Low-Protein Infant Formula Enriched with Alpha-Lactalbumin during Early Infancy May Reduce Insulin Resistance at 12 Months: A Follow-Up of a Randomized Controlled Trial.

High protein intake during infancy results in accelerated early weight gain and potentially later obesity. The aim of this follow-up study at 12 months was to evaluate if modified low-protein formulas fed during early infancy have long-term effects on growth and metabolism. In a double-blinded RCT, the ALFoNS study, 245 healthy-term infants received low-protein formulas with either alpha-lactalbumin-enriched whey (α-lac-EW; 1.75 g protein/100 kcal), casein glycomacropeptide-reduced whey (CGMP-RW; 1.76 g protein/100 kcal), or standard infant formula (SF; 2.2 g protein/100 kcal) between 2 and 6 months of age. Breastfed (BF) infants served as a reference. At 12 months, anthropometrics and dietary intake were assessed, and serum was analyzed for insulin, C-peptide, and insulin-like growth factor 1 (IGF-1). Weight gain between 6 and 12 months and BMI at 12 months were higher in the SF than in the BF infants (p = 0.019; p < 0.001, respectively), but were not significantly different between the low-protein formula groups and the BF group. S-insulin and C-peptide were higher in the SF than in the BF group (p < 0.001; p = 0.003, respectively), but more alike in the low-protein formula groups and the BF group. Serum IGF-1 at 12 months was similar in all study groups. Conclusion: Feeding modified low-protein formula during early infancy seems to reduce insulin resistance, resulting in more similar growth, serum insulin, and C-peptide concentrations to BF infants at 6-months post intervention. Feeding modified low-protein formula during early infancy results in more similar growth, serum insulin, and C-peptide concentrations to BF infants 6-months post intervention, probably due to reduced insulin resistance in the low-protein groups.

Solvent-free automated thermal desorption-gas chromatography/mass spectrometry for direct screening of hazardous compounds in consumer textiles.

The global production of textiles utilizes numerous large-volume chemicals that may remain to some extent in the finished garments. Arylamines, quinolines, and halogenated nitrobenzene compounds are possible mutagens, carcinogens and/or skin sensitizers. For prevention, control of clothing and other textiles must be improved, especially those imported from countries without regulations of textile chemicals. An automated analytical methodology with on-line extraction, separation, and detection would largely simplify screening surveys of hazardous chemicals in textiles. Automated thermal desorption-gas chromatography/mass spectrometry (ATD-GC/MS) was developed and evaluated as a solvent-free, direct chemical analysis for screening of textiles. It requires a minimum of sample handling with a total run time of 38 min including sample desorption, chromatographic separation, and mass spectrometric detection. For most of the studied compounds, method quantification limit (MQL) was below 5 µg/g for 5 mg of textile sample, which is sufficiently low for screening and control of quinoline and arylamines regulated by EU. Several chemicals were detected and quantified when the ATD-GC/MS method was applied in a limited pilot screening of synthetic fiber garments. A number of arylamines were detected, where some of the halogenated dinitroanilines were found in concentrations up to 300 µg/g. This is ten times higher than the concentration limit for similar arylamines listed by the EU REACH regulation. Other chemicals detected in the investigated textiles were several quinolines, benzothiazole, naphthalene, and 3,5-dinitrobromobenzene. Based on the present results, we suggest ATD-GC/MS as a screening method for the control of harmful chemicals in clothing garments and other textiles.

Patients' Perceptions of Exercise-Based Cardiac Telerehabilitation after a Myocardial Infarction-A Qualitative Study.

To be able to design telerehabilitation programs targeting the needs and preferences of end-users, patients' in-depth perspectives are needed. To date, such studies are lacking and, therefore, the aim of the present study was to describe patients' perceptions of performing exercise-based cardiac telerehabilitation after a myocardial infarction (MI). Individual semi-structured interviews were performed with 15 patients (3 women, median age 69 years) after an MI who had participated in exercise-based cardiac telerehabilitation for three months. The interviews were transcribed verbatim and analyzed with inductive content analysis. An overall theme was defined as "Cardiac telerehabilitation-a new alternative for exercising that is easily accessible and up to date". Four categories, including "The important role of a physical therapist with expert knowledge", "Prerequisites playing an important role in the willingness to participate", "Making exercise accessible and adjustable" and "Inspiring future exercise", and 15 subcategories were identified. Understanding the patient's perspective is an important key to further improving and successfully implementing exercise-based cardiac telerehabilitation, as an alternative or adjunct to traditional, centre-based programs. The findings can serve to improve patient-physiotherapist interactions and to inform important aspects related to exercise, technology and a sense of security from an exercise-based cardiac telerehabilitation program.

