Directing a Non-Heme Iron(III)-Hydroperoxide Species on a Trifurcated Reactivity Pathway.

The reactivity of [FeIII (tpena)]2+ (tpena=N,N,N'-tris(2-pyridylmethyl)ethylenediamine-N'-acetate) as a catalyst for oxidation reactions depends on its ratio to the terminal oxidant H2 O2 and presence or absence of sacrificial substrates. The outcome can be switched between: 1) catalysed H2 O2 disproportionation, 2) selective catalytic oxidation of methanol or benzyl alcohol to the corresponding aldehyde, or 3) oxidative decomposition of the tpena ligand. A common mechanism is proposed involving homolytic O-O cleavage in the detected transient purple low-spin (S=1/2 ) [(tpenaH)FeIII O-OH]2+ . The resultant iron(IV) oxo and hydroxyl radical both participate in controllable hydrogen-atom transfer (HAT) reactions. Consistent with the presence of a weaker σ-donor carboxylate ligand, the most pronounced difference in the spectroscopic properties of [Fe(OOH)(tpenaH)]2+ and its conjugate base, [Fe(OO)(tpenaH)]+ , compared to non-heme iron(III) peroxide analogues supported by neutral multidentate N-only ligands, are slightly blue-shifted maxima of the visible absorption band assigned to ligand-to-metal charge-transfer (LMCT) transitions and, corroborating this, lower FeIII /FeII redox potentials for the pro-catalysts.

Interactions between nanoparticles and lung surfactant investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

RATIONALE: Inhaled nanoparticles may cause adverse effects due to inactivation of lung surfactants. We have studied how three different nanoparticles interact with dipalmitoyl-phosphatidylcholine (DPPC), the main component in lung surfactant. METHODS: DPPC in solution was mixed with a suspension of nanoparticles, both in organic solvent, and allowed to interact for 40 min under conditions partly resembling the alveolar lining. Nanoparticles were isolated by centrifugation, washed, and re-suspended in ethanol/water 1:1 (v/v). The resulting solution was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) using dihydroxybenzoic acid as matrix. RESULTS: The developed methodology was successfully applied for quantitative detection of phospholipid lung surfactant bound to three different types of nanoparticles. Titanium dioxide nanoparticles had a strong affinity for binding of lipid lung surfactant in contrast to pristine and methylated silica nanoparticles. When the concentration of lipid surfactant was raised in the reaction mixture, the titanium dioxide nanoparticles showed an apparently non-linear binding process. CONCLUSIONS: This work demonstrates that MALDI-TOFMS can be used for direct determination of the binding of surfactant lipids to nanoparticles and represents an important initial step towards a simple and quantitative in vitro method for assessment of interactions of nanoparticles with lung surfactants.

Rapid screening of drug compounds in urine using a combination of microextraction by packed sorbent and rotating micropillar array electrospray ionization mass spectrometry.

RATIONALE: Screening of drugs from urine samples can be non-selective or laborous, using either immunological, gas chromatography/mass spectrometry (GC/MS) or liquid chromatography (LC)/MS methods. Therefore, a rapid screening method for selected drugs in urine sample was developed in a proof-of-principle manner, utilizing simple and fast techniques for both sample treatment and sample analysis. METHODS: Sample treament of spiked urine samples was performed with microextraction by packed sorbent (MEPS). Five different sorbent materials (C(2), C(8), C(18), M1 (cation exchanger), and Sil (pure silica)) were tested for the MEPS. The sample analysis was performed using a circular microchip with 60 micropillar electrospray ionization (µPESI) tips combined with a mass spectrometer (either a triple-quadrupole or ion-trap mass spectrometer) without any chromatographic step. RESULTS: The sample treatment/analysis setup was tested using three drug compounds at a concentration of 1 µM. We found that the C(2), C(8) and C(18) sorbents in combination with 96% alkaline methanol as an eluent worked the best. All compounds were easily detected and identified by MS/MS in spiked urine samples. The whole qualitative analytical procedure was rapid as the sample treatment together with the MS analysis took about 5 min per sample. CONCLUSIONS: A rapid screening method for selected drugs from urine samples was developed, providing adequate selectivity and sensitivity, as well as a short total analysis cycle time. This new method can provide a new alternative for screening purposes, as both the extraction and analysis steps could be totally automatized.

