Impact of radiotherapy on survival in resected or unresectable anaplastic thyroid carcinomas, a Rare Cancer Network study.

PURPOSE: Anaplastic thyroid carcinomas (ATC) are a heterogenous group of tumors of overall dismal prognosis. We designed models to identify relevant prognostic factors of survival of irradiated ATC patients including radiotherapy modalities (field size, dose). MATERIAL AND METHODS: Between 2000 and 2017, 166 ATC patients' treatments were divided into surgery and postoperative radiotherapy (poRT) or definitive radiotherapy (RT). Multiple imputation approach was used for missing data. Prognostic factors were identified using Lasso-penalized Cox modelling and predicted risk scores were built. RESULTS: Patients undergoing RT (n=70) had more adverse patient and disease characteristics than those undergoing poRT (n=96). Corresponding median survival rates were 5.4 and 12.1 months, respectively. PoRT patients undergoing poRT more likely received extended-field radiotherapy with prophylactic nodal irradiation, but rather received platinum- vs. adriamycin-based chemoradiotherapy. Radiotherapy was conventionally fractionated, delivered >60Gy in 51.9% and 61.7% and used extended fields in 88.5% and 71.2% of patients with poRT or RT. Radiotherapy interruption rates for toxicity were similar in the two groups. The best poRT-group model identified age>45yo, PS≥1, pathologic tumor stage≥pT4b,>N1 and R2 resection as poor prognostic factors. The best RT-group model (C-index of 0.72) identified PS≥3,>N1 and extended-field radiotherapy with prophylactic nodal irradiation (as opposed to tumour-bed irradiation only) as poor prognostic factors. CONCLUSION: In patients undergoing poRT, radiotherapy parameters had little influence over their survival irrespective of patient, disease characteristics, and quality of resection. In patients undergoing RT, extended-field radiotherapy improved survival in addition to PS and nodal stage.

Efficacy and safety of hypofractionated stereotactic radiotherapy for brain metastases using three fractions: A single-centre retrospective study.

PURPOSE: Hypofractionated stereotactic radiotherapy (HFSRT) has become a standard of care for patients with a limited number of brain metastases (BM). An increasing number of linear accelerators (LA) are able to accurately perform HFSRT including VersaHD® (Elekta®) LA. The main aim of this study was to report clinical outcomes of BM treated by HFSRT using 3×7.7Gy on 70% isodose line in terms of local control (LC). PATIENTS AND METHODS: Between November 2016 and October 2018, all patients suffering from histologically-proven primary with one or several newly diagnosed BM treated by HFSRT were retrospectively included and evaluated. Patients who had received prior treatment by neurosurgery or cerebral radiotherapy were excluded. RESULTS: Among 44 patients, 61 BM were treated. With a median follow-up of 31.9 months, LC rates at 6 and 12 months were 93.2% and 90.9, respectively. Single-BM was independently predictive of LC (P=0.025) and overall survival (P=0.013). Acute toxicity rates were acceptable: 65.9% of patients had grade 1 and 2 and no acute grade 3 toxicity according to the NCI-CTCAE (version 5.0). Regarding delayed toxicity, one case (2.3%) of radionecrosis was confirmed by magnetic resonance spectroscopy. CONCLUSION: In our single-centre retrospective analysis, BM treatment by HFSRT delivered in three fractions showed a 12-month LC rate of 90.9% without major toxicities, which suggests safety and efficiency of this technique. However, longer-term follow-up and prospective studies are still needed to confirm these results.

Tuning the dynamics of imidazolium-based ionic liquids via hydrogen bonding. I. The viscous regime.

