[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.

Lessons learned from three avian influenza simulation exercises in the southwest of France.

The Southwest of France raises different species of poultry. These production activities present structural vulnerabilities to severe infectious diseases such as highly pathogenic avian influenza. Indeed, many farms have free-range flocks, multi-age and multi-species productions, while being located near wild bird migratory corridors. These factors may partly explain the H5 virus epidemics that occurred between 2015 and 2021. Their serious economic and technical consequences and psychological impact have generated solidarity, collective learning and operational cohesiveness among all poultry professionals. Consequently, a decision was made to conduct annual simulation exercises for a major health event in order to maintain a high level of vigilance and responsiveness within different poultry sectors. Three exercises took place, in 2017, 2018 and 2019, in semi-real conditions (real dates and compressed time) and according to different scenarios. They took place outside an epidemic context and have in common to focus on the initial phase of the crisis (suspicions, results of preliminary analyzes), which is critical to assess the reactivity of industry personnel in order to mitigate infectious disease spread. The preparation of the simulation exercises was based on a common methodology. They were created by an organizing team and each included up to 60 people (industry personnel, observers and auditors). These simulations highlighted several critical points: poultry professionals have detailed knowledge of the field, but this information can only be effectively obtained and used if there is already a poultry industry decision-making structure in place (with good networking); there is a need (1) for better information sharing within the industry; (2) to develop an assistance structure for producers directly involved in a crisis; and (3) to increase collaboration with State services in peacetime. Finally, several technical issues were raised regarding control zones; blocking poultry movements; production site quarantine; depopulation strategies; self-financing capacity of the poultry industry in the absence of governmental involvement; and enhanced mapping tools with real-time traceability of animal transportation.

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.

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

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

[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.

Loss of nitric oxide release in passively sensitized guinea-pig aorta with purified immunoglobulin G1.

BACKGROUND: Vascular hyperresponsiveness can be reproduced by in vitro passive sensitization of isolated aorta with immunoglobulin G1 (IgG1) taken from ovalbumen-sensitized BFA guinea-pig. OBJECTIVE: The aim of the present work was to investigate the role of nitric oxide in the sensitization-induced alteration of the contractile and relaxant responses of guinea-pig aorta to noradrenaline (NA) and acetylcholine (ACh), respectively. METHODS: Cumulative concentration-response curves to NA or ACh were established before and after IgG1 sensitization and then after successive treatments. RESULTS: IgG1 in vitro passive sensitization of aorta caused a significant hyperreactivity to NA and completely inhibited the relaxation to ACh. After sensitization, the addition of an intact aortic ring (with endothelium) in the organ chamber restored the maximal response to NA and ACh close to control but was ineffective in the presence of hemoglobin. The restoration of the control reactivity to NA was also inhibited in the presence of L-NAME or when the added aortic ring was endothelium-denuded. Moreover, L-arginine, a nitric oxide (NO) precursor, was able to restore the control reactivity to NA. CONCLUSION: The present results show that IgG1 in vitro sensitization induced a loss of NO release from the vascular endothelium. This loss of NO probably plays a great role in vascular hyperreactivity by increasing the contractile response and decreasing the relaxant response to mediators and would be a component of allergic diseases pathogenesis.

Effect of guinea-pig purified immunoglobulin G1 on the responsiveness of tracheal, aortic, vas deferens and ileum smooth muscles.

BACKGROUND: Smooth muscles hyperresponsiveness is a common feature in anaphylaxis and allergic diseases. OBJECTIVE: The aim of the present work was to investigate the effect of in vitro passive sensitization with highly purified immunoglobulin G1 (IgG1) on the responsiveness of tracheal, aortic, vas deferens and ileum smooth muscles. METHODS: Firstly, IgG1, obtained from actively sensitized BFA guinea-pigs, was purified by Protein A-Sepharose column and characterized by enzyme-linked immunosorbent assay (ELISA) and immunoelectrophoresis analysis. Concentration-response curves to spasmogens (acetylcholine for trachea and vas deferens, noradrenaline for aorta and histamine for ileum) were established before and after in vitro passive sensitization with IgG1. RESULTS: Contractile responses and maximal contractions were significantly enhanced after passive sensitization for all the organs. Maximal contractions were significantly increased in the trachea (+46.7%), aorta (+51%), vas deferens (+114.2%) and ileum (+117.2%). At the end of the experiments, the application of the sensitizing antigen induced a significant Schultz-Dale reaction of the smooth muscles. CONCLUSION: The present results show that the in vitro application of purified IgG1 can produce non-specific smooth muscle hyperreactivity and hypersensitivity. So, IgG1 can be considered as the main factor involved in the genesis of sensitization-induced hyperresponsiveness, and probably play a great role in hyperreactivity observed during allergic diseases and anaphylaxis.

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)

Effect of temperature reduction on the vas deferens hyperresponsiveness of sensitized mice.