Linking soil O2, CO2, and CH4 concentrations in a Wetland soil: implications for CO2 and CH4 fluxes.

Oxygen (O(2)) availability and diffusivity in wetlands are controlling factors for the production and consumption of both carbon dioxide (CO(2)) and methane (CH(4)) in the subsoil and thereby potential emission of these greenhouse gases to the atmosphere. To examine the linkage between high-resolution spatiotemporal trends in O(2) availability and CH(4)/CO(2) dynamics in situ, we compare high-resolution subsurface O(2) concentrations, weekly measurements of subsurface CH(4)/CO(2) concentrations and near continuous flux measurements of CO(2) and CH(4). Detailed 2-D distributions of O(2) concentrations and depth-profiles of CO(2) and CH(4) were measured in the laboratory during flooding of soil columns using a combination of planar O(2) optodes and membrane inlet mass spectrometry. Microsensors were used to assess apparent diffusivity under both field and laboratory conditions. Gas concentration profiles were analyzed with a diffusion-reaction model for quantifying production/consumption profiles of O(2), CO(2), and CH(4). In drained conditions, O(2) consumption exceeded CO(2) production, indicating CO(2) dissolution in the remaining water-filled pockets. CH(4) emissions were negligible when the oxic zone was >40 cm and CH(4) was presumably consumed below the depth of detectable O(2). In flooded conditions, O(2) was transported by other mechanisms than simple diffusion in the aqueous phase. This work demonstrates the importance of changes in near-surface apparent diffusivity, microscale O(2) dynamics, as well as gas transport via aerenchymous plants tissue on soil gas dynamics and greenhouse gas emissions following marked changes in water level.

Nebulization ionization and desorption ionization analysis of reactive organofunctionalized silanes in nanofilm products.

Three different and recently developed desorption ionization techniques, transmission-mode desorption electrospray ionization (TM-DESI), low temperature plasma (LTP) ionization and nano-assisted laser desorption ionization (NALDI), are compared with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) for the analysis of two nanofilm products (NFPs) for surface coating, which contain hydrolysates and condensates of organo-functionalized silanes. The NFPs were characterized in different states from the liquid phase to the fully formed surface film. The LTP spectra were dominated by the silanes, while the corresponding di-, tri- and tetrasiloxanes were common in ESI, APCI and TM-DESI. This indicates readily condensation of the silanes during the ESI and APCI ionization processes leading to the observed siloxanes. NALDI showed larger siloxane structures than the other techniques, indicating film formation on the NALDI target. Real-time monitoring of the film formation on a glass surface by LTP showed a decreasing abundance of the silanes, while the abundances of the di-, tri and tetrasiloxanes increased significantly within the first 100 s. LTP was superior in showing the non-reacted content of the NFPs, while ESI, APCI and TM-DESI were characterized by artefact formation of siloxanes. NALDI was ideal for showing the siloxane structures of the formed film. The applicabilities of each of the ionization techniques were examined, showing the advantage of utilizing more than one ionization technique for the analysis of reactive species.

Real-time monitoring of the progress of polymerization reactions directly on surfaces at open atmosphere by ambient mass spectrometry.

