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The stereoselective photoisomerization of olefins via Energy Transfer (EnT) sensitization bears significant potential in the context of rational design of catalytic stereodivergent methodologies. Whereas approaches for controlling the access to E‐ and Z‐ isomers depend highly on the nature of the catalyst – and therefore are not easily implemented as a general strategy – EnT catalysis has emerged in recent years as an increasingly powerful tool for olefin geometry control in a nearly perfect step‐economic fashion. Moreover, this approach presents both high functional group tolerance and, most notably, has demonstrated ample multicatalytic compatibility. This feature has enabled the development of tandem stereodivergent catalytic strategies, which are the focus of this Review. [ABSTRACT FROM AUTHOR]

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome‐wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta‐analyzed with additional genome‐wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta‐analysis strategy revealed the ANKRD31‐rs4704171 and NDUFAF6‐rs10098778 and confirmed SCIMP‐rs7225151 and CD33‐rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta‐analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series. Highlights: We detected three gene categories operating differently in AD subgroups of patients.Vasculature regulation may be an essential part of the causative mechanism in pure AD.Two novel signals reached genome‐wide significance in ANKRD31 and NDUFAF6loci.We confirmed SCIMP‐rs7225151 and CD33‐rs3865444 to be genome‐wide significant.Genetic discoveries are strongly impacted by the presence of subgroups of AD. [ABSTRACT FROM AUTHOR]

In recent years, H2 activation at non‐transition‐metal centers has met with increasing attention. Here, a system in which H2 is activated and transferred to aldimines and ketimines using substoichiometric amounts of lithium bis(trimethylsilyl)amide is reported. Notably, the reaction tolerates the presence of acidic protons in the α‐position. Mechanistic investigations indicated that the reaction proceeds via a lithium hydride intermediate as the actual reductant. An alternative H2 activation: LiN(SiMe3)2, even in substoichiometric amounts, induces clean reduction of aldimines and ketimines with H2 as the reductant at moderate temperatures in the range 25–80 °C. Notably, the reaction tolerates the presence of acidic protons in the α‐position. Mechanistic investigations indicated that the reaction proceeds via a lithium hydride intermediate as the actual reductant. [ABSTRACT FROM AUTHOR]

Background: To develop a prediction rule to describe the risk of death as a result of enterococcal bloodstream infection.Methods: A prediction rule was developed by analysing data collected from 122 patients diagnosed with enterococcal BSI admitted to the Clínica Universidad de Navarra (Pamplona, Spain); and validated by confirming its accuracy with the data of an external population (Hospital del Mar, Barcelona).Results: According to this model, independent significant predictors for the risk of death were being diabetic, have received appropriate treatment, severe prognosis of the underlying diseases, have renal failure, received solid organ transplant, malignancy, source of the bloodstream infection and be immunosuppressed. The prediction rule showed a very good calibration (Hosmer-Lemeshow statistic, P = 0.93) and discrimination for both training and testing sets (area under ROC curve = 0.84 and 0.83 respectively).Conclusions: The predictive rule was able to predict risk of death as a result of enterococcal bloodstream infection as well as to identify patients, who being below the threshold value, will have a low risk of death with a negative predictive value of 96%. [ABSTRACT FROM AUTHOR]

Introduction: Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. Methods: We evaluated apolipoprotein E (APOE) ε4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta‐analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts. Results: Analysis of the FACEHBI cohort and the meta‐analysis demonstrated SCD individuals presented higher allelic frequencies of APOE ε4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. Discussion: The FACEHBI sample presents APOE ε4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype. Highlights: The FACEHBI sample presents APOE ε4 enrichment, suggesting it contains a pool of AD patients.APOE ε4 is a risk factor of being diagnosed with SCD.APOE ε4 only explains ≈10% of brain amyloid burden variability in SCD.The relationship between APOE and brain amyloid burden across clinical diagnoses highlights the importance of adjusting for clinical status when conducting GWAS of cerebral Aβ levels. [ABSTRACT FROM AUTHOR]