1. The present study was designed to investigate the effect of active sensitization on the responsiveness of mouse vas deferens before and after moderate cooling. Contractile responses to noradrenaline (NA) were isometrically recorded in the vas deferens of control and ovalbumen-sensitized mice at 37 degrees C and 22 degrees C. 2. Enhancement of the vas deferens reactivity to NA was observed in the sensitized vs control mice at 37 degrees C and 22 degrees C (P < 0.01). In sensitized mice, maximal contraction was significantly increased compared with controls, and sensitization-induced hyperresponsiveness was greater at 22 degrees C compared with 37 degrees C. At 37 degrees C, contractile responses to barium chloride were significantly enhanced in the sensitized mice compared with controls, whereas the reduction of the temperature to 22 degrees C produced a marked inhibition of vas deferens contractions in both groups. Caffeine-induced contractions of the vas deferens were similar in control and sensitized mice at 37 degrees C. After moderate cooling to 22 degrees C, vas deferens from sensitized mice became hyperresponsive compared with controls. 3. Ouabain (0.1 mM) produced an increase of NA-induced contraction in control and sensitized vas deferens at 37 degrees C (P < 0.01). It had no significant effect in the control at 22 degrees C but produced a marked inhibition of NA-induced contraction in the sensitized vas deferens at 22 degrees C. Contractions to NA in the presence of vanadate (1 mM) were depressed in control and sensitized mice at both temperatures. 4. These results suggest that sensitization-induced hyperresponsiveness of the mouse vas deferens is mediated by an increased mobilization of intracellular calcium. The involvement of an unknown ouabain-sensitive pathway in sensitization-induced alterations is also discussed.

Strain-related differences in the tracheal responsiveness of sensitized guinea pig.

The purpose of this study was to evaluate the strain-related differences in tracheal hyperresponsiveness in control and egg albumen-sensitized guinea pigs. Concentration-response curves to acetylcholine and barium chloride were established from tracheal rings of Dunkin-Hartley and BFA strain guinea pigs. In the Dunkin-Hartley strain, sensitization did not significantly increase the tracheal responsiveness to acetylcholine and barium chloride. By contrast, in the BFA strain, significant sensitization-induced hyperreactivity was achieved as the maximal contractions induced by acetylcholine and barium chloride, were enhanced from 6.5 +/- 1.2 and 3.2 +/- 0.4 mN in control to 10.0 +/- 1.4 and 5.6 +/- 0.8 mN, respectively, in sensitized animals. However, antigen challenge, performed in vitro, exhibited a similar amplitude of contraction in tracheal rings from both strains (Dunkin-Hartley 5.1 +/- 0.8 mN; BFA 5.9 +/- 0.5 mN). Finally, while the two guinea-pig strains developed specific sensitization to allergen, only tracheal rings from the BFA strain developed hyperresponsiveness to acetylcholine and barium chloride. The strain-related difference appears to be partly explained by a lower basal reactivity in the BFA strain both acetylcholine (Em 7.3 +/- 1.7 and 6.5 +/- 1.2 mN for Dunkin-Hartley and BFA, respectively) and barium chloride (Em 9.4 +/- 2.6 and 3.2 +/- 0.4 mN for Dunkin-Hartley and BFA, respectively). As the same procedure of sensitization provides different results in the genesis of hyperreactivity between the two guinea-pig strains used for asthma models, the BFA guinea-pig strain seems to be a better model because sensitized non-challenged animals could easily be dissociated from control ones, similar to that which occurs in asthmatic patients during provocation tests with cholinergic drugs.

Enhancement of the responsiveness of vas deferens and ileum smooth muscle in sensitized guinea pigs: in vitro study.

Changes in the reactivity of the ileum (to histamine and barium chloride) and vas deferens (to acetylcholine and barium chloride), isolated from actively egg albumen-sensitized guinea pigs, have been investigated. The study was performed on 2 guinea pig strains: the Dunkin-Hartley strain, usually used as an airway allergic model, and the BFA strain. In actively sensitized guinea pigs of both strains, concentration-response curves exhibited a significant dose-dependent upward shift compared to those obtained in control guinea pigs. The maximal contraction strength calculated from these curves was significantly enhanced in both sensitized guinea pig strains, without a change in EC50 values. This study showed that the active antigen sensitization procedure involved several smooth muscle functions, and not exclusively the trachea.

Effect of temperature reduction on the reactivity of the mouse vas deferens to adrenergic drugs.

1. Dose-response curves for noradrenaline, phenylephrine and clonidine were determined isometrically on the mouse vas deferens at 26 degrees C, 15 degrees C and compared to the one obtained at 37 degrees C. 2. In the presence of noradrenaline, reducing temperature induced an increase of both maximal developed tension and sensitivity to the drug. Reduction by 50% of the extracellular calcium concentration abolished the maximal contraction potentiation. 3. When reducing temperature to 26 degrees C, the maximal contraction was increased and depressed in the presence of phenylephrine and clonidine respectively. 4. The results suggest (a) that cooling increases the reactivity of mouse vas deferens by activation of alpha 1 adrenoceptors and depresses it by activation of alpha 2 adrenoceptors (b) that calcium ions could play an important role in the potentiation of the maximal contraction.

The efficacy of caffeine in the treatment of recurrent idiopathic apnea in premature infants.

This prospective controlled study was aimed at evaluating the efficacy of caffeine in treating recurrent idiopathic apnea in the premature infant. Eighteen preterm infants (29 to 35 weeks' gestation) were studied. Recordings during the first 24 hours and on the fifth day of caffeine treatment showed a significant decrease of severe apnea (P less than 0.01) and of mild apnea (P less than 0.001) in the treated group (group 1) as compared with the control group (group II). No treatment of apnea other than caffeine was required in group I, whereas six neonates in group II had such severe and frequent apneic episodes for more than 48 hours that withholding additional treatment was believed to be unethical. No undesirable side effects of caffeine treatment were observed.