skin examination (FBSE) to screen for melanoma changed over time. Methods. Meta-regression analyses of available data. Data Sources: MEDLINE, ISI, Cochrane Central Register of Controlled Trials. Results. Fifteen studies surveying 10,336 physicians were included in the analyses. Overall, 15%\u201382% of them reported to perform FBSE to screen for melanoma. The proportion of physicians using FBSE screening tended to decrease by 1.72% per year (P =0.086). Corresponding annual changes in European, North American, and Australian settings were 120.68% (P =0.494), 122.02% (P =0.044), and +2.59% (P =0.010), respectively. Changes were not influenced by national guide-lines. Conclusions. Considering the increasing incidence of melanoma and other skin malignancies, as well as their relative potential consequences, the FBSE implementation time-trend we retrieved should be considered a worrisome phenomenon

Citrullinated histone H3 as a novel prognostic blood marker in patients with advanced cancer

Citrullinated histone H3 (H3Cit) is a central player in the neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs). NETs have been shown to elicit harmful effects on the host, and were recently proposed to promote tumor progression and spread. Here we report significant elevations of plasma H3Cit in patients with advanced cancer compared with age-matched healthy individuals. These elevations were specific to cancer patients as no increase was observed in severely ill and hospitalized patients with a higher non-malignant comorbidity. The analysis of neutrophils from cancer patients showed a higher proportion of neutrophils positive for intracellular H3Cit compared to severely ill patients. Moreover, the presence of plasma H3Cit in cancer patients strongly correlated with neutrophil activation markers neutrophil elastase (NE) and myeloperoxidase (MPO), and the inflammatory cytokines interleukin-6 and -8, known to induce NETosis. In addition, we show that high levels of circulating H3Cit strongly predicted poor clinical outcome in our cohort of cancer patients with a 2-fold increased risk for short-term mortality. Our results also corroborate the association of NE, interleukin-6 and -8 with poor clinical outcome. Taken together, our results are the first to unveil H3Cit as a potential diagnostic and prognostic blood marker associated with an exacerbated inflammatory response in patients with advanced cancer

The role of dendritic cells in the immunopathogenesis of psoriasis

Psoriasis vulgaris is a chronic inflammatory skin disease that is marked by a complex interplay of dendritic cells (DCs), T-cells, cytokines, and downstream transcription factors as part of a self-sustaining type 1 cytokine network. As integral players of the immune system, DCs represent antigen-presenting cells that are crucial for efficient activation of T-cells and B-cells. DCs have also been linked to distinct chronic inflammatory conditions, including psoriasis. In the setting of psoriasis therapy, DC/T cell interactions serve as a potential target for biologic response modifiers. Here we describe the major DC subsets as well as the immunologic involvement of DCs within the context of psoriatic lesions

A Test of Highly Optimized Tolerance Reveals Fragile Cell-Cycle Mechanisms Are Molecular Targets in Clinical Cancer Trials

Robustness, a long-recognized property of living systems, allows function in the face of uncertainty while fragility, i.e., extreme sensitivity, can potentially lead to catastrophic failure following seemingly innocuous perturbations. Carlson and Doyle hypothesized that highly-evolved networks, e.g., those involved in cell-cycle regulation, can be resistant to some perturbations while highly sensitive to others. The “robust yet fragile” duality of networks has been termed Highly Optimized Tolerance (HOT) and has been the basis of new lines of inquiry in computational and experimental biology. In this study, we tested the working hypothesis that cell-cycle control architectures obey the HOT paradigm. Three cell-cycle models were analyzed using monte-carlo sensitivity analysis. Overall state sensitivity coefficients, which quantify the robustness or fragility of a given mechanism, were calculated using a monte-carlo strategy with three different numerical techniques along with multiple parameter perturbation strategies to control for possible numerical and sampling artifacts. Approximately 65% of the mechanisms in the G1/S restriction point were responsible for 95% of the sensitivity, conversely, the G2-DNA damage checkpoint showed a much stronger dependence on a few mechanisms; ∼32% or 13 of 40 mechanisms accounted for 95% of the sensitivity. Our analysis predicted that CDC25 and cyclin E mechanisms were strongly implicated in G1/S malfunctions, while fragility in the G2/M checkpoint was predicted to be associated with the regulation of the cyclin B-CDK1 complex. Analysis of a third model containing both G1/S and G2/M checkpoint logic, predicted in addition to mechanisms already mentioned, that translation and programmed proteolysis were also key fragile subsystems. Comparison of the predicted fragile mechanisms with literature and current preclinical and clinical trials suggested a strong correlation between efficacy and fragility. Thus, when taken together, these results support the working hypothesis that cell-cycle control architectures are HOT networks and establish the mathematical estimation and subsequent therapeutic exploitation of fragile mechanisms as a novel strategy for anti-cancer lead generation

The role of the mitochondria and the endoplasmic reticulum contact sites in the development of the immune responses

Abstract Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are dynamic modules enriched in subset of lipids and specialized proteins that determine their structure and functions. The MERCs regulate lipid transfer, autophagosome formation, mitochondrial fission, Ca2+ homeostasis and apoptosis. Since these functions are essential for cell biology, it is therefore not surprising that MERCs also play a critical role in organ physiology among which the immune system stands by its critical host defense function. This defense system must discriminate and tolerate host cells and beneficial commensal microorganisms while eliminating pathogenic ones in order to preserve normal homeostasis. To meet this goal, the immune system has two lines of defense. First, the fast acting but unspecific innate immune system relies on anatomical physical barriers and subsets of hematopoietically derived cells expressing germline-encoded receptors called pattern recognition receptors (PRR) recognizing conserved motifs on the pathogens. Second, the slower but very specific adaptive immune response is added to complement innate immunity. Adaptive immunity relies on another set of specialized cells, the lymphocytes, harboring receptors requiring somatic recombination to be expressed. Both innate and adaptive immune cells must be activated to phagocytose and process pathogens, migrate, proliferate, release soluble factors and destroy infected cells. Some of these functions are strongly dependent on lipid transfer, autophagosome formation, mitochondrial fission, and Ca2+ flux; this indicates that MERCs could regulate immunity

First measurement of the |t|-dependence of coherent J/ψ photonuclear production

The first measurement of the cross section for coherent J/ψ photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb–Pb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/ψ produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3−1.4)×10−3. The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky–Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio

First measurement of coherent ρ0 photoproduction in ultra-peripheral Xe–Xe collisions at √sNN = 5.44 TeV

The first measurement of the coherent photoproduction of ρ0 vector mesons in ultra-peripheral Xe–Xe collisions at sNN=5.44 TeV is presented. This result, together with previous HERA γp data and γ–Pb measurements from ALICE, describes the atomic number (A) dependence of this process, which is particularly sensitive to nuclear shadowing effects and to the approach to the black-disc limit of QCD at a semi-hard scale. The cross section of the Xe+Xe→ρ0+Xe+Xe process, measured at midrapidity through the decay channel ρ0→π+π−, is found to be dσ/dy=131.5±5.6(stat.)−16.9+17.5(syst.) mb. The ratio of the continuum to resonant contributions for the production of pion pairs is also measured. In addition, the fraction of events accompanied by electromagnetic dissociation of either one or both colliding nuclei is reported. The dependence on A of cross section for the coherent ρ0 photoproduction at a centre-of-mass energy per nucleon of the γA system of WγA,n=65 GeV is found to be consistent with a power-law behaviour σ(γA→ρ0A)∝Aα with a slope α=0.96±0.02(syst.). This slope signals important shadowing effects, but it is still far from the behaviour expected in the black-disc limit.publishedVersio

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion