[The morbidity and mortality review meetings in radiotherapy departments: Procedure, implementation and prospects of the "Proust" French national project]. / Revue de morbidité et mortalité en radiothérapie : procédure, implémentation et perspectives du projet national français « Proust ¼.

Radiation-induced acute and late toxicity depends on several parameters. The type, severity and duration of morbidity are mainly related to irradiated volume, total dose and its fractionation and the intrinsic radiosensitivity of the patients. The follow-up of these toxicities is essential. However, unlike many specialties, morbidity and mortality reviews procedures are not developed as part of quality governance programs in radiation therapy departments for the monitoring of toxicity which sometimes hinder the patients' quality of life. One French survey published within the framework of the project entitled Prospective Registration of Morbidity and Mortality, Individual Radiosensitivity and Radiation Technique (Proust), conclude that there was a lack of knowledge of morbidity and mortality reviews and considerable confusion between these reviews and other quality processes without perspective for the local morbidity and mortality reviews development in a large number of the participated centers. In this article, we will discuss the procedure of the "ideal morbidity and mortality reviews" and its implementation through a monocentric experience started in 2015. Thus, the Proust project is a unique opportunity to implement and standardize a national morbidity and mortality reviews implementation in radiation therapy departments by involving the French regions.

[News in gastrointestinal radiotherapy: The esophageal cancer]. / Actualités en radiothérapie digestive : le cancer de l'œsophage.

Esophageal cancers continue to have a poor prognosis, even if this has improved over the past 25 years due to better management. Pre-operative chemotherapy with Paclitaxel-Carboplatin followed by adjuvant immunotherapy with Nivolumab represents a major advance in the management of locally advanced oesophageal cancer. Pre-operatively, chemo-radiotherapy can be performed in combination with FOLFOX or Paclitaxel-Carboplatin. Several trials are currently ongoing to evaluate the benefit of immunotherapy in non-operable cancers. In contrast, dose escalation in locally advanced non-operable tumors and the combination of pre-operative chemo-radiotherapy with trastuzumab have not been shown to be beneficial.

[Radiation-induced sexual toxicity]. / Toxicité sexuelle induite par la radiothérapie.

Oncosexuality has recently become a new supportive care mission. Sexual morbidity is, routinely, underestimated and must be questioned. We report here the most frequent disorders for men and for women, how to prevent them and how to treat them.

Bulk and Surface Electronic Structure of the Dual-Topology Semimetal Pt_{2}HgSe_{3}.

We report high-resolution angle-resolved photoemission measurements on single crystals of Pt_{2}HgSe_{3} grown by high-pressure synthesis. Our data reveal a gapped Dirac nodal line whose (001) projection separates the surface Brillouin zone in topological and trivial areas. In the nontrivial k-space range, we find surface states with multiple saddle points in the dispersion, resulting in two van Hove singularities in the surface density of states. Based on density-functional theory calculations, we identify these surface states as signatures of a topological crystalline state, which coexists with a weak topological phase.

In situ strain tuning of the metal-insulator-transition of Ca2RuO4 in angle-resolved photoemission experiments.

Pressure plays a key role in the study of quantum materials. Its application in angle resolved photoemission (ARPES) studies, however, has so far been limited. Here, we report the evolution of the k-space electronic structure of bulk Ca2RuO4, lightly doped with Pr, under uniaxial strain. Using ultrathin plate-like crystals, we achieve uniaxial strain levels up to -4.1%, sufficient to suppress the insulating Mott phase and access the previously unexplored electronic structure of the metallic state at low temperature. ARPES experiments performed while tuning the uniaxial strain reveal that metallicity emerges from a marked redistribution of charge within the Ru t2g shell, accompanied by a sudden collapse of the spectral weight in the lower Hubbard band and the emergence of a well-defined Fermi surface which is devoid of pseudogaps. Our results highlight the profound roles of lattice energetics and of the multiorbital nature of Ca2RuO4 in this archetypal Mott transition and open new perspectives for spectroscopic measurements.

[The lung microbiota. Review]. / Le microbiote pulmonaire.