Combining results from impedance spectroscopy and oscillatory shear rheology, the present work focuses on the relation between the mass and charge flows and on how these are affected by the H-bonding in viscous ionic liquids (ILs). In particular, we compare the relaxational behaviors of the paradigmatic IL 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM-TFSI) and its OH-functionalized counterpart 1-(2-hydroxyethyl)-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (OHEMIM-TFSI). Our results and their analysis demonstrate that the presence of cationic OH-groups bears a strong impact on the overall dynamics of OHEMIM-TFSI, although no signatures of suprastructural relaxation modes could be identified in their dielectric and mechanical responses. To check whether at the origin of this strong variation is the H-bonding or merely the difference between the corresponding cation sizes (controlling both the hydrodynamic volume and the inter-charge distance), the present study includes 1-propyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (PMIM-TFSI), mixtures of EMIM-TFSI and PMIM-TFSI with lithium bis(trifluoromethylsulfonyl)imide (Li-TFSI), and mixtures of OHEMIM-TFSI with PMIM-TFSI. Their investigation clearly reveals that the dynamical changes induced by H-bonding are significantly larger than those that can be attributed to the change in the ion size. Moreover, in the mixtures of OHEMIM-TFSI with PMIM-TFSI, a dilution of the OH-groups leads to strong deviations from ideal mixing behavior, thus highlighting the common phenomenological ground of hydroxy-functionalized ILs and other H-bonded liquids.

How is charge transport different in ionic liquids? The effect of high pressure.

Modern ionic liquids (ILs) are considered green solvents for the future applications due to their inherited advantages and remarkable transport properties. One of the ubiquitous properties of ILs is their intrinsic ionic conductivity. However, understanding of the super-Arrhenius behavior of the ionic conductivity process at elevated pressure still remains elusive and crucial in glass science. In this work, we investigate the ion transport properties of 1-butyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide: [C4mim][NTf2], 1-butylimidazolium bis[(trifluoromethyl)-sulfonyl]imide: [C4Him][NTf2] and 1-butylimidazolium hydrogen sulfate: [C4Him][HSO4] ILs in the supercooled liquid state using dielectric spectroscopy at ambient and high pressure. We present the experimental data in the dynamic window of the conductivity formalism to examine the charge transport properties. The frequency-dependent ionic conductivity data have been analyzed using the time-temperature superposition principle. In the Arrhenius diagram, the thermal evolution of the dc-conductivity reveals similar temperature dependence for both protic and aprotic ILs thus making it difficult to distinguish the ion dynamics. However, our results demonstrate the key role of high pressure that unambiguously separates the charge transport properties of protic ILs from aprotic ones through the apparent activation volume parameter. We also highlight that the activation volume can be employed to assess the information connecting the ability of ionic systems to form H-bond networks and the impact of proton transfer involved in the conduction process.

Mixing Enthalpy for Binary Mixtures Containing Ionic Liquids.

A complete review of the published data on the mixing enthalpies of mixtures containing ionic liquids, measured directly using calorimetric techniques, is presented in this paper. The field of ionic liquids is very active and a number of research groups in the world are dealing with different applications of these fluids in the fields of chemistry, chemical engineering, energy, gas storage and separation or materials science. In all these fields, the knowledge of the energetics of mixing is capital both to understand the interactions between these fluids and the different substrates and also to establish the energy and environmental cost of possible applications. Due to the relative novelty of the field, the published data is sometimes controversial and recent reviews are fragmentary and do not represent a set of reliable data. This fact can be attributed to different reasons: (i) difficulties in controlling the purity and stability of the ionic liquid samples; (ii) availability of accurate experimental techniques, appropriate for the measurement of viscous, charged, complex fluids; and (iii) choice of an appropriate clear thermodynamic formalism to be used by an interdisciplinary scientific community. In this paper, we address all these points and propose a critical review of the published data, advise on the most appropriate apparatus and experimental procedure to measure this type of physical-chemical data in ionic liquids as well as the way to treat the information obtained by an appropriate thermodynamic formalism.

On the scaling behavior of electric conductivity in [C4mim][NTf2].

In this work we examine, for the first time, the molar conductivity behavior of the deeply supercooled room temperature ionic liquid [C4mim][NTf2] in the temperature, pressure and volume thermodynamic space in terms of density scaling (TV(γ))(-1) combined with the equation of state (EOS). The exponent γσ determined from the Avramov model analysis is compared with the coefficient obtained from the viscosity studies carried out at moderate temperatures. Therefore, the experimental results presented herein provide the answer to the long-standing question regarding the validity of thermodynamic scaling of ionic liquids over a wide temperature range, i.e. from the normal liquid state to the glass transition point. Finally, we investigate the relationship between the dynamic and thermodynamic properties of [C4mim][NTf2] represented by scaling exponent γ and Grüneisen constant γG, respectively.