In recent years, dihydrogen activation at non-metallic centers has received increasing attention. A system in which dihydrogen is trapped by a pyridylidene intermediate that is generated from a pyridinium salt and a base is now reported. The dihydropyridine formed in this process can act as reducing agent towards organic electrophiles. By coupling the hydrogen-activation step with subsequent hydride transfer from the dihydropyridine to an imine, a catalytic process was established. Treatment of the N-phenylimine of phenyl trifluoromethyl ketone with 5-20 mol % of N-mesityl-3,5-bis(2,6-dimethylphenyl)pyridinium triflate and 0.3-1.0 equivalents of LiN(SiMe3)2 under 50 bar of hydrogen gas resulted in high conversion into the corresponding amine. [ABSTRACT FROM AUTHOR]

The aim of this work was to study the effects of valence and age on visual image recognition memory. The International Affective Picture System ( IAPS) battery was used, and response time data were analyzed using analysis of variance, as well as an ex-Gaussian fit method. Older participants were slower and more variable in their reaction times. Response times were longer for negative valence pictures, however this was statistically significant only for young participants. This suggests that negative emotional valence has a strong effect on recognition memory in young but not in old participants. The τ parameter, often related to attention in the literature, was smaller for young than old participants in an ex-Gaussian fit. Differences on the τ parameter might suggest poorer attentional performance in old participants. [ABSTRACT FROM AUTHOR]

The empirical behaviour of two Hermitian densities-the Edgeworth asymptotic expansion, and the Gallant and Nychka () squared transformation-are assessed and compared to Hansen's (1994) asymmetric Student t. The comparison focuses on VaR measurements and overall probability fits. In and out of sample, Berkowitz's () extended procedures are also implemented. Results are moderately favourable to the Hermitians, supporting the semi-nonparametric interpretation, and multivariate developments. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Papillary fibroelastoma (PFE) is a rare benign tumour that attaches to the endocardial surface, mostly on cardiac valves. Though usually asymptomatic, it can be the source of several complications. To date, 49 cases have been reported of embolic stroke with a PFE as the probable origin. Case reports: (i) a 39-year-old male presented with ischemic embolic stroke; the presence of a PFE was assessed by means of transoesophageal echocardiography and confirmed by pathological findings; (ii) a 32-year-old woman presented with sudden onset of left hemiparesis; a cardiogenic embolic stroke was suspected, and a diagnosis of PFE was made based on echocardiographic and pathological findings. In both cases, surgical excision of the tumours was performed with no recurrences at follow-up. Two mechanisms can explain the formation of emboli in PFE: dislodgement of the tumour leaves or fibrin-platelet aggregation on the endocardial surface of these leaves. Transthoracic echocardiography may lead to the suspicion of a PFE, but transoesophageal echocardiography is required for confirmation. Prompt surgical excision is indicated in most cases. Anticoagulation is only recommended in situations of high surgical risk and during the wait for surgery. [ABSTRACT FROM AUTHOR]

Many studies indicate that the S-enantiomers of aryl-propionic (APA) nonsteroidal antiinflammatory drugs (NSAIDs) are the pharmacologically active enantiomers. S(+)-ketoprofen (dexketoprofen) stereoselectively inhibits cyclooxygenase (COX) in vitro but very little is known about the differential activity of ketoprofen enantiomers in vivo. We examined the analgesic, antiinflammatory, and antipyretic activities of S(+)-ketoprofen in rats and mice. First, we measured the antinociceptive action of S(+)- ketoprofen in abdominal pain models. After intravenous administration, 0.5 mg/kg S(+)-ketoprofen inhibited 92.1 ± 2.2% of writhing in mice. Stereoselectivity in the activity was detected; intravenous administration of the R(-)-enantiomer resulted in no statistically significant activity in a dose range of 0.15-1 mg/kg. Similar results were obtained after oral administration in mice. In the rat, S(+)- ketoprofen was a more potent analgesic than diclofenac by both intravenous and oral administration. There was no significant difference between the analgesic effect of S(+)~ ketoprofen treatment and the twofold dose of the racemic form in both the mouse and rat models. Second, we measured the antiinflammatory activity of S(+)-ketoprofen using a carrageenan-induced paw edema model in the rat. Intravenous administration of 5 mg/kg of S(+)-ketoprofen almost completely inhibited edema formation. After oral administration, S(+)-ketoprofen is both more potent and effective than diclofenac. Third, we measured antipyretic activity. S(+)-ketoprofen showed a marked antipyretic action (EDS0 = 1.6 mg/kg) and was the most potent of the NSAIDs tested. S(+)-ketoprofen is a potent antiinflammatory, analgesic, and antipyretic agent in vivo, consistent with its potent anti-COX activity. [ABSTRACT FROM AUTHOR]