In the last 20years, culture-independent DNA-based techniques ("shotgun sequencing") demonstrated that complex microbial communities reside on most epithelial surfaces, including the lower airways. Until the amniotic sac ruptures, a fetus is considered to be essentially sterile. Many factors affect the composition of the lung microbiota: inheritance, mode of delivery, diet, and age-related changes in adults. It interacts with the digestive and oropharyngeal microbiotas. Animal models show that these interactions play a role in innate pulmonary immunity and modulation of the inflammatory response. The microbial composition of the airway microbiota differs between healthy children and those with chronic lung disease. The advances in the comprehension of microbiome changes have resulted in new approaches concerning the microbiota for treatment and prevention of disease.

Functionalized cationic [4]helicenes with unique tuning of absorption, fluorescence and chiroptical properties up to the far-red range.

Unprecedented regioselective post-functionalization of racemic and enantiopure cationic diaza [4]helicenes is afforded. The peripheral auxochrome substituents allow a general tuning of the electrochemical, photophysical and chiroptical properties of the helical dyes (26 examples). For instance, electronic absorption and circular dichroism are modulated from the orange to near-infrared spectral range (575-750 nm), fluorescence quantum efficiency is enhanced up to 0.55 (631 nm) and circularly polarized luminescence is recorded in the red (|glum| ∼ 10-3).

Diagnosis of an uncommon case of myocarditis by cardiac magnetic resonance imaging: ventricular tachycardia caused by inflammatory left ventricular microaneurysms.

Cardiac magnetic resonance imaging (CMRI) has recently proved to be a powerful tool in the diagnosis of myocarditis. We report a case of myocarditis diagnosed with CMRI in a rare setting: An episode of ventricular tachycardia (VT) arising from the left ventricle associated with a unique ventricular microaneurysm in a patient free of coronary disease. Because of this benign feature, the patient was discharged with antiarrhythmics with no further investigation. A 9-month follow-up revealed no VT recurrence. This case demonstrates the importance of CMRI in patients suffering from apparently idiopathic VT originating in the left ventricle.

[Tako-Tsubo syndrome after anaphylaxis caused by succinylcholine during general anaesthesia]. / Un syndrome de Tako-Tsubo secondaire à un choc anaphylactique à la succinylcholine lors d'une anesthésie générale.

The Tako-Tsubo syndrome (or transient left ventricular apical balloning) is a new clinical entity, very similar to acute myocardial infarction, but different by its excellent short-term prognosis. It has been reported after a physical or an emotional stress, and it is diagnosed by a coronary angiogram and a left ventriculography. We report here a case of Tako-Tsubo syndrome related to an anaphylactic shock caused by succinylcholine during general anaesthesia of a female patient, wearing an unadjustable gastric band.

Arterial stiffness is associated with left atrial size in hypertensive patients.

BACKGROUND: Arterial stiffness is a strong predictor of cardiovascular events and particularly of stroke. A likely explanation is the development of atherosclerotic lesions at the carotid level, favored by increased local stiffness. Another possibility involves cardiac consequences of aortic stiffness and particularly left atrial dilatation with its subsequent risk of atrial fibrillation (AF) and cerebral embolism. AIMS: The present study investigated the link between arterial stiffness, pulse pressure and left atrial size, a determinant of AF risk. METHODS: Arterial stiffness was determined from pulse wave velocity (PWV) and pulse pressure (PP). Left atrial size was also measured. Several potential confounders were taken into account including indices of ventricular remodeling and diastolic function (estimated by NT-Pro brain natriuretic peptide (NT-proBNP) levels). RESULTS: Three-hundred and ten hypertensive patients, aged 53 +/- 13 years, were included. Mean 24-h blood pressure (BP) was 154 +/- 20 over 93 +/- 13 mmHg. Significant relationships were found between left atrial diameter (LAD) and PWV (r=0.27, P<0.001) and between LAD and 24-h PP (r=0.32, P<0.001). LAD was also correlated significantly, although not always tightly, with left ventricular dimensions, geometry and NT-proBNP. In two different multivariate models, LAD remained significantly correlated with PWV or with 24-h PP, independently of classical determinants like age, gender, body mass index, ventricular remodeling (i.e. dimensions and geometry) and filling pressure. CONCLUSION: These results led us to propose AF as a new possible pathophysiological link between arterial stiffness and stroke. These results also emphasize the cardiac consequences of arterial stiffness which can fuel a new approach to AF prevention.

