"Navigating in a maze without a map". Partners' experiences of hyperemesis gravidarum- a qualitative study.

OBJECTIVE: A supportive environment for women with Hyperemesis Gravidarum is crucial but not always provided. There is a lack of research regarding Hyperemesis Gravidarum, its impact on the family, and the partner's perception of supporting their spouse. Thus, this study aims to explore partners' experiences of Hyperemesis Gravidarum during their spousés pregnancy. METHODS: Data were gathered through 13 individual, semi-structured, in-depth, digital interviews with partners of women who had experienced Hyperemesis Gravidarum and analysed with Qualitative Content Analysis. The partners were recruited through advertisement on a social media platform and were exclusively males, representing 8 of 21 Swedish regions. The mean age was 34, and they had, on average, 1 previous child. The mean time from the experience to the interview was 12 months. FINDINGS: The main theme, "Navigating in a maze without a map", explains partners' situation as stressful and demanding when their spouse suffers from Hyperemesis Gravidarum, with insufficient support and guidance from healthcare providers. The analysis resulted in three themes: "Standing alone with a demanding responsibility", "Being in a lottery when facing healthcare", and "Climbing the mountain together." The themes display challenges within everyday life and healthcare, as well as strained relations within the family. CONCLUSION: Partners experience a need to support their spouse in every aspect of daily life and advocate for adequate healthcare. Healthcare professionals must support and acknowledge the partners' struggles during the demanding situation with Hyperemesis Gravidarum.

Influence of divalent cations on the extraction of organic acids in coffee determined by GC-MS and NMR.

The perceived flavor of coffee varies depending on the composition of the brewing water, and the influencing mechanisms are poorly understood. To investigate the effect of dissolved divalent cations on the extraction of organic acids in coffee, magnesium and calcium chloride salts were added pre- and post-brew. Citric, malic, lactic and quinic acid were analyzed using gas chromatography - mass spectrometry and nuclear magnetic resonance techniques. At concentrations typically found in drinking water, the salts resulted in limited variation of the acid content, while ten-fold higher salt concentrations produced more pronounced variations. Comparisons between pre- and post-brew additions showed similar acid content in most cases, suggesting that extraction of acids proceeds independent of the water composition. Interactions taking place post-brew may, however, influence the perceived flavor. A scientific basis for water quality recommendations in the coffee industry is long overdue and this work provides experimental and analytical contributions to continued research.

Oxylipin profiling by LC-ESI-MS/MS in canine serum and plasma to investigate ovulation-specific changes.

New biomarkers that are directly associated with canine ovulation would be of value to ensure mating on optimal days of heat. In this study, canine plasma and serum were analyzed with liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to quantify a broad range of oxylipins for the purpose of developing a method for biomarker discovery studies in canine reproduction. A majority of the 67 oxylipins probed for were detected at comparable levels in both sample types, but more oxylipins at higher concentrations were detected in serum than in plasma. Nine of the oxylipins were detected in a pilot study of serum at levels that significantly differed (p ≤ 0.1) between time-points before (n = 10), during (n = 10) and after (n = 10) ovulation, and might serve as putative biomarkers for canine ovulation. One oxylipin (20-HETE) was significantly altered after adjusting for multiple comparisons. In conclusion, the results showed that the LC-ESI-MS/MS method was suitable for quantification of canine oxylipins, revealing important similarities and differences between plasma and serum profiles as well as preliminary ovulation-specific changes in a subset of the investigated oxylipins.

Effects of conventionally treated and ozonated wastewater on the damselfly larva oxylipidome in response to on-site exposure.