Dexketoprofen, the pure S(+)-enantiomer of ketoprofen, is a promising new analgesic, but few clinical trials have yet examined its efficacy and tolerability. In this study, patients with a history of primary dysmenorrhea were treated with dexketoprofen doses of 12,5 and 25 mg, ketoprofen 50 mg, and placebo using a randomized, four-way crossover design. Efficacy analyses showed that dexketoprofen 12.5 and 25 mg and racemic ketoprofen 50 mg significantly reduced pain intensity compared with placebo from 1 h after dose to 4-6 h after dose. Interestingly, dexketoprofen at 12.5 mg was significantly superior to placebo at 30 min after dose. Mean pain relief scores also demonstrated that both doses of dexketoprofen and racemic ketoprofen were significantly superior to placebo at 1-6 h after the first dose. No indices of analgesic efficacy showed any significant differences between the two doses of dexketoprofen or between dexketoprofen and ketoprofen. After repeated dose administration, similar results were obtained. There were no significant effects of any treatment on activities of daily living, menstrual flow, or associated symptoms. Dexketoprofen was effective, well tolerated, and had no difference in the incidence of adverse events compared to ketoprofen or placebo. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of dexketoprofen trometamol were evaluated in two studies using healthy volunteers. In the first study, the relative bioavailability of a single oral capsule of dexketoprofen free acid 25 mg or dexketoprofen trometamol 25 mg (given as 37 mg of the trometamol salt) was compared to Ketoprofen 50 mg in 18 healthy volunteers. In the second study, the pharmacokinetics and tol-erability of oral dexketoprofen trometamol in tablet form were evaluated after either a single 25 mg dose (24 volunteers) or a repeated dose of 25 mg twice daily for 7 days (12 volunteers). The absorption of dexketoprofen from dexketoprofen trometamol capsules was bioequivalent to that of ketoprofen. On the other hand, the extent of absorption of dexketoprofen free acid was significantly lower than that for ketoprofen. Dexketoprofen trometamol showed the most rapid absorption rate, with highest Cmax and shortest tmax values, whereas dexketoprofen free acid had the slowest absorption rate, and ketoprofen had an intermediate absorption rate. After repeated-dose administration of dexketoprofen trometamol, the pharmacokinetic parameters were similar to those obtained after single dosesf indicating that no drug accumulation occurred. Dexketoprofen trometamol was well tolerated, with no clinically relevant adverse events reported. [ABSTRACT FROM AUTHOR]

A total of 125 outpatients with moderate to severe pain after surgical removal of one impacted third molar were randomly assigned to receive dexketoprofen trometamol 12.5 or 25 mg or dipyrone 575 mg. For first-dose assessments, patients rated their pain intensity and its relief at regular intervals. From 60 min post dose to the end of the 6-h observation period, both doses of dexketoprofen trometamol had higher pain relief scores than dipyrone: Between 3 and 6 h the differences were statistically significant In addition, peak measures (PIDmax and PARmax) were statistically superior after both doses of dexketoprofen trometamol compared to dipyrone, The overall efficacy assessed at the end of the first-dose phase was rated as good or excellent by 90%, 83.3%, and 70% of patients receiving dexketoprofen trometamol 25 mg, dexketoprofen trometamol 12.5 mgt and dipyrone, respectively. The number of patients who required remedication during the 6-h period was significantiy lower in both dexketoprofen groups. Repeated-dose data were also obtained. No significant differences were found in the efficacy after repeated doses, the number of doses taken, or the mean time elapsed between doses. The overall efficacy at the end of the repeated-dose phase was rated as good or excellent by 84.2%, 66.7%, and 70% of patients receiving dexketoprofen trometamol 25 mg, dexketoprofen trometamol 12.5 mg, and dipyrone, respectively. The frequency of adverse events was similar for all treatments and no serious adverse events were reported during the study. [ABSTRACT FROM AUTHOR]

