Oncological patterns of care and outcomes for 265 elderly patients with newly diagnosed glioblastoma in France

The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS _n?=?95) or biopsy (B _n?=?170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT _n?=?76), chemotherapy (CT _n?=?52), and concomitant radiochemotherapy (CRC _n?=?39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B?+?RT and/or CT, RS?±?RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT _n?=?41, 199_[155–280]; B-CRC _n?=?21, 318_[166–480]; B-RT _n?=?37, 149_[130–214]; RS-CT _n?=?11, 245_[211–na]; RS-CRC _n?=?18, 372_[349–593]; RS-RT _n?=?39, 269_[218–343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible.     

Molecular,cellular, and tissue impact of depleted uranium on xenobiotic-metabolizing enzymes

Enzymes that metabolize xenobiotics (XME) are well recognized in experimental models as representative indicators of organ detoxification functions and of exposure to toxicants. As several in vivo studies have shown, uranium can alter XME in the rat liver or kidneys after either acute or chronic exposure. To determine how length or level of exposure affects these changes in XME, we continued our investigation of chronic rat exposure to depleted uranium (DU, uranyl nitrate). The first study examined the effect of duration (1–18 months) of chronic exposure to DU, the second evaluated dose dependence, from a level close to that found in the environment near mining sites (0.2 mg/L) to a supra-environmental dose (120 mg/L, 10 times the highest level naturally found in the environment), and the third was an in vitro assessment of whether DU exposure directly affects XME and, in particular, CYP3A. The experimental in vivo models used here demonstrated that CYP3A is the enzyme modified to the greatest extent: high gene expression changed after 6 and 9 months. The most substantial effects were observed in the liver of rats after 9 months of exposure to 120 mg/L of DU: CYP3A gene and protein expression and enzyme activity all decreased by more than 40 %. Nonetheless, no direct effect of DU by itself was observed after in vitro exposure of rat microsomal preparations, HepG2 cells, or human primary hepatocytes. Overall, these results probably indicate the occurrence of regulatory or adaptive mechanisms that could explain the indirect effect observed in vivo after chronic exposure.     

Experimental Investigation of Integrated Circular Triple-Wire Pulse GMAW of Q960E High-Strength Steel for Construction Machinery

Multi-wire welding has received much attention in the machinery industry due to its high efficiency. The aim of this study was to investigate a novel pulse gas metal arc welding (GMAW) that has circular triple-wire electrodes. The effect of the pulse phage angle on arc stability was particularly studied. Research showed that for typical phase angles the arc stability from low to high is 180°, 0°, and 120°, and the arcs are very stable at 120°. The triple-wire welding was used to weld a 9 mm thick Q960E steel, which is typically used for the arm of construction machinery. When the welding heat input was controlled at 1.26–1.56 kJ/mm, the weld zone was dominated by acicular ferrite, and the coarse-grained zone of the heat-affected zone was a mixed structure of lath martensite and lath bainite. The tensile strength of the welded joint reached 85% of the base metal and the impact toughness was above 62 J, which can meet the requirements of construction machinery. This indicates that the triple-wire welding has great potential to achieve efficient and high-quality welding for the construction machinery.     

Practices and opinions regarding HPV vaccination among French general practitioners: evaluation through two cross-sectional studies in 2007 and 2010

Objectives

To use both quantitative and qualitative methods to investigate the evolution of practices and opinions regarding human papillomavirus (HPV) vaccination among French general practitioners.

Methods

A cross-sectional study (self-questionnaires) was performed in 2007 and repeated in 2010 among 271 general practitioners. Semi-structured interviews were conducted on 27 voluntary participants by a sociologist and analyzed according to content analysis.

Results

Acceptability of HPV vaccination had increased from 2007 to 2010 (79.9 vs. 87.1 %, respectively), just as the practice of HPV vaccination among 14-year-old girls (19.0 vs. 49.1 %, respectively). Though about 60 % reported complications associated with HPV vaccination, irrespective of year, the types of difficulties have varied: difficulties related to “questions asked by patients” had decreased, though concerns about side effects had remained stable. During interviews, difficulties related to “the reason for medical consultation” and “the target age” were often associated with addressing the issue of sexuality, especially when the parents were present.

