Perfluoro Alkyl Hypofluorites and Peroxides Revisited

A more convenient synthesis of the perfluoro alkyl hypofluorite (F3C)3COF as well as the hitherto unknown (C2F5)(F3C)2COF compound is reported. Both hypofluorites can be prepared by use of the corresponding tertiary alcohols RFOH and elemental fluorine in the presence of CsF. An appropriate access to these highly reactive hypofluorites is crucial. The hypofluorites are then transferred into their corresponding perfluoro bisalkyl peroxides RFOORF [RF=(F3C)3C, (C2F5)(F3C)2C] by treatment with partially fluorinated silver wool. NMR, gas‐phase infrared, and solid‐state Raman spectra of the perfluoro bisalkyl peroxides are presented and their chemical properties are discussed

Trifluoromethyl Fluorosulfonate (CF3OSO2F) and Trifluoromethoxy Sulfur Pentafluoride (CF3OSF5) – Two Gaseous Sulfur(VI) Compounds with Insulating Properties

In this work, we analyzed trifluoromethyl fluorosulfonate (CF3OSO2F) and trifluoromethoxy sulfur pentafluoride (CF3OSF5) regarding their potential use as dielectrics by investigating some of their intrinsic and extrinsic properties. Both compounds show a higher breakdown voltage than SF6 with averaged relative breakdown voltages of 1.3±0.2 for CF3OSO2F and 1.4±0.2 for CF3OSF5 compared to SF6 with 1.0. Like the dielectric (CF3)2CFCN, both compounds decompose during the breakdown process. The decomposition products were analyzed by IR spectroscopy and GCIR methods. Furthermore, the molecular structures of both gaseous compounds CF3OSO2F and CF3OSF5 have been determined by in situ crystallization, and their physical properties were determined as well

Development and External Validation of the International Early Warning Score for Improved Age- and Sex-Adjusted In-Hospital Mortality Prediction in the Emergency Department

Objectives: Early Warning Scores (EWSs) have a great potential to assist clinical decision-making in the emergency department (ED). However, many EWS contain methodological weaknesses in development and validation and have poor predictive performance in older patients. The aim of this study was to develop and externally validate an International Early Warning Score (IEWS) based on a recalibrated National Early warning Score (NEWS) model including age and sex and evaluate its performance independently at arrival to the ED in three age categories (18-65, 66-80, &gt; 80 yr). Design: International multicenter cohort study. Setting: Data was used from three Dutch EDs. External validation was performed in two EDs in Denmark. Patients: All consecutive ED patients greater than or equal to 18 years in the Netherlands Emergency department Evaluation Database (NEED) with at least two registered vital signs were included, resulting in 95,553 patients. For external validation, 14,809 patients were included from a Danish Multicenter Cohort (DMC). Measurements and Main Results: Model performance to predict in-hospital mortality was evaluated by discrimination, calibration curves and summary statistics, reclassification, and clinical usefulness by decision curve analysis. In-hospital mortality rate was 2.4% (n = 2,314) in the NEED and 2.5% (n = 365) in the DMC. Overall, the IEWS performed significantly better than NEWS with an area under the receiving operating characteristic of 0.89 (95% CIs, 0.89-0.90) versus 0.82 (0.82-0.83) in the NEED and 0.87 (0.85-0.88) versus 0.82 (0.80-0.84) at external validation. Calibration for NEWS predictions underestimated risk in older patients and overestimated risk in the youngest, while calibration improved for IEWS with a substantial reclassification of patients from low to high risk and a standardized net benefit of 5-15% in the relevant risk range for all age categories. Conclusions: The IEWS substantially improves in-hospital mortality prediction for all ED patients greater than or equal to18 years.</p

Glutamate-system defects behind psychiatric manifestations in a familial hemiplegic migraine type 2 disease-mutation mouse model