Long-range and targeted ectopic recombination between the two homeologous chromosomes 11 and 12 in Oryza species.

Whole genome duplication (WGD) and subsequent evolution of gene pairs have been shown to have shaped the present day genomes of most, if not all, plants and to have played an essential role in the evolution of many eukaryotic genomes. Analysis of the rice (Oryza sativa ssp. japonica) genome sequence suggested an ancestral WGD ∼50-70 Ma common to all cereals and a segmental duplication between chromosomes 11 and 12 as recently as 5 Ma. More recent studies based on coding sequences have demonstrated that gene conversion is responsible for the high sequence conservation which suggested such a recent duplication. We previously showed that gene conversion has been a recurrent process throughout the Oryza genus and in closely related species and that orthologous duplicated regions are also highly conserved in other cereal genomes. We have extended these studies to compare megabase regions of genomic (coding and noncoding) sequences between two cultivated (O. sativa, Oryza glaberrima) and one wild (Oryza brachyantha) rice species using a novel approach of topological incongruency. The high levels of intraspecies conservation of both gene and nongene sequences, particularly in O. brachyantha, indicate long-range conversion events less than 4 Ma in all three species. These observations demonstrate megabase-scale conversion initiated within a highly rearranged region located at ∼2.1 Mb from the chromosome termini and emphasize the importance of gene conversion in cereal genome evolution.

Evolutionary dynamics of Waxy and the origin of hexaploid Spartina species (Poaceae).

We investigated the evolutionary dynamics of duplicated copies of the granule-bound starch synthase I gene (GBSSI or Waxy) within polyploid Spartina species. Molecular cloning, sequencing, and phylogenetic analyses revealed incongruences between the expected species phylogeny and the inferred gene trees. Some genes within species were more divergent than expected from ploidy level alone, suggesting the existence of paralogous sets of Waxy loci in Spartina. Phylogenetic analyses indicate that this paralogy originated from a duplication that occurred prior to the divergence of Spartina from other Chloridoideae. Gene tree topologies revealed three divergent homoeologous sequences in the hexaploid S. alterniflora that are consistent with the proposal of an allopolyploid origin of the hexaploid clade. Waxy sequences differ in insertion-deletion events in introns, which may be used to diagnose gene copies. Both paralogous and homoeologous coding regions appear to evolving under selective constraints.

[Imported malaria: prevention should strengthened]. / Paludisme d'importation: il faut renforcer le message de prévention.

INTRODUCTION: The risk of acquiring malaria infection can largely be prevented by the regular use of chemoprophylactic drugs combined with protective measures against mosquito bites. In a retrospective study we had for aim to evaluate the compliance to malaria chemoprophylaxis in patients presenting with malaria infection. METHODS: We analyzed the compliance to the recommended malaria chemoprophylaxis of French travelers hospitalized in a department of infectious diseases because of malaria infection, between January 1999 and December 2003. RESULTS: Eighty-five patients, with a mean age of 34.1 years (16-65) were treated for malaria infection. Seventy-seven were due to Plasmodium falciparum. The outcome was favorable for all patients, despite four severe accesses. Forty-six patients (54%) did not take any chemoprophylaxis (CP), 19 (22%) had an inadequate CP for the risk, 13 (15%) badly complied with intermittent intake of CP and seven (8%) complied well with the recommended malaria CP. Among the 85 patients, 27 (32%) had come to the travelers' consultation and been given recommendations and a recommended malaria CP prescription before traveling. CONCLUSION: These results confirm that the majority of imported malaria cases is a consequence of bad compliance to CP. Understanding user profiles and factors predicting non-compliance may help us to improve pretravel counseling, thereby reducing the risk for travelers to acquire malaria infection.

Effect of matrix metalloprotease inhibitors on the 95 kDa metallopeptidase of Candida albicans.