Pharmaceutical residues discharged through insufficiently treated or untreated wastewater enter aquatic environments, where they may adversely impact organisms such as aquatic invertebrates. Ozonation, an advanced wastewater treatment technique, has been successfully implemented to enhance the removal of a broad range of pharmaceuticals, however diverse byproducts and transformation products that are formed during the ozonation process make it difficult to predict how ozonated wastewater may affect aquatic biota. The aim of this study was to investigate effects on fatty acid metabolites, oxylipins, in a common invertebrate species, damselfly larvae, after on-site exposure to conventional wastewater treatment plant (WWTP) effluent and additionally ozonated effluent at a full-scale WWTP. Subsequent ozonation of the conventionally treated wastewater was assessed in terms of i) removal of pharmaceuticals and ii) potential sub-lethal effects on the oxylipidome. Northern damselfly (Coenagrion hastulatum) larvae were exposed for six days in the treatment plant facility to either conventional WWTP effluent or ozonated effluent and the effects on pharmaceutical levels and oxylipin levels were compared with those from tap water control exposure. Ozonation removed pharmaceuticals at an average removal efficiency of 67% (ozone dose of 0.49 g O3/g DOC). Of 38 pharmaceuticals detected in the effluent, 16 were removed to levels below the limit of quantification by ozonation. Levels of two oxylipins, 12(13)-EpODE and 15(16)-EpODE, were reduced in larvae exposed to the conventionally treated wastewater in comparison to the tap water control. 15(16)-EpODE was reduced in the larvae exposed to ozonated effluent in comparison to the tap water control. One oxylipin, 8-HETE, was significantly lower in larvae exposed to conventional WWTP effluent compared to ozonated effluent. In conclusion, the study provides proof-of-principle that damselfly larvae can be used on-site to test the impact of differentially treated wastewater.

Feasibility and reliability of measures of bioactive lipids in human plasma and nasal mucosa.

Analysis of bioactive lipids is increasingly useful in clinical studies, and there is a need for non-invasive and easy-to-use sampling methods that meet the demands of reliability. Samples that can be taken by a non-professional and that can be taken repeatedly so as to provide more detailed information about the inflammatory process are often desired. In this study, the feasibility of non-invasive sampling of nasal mucosa and saliva for the analysis of bioactive lipid mediators (e.g. oxylipins and endocannabinoids) was evaluated in a pilot study (n = 10). In a second study, the reliability (relative and absolute) of sampling of these lipid mediators derived from nasal mucosa and from plasma was assessed by calculation of the intraclass correlation coefficient and Bland-Altman's limit of agreement. Samples were taken at the same time of day on two occasions from a cohort of individuals with and without building-related intolerance (n = 37). Nasal mucosa proved to be a suitable matrix for the analysis of bioactive lipids and was therefore included in the study on reliability together with the plasma samples. Relative reliability varied among the identified oxylipins and endocannabinoids. Arachidonic acid derivatives showed generally better reliability. Absolute reliability measures also varied indicating that only a subset of the oxylipins and endocannabinoids were suitable as biomarkers in either nasal mucosa or plasma and should therefore be used with caution for that purpose.

Wastewater effluent affects behaviour and metabolomic endpoints in damselfly larvae.

Wastewater treatment plant effluents have been identified as a major contributor to increasing anthropogenic pollution in aquatic environments worldwide. Yet, little is known about the potentially adverse effects of wastewater treatment plant effluent on aquatic invertebrates. In this study, we assessed effects of wastewater effluent on the behaviour and metabolic profiles of damselfly larvae (Coenagrion hastulatum), a common aquatic invertebrate species. Four key behavioural traits: activity, boldness, escape response, and foraging (traits all linked tightly to individual fitness) were studied in larvae before and after one week of exposure to a range of effluent dilutions (0, 50, 75, 100%). Effluent exposure reduced activity and foraging, but generated faster escape response. Metabolomic analyses via targeted and non-targeted mass spectrometry methods revealed that exposure caused significant changes to 14 individual compounds (4 amino acids, 3 carnitines, 3 lysolipids, 1 peptide, 2 sugar acids, 1 sugar). Taken together, these compound changes indicate an increase in protein metabolism and oxidative stress. Our findings illustrate that wastewater effluent can affect both behavioural and physiological traits of aquatic invertebrates, and as such might pose an even greater threat to aquatic ecosystems than previously assumed. More long-term studies are now needed evaluate if these changes are linked to adverse effects on fitness. The combination of behavioural and metabolomic assessments provide a promising tool for detecting effects of wastewater effluent, on multiple biological levels of organisation, in aquatic ecosystems.

Plasma and bronchoalveolar lavage fluid oxylipin levels in experimental porcine lung injury.