Using X-ray absorption spectra to monitor specific radiation damage to anomalously scattering atoms in macromolecular crystallography.

Radiation damage in macromolecular crystals is not suppressed even at 90 K. This is particularly true for covalent bonds involving an anomalous scatterer (such as bromine) at the 'peak wavelength'. It is shown that a series of absorption spectra recorded on a brominated RNA faithfully monitor the extent of cleavage. The continuous spectral changes during irradiation preserve an 'isosbestic point', each spectrum being a linear combination of 'zero' and 'infinite' dose spectra. This easily yields a good estimate of the partial occupancy of bromine at any intermediate dose. The considerable effect on the near-edge features in the spectra of the crystal orientation versus the beam polarization has also been examined and found to be in good agreement with a previous study. Any significant influence of the (C-Br bond/beam polarization) angle on the cleavage kinetics of bromine was also searched for, but was not detected. These results will be useful for standard SAD/MAD experiments and for the emerging 'radiation-damage-induced phasing' method exploiting both the anomalous signal of an anomalous scatterer and the 'isomorphous' signal resulting from its cleavage.

[Subacute infectious endocarditis due to the agent of cat scratch fever: Bartonella henselae]. / Endocardite infectieuse subaiguë due à l'agent de la maladie des griffes du chat: Bartonella henselae.

The diagnosis of severe mitral stenosis with left atrial thrombus was rectified at valvular replacement in a 48-year old immuno-competent man who was a cat owner. The mass in the left atrium was, in fact, a large endocarditic vegetation. Pre- and postoperative blood cultures were negative as was culture of the excised mitral valve. The diagnosis of infectious endocarditis (IE) due to Bartonella Henselae was made from a positive serological test (1600) and identification of the germ by genetic amplification. Antibiotic therapy was continued for 6 months and the patient was cured with a follow-up of 4 years. Bartonella Henselae IE is very rare (14 reported cases) and affects mainly the aortic valve, often giving rise to very large vegetations which, in half the cases, are complicated by systemic emboli. Germs like Batonella are sensitive to most antibiotics, especially the aminosides and macrolides. In Bartonella Henselae IE, valve replacement is the rule (13 out of 14 cases) and the prognosis is usually good. Sero-diagnosis of Bartonellosis should be part of the systematic investigation of all blood culture negative IE.

An insulinoma nuclear factor binding to GGGCCC motifs in human insulin gene.

Cell specific expression of the insulin gene is achieved through transcriptional mechanisms operating on 5' flanking DNA elements. In the enhancer of rat I insulin gene, two elements, the Nir and Far boxes, located at positions -104 and -233 respectively and containing the same octameric motif are essential for B cell specific transcription activity. Homologous sequences are present in the human insulin gene. While studying the binding of nuclear proteins from insulinoma cells to the -258/+241 region of the human insulin gene, we observed a previously undetected protein binding site in the intron I region between nucleotides +160 and +175. The binding activity was present in insulin producing cells such as RIN and HIT insulinoma cells but not in fibroblasts or insulin negative fibroblast x RIN hybrid cells. DNAse I footprinting and gel retardation/methylation interference experiments allowed us to define the core binding site of the intron binding factor as a GGGCCC hexamer. This factor is also capable to bind to a related sequence, contiguous to the Far-like element in rat and human insulin genes. The binding of the GGGCCC binding factor in this critical region of the insulin gene enhancer may participate in the regulation of insulin gene expression.

[Angiosarcoma of the breast. Apropos of 4 cases with a review of the literature]. / L'angiosarcome du sein. A propos de quatre cas avec revue de la littérature.

