[Definition and evaluation of a multidisciplinary patient's pharmacotherapy management method: The pharmaceutical care plan]. / Définition et évaluation d'une méthodologie interprofessionnelle d'optimisation de la pharmacothérapie des patients : le Plan de Médication Partagé.

The implementation of pharmaceutical monitoring as defined by the Council of Europe in its Resolution of March 2020 requires defining for each patient, objectives and a treatment plan, to share, monitor and update them in a manner coordinated, interprofessional and in partnership with the patient. It recognizes the central place of the pharmacist by encompassing all of its clinical pharmacy activities and emphasizes the need for interprofessional collaboration (Hepler CD, Strand LM. Opportunities and Responsibilities in Pharmaceutical Care. American Journal of Hospital Pharmacy. Mars 1990; 47(3): 533-543). This work first presents the pharmaceutical care plan as a multiprofessional methodology that meets the objectives of pharmaceutical monitoring, then in a second step its evaluation through two regional projects. The pharmaceutical care plan unites, around the patient, all the actors involved in their pharmacotherapy, throughout their care path. It makes it possible to control the iatrogenic drug risk and includes the patient's drug management with regard to curative, preventive and palliative objectives and in a global strategy for the care and promotion of patient health. This methodology is integrated into coordinated exercise strategies and care pathway approaches. Several levers will help support its deployment, such as inter-professional education and digital health tools.

A genome-wide association study identifies novel gene associations with facial skin wrinkling and mole count in Latin Americans.

BACKGROUND: Genome-wide association studies (GWASs) have identified genes influencing skin ageing and mole count in Europeans, but little is known about the relevance of these (or other genes) in non-Europeans. OBJECTIVES: To conduct a GWAS for facial skin ageing and mole count in adults < 40 years old, of mixed European, Native American and African ancestry, recruited in Latin America. METHODS: Skin ageing and mole count scores were obtained from facial photographs of over 6000 individuals. After quality control checks, three wrinkling traits and mole count were retained for genetic analyses. DNA samples were genotyped with Illumina's HumanOmniExpress chip. Association testing was performed on around 8 703 729 single-nucleotide polymorphisms (SNPs) across the autosomal genome. RESULTS: Genome-wide significant association was observed at four genome regions: two were associated with wrinkling (in 1p13·3 and 21q21·2), one with mole count (in 1q32·3) and one with both wrinkling and mole count (in 5p13·2). Associated SNPs in 5p13·2 and in 1p13·3 are intronic within SLC45A2 and VAV3, respectively, while SNPs in 1q32·3 are near the SLC30A1 gene, and those in 21q21·2 occur in a gene desert. Analyses of SNPs in IRF4 and MC1R are consistent with a role of these genes in skin ageing. CONCLUSIONS: We replicate the association of wrinkling with variants in SLC45A2, IRF4 and MC1R reported in Europeans. We identify VAV3 and SLC30A1 as two novel candidate genes impacting on wrinkling and mole count, respectively. We provide the first evidence that SLC45A2 influences mole count, in addition to variants in this gene affecting melanoma risk in Europeans.

SLX4 interacts with RTEL1 to prevent transcription-mediated DNA replication perturbations.

The SLX4 tumor suppressor is a scaffold that plays a pivotal role in several aspects of genome protection, including homologous recombination, interstrand DNA crosslink repair and the maintenance of common fragile sites and telomeres. Here, we unravel an unexpected direct interaction between SLX4 and the DNA helicase RTEL1, which, until now, were viewed as having independent and antagonistic functions. We identify cancer and Hoyeraal-Hreidarsson syndrome-associated mutations in SLX4 and RTEL1, respectively, that abolish SLX4-RTEL1 complex formation. We show that both proteins are recruited to nascent DNA, tightly co-localize with active RNA pol II, and that SLX4, in complex with RTEL1, promotes FANCD2/RNA pol II co-localization. Importantly, disrupting the SLX4-RTEL1 interaction leads to DNA replication defects in unstressed cells, which are rescued by inhibiting transcription. Our data demonstrate that SLX4 and RTEL1 interact to prevent replication-transcription conflicts and provide evidence that this is independent of the nuclease scaffold function of SLX4.

[Distinctive tabard: A solution to avoid work interruptions in the blood transfusion?] / Gilet distinctif : une solution pour éviter les interruptions de tâche dans le domaine transfusionnel ?

