Effective charge of the [pi]h11/2 orbital and the electric field gradient of Hg from the yrast structure of 206Hg

The γ-ray decay of excited states of the two-proton hole nucleus, 206Hg, has been identified using Gammasphere and 208Pb+238U collisions. The yrast states found include a T1/2 = 92(8)ns 10+ isomer located above the known 5- isomer. The B(E2;10+→8+) strength is used to derive the quadrupole polarization charge induced by the h11/2 proton hole. Also, the implied quadrupole moment has been used to provide an absolute scale for the electric field gradient of Hg in Hg metal

Escherichia coli MazF Leads to the Simultaneous Selective Synthesis of Both “Death Proteins” and “Survival Proteins”

The Escherichia coli mazEF module is one of the most thoroughly studied toxin–antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. MazF is an endoribonuclease that leads to the inhibition of protein synthesis by cleaving mRNAs at ACA sequences. Here, using 2D-gels, we show that in E. coli, although MazF induction leads to the inhibition of the synthesis of most proteins, the synthesis of an exclusive group of proteins, mostly smaller than about 20 kDa, is still permitted. We identified some of those small proteins by mass spectrometry. By deleting the genes encoding those proteins from the E. coli chromosome, we showed that they were required for the death of most of the cellular population. Under the same experimental conditions, which induce mazEF-mediated cell death, other such proteins were found to be required for the survival of a small sub-population of cells. Thus, MazF appears to be a regulator that induces downstream pathways leading to death of most of the population and the continued survival of a small sub-population, which will likely become the nucleus of a new population when growth conditions become less stressful

A Pilot Study of IL-2Rα Blockade during Lymphopenia Depletes Regulatory T-cells and Correlates with Enhanced Immunity in Patients with Glioblastoma

Preclinical studies in mice have demonstrated that the prophylactic depletion of immunosuppressive regulatory T-cells (T(Regs)) through targeting the high affinity interleukin-2 (IL-2) receptor (IL-2Rα/CD25) can enhance anti-tumor immunotherapy. However, therapeutic approaches are complicated by the inadvertent inhibition of IL-2Rα expressing anti-tumor effector T-cells.To determine if changes in the cytokine milieu during lymphopenia may engender differential signaling requirements that would enable unarmed anti-IL-2Rα monoclonal antibody (MAbs) to selectively deplete T(Regs) while permitting vaccine-stimulated immune responses.A randomized placebo-controlled pilot study was undertaken to examine the ability of the anti-IL-2Rα MAb daclizumab, given at the time of epidermal growth factor receptor variant III (EGFRvIII) targeted peptide vaccination, to safely and selectively deplete T(Regs) in patients with glioblastoma (GBM) treated with lymphodepleting temozolomide (TMZ).Daclizumab treatment (n = 3) was well-tolerated with no symptoms of autoimmune toxicity and resulted in a significant reduction in the frequency of circulating CD4+Foxp3+ TRegs in comparison to saline controls (n = 3)( p = 0.0464). A significant (p<0.0001) inverse correlation between the frequency of TRegs and the level of EGFRvIII specific humoral responses suggests the depletion of TRegs may be linked to increased vaccine-stimulated humoral immunity. These data suggest this approach deserves further study.ClinicalTrials.gov NCT00626015

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Análise do líquido cérebro-espinhal de três doenças do sistema nervoso central de cães

RESUMO: Foi realizado um estudo retrospectivo do líquido cérebro-espinhal de cães (LCE), atendidos pelo Serviço de Neurologia do Hospital Veterinário da Instituição, de 2004 a 2015, com o objetivo de analisar os resultados de cães com sinais neurológicos, comparar as alterações encontradas em dois locais de colheita no mesmo paciente e verificar se esse exame auxiliou o clínico em reforçar a suspeita clínica das principais doenças do sistema nervoso central. A pleocitose linfocítica esteve presente em 78,3% (29/37) das amostras de cães com cinomose e em 23,2% (10/43) de cães com DDIV. Houve dissociação albuminocitológica (DAC) em 73% (19/26) das amostras de cães com tumores IC e em 64,3% (9/14) de cães com tumores envolvendo a ME. Em cães com DDIV, houve significância estatística (p<0,05) entre o grau de disfunção neurológica e o total de células nucleadas (TCN) e total de proteínas (TP). Em 29 cães, houve a colheita do LCE da cisterna magna e da cisterna lombar e em 12 (41,4%) os resultados foram diferentes entre as duas amostras colhidas do mesmo cão, onde dois (6,9%) apresentaram alteração na amostra colhida cranial à lesão. Pode-se concluir que a pleocitose linfocítica foi a principal alteração encontrada no LCE de cães com cinomose e DDIV e DAC nas neoplasias, IC e ME, cães acometidos pela DDIV apresentaram sinais neurológicos mais severos conforme o TCN e o TP aumentaram e o LCE sofreu alteração, mesmo colhido cranial ao local da lesão e auxiliou o clínico em reforçar a suspeita clínica, mas não confirmou, as principais doenças neurológicas em cães