Migraine is a complex brain disorder, and understanding the complexity of this prevalent disease could improve quality of life for millions of people. Familial Hemiplegic Migraine type 2 (FHM2) is a subtype of migraine with aura and co-morbidities like epilepsy/seizures, cognitive impairments and psychiatric manifestations, such as obsessive-compulsive disorder (OCD). FHM2 disease-mutations locate to the ATP1A2 gene encoding the astrocyte-located α(2)-isoform of the sodium-potassium pump (α(2)Na(+)/K(+)-ATPase). We show that knock-in mice heterozygous for the FHM2-associated G301R-mutation (α(2)(+/G301R)) phenocopy several FHM2-relevant disease traits e.g., by mimicking mood depression and OCD. In vitro studies showed impaired glutamate uptake in hippocampal mixed astrocyte-neuron cultures from α(2)(G301R/G301R) E17 embryonic mice, and moreover, induction of cortical spreading depression (CSD) resulted in reduced recovery in α(2)(+/G301R) male mice. Moreover, NMDA-type glutamate receptor antagonists or progestin-only treatment reverted specific α(2)(+/G301R) behavioral phenotypes. Our findings demonstrate that studies of an in vivo relevant FHM2 disease knock-in mouse model provide a link between the female sex hormone cycle and the glutamate system and a link to co-morbid psychiatric manifestations of FHM2

The Effect of Aggressive Versus Conventional Lipid-lowering Therapy on Markers of Inflammatory and Oxidative Stress

Purpose Recent trial results are in favor of aggressive lipid lowering using high dose statins in patients needing secondary prevention. It is unclear whether these effects are solely due to more extensive lipid lowering or the result of the potentially anti-inflammatory properties of statins. We aimed to determine whether aggressive compared with conventional statin therapy is more effective in reducing systemic markers of inflammation and oxidative stress. Materials and methods This was a multi-centre, double-blind, placebo-controlled trial. Patients with previous cardiovascular disease, who did not achieve low density lipoprotein (LDL) cholesterol levels <2.6 mmol/l on conventional statin therapy (simvastatin 40 mg) were randomized to continue with simvastatin 40 mg or to receive atorvastatin 40 mg for 8 weeks and thereafter atorvastatin 80 mg for the final 8 weeks (aggressive treatment). Lipids, C-reactive protein, soluble cellular adhesion molecules, neopterin, von Willebrand Factor, and antibodies against oxidized LDL were measured at baseline and after 16 weeks. Results Lipid levels decreased significantly in the aggressive treatment group (LDL-C reduction 20.8%; P <0.001), whereas a slight increase was observed in the conventional group (LDL-C increase 3.7%; P = 0.037). A significant reduction in antibodies against oxidized LDL was seen in the aggressive (13.4%; P <0.001) and the conventional (26.8%; P <0.001) group, but there was no difference between groups (P = 0.25). Furthermore, no significant differences in change in other biomarkers was observed between both groups. Conclusions This study does not support the hypothesis that a more profound reduction in inflammatory and oxidative stress contributes to the benefits of aggressive statin therapy

Hydrostatic and osmotic pressure study of the RNA hydration

The tertiary structure of nucleic acids results from an equilibrium between electrostatic interactions of phosphates, stacking interactions of bases, hydrogen bonds between polar atoms and water molecules. Water interactions with ribonucleic acid play a key role in its structure formation, stabilization and dynamics. We used high hydrostatic pressure and osmotic pressure to analyze changes in RNA hydration. We analyzed the lead catalyzed hydrolysis of tRNAPhe from S. cerevisiae as well as hydrolytic activity of leadzyme. Pb(II) induced hydrolysis of the single phosphodiester bond in tRNAPhe is accompanied by release of 98 water molecules, while other molecule, leadzyme releases 86

Lipidomics Reveals Multiple Pathway Effects of a Multi-Components Preparation on Lipid Biochemistry in ApoE*3Leiden.CETP Mice