The progress of an on-surface polymerization process involving alkyl and perfluoroalkyl silanes and siloxanes was monitored in real-time via easy ambient sonic spray ionization mass spectrometry (EASI-MS). When sprayed on surfaces, the organosilicon compounds present in commercially available nanofilm products (NFPs) react by condensation to form a polymeric coating. A NFP for coating of floor materials (NFP-1) and a second NFP for coating tiles and ceramics (NFP-2) were applied to glass, filter paper or cotton surfaces and the progress of the polymerization was monitored by slowly scanning the surface. Via EASI(+)-MS monitoring, significant changes in the composition of hydrolysates and condensates of 1H,1H,2H,2H-perfluorooctyl triisopropoxysilane (NFP-1) and hexadecyl triethoxysilane (NFP-2) were observed over time. The abundances of the hydrolyzed species decreased compared with those of the non-hydrolysed species for both NFP-1 and NFP-2 and the heavier oligomers became relatively more abundant over a period of 15-20 min. A similar tendency favouring the heavier oligomers was observed via EASI(-)-MS. This work illustrates the potential of ambient mass spectrometry for the direct monitoring of polymerization reactions on surfaces.

Clinical features of facioscapulohumeral muscular dystrophy 2.

OBJECTIVE: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and FSHD2. The aim of our study was to critically evaluate the clinical features in patients with FSHD2 in order to establish whether these patients are phenotypically identical to FSHD1 and to establish the effects of the (epi-) genotype on the phenotype. METHODS: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. RESULTS: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. CONCLUSIONS: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process.

Characterization of nanofilm spray products by mass spectrometry.

The use of nanofilm spray products (NFPs) has been associated with a number of severe cases of airway injuries; however, the causative agents are unknown. To identify possible causative agents, 10 products from three different suppliers have been analysed using two mass spectrometric methods: (1) ESI-MS and ESI-MS/MS; (2) GC-MS and GC-MS/MS. The 10 products could be classified into three groups (NFPs 1-3). NFP 1 and NFP 2 contained hydrolysates and condensates of the organo-functionalized silanes 1H,1H,2H,2H-perfluorooctyl triisopropoxysilane and hexadecyl triethoxysilane, respectively. NFP 3 contained non-ionic detergents and abrasive as active ingredients. To verify the fluorosilane solution in NFP 1, a synthetic NFP 1 was prepared by hydrolysis and condensation of 1H,1H,2H,2H-perfluorooctyl triethoxysilane. After about 1month in acidic 2-propanol substitution of the ethoxy groups with isopropoxy groups had taken place and all silane was converted to disiloxanes, trisiloxanes and tetrasiloxanes.

Insulin-resistance and metabolic syndrome are related to executive function in women in a large family-based study.

While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)-levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population. All participants underwent physical examinations, biomedical measurements, and neuropsychological testing. Linear regression models were used to determine the association between MetS, HOMA-IR, adiponectin levels, CRP, and cognitive test scores. Cross-sectional analyses were performed in 1,898 subjects (mean age 48 years, 43% men). People with MetS had significantly higher HOMA-IR scores, lower adiponectin levels, and higher CRP levels. MetS and high HOMA-IR were associated with poorer executive function in women (P = 0.03 and P = 0.009). MetS and HOMA-IR are associated with poorer executive function in women.

[Facioscapulohumeral muscular dystrophy]. / Facioscapulohumerale spierdystrofie.

Facioscapulohumeral muscular dystrophy is clinically mainly characterized by progressive weakness of the facial, shoulder and upper arm muscles. It is an autosomal dominant heriditary disease, caused by a contraction of a repetitive DNA element at the end of the long arm of chromosome 4. This contraction causes the local relaxation of the chromatin structure and likely dysregulation of one or more genes. Oral health care providers can play a significant role in the early recognition, as the often asymmetric facial weakness is frequently the first symptom. Adequate oral health care is needed because of the facial weakness.

Shared genetic factors in migraine and depression: evidence from a genetic isolate.