Recent reports have disagreed on whether the bioavailability of S(+)-ketoprofen is affected by the presence of R(-)-ketoprofen. To examine this directly, we designed a randomized crossover study in beagle dogs. [14C]- S(+)-ketoprofen trometamol and R(-)-ketoprofen trometamol were administered in the following percentage ratios: A, 99:1; B, 95:5; C, 90:10; D, 70:30; E, 50:50. Treatments were administered as a single oral dose of 1 mg/kg trometamol salt Each of eight dogs received all five combinations in random order with a 1-week washout period between doses. Blood samples were taken before drug administration and at regular intervals for 240 min after dosing. A progressive increase in the plasma concentration of [14C]-S(+)-ketoprofen was observed on going from treatment E (lowest dose of S-enantiomer) to treatments containing the highest doses of [14C]-S(+)-ketoprofen. When the pharmacokinetic calculations were normalized to the dose of [14C]-S(+)-ketoprofen, we found no statistically significant differences among the normalized AUC and Cmax values of the five treatments. Therefore, S(+)-ketoprofen absorption was linear and was not influenced by the presence of R(-)-ketoprofen. Furthermore, there were no significant differences in tmax values among treatments, indicating that the rate of S(+)-ketoprofen absorption was also unaffected by the presence of R( -- )-ketoprofen. [ABSTRACT FROM AUTHOR]

This randomized three-way, crossover pharmacokinetic study was performed to determine whether food oran antacid alters the bioavailability of dexketoprofen trometamol A total of 24 healthy volunteers received three single 25 mg doses of dexketoprofen trometamol administered either in fasting condition, after an antacid (Maalox®), or after a high-fat breakfast. Each volunteer received the three treatments in a randomized order, with a 7-day washout period between treatments. Blood samples were taken at regular intervals up to 24 h after dose. Plasma dexketoprofen concentrations were determined by HPLC and the main outcome measures were area under curve of concentration vs. time (AUC0-∞), maximal plasma concentration (Cmax), and time to reach maximal concentration (tmax). Administration of an antacid 10 min before dexketoprofen trometamol had no clinically relevant effect on any of the pharmacokinetic parameters. Food did not alter the extent of absorption of dexketoprofen trometamol, but tmax was significantly increased and Cmax significantly decreased compared with the fasting state. In conclusion, we can state that neither antacid nor food has a significant effect on the overall bioavailability of dexketoprofen trometamol. [ABSTRACT FROM AUTHOR]

The efficacy and tolerability of single doses of dexketoprofen trometamol 12.5 mg, 25 mg, and 50 mg and ketoprofen 50 mg were compared in this double-blind, randomized, placebo-controlled study of 210 patients with moderate to severe pain after removal of one mandibular impacted third molar tooth. Pain intensity and pain relief were monitored for 6 h after administration of medication using visual analogue and verbal rating scales. All four active treatments were significantly more effective than placebo (P < 0.001). Dexketoprofen 25 mg and 50 mg produced an analgesic effect within 30 min of administration and their effect persisted for 6 h. Ketoprofen 50 mg produced a level of analgesia similar to those of the higher doses of dexketoprofen trometamol, but it had a slower onset. The 12.5-mg dose of dexketoprofen trometamol was significantly superior to placebo but produced a lower level and shorter duration of analgesia compared to the other active treatments. There were no significant differences between 25 and 50 mg of dexketoprofen trometamol in any measure of analgesic efficacy. No serious adverse events were observed and there were no significant differences in the incidence of adverse events among treatment groups. These results demonstrate that dexketoprofen trometamol 25 mg is at least as effective as the racemic ketoprofen 50 mg in the treatment of postsurgical dental pain. The more rapid onset of action compared to ketoprofen suggests that dexketoprofen trometamol is more appropriate for treatment of acute pain. [ABSTRACT FROM AUTHOR]

