Urologists have a duty to think about occupational urinary cancers.

More than 11% of employees are exposed to carcinogens in the usual course of their work. The benefits of recognition as an occupational disease (OD) allow victims of work firstly to benefit from a disability compensation. But there are collective challenges. It is important to understand that accidents at work and recognised OD are not financially covered by health insurance, which is financed by everyone, but by a specific branch, known as "professional risks/occupational risks", financed by employers alone. Being recognised as having an OD modifies the benefits: 100% coverage of all the costs inherent to the OD, including transport costs, increase of daily allowances, payment of a pension (or of a lump sum if the Permanent Incapacity rate is<10%). A survivor's pension may be paid to the beneficiaries in the event of the patient's death. OD "is presumed to be of occupational origin: any disease designated in a table of OD and contracted under the conditions set out in this table". Although the declaration of OD must be made by the victim (or his dependents) to the national health insurance fund, it can only exist on condition that a doctor has drawn up a descriptive Initial Medical Certificate (IMC), taking care to use the exact terms of the tables (15 ter and 16 bis) and the professional/occupational origin.

Intertwined Analytical, Experimental and Theoretical Studies on the Formation and Structure of a Copper Dienolate.

The reaction of a silyl dienolate, a Cu(II) salt and TBAT yielding the corresponding copper dienolate is addressed. A combined NMR and cyclic voltammetry analysis first highlight the role of TBAT in the Cu(II) to Cu(I) reduction and the structure of the precatalytic species. From these first results a second set of NMR and theoretical studies enable the determination of the structure and the mechanism of formation of the copper dienolate catalytic species. Finally, we showed that that the copper catalyst promote the E/Z s-cis/s-trans equilibration of the silyl dienolate precursor through a copper dienolate intermediate. All of these results unveil some peculiarities of the catalytic and asymmetric vinylogous Mukaiyama reaction.

Accurate measurement of effective Li-Li scalar coupling constants: the NMR missing link for alkyllithium aggregates.

Scalar coupling in organolithium systems can provide access to useful structural and dynamic informations. In this work, we propose a robust method for the accurate measurement of the effective 2JLi-Li coupling constant in tetramerics alkyllithium aggregates. This crucial information, unavalaible to date, gives a simple access to various structural factors, including the dynamics, solvation and the operative steric hindrance of alkyl chains.

Neonatal Mass Urine Screening Approach for Early Detection of Mucopolysaccharidoses by UPLC-MS/MS.

Mucopolysaccharidoses (MPSs) are lysosomal storage disorders caused by deficiencies of enzymes involved in the catabolism of glycosaminoglycans (GAGs). Various treatments such as enzyme replacement therapy and/or hematopoietic stem cell transplant are available for MPSs. Early initiation of treatment improves the outcome and delays the onset of symptoms, highlighting the need for newborn screening for MPSs. The main objective of this project was to devise and validate a multiplex urine filter paper method for GAG analysis using a tandem mass spectrometry (MS/MS) approach to screen newborns for MPSs. Eluted urine samples from 21-day-old newborns were evaporated and a methanolysis reaction was performed. Samples were resuspended and analyzed using a UPLC-MS/MS system. A one-minute chromatographic method allowed the absolute quantification of heparan sulfate (HS), dermatan sulfate (DS), and creatinine. Method validation revealed high precision (< 9% relative standard deviation) and accuracy (< 7% bias) for all analytes. The reference values normalized to creatinine obtained by the analysis of five hundred 21-day-old newborn urine samples were 34.6 +/-6.2 mg/mmol of creatinine and 17.3 +/-3.9 mg/mmol of creatinine for HS and DS, respectively. We present a rapid and efficient method for populational newborn urine screening using MS/MS, which could also be applied to high-risk screening.

Total synthesis of spiromastilactone A.

The total synthesis of spiromastilactone A is reported for the first time. A swift strategy is presented that involves a pivotal enantioselective nucleophilic 1,2-alkylation of an aldehyde prepared in four quantitative synthetic steps from commercial 2,4-dihydroxybenzoic acid. This key reaction, which was described very recently by our group and carried out here on a gram scale, involves cheap and easily accessible tricoordinated chiral lithium amido zincates. The resulting enantioenriched secondary alcohol is involved afterward in an efficient intramolecular cyclization providing the phthalide core of the target, and two quantitative additional steps aiming to deprotect the phenol groups then introduce chlorine atoms end the synthetic scheme. Spiromastilactone A is obtained in 44% overall yield in eight synthetic steps, among which six are quantitative, and the 89 : 11 enantiomeric ratio (78% ee value) is in favor of the right enantiomer (R configuration).

Chiral Lithium Amido Aryl Zincates: Simple and Efficient Chemo- and Enantio-Selective Aryl Transfer Reagents.

An enantioselective aryl transfer is promoted using chiral tricoordinated lithium amido aryl zincates that are easily accessible reagents and whose chiral appendage is simply recovered for reuse. The arylation reaction is run in good yields (60 % average on twenty substrates) and high enantiomeric excesses (95 % ee average). This occurs whatever the ortho, meta, or para substituent borne by the substrate and a complete chemoselectivity is observed with respect to the aldehyde function. Sensitive groups such as nitriles, esters, ketones, and enolisable substrates resist to the action of the ate reagent, warranting a large scope to this methodology.

Access to Anti or Syn 2-Amino-1,3-diol Scaffolds from a Common Decarboxylative Aldol Adduct.

A straightforward synthetic pathway allowing the access to anti or syn 2-amino-1,3-diol scaffolds is presented. The strategy relies on a diastereoselective organocatalyzed decarboxylative aldol reaction of a N-Boc-hemimalonate that is easily formed from commercial N-Boc-diethyl malonate. Although this method has been optimized previously with the N-Bz-hemimalonate analogue, this key step was reinvestigated with the N-Boc derivative to improve the required reaction time, the yield, and the diastereoselectivity. The new conditions enhance this transformation, and quantitative yields and anti/syn ratios up to 96:4 can be obtained. The anti aldol product was easily isolated in pure form and then taken forward as the key precursor in the preparation of both a set of ten N-/O-alkylated anti 2-amino-1,3-diol derivatives and the syn congeners.

Chiral Lithium Amido Zincates for Enantioselective 1,2-Additions: Auto-assembling Reagents Involving a Fully Recyclable Ligand.

A methodology consisting in carrying out enantioselective nucleophilic 1,2-additions (ee values up to 97 %) from cheap, easily accessible, and never described before, chiral lithium amido zincates is presented. These multicomponent reactants auto-assemble when mixing, in a 1:1 ratio, a homoleptic diorganozinc (R2 Zn) with a chiral lithium amide (CLA). The latter, obtained after a single reductive amination, plays the role of the chiral inductor and is fully recoverable thanks to a simple acid-base wash, allowing being recycled and re-use without loss of stereochemical information.

Synthesis and Identification of Aryl and Alkyl Gem-Dilithium Phosphido-Boranes: A Boost to the Chemistry of Phosphandiides.

The synthesis and identification of unprecedented gem-dianionic phosphorus compounds, that is, gem-dilithium phosphido-boranes Li2 [RP⋅BH3 ], with R=Ph or Cy, are reported in THF solution. These were obtained by double deprotonation of the corresponding primary phosphine-borane precursors RPH2 ⋅BH3 . Their in-depth structural study, based on multinuclear (1 H, 6 Li, 7 Li, 11 B, 13 C, 31 P) mono- and bi-dimensional NMR analyses, indicates a strong influence of the phosphorus substituent on the structure of the gem-dianionic phosphorus structure; a monomeric arrangement was obtained when R=phenyl, whereas a cyclic oligomer was observed for R=cyclohexyl. These compounds represent a new type of useful reagent, and their access paves the way for the concept of "RP synthons" (i.e., RP2- phosphandiides), likely to be the most flexible precursors of a variety of phosphorus targets.

A Combined 1 H/6 Li†NMR DOSY Strategy Finally Uncovers the Structure of Isopropyllithium in THF.

Despite its common use in synthesis, the structure of isopropylliyhium in THF has never been determined, a dimer being generally proposed but not supported. This paper fills this data gap through a sophisticated NMR study that shows that, in THF at low-temperature, isopropyllithium is in the form of a 1:2 mixture of a trisolvated monomer and a disolvated dimer in equilibrium. The presence of the monomer, never evoked before, together with a hypo-solvation of the dimer hinted by DFT calculations, provides a rational explanation to the remarkable reactivity of this organolithium reagent in ethereal solvents.

Chiral Lithium Amides: Tuning Asymmetric Synthesis on the Basis of Structural Parameters.

An overview on the structural arrangements adopted by Chiral Lithium Amides (CLAs), alone or in mixed complexes, is presented. These species are important reagents for asymmetric synthesis and understanding their organization is essential to improve their design and the reaction conditions.

Direct Carboxylation of Aryl Tosylates by CO2 Catalyzed by In situ-Generated Ni(0).

A novel Ni(0) -catalyzed carboxylation of aryl tosylates with carbon dioxide has been achieved under moderate temperatures and atmospheric pressure. In this procedure, the active Ni(0) species is generated in situ by simply mixing the Ni(0) precatalyst [NiBr2 (bipy)] with an excess of manganese metal. This approach requires neither a glove-box nor the tedious preparation of sophisticated intermediate organometallic derivatives. This mild, convenient, and user-friendly process is successfully applied to the valorization of carbon dioxide and the synthesis of versatile reactants with broad tolerance of substituents.

[Contribution of intervention to research in the context of a serious disease]. / Ce que l’intervention fait à la recherche dans un contexte de maladie grave.

By placing in perspective two ongoing studies based on interventional research dynamics in the field of cancer, this article proposes a review of the specific effects of this type of research. Although this approach is often poorly regarded in the field of academic sociology, it is particularly adapted to the analysis of ongoing processes, providing access to certain phenomena that would be otherwise impossible to observe. The research worker's active involvement, the experience that he/she shares with the subjects studied and the partnerships formed with institutional bodies are the basis for the production of original scientific knowledge, but also sometimes uncomfortable configurations.

A Lithium Amide Protected Against Protonation in the Gas Phase: Unexpected Effect of LiCl.

In cold THF and in the presence of LiCl, a lithium pyrrolidinylamide forms a 1:1 mixed aggregate, which is observed directly by ESI-MS. Gas-phase protonation of this species leads to selective transfer of H(+) to the chlorine, suggesting that LiCl shields the amide nitrogen and prevents its direct protonation.

Probing solvent effects on mixed aggregates associating a chiral lithium amide and n-BuLi by NMR: from structure to reactivity.

An NMR study of a 1 : 1 mixture of a chiral lithium amide (4a) and n-BuLi shows that depending on the solvent employed (Et2O or THF) a mixed aggregate can form in proportions that are directly related to the ees measured during the enantioselective alkylation of o-tolualdehyde by these same species.

First substoichiometric version of the catalytic enantioselective addition of an alkyllithium to an aldehyde.

A substoichiometric enantioselective version of the extremely fast nucleophilic addition of Alk-Li to RCHO is made possible thanks to a thorough analysis of the aggregation phenomena involved in the reaction: calculated quantities of LiCl must be added to the medium at the right time to keep the catalytic cycle running.