OBJECTIVE: To investigate the co-occurrence of migraine and depression and assess whether shared genetic factors may underlie both diseases. METHODS: Subjects were 2,652 participants of the Erasmus Rucphen Family genetic isolate study. Migraine was diagnosed using a validated 3-stage screening method that included a telephone interview. Symptoms of depression were assessed using the Center for Epidemiologic Studies Depression scale and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). The contribution of shared genetic factors in migraine and depression was investigated by comparing heritability estimates for migraine with and without adjustment for symptoms of depression, and by comparing the heritability scores of depression between migraineurs and controls. RESULTS: We identified 360 migraine cases: 209 had migraine without aura (MO) and 151 had migraine with aura (MA). Odds ratios for depression in patients with migraine were 1.29 (95% confidence interval [CI] 0.98-1.70) for MO and 1.70 (95% CI 1.28-2.24) for MA. Heritability estimates were significant for all migraine (0.56), MO (0.77), and MA (0.96), and decreased after adjustment for symptoms of depression or use of antidepressant medication, in particular for MA. Comparison of the heritability scores for depression between patients with migraine and controls showed a genetic correlation between HADS-D score and MA. CONCLUSIONS: There is a bidirectional association between depression and migraine, in particular migraine with aura, which can be explained, at least partly, by shared genetic factors.

On-line monitoring of the dynamics of trihalomethane concentrations in a warm public swimming pool using an unsupervised membrane inlet mass spectrometry system with off-site real-time surveillance.

To study the long-term dynamics of trihalomethanes (THMs) in a warm (31-33 degrees C) public swimming pool, we built a robust membrane inlet mass spectrometer that could perform unsupervised, on-site monitoring of the concentration of these compounds with off-site, real-time surveillance. The instrument was installed in a technical room below the pool and operated continuously for more than a year practically only interrupted for filament replacements every 6-8 weeks. One to two days after a filament replacement, the instrument stabilized and kept its calibration until shortly before the next filament burnout. The on-line monitoring of THMs revealed a daily rhythm in the concentrations of chloroform and bromodichloromethane. They increased during the pool's closing hours and decreased during opening hours with the minimum concentration being approximately half of the maximum. Over the 1 year monitoring period, the variation in the maximum registered daily concentration was 30-100 microg/L for chloroform. The variation of bromodichloromethane was 5-10 microg/L, except during bursts of 1-2 days duration, where the concentration of bromodichloromethane could reach 100 microg/L. The burst in bromodichloromethane concentration was directly correlated with salt addition (sodium chloride) to the pool water for use in the pool's electrolytic in-line chlorination system. A correlation between THM removal from the pool water and the operation of a strong water jet system was also found.

Menopause impacts the relation of plasma adiponectin levels with the metabolic syndrome.

OBJECTIVE: Plasma adiponectin is negatively correlated with metabolic syndrome (MetS) components obesity and insulin sensitivity. Here, we set out to evaluate the effect of menopause on the association of plasma adiponectin with MetS. DESIGN: Data on plasma adiponectin and MetS were available from 2256 individuals participating in the Erasmus Rucphen Family study. Odds ratios for MetS were calculated by logistic regression analysis using plasma adiponectin quartiles. The discriminative accuracy of plasma adiponectin for MetS was determined by calculating the area under the curve (AUC) of receiver operator. Analyses were performed in women and men, pre- and postmenopausal women and younger and older men. RESULTS: Virtually all determinants of MetS differed significantly between groups. Low plasma adiponectin showed the highest risk for MetS in postmenopausal women (odds ratio = 18.6, 95% CI = 7.9-44.0). We observed a high discriminative accuracy of age and plasma adiponectin for MetS not only in postmenopausal women (AUC = 0.76) but also in other subgroups (AUC from 0.67 to 0.87). However, in all groups, the discriminative accuracy of age and body mass index (BMI) for MetS was similar to the discriminative accuracy of age and plasma adiponectin. CONCLUSIONS: Low plasma levels of adiponectin are associated with increased prevalence of MetS, especially in postmenopausal women. Age and BMI have similar discriminatory accuracies for presence of MetS when compared with age and plasma adiponectin. Thus, we conclude that the association of plasma adiponectin with MetS is significantly affected by menopause but challenge the additional value of adiponectin for the discriminatory accuracy for presence of MetS.

