Proton-Stabilized Photochemically Reversible E/Z Isomerization of Spiropyrans

Spiropyrans undergo C-spiro-O bond breaking to their ring-open protonated E-merocyanine form upon protonation and irradiation via an intermediate protonated Z-merocyanine isomer. We show that the extent of acid-induced ring opening is controlled by matching both the concentration and strength of the acid used and with strong acids full ring opening to the Z-merocyanine isomer occurs spontaneously allowing its characterization by H-1 NMR spectroscopy as well as UV/vis spectroscopy, and reversible switching between Z/E-isomerization by irradiation with UV and visible light. Under sufficiently acidic conditions, both E- and Z-isomers are thermally stable. Judicious choice of acid such that its pK(a) lies between that of the E- and Z-merocyanine forms enables thermally stable switching between spiropyran and E-merocyanine forms and hence pH gating between thermally irreversible and reversible photochromic switching

395 OSTEOPHYTES AND JOINT SPACE NARROWING ARE INDEPENDENTLY ASSOCIATED WITH PAIN IN FINGER JOINTS IN HAND OSTEOARTHRITIS

Objective To study the associations between structural abnormalities on ultrasound (US) or conventional x-rays (CR) and pain in hand osteoarthritis (HOA). Methods In 55 consecutive patients with HOA (mean age 61 years, 86% women) fulfilling the American College of Rheumatology criteria, pain in 30 separate hand joints was assessed upon palpation; osteophytes were assessed by US and CR and joint space narrowing (JSN) by CR. Associations between structural abnormalities and pain per joint were analysed using generalised estimated equations to account for patient effects and adjusted for age, sex, body mass index, US inflammatory features and other remaining structural abnormalities. Results In 1649 joints, 69% and 46% had osteophytes on US and CR, respectively and 47% had JSN. Osteophytes and JSN showed independent associations with pain per joint adjusted: OR for osteophytes: 4.8 (95% CI 3.1 to 7.5) for US and 4.1 (95% CI 2.4 to 7.1) for CR; for JSN: 4.2 (95% CI 2.0 to 9.0). Conclusions Osteophytes and JSN are independently associated with pain in individual HOA joints, taking into account patient effects

Marine aggregate extraction regulation in EU member states

This paper provides a brief review of regulations and procedures relevant to the authorization of marine aggregate (MA) operations in eight EU Member States. MA operations are affected by a multi-level legislative/regulatory regime, consisting of international conventions (e.g. the UNCLOS 1982, OSPAR, Helsinki, ICES, Barcelona and Espoo Conventions), secondary EC legislation (e.g. the Environmental Impact Assessment Directives (85/337/EEC and 97/11 EC) and the Freedom of Access to Environmental Information Directive (2003/4/EC)) and national legislation or regulation. It appears that rules and procedures relevant to MA extraction vary considerably between the considered Member States. In general, relevant information is not easily available in accurate, comprehensive and up-to date form. As a result, it is difficult to assess whether and to which extent national practice in relation to MA extraction authorization is in substantive compliance with the requirements of existing international and European rules and regulations aimed at sustainable development and protection of the marine and coastal environment

Synthesis and evaluation of dopamine D-3 receptor antagonist C-11-GR218231 as PET tracer for P-glycoprotein

While searching for a PET method to determine the density and occupancy of the dopamine D-3 receptor, we found evidence that suggested that the dopamine D-3 antagonist GR218231 could be a substrate of the P-glycoprotein efflux pump. P-glycoprotein protects the brain against toxic substances and xenobiotics, but it also hampers the delivery of various drugs into the brain. In this study, we aimed to explore whether radiolabeled GR218231 could be applied as a PET tracer for monitoring P-glycoprotein activity in the blood-brain barrier. Such an imaging technique could be useful for the development of new drugs and novel strategies to deliver drugs to the brain and for identification of undesirable drug-drug interactions. Methods: As a potential PET tracer, GR218231 was labeled with C-11 by reaction of the newly synthesized desmethyl precursor with C-11-methyl triflate. The biodistribution of C-11-GR218231 was determined in rats. To assess specific binding to the dopamine D3 receptor, blocking experiments with unlabeled GR218231 (0.2 and 2.5 mg/kg) were performed. To demonstrate the influence of P-glycoprotein on cerebral uptake of C-11-GR218231, the efflux pump was modulated with 50 mg/kg cyclosporine A. The sensitivity of C-11-GR218231 for P-glycoprotein modulation was assessed in dose-response studies, using escalating cyclosporine A dosages. Results: C-11-GR218231 was prepared in 53% +/- 8% decay-corrected radiochemical yield and had a specific activity of 15 +/- 10 GBq/mu mol (mean +/- SD). Biodistribution studies in rats revealed a low and homogeneous uptake in the brain. Pretreatment of the animals with unlabeled GR218231 did not demonstrate any specific binding. Modulation of P-glycoprotein with cyclosporine A caused a 12-fold higher C-11-GR218231 uptake in the brain, indicating that the low cerebral tracer uptake was caused by the P-glycoprotein efflux pump in the blood-brain barrier. Cyclosporine A close-escalation studies showed a dose-dependent sigmoidal increase in C-11-GR218231 uptake in brain and spleen (median effective dose [ED50], 23.3 +/- 0.6 and 38.4 +/- 2.4 mg/kg, respectively), whereas a dose-dependent decrease was observed in the pancreas (ED50, 36.0 +/- 4.4 mg/kg). Conclusion: Although C-11-GR218231 is unsuited for dopamine D3 receptor imaging with PET, it appears to be an attractive PET tracer for visualization and quantification of P-glycoprotein activity in the blood-brain barrier

Risk of adverse pregnancy outcomes of late- and postterm pregnancies in advanced maternal age : A national cohort study

© 2020 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).Peer reviewedPublisher PD

Elective induction of labour and expectant management in late-term pregnancy : A prospective cohort study alongside the INDEX randomised controlled trial

Funding Information: BWM reports consultancy for ObsEva. BMW has received research funding from Ferring and Merck. The original RCT was funded by ZonMw: number NTR3431 , Netherlands Trial Registy . BWM is supported by a NHMRC Investigator grant (GNT1176437). Publisher Copyright: © 2022 The AuthorsPeer reviewedPublisher PD

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

De bepaling van calcium en fosfor in melk met behulp van ICP-AES

Een methode, gebaseerd op een monstervoorbewerking met trichloorazijnzuur en meting met behulp van ICP-AES, werd uitgetest voor de bepaling van Ca en P in melk. De resultaten van deze methode werden vergeleken met de resultaten, welke door de afdeling Algemene Chemie met behulp van fotometrische technieken werden verkregen