Inflammatory signaling pathways involving eicosanoids and other regulatory lipid mediators are a subject of intensive study, and a role for these in acute lung injury is not yet well understood. We hypothesized that oxylipin release from lung injury could be detected in bronchoalveolar lavage fluid and in plasma. In a porcine model of surfactant depletion, ventilation with hyperinflation was assessed. Bronchoalveolar lavage and plasma samples were analyzed for 37 different fatty acid metabolites (oxylipins). Over time, hyperinflation altered concentrations of 4 oxylipins in plasma (TXB2, PGE2, 15-HETE and 11-HETE), and 9 oxylipins in bronchoalveolar lavage fluid (PGF2α, PGE2, PGD2, 12,13-DiHOME, 11,12-DiHETrE, 13-HODE, 9-HODE, 15-HETE, 11-HETE). Acute lung injury caused by high tidal volume ventilation in this porcine model was associated with rapid changes in some elements of the oxylipin profile, detectable in lavage fluid, and plasma. These oxylipins may be relevant in the pathogenesis of acute lung injury by hyperinflation.

Metabolomics reveals changes in metabolite profiles due to growth and metamorphosis during the ontogeny of the northern damselfly.

Many insects have complex life cycles where a drastic ontogenetic change happens between the larval stages and the adult stage, i.e. metamorphosis. Damselflies (order Odonata, suborder Zygoptera) are widely distributed and ecologically important semi-aquatic insects with a complex life cycle. Phenotypic changes over damselfly ontogeny have been documented, however, if and how metabolite profiles are also changing is currently unknown. Here we used a metabolomics methodology to gain insights into the metabolic changes during the life cycle of the Northern damselfly (Coenagrion hastulatum). Hatchlings of wild-caught damselflies were reared in the laboratory and metabolomics analyses using liquid chromatography and gas chromatography coupled to mass spectrometry were carried out at three larval stages and on adult damselflies. Additionally, a subset of larvae was exposed to wastewater effluent to assess how metabolite profiles responded to an environmental stressor. A total of 212 compounds belonging to several classes (e.g. amino acids, fatty acids, sugars) were annotated. Across metamorphosis, we found that damselflies shifted from protein catabolism to lipid catabolism. Wastewater effluent exposure resulted in ontogenetic stage-dependent changes of individual metabolites, but not to a marked extent. Overall, our study is one of the first to describe changes of metabolite profiles during ontogeny of an insect, and it provides a first step towards a greater understanding of the physiological changes occurring during general insect-but especially damselfly-ontogeny.

Oxylipins at intermediate larval stages of damselfly Coenagrion hastulatum as biochemical biomarkers for anthropogenic pollution.

Aquatic pollution resulting from anthropogenic activities requires adequate environmental monitoring strategies in sentinel organisms. Thus, biochemical biomarkers have been used as early-warning tools of biological effects in aquatic organisms. However, before using these markers for environmental monitoring, knowledge about their developmental variation is vital. In this study, we assessed baseline levels and developmental variations of a group of potential biomarkers, oxylipins, during the lifespan of the Northern damselfly (Coenagrion hastulatum) using liquid chromatography-tandem mass spectrometry. Effects of wastewater exposure on baseline levels were studied in a subset of damselflies to investigate the responsiveness due to anthropogenic pollution. Thirty-eight oxylipins deriving from four polyunsaturated fatty acids via two enzymatic pathways were detected in damselflies at three larval stages and in the adult form. Overall, oxylipin baseline levels showed developmental variation, which was lowest in the intermediate larval stages. Effects of exposure to wastewater effluent on oxylipin baseline levels were dependent on the life stage and were greatest in the early and intermediate larval stages. The study provides first insights into oxylipin profiles of damselflies at different stages of development and their developmental variation. Based on our results, we propose further strategies for incorporating oxylipins in damselfly larvae as biochemical markers for anthropogenic pollution.

Polyunsaturated Fatty Acids and Their Metabolites in Hyperemesis Gravidarum.

Polyunsaturated fatty acids (PUFAs) have been studied in relation to pregnancy. However, there is limited knowledge on PUFAs and their metabolites in relation to hyperemesis gravidarum (HG), a pregnancy complication associated with nutritional deficiencies and excessive vomiting. In order to survey the field, a systematic review of the literature was performed, which also included nausea and vomiting of pregnancy (NVP) due to its close relationship with HG. In the very few published studies found, the main subjects of the research concerned free fatty acids (four records), lipid profiles (three records), and bioactive lipids (one article about prostaglandin E2 and one about endocannabinoids). The authors of these studies concluded that, although no cause-and-effect relationship can be established, HG is linked to increased sympathetic responsiveness, thermogenic activity and metabolic rate. In addition, NVP is linked to a metabolic perturbance (which lasts throughout pregnancy). The low number of retrieved records underlines the need for more research in the area of PUFAs and HG, especially with regard to the underlying mechanism for the detected effects, potentially involving growth differentiation factor 15 (GDF15) since evidence for GDF15 regulation of lipid metabolism and the role for GDF15 and its receptor in nausea and vomiting is emerging.