Background: Causes and consequences of the complex changes in lipids occurring in the metabolic syndrome are only partly understood. Several interconnected processes are deteriorating, which implies that multi-target approaches might be more successful than strategies based on a limited number of surrogate markers. Preparations from Chinese Medicine (CM) systems have been handed down with documented clinical features similar as metabolic syndrome, which might help developing new intervention for metabolic syndrome. The progress in systems biology and specific animal models created possibilities to assess the effects of such preparations. Here we report the plasma and liver lipidomics results of the intervention effects of a preparation SUB885C in apolipoprotein E3 Leiden cholesteryl ester transfer protein (ApoE*3Leiden.CETP) mice. SUB885C was developed according to the principles of CM for treatment of metabolic syndrome. The cannabinoid receptor type 1 blocker rimonabant was included as a general control for the evaluation of weight and metabolic responses. Methodology/Principal Findings: ApoE*3Leiden.CETP mice with mild hypercholesterolemia were divided into SUB885C-, rimonabant- and non-treated control groups. SUB885C caused no weight loss, but significantly reduced plasma cholesterol (-49%, p <0.001), CETP levels (-31%,

Plasma and Liver Lipidomics Response to an Intervention of Rimonabant in ApoE*3Leiden.CETP Transgenic Mice

Background: Lipids are known to play crucial roles in the development of life-style related risk factors such as obesity, dyslipoproteinemia, hypertension and diabetes. The first selective cannabinoid-1 receptor blocker rimonabant, an anorectic anti-obesity drug, was frequently used in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m2 with associated risk factors such as type II diabetes and dyslipidaemia in the past. Less is known about the impact of this drug on the regulation of lipid metabolism in plasma and liver in the early stage of obesity. Methodology/Principal Findings: We designed a four-week parallel controlled intervention on apolipoprotein E3 Leiden cholesteryl ester transfer protein (ApoE&z.ast;3Leiden.CETP) transgenic mice with mild overweight and hypercholesterolemia. A liquid chromatography-linear ion trap-Fourier transform ion cyclotron resonance-mass spectrometric approach was employed to investigate plasma and liver lipid responses to the rimonabant intervention. Rimonabant was found to induce a significant body weight loss (9.4%, p<0.05) and a significant plasma total cholesterol reduction (24%, p<0.05). Six plasma and three liver lipids in ApoE&z.ast;3Leiden.CETP transgenic mice were detected to most significantly respond to rimonabant treatment. Distinct lipid patterns between the mice were observed for both plasma and liver samples in rimonabant treatment vs. non-treated controls. This study successfully applied, for the first time, systems biology based lipidomics approaches to evaluate treatment effects of rimonabant in the early stage of obesity. Conclusion: The effects of rimonabant on lipid metabolism and body weight reduction in the early stage obesity were shown to be moderate in ApoE&z.ast;3Leiden.CETP mice on high-fat diet. © 2011 Hu et al

Treating attention-deficit/hyperactivity disorder beyond symptom control alone in children and adolescents: a review of the potential benefits of long-acting stimulants

Attention-deficit/hyperactivity disorder (ADHD), one of the most common neuropsychiatric conditions of childhood, often has a chronic course and persists into adulthood in many individuals. ADHD may have a clinically important impact on health-related quality of life in children, a significant impact on parents’ emotional health and interfere with family activities/cohesion. To date, the main targets of ADHD treatment have focused on reducing the severity of symptoms during the school day and improving academic performance. However, the treatment of ADHD should reach beyond symptom control to address the issues of social competencies and improvement of health-related quality of life from the perspectives of individuals with ADHD and their families, to support them in reaching their full developmental potential. Methylphenidate (MPH) is recognised as the first-line choice of pharmacotherapy for ADHD in children and adolescents. This paper focuses on the importance and benefits to child development of ADHD symptom control beyond the school day only, i.e. extending into late afternoon and evening and uses the example of an extended-release MPH formulation (OROS® MPH) to demonstrate the potential benefits of active full day coverage (12 h) with a single daily dose. Concerns of long-term stimulant treatment are also discussed