Low-Protein Formulas with Alpha-Lactalbumin-Enriched or Glycomacropeptide-Reduced Whey: Effects on Growth, Nutrient Intake and Protein Metabolism during Early Infancy: A Randomized, Double-Blinded Controlled Trial.

Protein intake is higher in formula-fed than in breast-fed infants during infancy, which may lead to an increased risk of being overweight. Applying alpha-lactalbumin (α-lac)-enriched whey or casein glycomacropeptide (CGMP)-reduced whey to infant formula may enable further reduction of formula protein by improving the amino acid profile. Growth, nutrient intake, and protein metabolites were evaluated in a randomized, prospective, double-blinded intervention trial where term infants received standard formula (SF:2.2 g protein/100 kcal; n = 83) or low-protein formulas with α-lac-enriched whey (α-lac-EW;1.75 g protein/100 kcal; n = 82) or CGMP-reduced whey (CGMP-RW;1.76 g protein/100 kcal; n = 80) from 2 to 6 months. Breast-fed infants (BF; n = 83) served as reference. Except between 4 and 6 months, when weight gain did not differ between α-lac-EW and BF (p = 0.16), weight gain was higher in all formula groups compared to BF. Blood urea nitrogen did not differ between low-protein formula groups and BF during intervention, but was lower than in SF. Essential amino acids were similar or higher in α-lac-EW and CGMP-RW compared to BF. Conclusion: Low-protein formulas enriched with α-lac-enriched or CGMP-reduced whey supports adequate growth, with more similar weight gain in α-lac-enriched formula group and BF, and with metabolic profiles closer to that of BF infants.

Diversity and population structure of Nordic potato cultivars and breeding clones.

BACKGROUND: The genetic diversity and population structure of breeding germplasm is central knowledge for crop improvement. To gain insight into the genetic potential of the germplasm used for potato breeding in a Nordic breeding program as well as all available accessions from the Nordic genebank (NordGen), 133 potato genotypes were genotyped using the Infinium Illumina 20 K SNP array. After SNP filtering, 11 610 polymorphic SNPs were included in the analysis. In addition, data from three important breeding traits - percent dry matter and uniformity of tuber shape and eye - were scored to measure the variation potato cultivars and breeding clones. RESULTS: The genetic diversity among the genotypes was estimated using principal coordinate analysis based on the genetic distance between individuals, as well as by using the software STRUCTURE. Both methods suggest that the collected breeding material and the germplasm from the gene-bank are closely related, with a low degree of population structure between the groups. The phenotypic distribution among the genotypes revealed significant differences, especially between farmer's cultivars and released cultivars and breeding clones. The percent heterozygosity was similar between the groups, with a mean average of 58-60%. Overall, the breeding germplasm and the accessions from the Nordic genebank seems to be closely related with similar genetic background. CONCLUSION: The genetic potential of available Nordic potato breeding germplasm is low, and for genetic hybridization purposes, genotypes from outside the Nordic region should be employed.

Disperse azo dyes, arylamines and halogenated dinitrobenzene compounds in synthetic garments on the Swedish market.

BACKGROUND: Azobenzene disperse dyes (azo DDs) are well-known as textile allergens, but the knowledge of their occurrence in garments is low. The numerous azo DDs and dye components found in textiles constitute a potential health risk, but only seven azo DDs are included in the European baseline patch test series (EBS). OBJECTIVES: To investigate non-regulated azo DDs and dye components in synthetic garments on the Swedish market. METHODS: High-performance liquid chromatography/mass spectrometry, gas chromatography/mass spectrometry and computerized data mining. RESULTS: Sixty-two azo DDs were detected, with Disperse Red 167:1 occurring in 67%, and 14 other DDs each found in >20% of the garments. Notably, the EBS dyes were less common, three even not detected, while arylamines were frequently detected and exceeded 1 mg/g in several garments. Also, halogenated dinitrobenzenes were identified in 25% of the textiles. CONCLUSION: Azo DDs and dye components, in complex compositions and with large variations, occurred frequently in the synthetic garments. The arylamines were shown to occur at much higher levels compared to the azo DDs, suggesting the former constitute a potentially higher health risk. The role of arylamines and halogenated dinitrobenzenes in textile allergy has to be further investigated.