Release of VOCs and particles during use of nanofilm spray products.

Here, we present emission data on VOCs and particles emitted during simulated use of four commercial nanofilm spray products (NFPs) used for making easy-to-clean or self-cleaning surfaces on floors, ceramic tiles, and windows. The aim was to characterize the emitted VOCs and to provide specific source strength data for VOCs and particles released to the airduring use of the products. Containers with NFP were mounted on a spray-stand inside a closed stainless steel chamber with no air exchange. NFPs were sprayed in amounts corresponding to 1 m2 surface toward a target plate at a distance of 35 cm. Released VOCs were measured by a combination of air sampling on Tenax TA adsorbent followed by thermal desorption GC/MS and GC/FID analysis and real time measurements using a miniature membrane inlet mass spectrometer. Particles were measured using a fast mobility particle sizer and an aerosol particle sizer. A number of VOCs were identified, including small alcohols, ketones and ethers, chlorinated acetones, a perfluorinated silane, limonene, and cyclic siloxanes. The number of generated particles was on the order of 3 x 10(8) to 2 x 10(10) particles/m3 per g sprayed NFP and were dominated by nanosize particles.

Early seizures and cerebral oedema after trivial head trauma associated with the CACNA1A S218L mutation.

OBJECTIVE: To study the clinical spectrum of CACNA1A S218L mutation carriers with special attention to "early seizures and cerebral oedema after trivial head trauma (ESCEATHT)", a combination of symptoms which resembles the "juvenile head trauma syndrome". PATIENTS AND METHODS: In two patients with ESCEATHT all exons of CACNA1A were sequenced. Both patients also had hemiplegic migraine and ataxia. Subsequently, we screened the literature for S218L mutation carriers. RESULTS: In both patients, a de novo S218L mutation in the CACNA1A gene was found. In addition, we identified 11 CACNA1A S218L carriers from the literature. Of these 13 S218L mutation carriers, 12 (92%) had ataxia or cerebellar symptoms and nine (69%) had hemiplegic migraine that could be triggered by trivial head trauma. Three mutation carriers had the complete ESCEATHT phenotype. Seven (54%) had seizures (four had early post-traumatic seizures) and five (38%) had oedema as detected by MRI/CT. CONCLUSIONS: The CACNA1A S218L mutation is associated with familial hemiplegic migraine, ataxia and/or ESCEATHT. A minority of S218L mutation carriers have the complete ESCEATHT phenotype but a high percentage of patients had one or more ESCEATHT symptoms. As the S218L mutation enhances the propensity for cortical spreading depression (CSD), we postulate a role for CSD not only in hemiplegic migraine but also in early seizures and cerebral oedema after trivial head trauma. As this combination of symptoms is part of the unexplained "juvenile head trauma syndrome", a similar molecular mechanism may underlie this disorder.

Analysis of semivolatile pharmaceuticals and pollutants in organic micro extracts using hot cell membrane inlet mass spectrometry.

This paper presents the first membrane inlet method that can be used together with field portable mass spectrometers for the analysis of semivolatile pharmaceuticals (pethidine, benzophenone, and cocaine) and environmental pollutants (terbutryne and butylated hydroxyl toluene (BHT)) dissolved in organic micro extracts. A microliter of the organic extract is simply injected into a closed hot cell membrane inlet (hc-MIMS), and an electron ionization mass spectrum of the vaporized semivolatile sample molecules can be recorded shortly thereafter. Detection limits at low picomole quantities or low/sub ng/microL concentrations in the extract are demonstrated for solutes in methanol, ethanol, acetone, and toluene. A linear correlation between analyte concentration and signal was found in the range of 1-100 ng/microL, and the relative standard deviation (RSD) was approximately 10%. As a practical example we demonstrate the detection of cocaine in extracts from dried coca leaves. The analysis of organic micro extracts using hc-MIMS represents a considerable extension of the type and complexity of analytes that can be measured using a field portable MIMS system, since it does not require special and field tedious modifications to the standard MIMS system.

