Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update

Daptomycin pharmacokinetics may not depend on renal function only and it significantly differs between healthy volunteers and severely ill patients. Herein, we propose a population pharmacokinetics model based on 424 plasma daptomycin concentrations collected from 156 patients affected by severe Gram-positive infections during a routine therapeutic drug monitoring protocol. Model building and validation were performed using NONMEM 7.2 (ICON plc), Xpose4 and Perl-speaks-to-NONMEM. The final pop-PK model was a one-compartment first-order elimination model, with a 2.7% IIV for drug clearance (Cl), influence of creatinine clearance on drug clearance and of sex on distribution volume. After model validation, we simulated 10,000 patients with the Monte-Carlo method to predict the efficacy and tolerability of different daptomycin daily dosages. For the most common 6 mg/kg daily dose, the simulated probability of overcoming the toxic minimum concentration (24.3 mg/L) was 14.8% and the efficacy (expressed as a cumulative fraction of response) against methicillin-resistant S. aureus, S. pneumoniae and E. faecium was 95.77%, 99.99% and 68%, respectively. According to the model-informed precision dosing paradigm, pharmacokinetic models such as ours could help clinicians to perform patient-tailored antimicrobial dosing and maximize the odds of therapy success without neglecting toxicity risk

Desenvolvimento de lesões perirradiculares em ratos normais e diabéticos

Evidence suggests that diabetic patients are more significantly affected by problems of endodontic origin. This study sought to radiographically and histologically examine the development of periradicular inflammation in control and in diabetic rats after induction of pulpal infection. The pulps of the mandibular first molars of normal and streptozotocin-induced diabetic rats were exposed and left in contact with their oral cavities for 21 and 40 days. Afterwards, the animals were sacrificed, the mandibles were surgically removed, fixed in formalin and then radiographed in a standardized position. The radiographic images of the periradicular lesions were scanned and computerized images were evaluated for the total area of the lesions using a specific software. Representative specimens were also prepared for histopathological analysis. Radiographic analysis revealed that diabetic rats presented significantly larger periradicular lesions when compared with control rats, regardless of the experimental period (pEvidências indicam que pacientes diabéticos são mais significativamente afetados por problemas de origem endodôntica. Este estudo avaliou radiográfica e histologicamente o desenvolvimento de inflamação perirradicular em ratos controle e diabéticos depois da indução de infecção pulpar. As polpas dos primeiros molares inferiores de ratos normais ou diabéticos foram expostas e deixadas em contato com a cavidade oral por 21 e 40 dias. Em seguida, os animais foram sacrificados, as mandíbulas removidas cirurgicamente, fixadas em formalina e depois radiografadas em posição padronizada. As imagens radiográficas das lesões perirradiculares foram escaneadas e as imagens computadorizadas avaliadas quanto à área total das lesões usando software específico. Espécimes representativos foram preparados também para análise histológica. A análise radiográfica revelou que os ratos diabéticos apresentaram lesões periradiculares significativamente maiores quando comparados com os ratos normais, independentemente do período experimental (

Caminhoneiro de transporte rodoviário de cargas: busca de tratamentos odontológicos

O objetivo desta pesquisa foi explorar hábitos dos caminhoneiros na busca por tratamentos odontológicos. O método da pesquisa utilizado foi quantitativo, exploratório-descritivo e de corte transversal, com 270 sujeitos de pesquisa. O estudo incluiu caminhoneiros com idade de vinte e um a sessenta anos que atuam no ramo de transporte rodoviário de cargas e trafegam na Rodovia Presidente Dutra. Apesar de não estatisticamente diferente, foi detectada tendência de quanto maior o grau de instrução, maior a renda; e quanto maior o grau de instrução, são buscadas melhores formas de tratamentos odontológicos; o fator renda não teve influência forma busca de tratamento odontológico. Como sugestão de futura pesquisa, fazer uma pesquisa mais ampla, de forma a possibilitar melhores análises estatísticas

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Measurement of the correlation between the polar angles of leptons from top quark decays in the helicity basis at √s = 7 TeV using the ATLAS detector

A measurement of the correlations between the polar angles of leptons from the decay of pair-produced t and t̄ quarks in the helicity basis is reported, using proton-proton collision data collected by the ATLAS detector at the LHC. The dataset corresponds to an integrated luminosity of 4.6  fb−¹ at a center-of-mass energy of √s = 7  TeV collected during 2011. Candidate events are selected in the dilepton topology with large missing transverse momentum and at least two jets. The angles θ1 and θ2 between the charged leptons and the direction of motion of the parent quarks in the tt̄ rest frame are sensitive to the spin information, and the distribution of cosθ1 ⋅ cosθ2 is sensitive to the spin correlation between the t and t̄ quarks. The distribution is unfolded to parton level and compared to the next-to-leading order prediction. A good agreement is observed

Search for massive, long-lived particles using multitrack displaced vertices or displaced lepton pairs in pp collisions at √s = 8 TeV with the ATLAS detector

Many extensions of the Standard Model posit the existence of heavy particles with long lifetimes. This article presents the results of a search for events containing at least one long-lived particle that decays at a significant distance from its production point into two leptons or into five or more charged particles. This analysis uses a data sample of proton-proton collisions at √s=8  TeV corresponding to an integrated luminosity of 20.3  fb−1 collected in 2012 by the ATLAS detector operating at the Large Hadron Collider. No events are observed in any of the signal regions, and limits are set on model parameters within supersymmetric scenarios involving R-parity violation, split supersymmetry, and gauge mediation. In some of the search channels, the trigger and search strategy are based only on the decay products of individual long-lived particles, irrespective of the rest of the event. In these cases, the provided limits can easily be reinterpreted in different scenarios

Measurement of the CP-violating phase ϕs and the Bs0 meson decay width difference with Bs0 → J/ψϕ decays in ATLAS

A measurement of the Bs0 decay parameters in the Bs0 → J/ψϕ channel using an integrated luminosity of 14.3 fb−1 collected by the ATLAS detector from 8 TeV pp collisions at the LHC is presented. The measured parameters include the CP -violating phase ϕs, the decay width Γs and the width difference between the mass eigenstates ΔΓs. The values measured for the physical parameters are statistically combined with those from 4.9 fb−1 of 7 TeV data, leading to the following: ϕ s =−0.090±0.078(stat.)±0.041(syst.)rad ΔΓ s =0.085±0.011(stat.)±0.007(syst.)ps −1 Γ s =0.675±0.003(stat.)±0.003(syst.)ps −1 In the analysis the parameter ΔΓs is constrained to be positive. Results for ϕs and ΔΓs are also presented as 68% and 95% likelihood contours in the ϕs-ΔΓs plane. Also measured in this decay channel are the transversity amplitudes and corresponding strong phases. All measurements are in agreement with the Standard Model predictions