Rôle d’une désorganisation de la chromatine dans la neurodégénérescence due à une expansion de polyglutamine dans l’ataxine-7

International audienc

In Vitro Stability of Low-Concentration Ziconotide Alone or in Admixtures in Intrathecal Pumps

ObjectivesZiconotide is often administered in combination with other analgesics via an intrathecal pump. Studies have established that ziconotide is stable when delivered alone in high concentrations. No stability data are available, however, for ziconotide given in low concentrations and/or with other analgesics as usually occurs in clinical oncology practice. The objective of this study was to assess the in vitro stability of ziconotide alone and combined with other analgesics in intrathecal pumps at 37°C, as well as in syringes at 5°C, to evaluate conditions for storing and transporting preparations. Materials and Methods Various ziconotide concentrations (0.1, 0.25, 0.5, and 0.75 μg/mL) were combined with an admixture of ropivacaine (7.5 mg/mL), morphine (7.5 mg/mL), and clonidine (15 μg/mL) in 20-mL intrathecal pumps at 37°C and in syringes at 5°C. Solutions of ziconotide alone in concentrations of 0.25, 0.5, 0.75, and 1 μg/mL were introduced into pumps at 37°C and syringes at 5°C. Assays were performed using ultra high pressure liquid chromatography. Results In admixtures, mean ziconotide concentrations decreased linearly to 53.4% (±3.33%) of baseline after 35 days. When ziconotide was introduced alone in pumps at 37°C, the residual concentration on day 31 was 35.54% (±0.04%) with 0.25 μg/mL, 39.37% (±0.15%) with 0.5 μg/mL, and 44.49% (±0.18%) with 1 μg/mL. Ziconotide alone or combined with the other analgesics was stable in syringes stored at 5°C. The preparations complied with the prescriptions, with a mean error of less than 10%, except with the lowest ziconotide concentration (0.1 μg/mL). Conclusions At the low ziconotide concentrations studied, the degradation of ziconotide admixed with other drugs was linear and only weakly influenced by the baseline concentration. Linear regression with intrapolation to 30 days showed that the degradation of ziconotide admixed with other drugs was consistent with previously published data

Numerical method for the 2D simulation of the respiration

International audienceIn this article we are interested in the simulation of the air flow in the bronchial tree. The model we use has already been described by Baffico, Grandmont and Maury and is based on a three part description of the respiratory tract. This model leads, after time discretization, to a Stokes system with non standard dissipative boundary conditions that cannot be easily and directly implemented in most FEM software, in particular in FreeFEM++. The objective is here to provide a new numerical method that could be implemented in any softwares. After describing the method, we illustrate it by two-dimensional simulations

Hereditary Systemic Angiopathy (HSA) with cerebral calcifications, retinopathy, progressive nephropathy, and hepatopathy

Several hereditary conditions affecting cerebral, retinal and systemic microvessels have recently been described. They include CADASIL, CRV, and HERNS. We here report on a variant form of a hereditary systemic angiopathy (HSA) affecting two generations of a Caucasian family. Clinical symptoms of HSA appear in the mid-forties and are characterized by visual impairment, migrainelike headache, skin rash, epileptic seizures, progressive motor paresis and cognitive decline. Late symptoms include hepatic and renal failure. Retinal capillary microaneurysms and arteriolar tortuosity are associated with marked optic disc atrophy. Radiological hallmarks consist of multiple cerebral calcifications and tumor-like subcortical white matter lesions. Brain, peripheral nerve, muscle, kidney and colon biopsies have revealed a multi organ small vessel involvement with partly altered endothelium, perivascular inflammation and thrombotic microangiopathy. No curative therapeutic options are known for hereditary cerebral vasculopathies. The use of cyclophosphamide, azathioprine and methotrexate was of no benefit in our cases of HSA. Early diagnosis of hereditary systemic angiopathies is important in order to prevent patients from repetitive invasive diagnostic measures and to avoid the use of inappropriate and potentially harmful drug

Rochberg's abstract coboundary theorem revisited

International audienceRochberg's coboundary theorem provides conditions under which the equation (I-T)y = x is solvable in y. Here T is a unilateral shift on Hilbert space, I is the identity operator and x is a given vector. The conditions are expressed in terms of Wold-type decomposition determined by T and growth of iterates of T at x. We revisit Rochberg's theorem and prove a result for isometries. When T is merely a contraction,x is a coboundary under an additional assumption. Some applications to L2-solutions of the functional equation f(x) - f(2x) = F(x), considered by Fortet and Kac, are given