A 95 kDa metallopeptidase of Candida albicans could be involved in the process of dissemination of the yeast. Matrix metalloproteases (MMPs) are also responsible for collagen breakdown in inflammatory and malignant processes. We tested six compounds on the C. albicans enzyme. Doxycycline, gentamicin, cefalothin, galardin, and elaidic and oleic acids are known for their capacity to inhibit some MMPs. Amongst these agents, only oleic acid was able to markedly inhibit the purified metallopeptidase at very low concentrations. Moreover, this fatty acid inhibited the secretion of the enzyme in the culture medium without altering the yeast viability.

Influence of sub-inhibitory concentrations of conventional antifungals on metabolism of Candida albicans and on its adherence to polystyrene and extracellular matrix proteins.

Five antifungal agents with different mechanisms of action were compared for their ability to affect mitochondrial dehydrogenase activity and adherence capacity of Candida albicans to polystyrene and extracellular matrix proteins. Only amphotericin B inhibited mitochondrial dehydrogenase activity when the culture medium was supplemented with galactose. 5-Fluorocytosine and terbinafine did not affect this activity, whereas itraconazole and fluconazole improved it. Furthermore, in these experimental conditions, the effect of sub-inhibitory concentrations of antifungals on adherence was dependent on the tested antifungal and the adherence surface: amphotericin B inhibited adherence to polystyrene and fibrinogen, but improved adherence to extracellular matrix. For all surfaces tested, when culture medium was supplemented with galactose, fluorocytosine did not affect adherence, and itraconazole, fluconazole and terbinafine inhibited adherence. Our results also confirmed the influence of the carbohydrates: sub-minimum inhibitory concentrations (MIC) of itraconazole increased or did not modify the mitochondrial metabolism of yeasts when the culture medium was supplemented with galactose, but this antifungal always decreased mitochondrial metabolism when the culture medium was supplemented with glucose. These data indicate that antifungals used below their MIC values can have various effects. It is important to distinguish the effects of antifungals on the metabolism of C. albicans from effects on its adherence capacity. The former effects are linked to the viability of the yeast and the latter depends on the colonization of cellular as opposed to inert surfaces.

Quantitative trait loci for resistance against Yellow rust in two wheat-derived recombinant inbred line populations.

Yellow rust, which is a major disease in areas where cool temperatures prevail, can strongly influence grain yield. To control this disease, breeders have extensively used major specific resistance genes. Unfortunately this kind of resistance is rapidly lost due to pathogen adaptation. More-durable resistance against yellow rust can be achieved using quantitative resistance derived from cultivars with well-established durable resistance. The winter wheat Camp Remy has maintained a high level of resistance for over 20 years. In order to map quantitative trait loci (QTLs) for durable yellow rust resistance, we analysed a set of 98 F(8) recombinant inbred (RI) lines derived from the cross Camp RemyxMichigan Amber. We also mapped QTLs for adult resistance to yellow rust using the International Triticae Mapping Initiative RI population (114 lines derived from the cross Opata85xsynthetic hexaploid). Two and five QTLs, respectively, were identified from these two populations. This work has highlighted the importance of the centromeric region of chromosome 2B and the telomeric regions of chromosomes 2AL and 7DS in durable yellow rust resistance. The same chromosomal regions are also implicated in resistance to other pathogens.

Imported Plasmodium vivax malaria in France: geographical origin and report of an atypical case acquired in Central or Western Africa.

A total of 73 cases of Plasmodium vivax infections acquired in Western or Central Africa were diagnosed on microscopical criteria in French travellers from 1995 to 1998. We report a case of P. vivax infection in a non immune traveller confirmed by polymerase chain reaction and presenting an atypical P. ovale morphology. The infection was acquired in Western or Central Africa. These microscopical observations, together with the molecular evidence for P. vivax in Western and Central Africa suggest that P. vivax is transmitted in this area despite lacking the Duffy receptor in autochthonous population.

Wheat transformation with glutenin gene.

The rheological properties of wheat grains are associated with the composition of the starchy endosperm in high molecular weight (HMW) glutenin proteins. The HMW glutenin 1xDy12 subunit gene was co introduced with the screenable bar and the reporter gus marker genes in the commercial spring wheat Minaret cultivar (cv). The gene of interest and the marker genes were carried by two separated plasmids, the pBS10BH1 and the pAhC25 respectively. Seven days old calli initiated from immature embryos were bombarded by use of the PDS-1000/He device. A number of different bombardment and culture conditions were tested. These parameters were evaluated on the basis of GUS transient expression. Among those a 4 degrees C cold pre-treatment of the spikes before immature embryos were excised, the culture medium incorporating activated charcoal, silver nitrate and glucose yielded higher GUS transient expression rate. The selective agent bialaphos was maintained at various stages during culture from induction of somatic embryogenesis to rooting of regenerated plantlets. 137 bialaphos resistant plants were obtained among which 109 were carried to maturity. Transgenic plants were characterized by PCR, Southern and SDS-PAGE analysis of the glutenin content.

The effects of subcurative doses of chloroquine on Plasmodium vinckei petteri gametocytes and on their infectivity to mosquitoes.

The effects of subcurative doses of chloroquine on rodent and human Plasmodium transmission to the mosquito have been studied by several authors who showed a short-term (12 h) enhancement of gametocyte infectivity by the drug, restricted to chloroquine-resistant strains, and a long term (4-6 days) enhancement of gametocytogenesis of chloroquine-sensitive strains of Plasmodium chabaudi. We investigated both short- and long-term effects of chloroquine on Plasmodium vinckei petteri, a chloroquine-sensitive rodent Plasmodium strain. Chloroquine treatment reduced the index of gametocytogenesis to 73% (5 mg/kg) and 55% (2.5 mg/kg) of controls, on day 6 post-infection (p.i.). The reduction was statistically significant with 5 mg/kg chloroquine. However, the reduction of gametocyte numbers did not affect the transmission capabilities of the strain. Our experiments showed that doses of 1 mg/kg chloroquine had no effect on the oocyst counts, 12 h post-administration to mice. A statistically non-significant 61% reduction of oocyst numbers was observed in mosquitoes fed on mice treated with 5 mg/kg chloroquine. The effect of 5 mg/kg chloroquine administration on the infectivity of gametocytes to mosquitoes fed 1 h post-treatment was also investigated. An overall 41% reduction of oocyst numbers was observed. This immediate effect was statistically significant in 73% of the mice. These results are consistent with the hypothesis that the short-term enhancing effect of chloroquine on transmission is restricted to the drug-resistant strains of Plasmodium.

Toxoplasma gondii: purification and characterization of an immunogenic metallopeptidase.

A Toxoplasma gondii aminopeptidase specific for the fluorogenic substrate L-arginine 7-amino-4-methylcoumarin was identified in cell-free extract. This enzyme was purified by high-performance liquid chromatography using first size exclusion, then anion exchange, followed by a second size exclusion. The purified enzyme exhibited a pl of 4.7 by chromatofocusing and had an apparent molecular weight of 110 kDa, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. The purification factor was 80.9 and the yield was 14%. The optimal activity was at pH 7.4 and was strongly inhibited by EDTA and o-phenanthroline. Antibodies against this T. gondii metallopeptidase were detected by immunoprecipitation and immunoblotting in human sera obtained from patients undergoing toxoplasmosis.

Possible role of catheters in Saccharomyces boulardii fungemia.

Four cases of Saccharomyces boulardii fungemia, a very rare side effect of Saccharomyces boulardii therapy, are reported. The clinical impact of Saccharomyces boulardii infection appeared to be moderate. However, even though organ involvement was never demonstrated, septic shock with no other etiology was observed in one of our patients. All patients had an indwelling vascular catheter. Contamination of the air, environmental surfaces, and hands following the opening of a packet suggests that catheter contamination may have been a source of infection. To prevent catheter contamination it is recommended that packets or capsules of Saccharomyces boulardii be opened with gloves, outside the patient's room.

Case report and review. Onychomycosis due to Candida parapsilosis.

We report a case of onychomycosis with melanonychia due to Candida parapsilosis alone. Candida parapsilosis is now identified in the great majority of candidal onychomycosis, mainly in association with other yeasts. The criteria allowing the distinction between invasion and colonization, the risk factors and the treatment of C. parapsilosis onychomycosis are discussed.