Conclusions

Although the high level of acceptability of HPV vaccination among general practitioners, which increased from 2007 to 2010, there remain difficulties in addressing this practice.     

Synthesis and cytotoxicity against tumor cells of pincer N-heterocyclic ligands and their transition metal complexes

The complexes: [CoL₂](ClO₄)₂ (1), [FeL₂](ClO₄)₂ (2), [NiL₂](ClO₄)₂ (3) and [MnLCl₂] (4), with L = diethyl-1,1′-(pyridine-2,6-diyl)bis(5-methyl-1H-pyrazole-3-carboxylate), were synthesized and fully characterized. Structural analysis revealed two distinct patterns influenced by the counter ions where L acts as a tridentate chelating ligand. The in vitro antitumor activity of L and L′ (diethyl 2,2′-(pyridine-2,6-diylbis(5-methyl-1H-pyrazole-3,1-diyl)) diacetate) as well as their metal complexes, was tested by the measurement of their cytostatic and cytotoxic properties towards the blood cancer mastocytoma cell line P815. We have also investigated their interactions with the antioxidant enzyme system. As a result, [MnL′Cl₂] (1′) exhibited the strongest activity compared to reference cis-platin with no cytotoxicity towards normal cells PBMCs (Peripheral Blood Mononuclear Cells). On the other hand, the antioxidant enzyme activity showed that the efficiency of metal complex 1′ against P815 tumor cells was via the rise in the SOD activity and inhibition of CAT enzyme activity. This proof of concept study allows disclosure of a new class of molecules in cancer therapeutics.

The complexes: [CoL₂](ClO₄)₂ (1), [FeL₂](ClO₄)₂ (2), [NiL₂](ClO₄)₂ (3) and [MnLCl₂] (4), with L = diethyl-1,1′-(pyridine-2,6-diyl)bis(5-methyl-1H-pyrazole-3-carboxylate), were synthesized and fully characterized.     

Radiosynthesis of (E)-N-(2-[11C]methoxybenzyl)-3-phenyl-acrylamidine, a novel subnanomolar NR2B subtype-selective NMDA receptor antagonist.

Recently, a novel series of amidines has been described, exhibiting high NR2B-subtype selective N-methyl-D-aspartate (NMDA) antagonist activity with nanomolar or subnanomolar affinity. Within the styrylamidine subclass, (E)-N-(2-methoxybenzyl)-3-phenyl-acrylamidine (1), displayed the highest affinity (Ki=0.7 nM versus [(3)H]ifenprodil) and was considered an appropriate candidate for isotopic labelling with carbon-11 (T(1/2): 20.38 min) at its methoxy group for imaging of NMDA receptors with PET. Derivative 1 has been labelled from the corresponding nor-analogue using [(11)C]methyl triflate and the following experimental conditions : (1) trapping at -10 degrees C of [(11)C]methyl triflate in 300 microL of acetone containing 0.6-0.8 mg of precursor 5 (2.4-3.2 micromol) and 5 microL of a 3M solution of NaOH in water (about 5 eq.); (2) concentration to dryness of the reaction mixture (at 110 degrees C, using a helium stream for 1-2 min); (3) taking up the residue with 0.5 mL of the HPLC mobile phase and (4) purification using semi-preparative HPLC (SymmetryPrep) C-18, Waters, 300 x 7.8 mm). Typically, starting from a 1.5 Ci (55.5 GBq) [(11)C]CO(2) production batch, 120-240 m Ci (4.44-8.88 GBq) of [(11)C]-1 (20-40% decay-corrected radiochemical yield, n=5) was obtained within a total synthesis time of 25-30 min. Specific radioactivities ranged from 0.8 to 1.2 Ci/micromol (29.6-44.4 GBq/micromol) at the end of radiosynthesis. No attempts were made to further optimise these reactions, as sufficient material was obtained to allow for preliminary pharmacological characterisation.