At the Interface of Isomorphous Behavior in a 3 × 3 Isomer Grid of Monochlorobenzamides: Analyses of the Interaction Landscapes via Contact Enrichment Studies

International audienceThe physicochemical properties of a 33 isomer grid of mono-chlorobenzamides (Clxx) are reported with comprehensive studies of their crystal structures and interaction environments (Clx = para-/meta-/ortho-chlorobenzoyl and x = para-/meta-/ortho-aminopyridine substitutions). The nine compound Clxx series was synthesised from the three p-/m-/o-chlorobenzoyl chlorides and three p-/m-/o-aminopyridine isomers using standard synthetic procedures. Clxx exhibits some similarities to the related Fxx and Brxx congeners e.g. the isomorphous behaviour of Clpp (para-Chloro-N'-(para-pyridyl)benzamide) with several close relatives, and there are five isomorphous pairs of Clxx and Brxx crystal structures. Notably Clmp and Clpm both crystallise with Z'=4 in space group P but show important differences. The overall lack of isomers crystallising with solvate molecules is noteworthy, except for Clmm(H 2 O). In all Clxx crystal structures, strong N-H…N hydrogen bonds form, however, Clpo also crystallises as the unexpected Clpo_O polymorph with N-H…O=C intermolecular hydrogen bonding. The Clxo triad (with ortho-pyridines) exhibits the expected cyclic N-H…N dimer formation with R 2 2 (8) hydrogen bonded rings. The H C atom type, forming weak C-H…Cl hydrogen bonds, is the only favoured interaction partner of chlorine in Clxx. Conformational analyses (gas phase) together with crystal contact enrichment studies place Clxx in context and at the interface of hydrogen and halogen bonding interactions, though strong hydrogen bonding dominates. In Clxx the interaction energies with nearest neighbours are shown to contribute to most of the lattice electrostatic energies. The melting temperatures T m show correlation with both molecular symmetry (Carnelley's rule) and total electrostatic energy of the weak interactions; in addition, these T m values can be well predicted from a linear fit combining both descriptors. In Clxx, N-H…N hydrogen bonds dominate, largely in the absence of solvates, and with five Clxx forming isomorphous pairs with Brxx analogues; Clpp being isomorphous with several close benzamide relatives. Analysis of T m reveals correlations involving both symmetry and electrostatic energies

Overtreatment and associated risk factors among multimorbid older patients with diabetes.

BACKGROUND In multimorbid older patients with type 2 diabetes mellitus (T2DM), the intensity of glucose-lowering medication (GLM) should be focused on attaining a suitable level of glycated hemoglobin (HbA1c ) while avoiding side effects. We aimed at identifying patients with overtreatment of T2DM as well as associated risk factors. METHODS In a secondary analysis of a multicenter study of multimorbid older patients, we evaluated HbA1c levels among patients with T2DM. Patients were aged ≥70 years, with multimorbidity (≥3 chronic diagnoses) and polypharmacy (≥5 chronic medications), enrolled in four university medical centers across Europe (Belgium, Ireland, Netherlands, and Switzerland). We defined overtreatment as HbA1c  < 7.5% with ≥1 GLM other than metformin, as suggested by Choosing Wisely and used prevalence ratios (PRs) to evaluate risk factors of overtreatment in age- and sex-adjusted analyses. RESULTS Among the 564 patients with T2DM (median age 78 years, 39% women), mean ± standard deviation HbA1c was 7.2 ± 1.2%. Metformin (prevalence 51%) was the most frequently prescribed GLM and 199 (35%) patients were overtreated. The presence of severe renal impairment (PR 1.36, 1.21-1.53) and outpatient physician (other than general practitioner [GP], i.e. specialist) or emergency department visits (PR 1.22, 1.03-1.46 for 1-2 visits, and PR 1.35, 1.19-1.54 for ≥3 visits versus no visits) were associated with overtreatment. These factors remained associated with overtreatment in multivariable analyses. CONCLUSIONS In this multicountry study of multimorbid older patients with T2DM, more than one third were overtreated, highlighting the high prevalence of this problem. Careful balancing of benefits and risks in the choice of GLM may improve patient care, especially in the context of comorbidities such as severe renal impairment, and frequent non-GP healthcare contacts

Anatomical distribution of Toxoplasma gondii in naturally and experimentally infected lambs