Four cases of angiosarcoma of the breast were treated at Centre Léon-Bérard in Lyon. It is a rare malignant vascular tumor, constituting < 1% of all primary breast lesions. Radical local surgery is the treatment of choice; however, local recurrences and metastases are frequently observed. The 3-year disease-free survival rate is < 15%. The role of irradiation and adjuvant chemotherapy remains to be evaluated. Doxorubicin-ifosfamide-GM CSD gave a positive response in one case with metastases.

Extinction of the human insulin gene expression in insulinoma x fibroblast somatic cell hybrids involves cis-acting DNA elements.

Insulin gene expression in rat insulinoma (RIN) cells is extinct in RIN x fibroblast hybrids and can reappear upon loss of DNA contributed by the fibroblast parent. (Besnard et al., Exp. Cell Res. 185:101-108, 1989). In the present study, we looked for the role of 5'-flanking sequences of the human insulin gene in the negative control observed in the hybrids. RIN cells were transformed with composite genes which consisted of the coding sequence of the gpt gene placed under the control of 5'-flanking regions of the human insulin gene (Ins.gpt gene). Upon hybridization of these cells with mouse fibroblasts, the expression of both Ins.gpt and endogenous rat insulin genes were suppressed together. The results obtained indicate that cis-acting DNA elements are involved in the negative control of the gene. These elements are located in a fragment spread from -258 to +241 of the transcription origin of the human insulin gene.

Reversible extinction of insulin gene expression in insulinoma x fibroblast somatic cell hybrids.

To investigate for the presence of regulator(s) repressing the expression of insulin gene in cells other than pancreatic beta cells, rat insulinoma (RIN) cells secreting insulin were hybridized with fibroblasts from various species. In RIN x L mouse fibroblast hybrids, which maintained most of the parental chromosomes, no insulin transcripts were detected. In three RIN x Indian muntjac fibroblast hybrids and one RIN x human fibroblast hybrid which had lost DNA from the fibroblast parent through subculture, expression of the insulin gene was first extinguished and then reexpressed. This suggests that negative regulator(s), present in fibroblasts, can turn off insulin gene expression in RIN x fibroblast hybrids as long as the gene(s) contributed by the fibroblast are maintained.

A mouse minialbumin gene is specifically expressed in differentiated hepatoma cells but not in transgenic mice.

A mouse genomic DNA fragment including the albumin gene in which central exons 9-12 had been deleted and flanked by 2.2 kb in 5' and 4.3 kb in 3' (minialbumin gene), was introduced into rat hepatoma cells and also into mouse embryos to produce transgenic mice. The minialbumin gene was specifically transcribed in stably transfected differentiated clones and a 47-k Da minialbumin was synthesized and secreted into the culture medium. In contrast, the transgene was not expressed in any of the seven independent transgenic mouse lines examined. This suggests that expression of the albumin gene in developing animals requires cis-regulating elements additional to those located within the immediate flanking regions of the gene, which are sufficient to elicit specific expression in differentiated hepatoma cells in culture.

Selection against expression of the Escherichia coli gene gpt in hprt+ mouse teratocarcinoma and hybrid cells.

Thioxanthine is toxic for mammalian cells transformed by the dominant selectable marker gpt. It allowed us to select, in the presence of the endogenous hypoxanthine-guanine phosphoribosyltransferase gene, mutants that did not express gpt any more and also hybrid cells that had lost the chromosome carrying it. The gpt marker is thus dominant in negative as well as in positive selection, which makes it potentially very useful for genetic studies of mammalian cells.

Expression of the human beta-globin gene in mouse teratocarcinoma cells.

We have stably transformed PCC4 and F9 teratocarcinoma stem cells with the human beta-globin gene. The transformed PCC4 cells retained their ability to produce in host mice tumours containing various differentiated tissues. Three of the five clones examined had human beta-globin transcripts, with correct 5' termini; however, some transcripts were also initiated upstream from the natural cap site in two of the three clones. The expression of the human beta-globin gene was maintained when the stem cell phenotype was changed, either into endodermal cell type by retinoic acid treatment of the F9 clones, or into fibroblastic cell type by cell hybridization of transformed PCC4 cells with L fibroblasts. Thus, the human beta-globin gene introduced into early embryonic cells can be expressed constitutively and its expression is maintained when the pattern of gene expression in the cells is changed.