Detection of Benzo[a]pyrene Diol Epoxide Adducts to Histidine and Lysine in Serum Albumin In Vivo by High-Resolution-Tandem Mass Spectrometry.

Electrophilic diol epoxide metabolites are involved in the carcinogenicity of benzo[a]pyrene, one of the widely studied polycyclic aromatic hydrocarbons (PAHs). The exposure of humans to this PAH can be assessed by measuring stable blood protein adducts, such as to histidine and lysine in serum albumin, from their reactive metabolites. In this respect, measurement of the adducts originating from the genotoxic (+)-anti-benzo[a]pyrene diol epoxide is of interest. However, these are difficult to measure at such low levels as are expected in humans generally exposed to benzo[a]pyrene from air pollution and the diet. The analytical methods detecting PAH-biomarkers still suffer from low selectivity and/or detectability to enable generation of data for calculation of in vivo doses of specific stereoisomers, for evaluation of risk factors and assessing risk from exposures to PAH. Here, we suggest an analytical methodology based on high-pressure liquid chromatography (HPLC) coupled to high-resolution tandem mass spectrometry (MS) to lower the detection limits as well as to increase the selectivity with improvements in both chromatographic separation and mass determination. Method development was performed using serum albumin alkylated in vitro by benzo[a]pyrene diol epoxide isomers. The (+)-anti-benzo[a]pyrene diol epoxide adducts could be chromatographically resolved by using an HPLC column with a pentafluorophenyl stationary phase. Interferences were further diminished by the high mass accuracy and resolving power of Orbitrap MS. The achieved method detection limit for the (+)-anti-benzo[a]pyrene diol epoxide adduct to histidine was approximately 4 amol/mg serum albumin. This adduct as well as the adducts to histidine from (-)-anti- and (+/-)-syn-benzo[a]pyrene diol epoxide were quantified in the samples from benzo[a]pyrene-exposed mice. Corresponding adducts to lysine were also quantified. In human serum albumin, the anti-benzo[a]pyrene diol epoxide adducts to histidine were detected in only two out of twelve samples and at a level of approximately 0.1 fmol/mg.

Suspect and non-target screening of chemicals in clothing textiles by reversed-phase liquid chromatography/hybrid quadrupole-Orbitrap mass spectrometry.

The global manufacturing of clothing is usually composed of multistep processes, which include a large number of chemicals. However, there is generally no information regarding the chemical content remaining in the finished clothes. Clothes in close and prolonged skin contact may thus be a significant source of daily human exposure to hazardous compounds depending on their ability to migrate from the textiles and be absorbed by the skin. In the present study, twenty-four imported garments on the Swedish market were investigated with respect to their content of organic compounds, using a screening workflow. Reversed-phase liquid chromatography coupled to electrospray ionization/high-resolution mass spectrometry was used for both suspect and non-target screening. The most frequently detected compound was benzothiazole followed by quinoline. Nitroanilines with suspected mutagenic and possible skin sensitization properties, and quinoline, a carcinogenic compound, were among the compounds occurring at the highest concentrations. In some garments, the level of quinoline was estimated to be close to or higher than 50,000 ng/g, the limit set by the REACH regulation. Other detected compounds were acridine, benzotriazoles, benzothiazoles, phthalates, nitrophenols, and organophosphates. Several of the identified compounds have logP and molecular weight values enabling skin uptake. This pilot study indicates which chemicals and compound classes should be prioritized for future quantitative surveys and control of the chemical content in clothing as well as research on skin transfer, skin absorption, and systemic exposure. The results also show that the current control and prevention from chemicals in imported garments on the Swedish market is insufficient.

Trait Expression and Environmental Responses of Pea (Pisum sativum L.) Genetic Resources Targeting Cultivation in the Arctic.