First mutation in the voltage-gated Nav1.1 subunit gene SCN1A with co-occurring familial hemiplegic migraine and epilepsy.

Almost all mutations in the SCN1A gene, encoding the alpha(1) subunit of neuronal voltage-gated Na(V)1.1 sodium channels, are associated with severe childhood epilepsy. Recently, two mutations were identified in patients with pure familial hemiplegic migraine (FHM). Here, we identified a novel SCN1A L263V mutation in a Portuguese family with partly co-segregating hemiplegic migraine and epilepsy. The L263V mutation segregated in five FHM patients, three of whom also had epileptic attacks, occurring independently from their hemiplegic migraine attacks. L263V is the first SCN1A mutation associated with FHM and co-occurring epilepsy in multiple mutation carriers, and is the clearest molecular link between migraine and epilepsy thus far. The results extend the clinical spectrum associated with SCN1A mutations and further strengthen the molecular evidence that FHM and epilepsy share, at least in part, similar molecular pathways.

Fast and direct screening of solid materials for their potential liberation of hydrophobic organic compounds using hot cell membrane inlet mass spectrometry.

We demonstrate that solid materials can be screened directly and without any pretreatment for their potential liberation of chemicals into the surroundings using a hot (150-250 degrees C) sample cell membrane inlet mass spectrometer with electron ionization. Three very different types of solids were tested: polymers (in this context regarded as a solid), tea leaves and pesticide-contaminated soil. From the polymers phthalates and other additives were liberated; from the tea leaves flavor additives and caffeine were liberated; and from the contaminated soil degradation products of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) were liberated. In all cases we detected characteristic compounds directly from the untreated sample with an analytical turnover of 8-10 samples per hour. Improved selectivity of compounds penetrating the membrane was achieved either by operating the hot cell at different temperatures or by using variations in the time trend of individual ions following insertion of a piece of the solid material into the hot cell.

Prevalence and heritability of the metabolic syndrome and its individual components in a Dutch isolate: the Erasmus Rucphen Family study.

BACKGROUND: Metabolic syndrome (MetS) is defined by a combination of abnormalities that are all individual risk factors for the development of type 2 diabetes and/or cardiovascular disease. The aetiology of MetS includes both an environmental and genetic component. We studied the prevalence and heritability of MetS and its individual components Dutch genetic isolate. METHODS: The Erasmus Rucphen Family study (ERF) consists of some 3000 genealogically documented individuals from a Dutch genetic isolate. Data on waist circumference (WC), blood pressure (BP), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and fasting plasma glucose values (FPG) are available. MetS was defined according to the International Diabetes Federation (IDF) (2003) and National Cholesterol Education program Adult Panel III (NCEP ATPIII) criteria. Variance component analysis was applied to extended family data to test for evidence of heritability. RESULTS: The prevalence of MetS in the ERF cohort ranged from 23-37% depending on MetS definition and gender considered. Low HDL-C and high WC are the main contributors to MetS. The heritability of MetS corrected for sibship effect was 10.6% (p = 0.01) according to IDF and 13.2% (p = 0.07) according to NCEP ATPIII criteria. In addition, the heritability of individual components of MetS were analysed and found to range from 21.9-42.9%. The highest heritability was found for HDL-C (42.9%, p<0.0001) and WC (37.8%, p<0.0001). In addition, WC, systolic BP, HDL-C and TG showed low to moderate genetic correlation (RhoG) between genders, whereas FPG and diastolic BP showed absolute genetic correlation between genders. CONCLUSION: Although the prevalence of MetS was high, the heritability of MetS in the ERF population was found to be moderate. The high heritability of the individual components of MetS indicates that the genetic dissection of MetS should be approached from its individual components.