Consumption of raw or undercooked meat containing Toxoplasma gondii tissue cysts is one of the main sources of infection for humans worldwide. Among the various species intended for human consumption, sheep appear to be a high risk for human infection. The present study focused on the detailed anatomical distribution of Toxoplasma gondii in naturally and experimentally infected lambs using fresh and frozen samples of various pieces of meat, from a public health perspective. The first objective was to rank the edible parts intended for human consumption according to the detectable parasite burden by real-time PCR targeting the 529-bp repeated element. The second objective was to evaluate the impact of freezing by comparing the detection efficiency of the quantitative PCR between fresh and frozen tissues, as imports of lamb carcasses/cuts may arrive frozen or chilled. The highest estimated parasite loads were observed in skeletal muscles, and more particularly in edible portions such as quadriceps femoris muscle, intercostal muscles, deltoid muscle and diaphragm, with a significant difference in detectable parasite burden between fresh and frozen samples (p < 0.0001) or natural and experimental infection (p < 0.0001). Thoracic and pelvic limbs (3278–1048 parasites/g muscle) were ranked at the top of the list. Toxoplasma gondii DNA was detected in all the edible parts of lamb studied. These results suggest that lamb meat represents a risk for consumers. Further investigations are needed in order to confirm these differences in larger numbers of animals and in different breeds

Inhibition of ectopic glioma tumor growth by a potent ferrocenyl drug loaded into stealth lipid nanocapsules.

UNLABELLED: In this work, a novel ferrocenyl complex (ansa-FcdiOH) was assessed for brain tumor therapy through stealth lipid nanocapsules (LNCs). Stealth LNCs, prepared according to a one-step process, showed rapid uptake by cancer cells and extended blood circulation time. The ferrocenyl complex was successfully encapsulated into these LNCs measuring 40nm with a high loading capacity (6.4%). In vitro studies showed a potent anticancer effect of ansa-FcdiOH on 9L cells with a low IC50 value (0.1μM) associated with an oxidative stress and a dose-dependent alteration of the cell cycle. Repeated intravenous injections of stealth ansa-FcdiOH LNCs in ectopic glioma bearing rats induced a significant tumor growth inhibition, supported by a reduced number of proliferative cells in tumors compared to control group. Additionally, no liver damage was observed in treated animals. These results indicated that stealth ansa-FcdiOH LNCs might be considered as a potential new approach for cancer chemotherapy. FROM THE CLINICAL EDITOR: In this study, a novel ferrocenyl complex was assessed for brain tumor therapy through stealth lipid nanocapsules, demonstrating no liver damage, and superior tumor volume reduction compared to saline and stealth lipid nanocapsules alone in an ectopic glioma model

Overtreatment and associated risk factors among multimorbid older patients with diabetes

Background: In multimorbid older patients with type 2 diabetes mellitus (T2DM), the intensity of glucose-lowering medication (GLM) should be focused on attaining a suitable level of glycated hemoglobin (HbA 1c) while avoiding side effects. We aimed at identifying patients with overtreatment of T2DM as well as associated risk factors. Methods: In a secondary analysis of a multicenter study of multimorbid older patients, we evaluated HbA 1c levels among patients with T2DM. Patients were aged ≥70 years, with multimorbidity (≥3 chronic diagnoses) and polypharmacy (≥5 chronic medications), enrolled in four university medical centers across Europe (Belgium, Ireland, Netherlands, and Switzerland). We defined overtreatment as HbA 1c < 7.5% with ≥1 GLM other than metformin, as suggested by Choosing Wisely and used prevalence ratios (PRs) to evaluate risk factors of overtreatment in age- and sex-adjusted analyses. Results: Among the 564 patients with T2DM (median age 78 years, 39% women), mean ± standard deviation HbA 1c was 7.2 ± 1.2%. Metformin (prevalence 51%) was the most frequently prescribed GLM and 199 (35%) patients were overtreated. The presence of severe renal impairment (PR 1.36, 1.21–1.53) and outpatient physician (other than general practitioner [GP], i.e. specialist) or emergency department visits (PR 1.22, 1.03–1.46 for 1–2 visits, and PR 1.35, 1.19–1.54 for ≥3 visits versus no visits) were associated with overtreatment. These factors remained associated with overtreatment in multivariable analyses. Conclusions: In this multicountry study of multimorbid older patients with T2DM, more than one third were overtreated, highlighting the high prevalence of this problem. Careful balancing of benefits and risks in the choice of GLM may improve patient care, especially in the context of comorbidities such as severe renal impairment, and frequent non-GP healthcare contacts

6 MeV Electron exposure effects on OFDR-based distributed fiber sensors

The impact of exposing an optical fiber to 6-MeV electrons on the performances of optical frequency domain reflectometry (OFDR) distributed sensors is investigated. Six different types of optical fibers with different core compositions and coatings have been tested: four fibers are metal coated (copper, gold, or aluminum) for high-temperature >300 °C) operations while the two others have telecom-grade acrylate coatings for operation below 80 °C. The fiber Rayleigh signature used to perform the OFDR sensing remains almost unaffected after an electron exposure. Indeed, the measured radiation-induced temperature errors are lower than about 3 °C, close to the setup uncertainties, when the OFDR operates as a temperature sensor