In the Arctic part of the Nordic region, cultivated crops need to specifically adapt to adverse and extreme climate conditions, such as low temperatures, long days, and a short growing season. Under the projected climate change scenarios, higher temperatures and an earlier spring thaw will gradually allow the cultivation of plants that could not be previously cultivated there. For millennia, Pea (Pisum sativum L.) has been a major cultivated protein plant in Nordic countries but is currently limited to the southern parts of the region. However, response and adaptation to the Arctic day length/light spectrum and temperatures are essential for the productivity of the pea germplasm and need to be better understood. This study investigated these factors and identified suitable pea genetic resources for future cultivation and breeding in the Arctic region. Fifty gene bank accessions of peas with a Nordic landrace or cultivar origin were evaluated in 2-year field trials at four Nordic locations in Denmark, Finland, Sweden, and Norway (55° to 69° N). The contrasting environmental conditions of the trial sites revealed differences in expression of phenological, morphological, crop productivity, and quality traits in the accessions. The data showed that light conditions related to a very long photoperiod partly compensated for the lack of accumulated temperature in the far north. A critical factor for cultivation in the Arctic is the use of cultivars with rapid flowering and maturation times combined with early sowing. At the most extreme site (69°N), no accession reached full maturation. Nonetheless several accessions, predominantly landraces of a northern origin, reached a green harvest state. All the cultivars reached full maturation at the sub-Arctic latitude in northern Sweden (63°N) when plants were established early in the season. Seed yield correlated positively with seed number and aboveground biomass, but negatively with flowering time. A high yield potential and protein concentration of dry seed were found in many garden types of pea, confirming their breeding potential for yield. Overall, the results indicated that pea genetic resources are available for breeding or immediate cultivation, thus aiding in the northward expansion of pea cultivation. Predicted climate changes would support this expansion.

Tracing colophonium in consumer products.

BACKGROUND: Colophonium (rosin) can cause allergic contact dermatitis, mainly due to autoxidation of abietic acid (AbA). Products containing ≥0.1% colophonium should be labeled with EUH208 - "Contains rosin; colophony. May produce an allergic reaction." How should this be measured? OBJECTIVE: To compare the results from different strategies for estimating colophonium levels in consumer products: (a) from AbA, and (b) the sum of all major resin acids. To investigate the ratio of 7-oxodehydroabietic acid (7-O-DeA)/AbA as indication of autoxidation. METHODS: Resin acids were extracted from consumer products, derivatized, and then separated by gas chromatography/mass spectrometry (GC/MS). RESULTS: Resin acids were detected in 9 of 15 products. No product contained colophonium ≥0.1%. Estimation based on AbA resulted in underestimation of the colophonium levels in four of nine products. For three products, the obtained levels from this strategy were only one of two compared to when estimating from the sum of all resin acids. The ratio 7-O-DeA/AbA varied from 74% to 1.4%. CONCLUSIONS: We propose to measure colophonium based on the sum of all detectable major resin acids, including 7-O-DeA. The ratio of 7-O-DeA/AbA should be used as a marker of autoxidation, indicating an increased risk of sensitization. The presented analytical method is simple to use and suitable for further screening studies.

Passive and active suicidal ideation in Swedish 85-year-olds: Time trends 1986-2015.

BACKGROUND: Older adults have high suicide rates. We investigated potential time trends in the prevalence of passive and active suicidal ideation in 85-year-olds. Further, we examined factors associated with such ideation in this age group. METHODS: Population-based samples of 85-year-olds were interviewed in 1986 (N = 347), 2008 (N = 426) and 2015 (N = 320). Past-month passive/active suicidal ideation was evaluated with the Paykel questions. RESULTS: Reporting any type of passive or active suicidal ideation was less common in 2008 (7.3%, p < 0.001) and 2015 (7.2%, p < 0.001) compared to 1986 (16.4%). The change was driven by decreases in passive ideation. Passive/active suicidal ideation was associated with higher MADRS score (OR: 1.2, 95% CI: 1.1-1.2, p < 0.001), institution residence (OR: 3.9, 95% CI: 1.7-8.9, p = 0.001) and feelings of loneliness (OR: 2.7, 95% CI: 1.4-5.2, p = 0.003). When stratified by sex, it was associated with institution residence (OR: 3.7, 95% CI: 1.4-9.9, p = 0.008) and feelings of loneliness (OR: 3.0, 95% CI: 1.4-6.3, p = 0.005) in women. In men, we observed a tenfold higher risk in those without partners (OR: 9.8, 95% CI: 2.9-33.5, p < 0.001). LIMITATIONS: While differential three-year mortality was not observed in 1986, mortality was higher among non-participants in 2008 and 2015. This might have inflated cohort differences in passive/active suicidal ideation. CONCLUSION: An initial decrease in the prevalence of passive/active suicidal ideation in 85-year-olds was observed but this positive trend did not persist. Results underline that preventive strategies targeting loneliness and focusing on institutional settings are needed, as are interventions for men without partners.