The stereoselective inhibition of inducible cyclooxygenase (COX-2) by chiral nonsteroidal antiinflammatory drugs (NSAIDs)-ketoprofen, flurbiprofen, and ketorolac-has been investigated. The activity and inhibition of COX-2 was assessed in three different in vitro systems: guinea pig whole blood, lipopolysaccharide (LPS)-stimulated human monocytes, and purified preparations of COX-2 from sheep placenta. The results were compared with the inhibition of constitutive cyclooxygenase (COX-1) in three parallel in vitro models: clotting guinea pig blood, human polymorphonuclear leukocytes, and purified COX-1 from ram seminal vesicles. In the whole blood model, both isoenzymes were inhibited by S- enantiomers with equal potency but S- ketoprofen was the most active on COX-2 (IC50 = 0.024 μmol/L). In contrast, both isoenzymes were inhibited less than 40% by all three R- enantiomers at high concentration (>1 μmol/L). The inhibition of COX by the R- enantiomers may be attributed to contamination with the S- enantiomers (approximately 0.5%). A significant degree of enantioselectivity in COX-2 inhibition was also observed in intact cells. The S- enantiomers inhibited COX-2 from monocytes with IC50 values in the range of 2 to 25 nmol/L, being 100 to 500-fold more potent than the corresponding R- enantiomers. Finally, S- ketoprofen inhibited COX-2 from sheep placenta (IC50 = 5.3 μmol/L) with slightly less potency than S- ketorolac (IC50 = 0.9 μmol/L) and S-flurbiprofen (IC50 = 0.48 μmol/L), whereas the R- enantiomers were found to be essentially inactive (IC50 ≥ 80 μmol/L). It is concluded that the chiral NSAIDs studied here inhibit with comparable stereoselectivity both COX-2 and COX-1 isoenzymes, and that the inhibition of COX-2 previously observed for racemic NSAIDs should be attributed almost exclusively to their S-enantiomers. [ABSTRACT FROM AUTHOR]

It′s hip to be square: The search for methods for the enantioselective construction of carbocycles continues to fuel new discoveries. Now, the treatment of mixtures of sulfonylallenamides and styrenes with gold(I)‐phosphoramidite complexes results in the formation of cyclobutene carbon frameworks in high yield and optical purity. [ABSTRACT FROM AUTHOR]

Occupational airborne contact dermatitis from disinfectants are not frequent. They are usually seen in hospitals, were the exposure is more common. We report a case of a young woman, with an intense eczematous eruption that developed hours after an accidental contact with a cleaning solution. [ABSTRACT FROM AUTHOR]

In recent years, H2 activation at non‐transition‐metal centers has met with increasing attention. Here, a system in which H2 is activated and transferred to aldimines and ketimines using substoichiometric amounts of lithium bis(trimethylsilyl)amide is reported. Notably, the reaction tolerates the presence of acidic protons in the α‐position. Mechanistic investigations indicated that the reaction proceeds via a lithium hydride intermediate as the actual reductant. An alternative H2 activation: LiN(SiMe3)2, even in substoichiometric amounts, induces clean reduction of aldimines and ketimines with H2 as the reductant at moderate temperatures in the range 25–80 °C. Notably, the reaction tolerates the presence of acidic protons in the α‐position. Mechanistic investigations indicated that the reaction proceeds via a lithium hydride intermediate as the actual reductant. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the case of a 7-year-old Ecuadorian child, who was diagnosed with phacomatosis spilorosea appearing as reddish patches of the skin.

Das Abfangen von H2 mit einem Pyridyliden, das aus dem Pyridinium ‐ Salz und einer Base gewonnen wurde, beschreiben A. Pfaltz, P. Mauleón et al. in ihrer Zuschrift auf S. 9678 ff. Diese Wasserstoff ‐ Aktivierung kann mit einem Hydridtransfer zu einem Imin in einem katalytischen Prozess kombiniert werden. So liefert das N ‐ Phenylimin von Phenyltrifluormethylketon in Gegenwart von N ‐ Mesityl ‐ 3,5 ‐ bis(2,6 ‐ dimethylphenyl)pyridiniumtriflat und LiN(SiMe3)2 unter Wasserstoffatmosphðre (50 bar) mit hohem Umsatz das entsprechende Amin. [ABSTRACT FROM AUTHOR]

The trapping of H2 with a pyridylidene generated from a pyridinium salt and base is reported by A. Pfaltz, P. Mauleón et al. in their Communication on page 9542 ff. By coupling H2 activation with subsequent hydride transfer to an imine, a catalytic process was established. Treatment of the N‐phenylimine of phenyl trifluoromethyl ketone with N‐mesityl‐3,5‐bis(2,6‐dimethylphenyl)pyridinium triflate and LiN(SiMe3)2 under 50 bar of H2 resulted in high conversion into the corresponding amine. [ABSTRACT FROM AUTHOR]