AIM: In the blood transfusion, the interruption of work (IW) can lead to serious incidents and/or adverse effects. The aim of our work is to evaluate the wearing of a distinctive tabard in the IW. METHODS: Several voluntary departments from 5 establishments of health in the Center-Val de Loire region have participated in this work from October to December 2017. The survey was given to nurses (identified by the first three letters of the first name) before and after wearing the tabard (for 2 months) for all transfusions realized in their respective department. We matched the survey by nurse and by department. The Student t test was conducted to evaluate the contribution of the tabard during IW. RESULTS: One hundred and one survey (31 in surgery, 70 in medicine) were collected before wearing and 91 (27 in surgery, 64 in medicine) after wearing the tabard. Before wearing the tabard, the number of nurse having or not IW was the same. After wearing the tabard, 42% had an IW and 58% didn't had IW (P=0.43; χ2). Sixty-four surveys were matched (27 exclusions : different IDEs) according to IW before and after wearing the tabard. The wearing of the tabard allows a statistically significant decrease IW (z=2.61, P=0.009, student test). CONCLUSION: Wearing the tabard during blood transfusions is statistically significant means of reducing IW. It's probably a first solution to increase the security of the act, to which must be added other means (poster, phone management, poster and information campaign). It's easier to eliminate IW than to manage.

Possible role of disturbed Na+ homeostasis in mouse vas deferens contractile hyperreactivity after immunological sensitization.

In the present study we have investigated the involvement of sensitized mice immunoglobulins and some electrophysiological alterations that participate to the antigenic sensitization-induced hyperreactivity of isolated mouse vas deferens. Active sensitization was performed by subcutaneous injection of egg albumen. Contractile responses to noradrenaline were isometrically recorded in the isolated vas deferens. Low external Na(+)-induced contractions and rapid cooling contractures were evaluated. Resting membrane potential (Er) and intracellular Na activity were measured in control and actively sensitized vas deferens by using conventional KCl-filled and Na(+)-sensitive microelectrodes respectively. Active sensitization-induced hyperreactivity to noradrenaline was reproduced by in vitro passive sensitization of control vas deferens with sensitized mice immunoglobulins. The inhibition of the nitric oxide synthesis by N-nitro-L-arginine methyl ester (L-NAME) did not change control vas deferens reactivity in vitro to noradrenaline and acetylcholine. Rapid cooling contractures, performed after lowering external Na+ concentration, were not altered by active sensitization. However, sensitization increased significantly the strength of the low external Na+-induced contractions. In control vas deferens Er was a mean of -49.2+/-0.3 mV (mean+/-SEM). Sensitization resulted in reduction of Er by 14 mV. In sensitized preparations, relative insensitivity of Er to ouabain, external K+ removal and cooling were observed. The intracellular Na+ activity was increased by about 40% in sensitized vas deferens. It is concluded that sensitization-induced hyperreactivity is mediated by immunoglobulins and produced smooth muscle cells depolarisation. The low Er of sensitized muscle may be partly the result of an increase in membrane permeability to Na+ which could interfere with intracellular Ca2+ homeostasis.

Effect of moderate cooling on contractile responses in mouse vas deferens and its relation to calcium.

Isolated mouse vas deferens preparations were used to study the effect of temperature on noradrenaline-induced contractions. Preparations were suspended in the organ bath containing Krebs-Henseleit solution for isometric tension recording. Contractile responses to noradrenaline were investigated in the mouse vas deferens after moderate cooling from 37 to 26 or 22 degrees C. A significant increase of the phasic contractions to noradrenaline was observed at 26 or 22 degrees C compared with responses obtained at 37 degrees C (about 12.3 and 35.6% increase at 26 and 22 degrees C, respectively). The secondary noradrenaline-induced sustained contraction was also significantly enhanced after moderate cooling to 26 degrees C. The potentiation of noradrenaline-induced contraction at 26 degrees C remained in a Ca(2+)-free EGTA (1 mM)-containing solution. However, sustained contraction was suppressed after removal of the calcium from the medium at 37 and 26 degrees C. Contraction to caffeine was significantly enhanced at 22 degrees C compared with 37 degrees C. By contrast, barium chloride-induced contraction of the vas deferens was markedly decreased after moderate cooling to 22 degrees C. In the presence of ouabain (0.1 mM), the noradrenaline-induced peak contraction was significantly increased at 37 degrees C. However, potentiation of the noradrenaline response at 22 degrees C was unaffected by the Na+/K+ pump inhibitor. Noradrenaline-induced peak contractions were depressed in the presence of vanadate (1 mM) and cyclopiazonic acid (10 microM), two Ca(2+)-ATPase inhibitors, at 37 degrees C and also at 22 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)