Measurements of Atmospheric Proteinaceous Aerosol in the Arctic Using a Selective UHPLC/ESI-MS/MS Strategy.

In this article, an analytical methodology to investigate the proteinaceous content in atmospheric size-resolved aerosols collected at the Zeppelin observatory (79 °N, 12 °E) at Ny Ålesund, Svalbard, from September to December 2015, is proposed. Quantitative determination was performed after acidic hydrolysis using ultrahigh-performance liquid chromatography in reversed-phase mode coupled to electrospray ionization tandem mass spectrometry. Chromatographic separation, as well as specificity in the identification, was achieved by derivatization of the amino acids with N-butyl nicotinic acid N-hydroxysuccinimide ester prior to the analysis. The chromatographic run was performed within 11 min and instrumental levels of detection (LODs) were between 0.2 and 8.1 pg injected on the column, except for arginine which exhibited an LOD of 37 pg. Corresponding method LODs were between 0.01 and 1.9 fmol/m3, based on the average air sampling volume of 57 m3. The sum of free amino acids and hydrolyzed polyamino acids was shown to vary within 6-2914 and 0.02-1417 pmol/m3 for particles in sizes < 2 and 2-10 µm in equivalent aerodynamic diameter, respectively. Leucine, alanine, and valine were the most abundant among the amino acids in both aerosol size fractions. In an attempt to elucidate source areas of the collected aerosols, 5- to 10-day 3D backward trajectories reaching the sampling station were calculated. Overall, the method described here provides a first time estimate of the proteinaceous content, that is, the sum of free and polyamino acids, in size-resolved aerosols collected in the Arctic. Graphical Abstract ᅟ.

Allergic contact dermatitis caused by hydroperoxides of limonene and dose-response relationship-A repeated open application test (ROAT) study.

BACKGROUND: Contact allergy to oxidized limonene, with hydroperoxides of limonene (Lim-OOHs) as the main allergens, is common. However, high proportions of weak positive and doubtful patch test reactions have been reported. OBJECTIVES: To determine the clinical relevance, elicitation threshold and dose-response relationship of Lim-OOHs in individuals with a positive or doubtful patch test reaction to standard Lim-OOHs 0.3% pet. METHODS: A multicentre 3-week double-blind vehicle-controlled repeated open application test (ROAT) study with a simulated fine fragrance containing Lim-OOHs at 1260, 420 and 140 ppm, equal to a dose/area per application of Lim-OOHs of 3.0, 0.99 and 0.33 µg/cm2 , was performed. RESULTS: Among 11 subjects allergic to Lim-OOHs, 11 (100%), 7 (64%), and 3 (27%), respectively, reacted to the applied doses. No reactions were seen in 17 healthy controls exposed to the highest dose. This difference in reactivity was statistically significant (P < 0.0001). Among 13 subjects with doubtful patch test reactions to Lim-OOHs, two (15%) had positive ROAT reactions to the highest Lim-OOH dose applied (P = 0.36 as compared with controls). CONCLUSIONS: Contact allergy to Lim-OOHs is of clinical relevance in patients with positive patch test reactions. A doubtful patch test reaction to Lim-OOHs 0.3% pet. can be of clinical relevance.

Effect of a spacer on total systemic and lung bioavailability in healthy volunteers and in vitro performance of the Symbicort® (budesonide/formoterol) pressurized metered dose inhaler.

INTRODUCTION: Many patients with chronic obstructive pulmonary disease or asthma experience difficulties in coordinating inhalation with pressurized metered-dose inhaler (pMDI) actuation. The use of a spacer device can improve drug delivery in these patients. The aim of this study was to establish the relative bioavailability of single doses of Symbicort® (budesonide/formoterol) pMDI 160/4.5 µg/actuation (2 actuations) used with and without a spacer device. In addition, an in vitro study was conducted to characterize performance of the inhaler when used in conjunction with a spacer device. METHODS: A Phase I, randomized, open-label, single-dose, single-center, crossover study in 50 healthy volunteers (NCT02934607) assessed the relative bioavailability of single-dose Symbicort® pMDI 160/4.5 µg/actuation (2 actuations) with and without a spacer (AeroChamber Plus® Flow-Vu®). Inhaled doses were administered without or with activated charcoal (taken orally) to estimate total systemic exposure and exposure through the lung, respectively. The in vitro study characterized the effect of the spacer with respect to delivered dose, fine particle dose, and dose during simulated breathing of budesonide and formoterol. RESULTS: In terms of total systemic exposure, use of the spacer increased the relative bioavailability determined by AUC(0-last) and Cmax by 68% (spacer:no spacer treatment ratio, 167.9%; 90% CI, 144.1 to 195.6) and 99% (ratio, 198.7%; 90% CI, 164.4 to 240.2) for budesonide, and 77% (ratio, 176.6%; 90% CI, 145.1 to 215.0) and 124% (ratio, 223.6%; 90% CI, 189.9 to 263.3) for formoterol, respectively, compared with pMDI alone. Similarly, the lung exposure of budesonide and formoterol increased (AUC(0-last) and Cmax by 146% [ratio, 246.0%; 90% CI, 200.7 to 301.6] and 127% [ratio, 226.5%; 90% CI, 186.4 to 275.4] for budesonide, and 173% [ratio, 272.8%; 90% CI, 202.5 to 367.4] and 136% [ratio, 236.2%; 90% CI, 192.6 to 289.6] for formoterol, respectively) when the pMDI was administered through the spacer. When assessed by AUC(0-last) quartile without spacer, subjects in the lowest exposure quartile (indicating poor inhalation technique) with Symbicort® pMDI 160/4.5 µg/actuation (2 actuations) had markedly increased total systemic and lung exposure when the same dose was administered with the spacer. In contrast, for subjects in the highest exposure quartile with pMDI alone, total systemic and lung exposure of formoterol and budesonide was similar with and without the spacer. In the in vitro study, the fine particle dose (<5 µm) of both budesonide and formoterol from the spacer at delay time (i.e. pause period after actuation) = 0 s (instantaneous) after actuation was similar to the fine particle dose when not using the spacer. The delivered doses of budesonide and formoterol from the spacer were both lower compared with the doses administered without the spacer. There was also a decrease in delivered dose with increasing delay time. CONCLUSIONS: The clinical study demonstrated that in subjects with poor inhalation technique the use of the AeroChamber Plus® Flow-Vu® spacer increased the bioavailability of Symbicort® pMDI to a level observed in subjects with good inhalation technique without a spacer. The findings from the in vitro study support the fine particle dose characteristics of Symbicort® pMDI with the AeroChamber Plus® Flow-Vu® spacer.

A two-dimensional non-comprehensive reversed/normal phase high-performance liquid chromatography/tandem mass spectrometry system for determination of limonene and linalool hydroperoxides.

A two-dimensional non-comprehensive high-performance liquid chromatographic (HPLC) system coupled to electrospray ionization tandem mass spectrometry was developed for the determination of skin allergenic hydroperoxides of limonene and linalool. These compounds are some major components behind skin sensitization and contact (skin) allergy to fragrances. Fragrance hydroperoxides usually occur in complex compositions, often as constituents of the natural essential oils added to a large number of commercial products. Their similarities to interfering compounds, many with identical elemental composition, make the determination difficult even when using selective detection methods like mass spectrometry. In this work, a first-dimension chromatographic heart-cut isolation of the hydroperoxides on a reversed-phase HPLC system was combined with a second-dimension normal-phase HPLC system for separation of the hydroperoxides. The intersystem transfer was made by trapping the heart-cut fraction on a short graphitized carbon column, exchanging the mobile phase and back-flushing the hydroperoxides into the second dimension. Each analysis was performed within 60 min without any pretreatment, except dilution, prior to injection. The obtained instrumental limits of detection (LODs) at a signal-to-noise ratio of 3 were lower than 1.2 ng injected on column and method LODs were below 0.3 ppm. An after-shave product was shown to contain the highest concentrations of the measured hydroperoxides, with 445 ±â€¯23 ppm of total linalool hydroperoxides. This level is likely able to elicit skin reactions in already sensitized individuals.

Investigation of ultrahigh-performance liquid chromatography/travelling-wave ion mobility/time-of-flight mass spectrometry for fast profiling of fatty acids in the high Arctic sea surface microlayer.

RATIONALE: Fatty acids are enriched in the ocean surface microlayer (SML) and have as a consequence been detected worldwide in sea spray aerosols. In searching for a relationship between the properties of the atmospheric aerosol and its ability to form cloud condensation nuclei and to promote cloud droplet formation over remote marine areas, the role of surface active fatty acids sourced from the SML is of interest to be investigated. Here we present a fast method for profiling of major fatty acids in SML samples collected in the high Arctic (89°N, 1°W) in the summer of 2001. METHODS: Ultrahigh-performance liquid chromatography (UHPLC)/travelling-wave ion mobility spectrometry (TWIMS)/time-of-flight (TOF) mass spectrometry (MS) for profiling was evaluated and compared with UHPLC/TOFMS. Except for evaporation and centrifugation, no sample preparation was necessary prior to the analysis. RESULTS: TOFMS data on accurate mass, isotopic ratios and fragmentation patterns enabled identification of the fatty acids. The TWIMS dimension added to the selectivity by extensive reduction of the noise level and the entire UHPLC/TWIMS/TOFMS method provided a fast profiling of the acids, ranging from C8 to C24 . Hexadecanoic and octadecanoic acids were shown to yield the highest signals among the FAs detected in a high Arctic SML sample, followed by the unsaturated octadecenoic and octadecadienoic acids. The predominance of signal from even-numbered carbon chains indicates a mainly biogenic origin of the detected FAs. CONCLUSIONS: This study presents a fast alternative method for screening and profiling of FAs, which has the advantage of not requiring any complicated sample preparation, thus limiting the loss of analytes. Almost no manual handling, together with the very small sample volumes needed, is certainly beneficial for the determination of trace amounts and should open up the field of applications to also include atmospheric aerosol and fog.

The Fate of a Hapten - From the Skin to Modification of Macrophage Migration Inhibitory Factor (MIF) in Lymph Nodes.

Skin (contact) allergy, the most prevalent form of immunotoxicity in humans, is caused by low molecular weight chemicals (haptens) that penetrate stratum corneum and modify endogenous proteins. The fate of haptens after cutaneous absorption, especially what protein(s) they react with, is largely unknown. In this study the fluorescent hapten tetramethylrhodamine isothiocyanate (TRITC) was used to identify hapten-protein conjugates in the local lymph nodes after topical application, as they play a key role in activation of the adaptive immune system. TRITC interacted with dendritic cells but also with T and B cells in the lymph nodes as shown by flow cytometry. Identification of the most abundant TRITC-modified protein in lymph nodes by tandem mass spectrometry revealed TRITC-modification of the N-terminal proline of macrophage migration inhibitory factor (MIF) - an evolutionary well-conserved protein involved in cell-mediated immunity and inflammation. This is the first time a hapten-modified protein has been identified in lymph nodes after topical administration of the hapten. Most haptens are electrophiles and can therefore modify the N-terminal proline of MIF, which has an unusually reactive amino group under physiological conditions; thus, modification of MIF by haptens may have an immunomodulating role in contact allergy as well as in other immunotoxicity reactions.

Case Study on Screening Emerging Pollutants in Urine and Nails.

Alternative plasticizers and flame retardants (FRs) have been introduced as replacements for banned or restricted chemicals, but much is still unknown about their metabolism and occurrence in humans. We identified the metabolites formed in vitro for four alternative plasticizers (acetyltributyl citrate (ATBC), bis(2-propylheptyl) phthalate (DPHP), bis(2-ethylhexyl) terephthalate (DEHTP), bis(2-ethylhexyl) adipate (DEHA)), and one FR (2,2-bis (chloromethyl)-propane-1,3-diyltetrakis(2-chloroethyl) bisphosphate (V6)). Further, these compounds and their metabolites were investigated by LC/ESI-Orbitrap-MS in urine and finger nails collected from a Norwegian cohort. Primary and secondary ATBC metabolites had detection frequencies (% DF) in finger nails ranging from 46 to 95%. V6 was identified for the first time in finger nails, suggesting that this matrix may also indicate past exposure to FRs as well as alternative plasticizers. Two isomeric forms of DEHTP primary metabolite were highly detected in urine (97% DF) and identified in finger nails, while no DPHP metabolites were detected in vivo. Primary and secondary DEHA metabolites were identified in both matrices, and the relative proportion of the secondary metabolites was higher in urine than in finger nails; the opposite was observed for the primary metabolites. As many of the metabolites present in in vitro extracts were further identified in vivo in urine and finger nail samples, this suggests that in vitro assays can reliably mimic the in vivo processes. Finger nails may be a useful noninvasive matrix for human biomonitoring of specific organic contaminants, but further validation is needed.