Rochberg's abstract coboundary theorem revisited

Rochberg's coboundary theorem provides conditions under which the equation $(I-T)y = x$ is solvable in $y$. Here $T$ is a unilateral shift on Hilbert space, $I$ is the identity operator and $x$ is a given vector. The conditions are expressed in terms of Wold-type decomposition determined by $T$ and growth of iterates of $T$ at $x$. We revisit Rochberg's theorem and prove the following result. Let $T$ be an isometry acting on a Hilbert space $\mathcal{H}$ and let $x \in \mathcal{H}$. Suppose that $\sum_{k=0}^\infty k \| T^{*k} x \| < \infty$. Then $x$ is in the range of $(I-T)$ if (and only if) $\|\sum_{k= 0}^n T^k x \| = o(\sqrt{n}).$ When $T$ is merely a contraction, $x$ is a coboundary under an additional assumption. Some applications to $L^2$-solutions of the functional equation $f(x)-f(2x) = F(x)$, considered by Fortet and Kac, are given.Comment: 13 page

Particle approximation of the one dimensional Keller-Segel equation, stability and rigidity of the blow-up

We investigate a particle system which is a discrete and deterministic approximation of the one-dimensional Keller-Segel equation with a logarithmic potential. The particle system is derived from the gradient flow of the homogeneous free energy written in Lagrangian coordinates. We focus on the description of the blow-up of the particle system, namely: the number of particles involved in the first aggregate, and the limiting profile of the rescaled system. We exhibit basins of stability for which the number of particles is critical, and we prove a weak rigidity result concerning the rescaled dynamics. This work is complemented with a detailed analysis of the case where only three particles interact

Les thérapies ciblées par voie orale dans la prise en charge du cancer du rein métastatique (importance du lien ville / hôpital pour le patient dans la gestion de son traitement et des effets secondaires. Exemple de l ICO-Paul Papin)

La prise en charge actuelle du cancer du rein avancé et/ou métastatique est le reflet des grandes avancées thérapeutiques réalisées ces dernières années dans le domaine de la cancérologie. L apparition des thérapies ciblées, anti-angiogéniques et inhibiteurs de mTOR, offre de nouveaux espoirs dans le pronostic du cancer du rein, jusque là réfractaire aux chimiothérapies conventionnelles. Ces molécules, administrables par voie orale et disponibles en officine pour la plupart d entre elles, améliorent l autonomie et la qualité de vie des patients. Elles renforcent le rôle du pharmacien d officine situé en première ligne auprès des patients, notamment dans la gestion des effets indésirables imputables aux traitements, sources de mauvaise observance. L étude réalisée à l Institut de Cancérologie de l Ouest-Paul Papin (ICO-Paul Papin) s inscrit dans une démarche d amélioration de la coordination des soins avec les pharmaciens d officine, un des objectifs présent dans les dernières directives gouvernementales, loi Hôpital Patient Santé Territoire (HPST) et Plan Cancer 2009-2013. Les pharmaciens de l ICO-Paul Papin verront dans les années à venir un renforcement de leur rôle auprès des patients avec la mise en place de l éducation thérapeutique. Conscients de l importance du lien ville-hôpital, cette étude auprès des pharmaciens d officine permet de soulever deux questions : La création d un lien entre les pharmaciens d officine et l ICO-Paul Papin est-elle faisable ? Comment peut-il s organiser ?Management of advanced or metastatic renal cell carcinoma reflects the major therapeutic advances in recent years in the field of oncology. The advent of targeted therapies, anti-angiogenics and mTOR-inhibitors offers new hope in the prognosis of kidney cancer previously refractory to conventional chemotherapy. These molecules can be administered orally and available in community pharmacy for the majority, improve the independence and quality of life of patients. They consolidate the role of community pharmacist in first line with patients particularly in the management of adverse events, attributable to treatment source of poor compliance. The study conducted in Institut de Cancérologie de l Ouest-Paul Papin (ICO Paul Papin) is part of an effort to improve coordination with community pharmacist one of the objectives in the latest government directives: Hospital Patient Health and Territory s law (HPST) and Cancer Plan 2009-2013. ICO-Paul Papin s Pharmacists will see a strengthening of their role with patients in the future with the development of therapeutic education. Recognizing the importance of city-hospital s link, this survey with community pharmacists can raise two questions: Does the creation of a link between community pharmacists and ICO-Paul Papin is workable? How can it be organized?ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study.

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4–1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0–2 weeks, 3–4 weeks and 5–6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3–4.8), 3.9 (2.6–5.1) and 3.6 (2.0–5.2), respectively). Surgery performed ≥ 7 weeks after SARSCoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9–2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2– 8.7) vs. 2.4% (95%CI 1.4–3.4) vs. 1.3% (95%CI 0.6–2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay

Transcription factor IID parks and drives preinitiation complexes at sharp or broad promoters

Core promoters are sites where transcriptional regulatory inputs of a gene are integrated to direct the assembly of the preinitiation complex (PIC) and RNA polymerase II (Pol II) transcription output. Until now, core promoter functions have been investigated by distinct methods, including Pol II transcription initiation site mappings and structural characterization of PICs on distinct promoters. Here, we bring together these previously unconnected observations and hypothesize how, on metazoan TATA promoters, the precisely structured building up of transcription factor (TF) IID-based PICs results in sharp transcription start site (TSS) selection; or, in contrast, how the less strictly controlled positioning of the TATA-less promoter DNA relative to TFIID-core PIC components results in alternative broad TSS selections by Pol II