National records of 3000 European bee and hoverfly species: A contribution to pollinator conservation

peer reviewedPollinators play a crucial role in ecosystems globally, ensuring the seed production of most flowering plants. They are threatened by global changes and knowledge of their distribution at the national and continental levels is needed to implement efficient conservation actions, but this knowledge is still fragmented and/or difficult to access. As a step forward, we provide an updated list of around 3000 European bee and hoverfly species, reflecting their current distributional status at the national level (in the form of present, absent, regionally extinct, possibly extinct or non-native). This work was attainable by incorporating both published and unpublished data, as well as knowledge from a large set of taxonomists and ecologists in both groups. After providing the first National species lists for bees and hoverflies for many countries, we examine the current distributional patterns of these species and designate the countries with highest levels of species richness. We also show that many species are recorded in a single European country, highlighting the importance of articulating European and national conservation strategies. Finally, we discuss how the data provided here can be combined with future trait and Red List data to implement research that will further advance pollinator conservation

Evaluation de la prise en charge du septis en département de médecine d'urgence (étude prospective observationnelle et proposition d'un protocole de prise en charge optimisée)

Avec 59% d'hommes et 60 ans d'âge moyen (69% et 66 ans pour les sepsis sévères), les caractéristiques générales ainsi que la clinique de l'échantillon sont comparables aux données actuelles de la littératures [i.e.= littérature].En revanche, ce n'est pas le cas concernant la mortalité qui est plus élevée (41% de patients en sepsis sévère décédés).Tous nos patients présentaient, dès l'entrée, les critères de sepsis.36% des états septiques graves ont été diagnostiqués, uniquement après aggravation clinique, en cours de séjour.D'où l'importance de la réévaluation régulière des patients septiques et la nécessité de définir une stratification de l'évolutivité potentielle pour chaque sepsis.La fréquence respiratoire est le critère de SRIS le plus faiblement apprécié alors même qu'il se trouve être le plus fréquemment positif (avec la fréquence cardiaque) chez les patients en sepsis sévère.L'évaluation clinique et paraclinique, ainsi que la procédure thérapeutique (principalement au niveau du type de prise en charge hémodynamique et anti-infectieuse, et du délai de mise en place) du patient septique dans notre service ne sont pas optimales et paraissent éloignées des recommandations internationales.Seulement 25% des sepsis sévères et 24% des sepsis simples ont eu une évaluation clinico-biologique complète des différentes fonctions organiques (en omettant la quantification de la diurèse pour les sepsis simples).De plus, grâce à ces données recueillies nous avons identifié 24% de sepsis graves parmi les sepsis simples et 27% de chocs septiques cryptiques parmi les sepsis graves classés comme tel par les médecins urgentistes.On a constaté chez ces patients une augmentation de la mortalité (non significative) et un allongement significative de la durée d'hospitalisation.Parmi les critères des scores RISSC et MEDS, seule [i.e.= seules] l'hyperthermie et l'hypernatrémie n'ont pas été retrouvés comme facteurs prédictifs de mortalité ; d'autres, n'appartenant pas à l'un de ces scores, ont été mis en évidence : l'hypothermie (90bpm, la fréquence respiratoire >20cpm, l'existence de plus d'une dysfonction organique, la lactatémie et la troponinémie élevée, et la PaO2 et le temps de prothrombine abaisséMONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Qualité de l'apprentissage de l'intubation oro-trachéale en laboratoire de simulation versus bloc opératoire, son intérêt pour les patients

La formation à l'incubation est malaisée pour les interne en médecine générale, qu'ils se destinent à la pratique des urgences ou non, elle est pourtant nécessaire. le développement des techniques de simulation adaptées à la formation dans le domaine de la santé permet de proposer des solutions alternatives concrètes, grâce notamment à du matériel dit de haute fidélité . Le propos de cette étude est de comparer la formation des internes à l'intubation oro-trachéale en laboratoire de simulation haute fidélité par rapport à une formation classique au bloc opératoire, grâce à une étude prospective. Deux groupes d'internes ont reçu l'un une formation à l'intubation en laboratoire de simulation haute fidélité, l'autre au lit du malade au bloc opératoire. Chaque tentative a été évaluée par une grille de notation comprenant items techniques et non techniques. les internes ont ensuite été chacun évalués sur deux intubations au bloc opératoire, sur patient. Les résultats retrouvent une différence significative en faveur de la formation en simulation pour ce qui est de la réussite du geste sur le premier patient rencontré, et une absence de différence entre les deux groupes d'étudiants au terme de leur formation respective. La formation à l'intubation en laboratoire de simulation haute fidélité semble donc avoir toute sa place dans une stratégie pédagogique moderne, permettant une formation initiale équivalent à la formation de référenceMONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF