First, Do No Harm: The Risks Of Overtreating Children With Epilepsy

Background: Although overtreatment with antiepileptic drugs contributes to the morbidity associated with epilepsy, many children still are overtreated. Objective: To evaluate if the withdrawal of at least one antiepileptic drug (AED) in children with refractory epilepsy using polytherapy enable a better seizure control. Method: This was a prospective study. Children with refractory epilepsy using at least two AEDs were included. Once the patient, or guardian, agreed to participate in the study, one or more AED were slowly tapered off. The remaining AEDs dosages could be adjusted as needed, but a new AED could not be introduced. Results: Fifteen patients were evaluated, three girls; ages ranging from 3 to 18 (mean=8.7 years). After at least one AED withdrawal, two (13.5%) patients became seizure free, seizures improved >50% in 5 (33.5%) patients, did not change in 5 (33.5%), and seizure frequency became worse in 3 (20%). Adverse events improved in 12 patients (80%). Conclusion: The withdrawal of at least one AED is a valuable option in the treatment of selected children with refractory epilepsy.65114Camfield, C.S., Camfield, P., Gordon, K., Smith, B., Dooley, J., Outcome of childhood epilepsy: A population-based study with a simple scoring system for those treated with medication (1993) J Pediatr, 122, pp. 861-868Silva, M., MacArdle, B., MaGowan, M., Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy (1996) Lancet, 347, pp. 709-713Baulac, M., Rational conversion from antiepileptic polytherapy to monotherapy (2003) Epileptic Disord, 5, pp. 125-132Holmes, G.L., Overtreatment in children with epilepsy (2002) Epilepsy Res, 52, pp. 35-42Fischbacher, E., Effect of reduction of anticonvulsants on wellbeing (1982) Br Med J (Clin Res Ed), 285, pp. 423-424Schmidt, D., Reduction of two-drug therapy in intractable epilepsy (1983) Epilepsia, 24, pp. 368-376Alvarez, N., Discontinuance of antiepileptic medications in patients with developmental disability and diagnosis of epilepsy (1989) Am J Ment Retard, 93, pp. 593-595Guerrini, R., Belmonte, A., Genton, P., Antiepileptic drug-induced worsening of seizures in children (1998) Epilepsia, 39 (SUPPL. 3), pp. S2-S10TS, K., Holmes, G.L., EEG and clinical predictors of medically intractable childhood epilepsy (1999) Clin Neurophysiol, 110, pp. 1245-1251Huttenlocker, P.R., Hapke, R.J., A follow-up study of intractable seizures in childhood (1990) Ann Neurol, 28, pp. 699-705Ferngren, H., Akerstrom, I., Rane, A., Mono or polypharmacotherapy in institutionalized epileptic children with severe mental retardation? A team approach for optimizing antiepileptic therapy (1991) Acta Paediatr Scand, 80, pp. 458-465Dooley, J., Gordon, K., Camfield, C., Smith, E., Discontinuation of anticonvulsant therapy in children free of seizures for 1 year: A prospective study (1996) Neurology, 46, pp. 969-974Shinnar, S., Berg, A.T., Moshé, S.L., Discontinuing antiepileptic drugs in children with epilepsy:a prospective study (1994) Ann Neurol, 35, pp. 534-545Shorvon, S.D., Reynolds, E.H., Unnecessary polypharmacy for epilepsy (1977) Br Med J, 1, pp. 1635-1637Vickery, B.G., Hay, R., Engel, J., Outcome assessment for epilepsy surgery: The impact of measuring health-related quality of life (1995) Ann Neurol, 37, pp. 158-16

Adipose proinflammatory cytokine expression through sympathetic system is associated with hyperglycemia and insulin resistance in a rat ischemic stroke model

Wang YY, Lin SY, Chuang YH, Chen CJ, Tung KC, Sheu WH. Adipose proinflammatory cytokine expression through sympathetic system is associated with hyperglycemia and insulin resistance in a rat ischemic stroke model. Am J Physiol Endocrinol Metab 300: E155-E163, 2011. First published October 26, 2010; doi:10.1152/ajpendo.00301.2010.Patients who experience acute ischemic stroke may develop hyperglycemia, even in the absence of diabetes, but the exact mechanisms are still unclear. Adipose tissue secretes numerous proinflammatory cytokines and is involved in the regulation of glucose metabolism. This study aimed to determine the effects of acute stroke on adipose inflammatory cytokine expression. In addition, because sympathetic activity is activated after acute stroke and catecholamines can regulate the expression of several adipocytokines, this study also evaluated whether alterations in adipose proinflammatory cytokines following acute stroke, if any, were medicated by sympathetic system. Acute ischemic brain injury was induced by ligating the right middle cerebral artery and bilateral common carotid arteries in male adult Sprague-Dawley rats. Adipose tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) mRNA and protein levels were determined by RT-PCR and enzyme-linked immunoassay, respectively. The stroke rats developed glucose intolerance on days 1 and 2 after cerebral ischemic injury. The fasting blood insulin levels and insulin resistance index measured by homeostasis model assessment were higher in the stroke rats compared with the sham group. Epididymal adipose TNF-alpha and MCP-1 mRNA and protein levels were elevated one-to twofold, in association with increased macrophage infiltration into the adipose tissue. When the rats were treated with a nonselective beta-adrenergic receptor blocker, propranolol, before induction of cerebral ischemic injury, the acute stroke-induced increase in TNF-alpha and MCP-1 was blocked, and fasting blood insulin concentration and homeostasis model assessment-insulin resistance were decreased. These results suggest a potential role of adipose proinflammatory cytokines induced by the sympathetic nervous system in the pathogenesis of glucose metabolic disorder in rats with acute ischemic stroke

EGFR L858R Mutation and Polymorphisms of Genes Related to Estrogen Biosynthesis and Metabolism in Never-Smoking Female Lung Adenocarcinoma Patients

Purpose: To assess whether polymorphisms of genes related to estrogen biosynthesis and metabolism are associated with EGFR mutations. Experimental Design: We studied 617 patients with lung adenocarcinoma, including 302 never-smoking women. On the basis of multiple candidate genes approach, the effects of polymorphisms of CYP17, CYP19A1, ER alpha, and COMT in association with the occurrence of EGFR mutations were evaluated using logistic regression analysis. Results: In female never-smokers, significant associations with EGFR L858R mutation were found for the tetranucleotide (TTTA)(n) repeats in CYP19A1 (odds ratio, 2.6; 95%CI, 1.2-5.7 for 1 or 2 alleles with (TTTA)(n) repeats > 7 compared with both alleles with (TTTA) n repeats <= 7), and the rs2234693 in ERa (OR, 2.1; 95% CI, 1.1-4.0 for C/T and C/C genotypes compared with T/T genotype). The C/C genotype (vs. T/T genotype) of ERa was significantly associated with EGFR L858R mutation (OR, 3.0; 95% CI, 1.1-8.1), in-frame deletion (OR, 2.9; 95% CI, 1.1-7.6) and other mutations (OR, 4.3; 95% CI, 1.3-14.0). The genotype of COMT rs4680 was significantly associated with EGFR L858R mutation in female and male never-smokers showing OR's (95% CI) of 1.8 (1.0-3.2) and 3.6 (1.1-11.3), respectively, for genotypes G/A and G/G compared with genotype A/A. The number of risk alleles of CYP17, CYP19A1, ERa, and COMT was associated with an increasing OR of EGFR L858R mutation in female never-smokers (P = 0.0002 for trend). Conclusions: The L858R mutation of EGFR is associated with polymorphisms of genes related to estrogen biosynthesis and metabolism in never-smoking female lung adenocarcinoma patients. Clin Cancer Res; 17(8); 2149-58. (C) 2011 AACR

Global Search for New Physics with 2.0/fb at CDF

Data collected in Run II of the Fermilab Tevatron are searched for indications of new electroweak-scale physics. Rather than focusing on particular new physics scenarios, CDF data are analyzed for discrepancies with the standard model prediction. A model-independent approach (Vista) considers gross features of the data, and is sensitive to new large cross-section physics. Further sensitivity to new physics is provided by two additional algorithms: a Bump Hunter searches invariant mass distributions for "bumps" that could indicate resonant production of new particles; and the Sleuth procedure scans for data excesses at large summed transverse momentum. This combined global search for new physics in 2.0/fb of ppbar collisions at sqrt(s)=1.96 TeV reveals no indication of physics beyond the standard model.Comment: 8 pages, 7 figures. Final version which appeared in Physical Review D Rapid Communication

Observation of Orbitally Excited B_s Mesons

We report the first observation of two narrow resonances consistent with states of orbitally excited (L=1) B_s mesons using 1 fb^{-1} of ppbar collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the Fermilab Tevatron. We use two-body decays into K^- and B^+ mesons reconstructed as B^+ \to J/\psi K^+, J/\psi \to \mu^+ \mu^- or B^+ \to \bar{D}^0 \pi^+, \bar{D}^0 \to K^+ \pi^-. We deduce the masses of the two states to be m(B_{s1}) = 5829.4 +- 0.7 MeV/c^2 and m(B_{s2}^*) = 5839.7 +- 0.7 MeV/c^2.Comment: Version accepted and published by Phys. Rev. Let

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV

Isolated photon production is measured in proton-proton and lead-lead collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80 GeV with the CMS detector at the LHC. The measured ET spectra are found to be in good agreement with next-to-leading-order perturbative QCD predictions. The ratio of PbPb to pp isolated photon ET-differential yields, scaled by the number of incoherent nucleon-nucleon collisions, is consistent with unity for all PbPb reaction centralities.Comment: Submitted to Physics Letters

Influence of Dietary Oil Content and Conjugated Linoleic Acid (CLA) on Lipid Metabolism Enzyme Activities and Gene Expression in Tissues of Atlantic Salmon (Salmo salar L.)

The overall objective is to test the hypothesis that conjugated linoleic acid (CLA) has beneficial effects in Atlantic salmon through affecting lipid and fatty acid metabolism. The specific aims of the present study were to determine the effects of CLA on some key pathways of fatty acid metabolism including fatty acid oxidation and highly unsaturated fatty acid (HUFA) synthesis. Salmon smolts were fed diets containing two levels of fish oil (low, ~18% and high, ~34%) containing three levels of CLA (a 1:1 mixture of 9-cis,trans-11 and trans-10,cis-12 at 0, 1 and 2% of diet) for 3 months. The effects of dietary CLA on HUFA synthesis and β-oxidation were measured and the expression of key genes in the fatty acid oxidation and HUFA synthesis pathways, and potentially important transcription factors, peroxisome proliferators activated receptors (PPARs), determined in selected tissues. Liver HUFA synthesis and desaturase gene expression was increased by dietary CLA and decreased by high dietary oil content. Carnitine palmitoyltransferase-I (CPT-I) activity and gene expression were generally increased by CLA in muscle tissues although dietary oil content had relatively little effect. In general CPT-I activity or gene expression was not correlated with β-oxidation. Dietary CLA tended to increase PPARα and β gene expression in both liver and muscle tissues, and PPARγ in liver. In summary, gene expression and activity of the fatty acid pathways were altered in response to dietary CLA and/or oil content, with data suggesting that PPARs are also regulated in response to CLA. Correlations were observed between dietary CLA, liver HUFA synthesis and desaturase gene expression, and liver PPARα expression, and also between dietary CLA, CPT-I expression and activity, and PPARα expression in muscle tissues. In conclusion, this study suggests that dietary CLA has effects on fatty acid metabolism in Atlantic salmon and on PPAR transcription factors. However, further work is required to assess the potential of CLA as a dietary supplement, and the role of PPARs in the regulation of lipid metabolism in fish

Measurement of the ttbar Production Cross Section in ppbar collisions at sqrt s = 1.96 TeV in the All Hadronic Decay Mode

We report a measurement of the ttbar production cross section using the CDF-II detector at the Fermilab Tevatron. The analysis is performed using 311 pb-1 of ppbar collisions at sqrt(s)=1.96 TeV. The data consist of events selected with six or more hadronic jets with additional kinematic requirements. At least one of these jets must be identified as a b-quark jet by the reconstruction of a secondary vertex. The cross section is measured to be sigma(tbart)=7.5+-2.1(stat.)+3.3-2.2(syst.)+0.5-0.4(lumi.) pb, which is consistent with the standard model prediction.Comment: By CDF collaboratio