Novel metabolomic method to assess the effect-based removal efficiency of advanced wastewater treatment techniques.

Unprecedented levels of chemicals of anthropogenic origin are currently released into surface waters globally. Wastewater treatment plant effluent has been identified as a major source, containing a broad mixture of pharmaceuticals and consumer chemicals. Therefore, there is a need for implementation of advanced wastewater treatment techniques, such as ozonation and adsorption methods, to reduce the contamination. However, there are conflicting findings on the toxicity of treated effluent and only limited possibilities for assessing the effect-based removal efficiency (EBRE) of different treatment techniques. Here, we describe a metabolomics approach to detect perturbations in fatty acid catabolic pathways as a proxy for biological effects. Metabolites in three fatty acid pathways were analyzed in a common damselfly larva (Coenagrion hastulatum) by liquid chromatography coupled to mass spectrometry. The larvae were exposed for one week to either conventionally treated effluent (activated sludge treatment), effluent additionally treated with ozone or effluent additionally treated with biochar filtration and results were compared with those from tap water control exposure. Five lipoxygenase-derived oxylipins (9,10,13-TriHOME, 9,12,13-TriHOME, 9-HODE, 9-HOTrE, and 13-HOTrE) decreased in response to conventionally treated effluent exposure. By using an additional treatment step, oxylipin levels were restored with exception of 9,10,13-TriHOME (ozonated effluent), and 9-HOTrE and 13-HOTrE (effluent filtered with biochar). In conclusion, exposure to wastewater effluent affected fatty acid metabolite levels in damselfly larvae, and a subset of the analyzed metabolites may serve as indicators for biological effects in biota in response to effluent exposure. To that effect, our findings suggest a new metabolomics protocol for assessing EBRE.

Oxylipins in cerebrospinal fluid in clinically isolated syndrome and relapsing remitting multiple sclerosis.

Although oxylipins are involved in inflammation, data on these lipid mediators in multiple sclerosis are sparse. In this study, a panel of oxylipins were analysed swith liquid chromatography tandem mass spectrometry in cerebrospinal fluid (CSF) from 41 treatment naïve patients with clinically isolated syndrome (CIS) or relapsing remitting MS (RRMS) and 22 healthy controls. CSF levels of 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE) were significantly higher in patients than in healthy controls (9-HODE median 380 nM (interquartile range 330-450 nM) in patients and 290 nM (interquartile range 250-340 nM) in controls, 13-HODE median 930 nM (interquartile range 810-1080 nM) in patients and 690 nM (interquartile range 570-760 nM) in controls, p < 0.001 in Mann-Whitney U tests). 9-HODE and 13-HODE performed well for separation of patients and healthy controls (AUC 0.85 and 0.88, respectively, in ROC curve analysis). However, baseline CSF levels of the oxylipins did not differ between patients with signs of disease activity during one, two and four years of follow-up and patients without. In conclusion, this study indicates that 9-HODE and 13-HODE levels are increased in CSF from CIS and RRMS patients compared with healthy controls, but does not support 9-HODE or 13-HODE as prognostic biomarkers of disease activity in patients during follow-up.

Effects of triclosan in breast milk on the infant fecal microbiome.

Triclosan is frequently used for its antimicrobial properties and has been detected in human serum, urine, and breast milk. Animal and molecular studies have shown that triclosan exerts a wide range of adverse health effects at both high (ppm) and low (ppb) concentrations. Since triclosan is of growing concern to human and environmental health, there is a need to improve extraction procedures and to study additional effects from triclosan exposure. In this study, we have improved triclosan extraction from breast milk by using salt (MgSO4) to reduce emulsion formation and increase water polarity and water (∼80%) to enhance the overall extraction efficiency (∼3.5 fold). This extraction method was applied to breast milk samples collected from donors who i) recorded their use of triclosan-containing personal care products and ii) provided matching infant stool samples. Of the participants who had detectable amounts of triclosan in their breast milk, nine (75%) of them reported daily use of triclosan-containing personal care products. Levels of triclosan in breast milk were compared to the donor's infant's fecal microbiome. We found that the bacterial diversity in the fecal microbiome of the infants exposed to breast milk with detectable triclosan levels differed compared to their peers exposed to milk containing non-detectable amounts. This finding implies that exogenous chemicals are impacting microbiome diversity.

Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust.

Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF2α, 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes.

Cord blood eicosanoid signatures and newborn gestational age.

Beyond prostaglandins, the function of eicosanoids and other oxylipins in pregnancy and labor is poorly understood. In contrast to earlier work focusing on preterm infants, we investigated how oxylipin levels in newborns (measured in cord blood) vary during the last weeks of pregnancy in 190 mother-newborns (≥37 weeks of gestation) of the ENVIRONAGE birth cohort, Belgium. We found increased levels of PGE2 (p=0.003), PGF2α (p=0.042), 8,9-DHET (p=0.037), 11-HETE (p=0.034), and 15-HETrE (p=0.008) associated with full term pregnancy compared to early term labor. Furthermore, late vs early term was associated with increased levels of PGE2 (p=0.012) and TXB2 (p=0.033), while late vs full term was associated with decreased levels of 14,15-DHET (p=0.029), 11,12-DHET (p=0.033), and 5-HETE (p=0.045). To summarize, nine eicosanoids, derived via three enzymatic pathways, were significantly associated with gestational age. Eight of these were derived from arachidonic acid, and one from dihomo-γ-linolenic acid.

Levels of oxylipins, endocannabinoids and related lipids in plasma before and after low-level exposure to acrolein in healthy individuals and individuals with chemical intolerance.

Oxylipins and endocannabinoids play important biological roles, including effects upon inflammation. It is not known whether the circulating levels of these lipids are affected by inhalation of the environmental pollutant acrolein. In the present study, we have investigated the consequences of low-level exposure to acrolein on oxylipin, endocannabinoid and related lipid levels in the plasma of healthy individuals and individuals with chemical intolerance (CI), an affliction with a suggested inflammatory origin. Participants were exposed twice (60min) to heptane and a mixture of heptane and acrolein. Blood samples were collected before exposure, after and 24h post-exposure. There were no overt effects of acrolein exposure on the oxylipin lipidome or endocannibinoids detectable in the bloodstream at the time points investigated. No relationship between basal levels or levels after exposure to acrolein and CI could be identified. This implicates a minor role of inflammatory mediators on the systemic level in CI.

Plasma levels of the endocannabinoid anandamide, related N-acylethanolamines and linoleic acid-derived oxylipins in patients with migraine.

There is evidence that patients with migraine have deficient levels of the endogenous cannabinoid receptor ligand anandamide (AEA). It is not known, however, if this is a localised or generalised phenomenon. In the present study, levels of AEA, related N-acylethanolamines (NAEs) and linoleic acid-derived oxylipins have been measured in the blood of 26 healthy women and 38 women with migraine (26 with aura, 12 without aura) who were matched for age and body-mass index. Blood samples were taken on two occasions: the first sample near the start of the menstrual cycle (when present) and the second approximately fourteen days later. For a subset of migraine patients, two additional blood samples were taken, one during a migraine attack and one approximately 1 month later (to be at the same stage in the menstrual cycle, when present). NAEs and oxylipins were measured by liquid chromatography coupled to mass spectrometry. Twenty-nine lipids were quantified, of which 16 were found to have a high reproducibility of measurement. There were no significant differences in the levels of AEA, the related NAEs stearoylethanolamide and oleoylethanolamide or any of the nine linoleic acid-derived oxylipins measured either between migraine patients with vs. without aura, or between controls and migraine patients (after stratification to take into account whether or not the individuals had regular menstruation cycles) in either of the first two samples. Levels of linoleoylethanolamide were lower in the patients with vs. without aura on the second sample but not in the first sample, but the biological importance of this finding is unclear. Due to time-dependent increases in their concentrations ex vivo prior to centrifugation, AEA and oleoylethanolamide levels in the samples collected during migraine attacks were not analysed, but for the other fourteen lipids, there were no significant differences in plasma concentrations during migraine vs. one month later. It is concluded that migraine is not associated with a generalised (as opposed to localised) deficiency in these lipids.

Metabolite quantification by NMR and LC-MS/MS reveals differences between unstimulated, stimulated, and pure parotid saliva.

Saliva is a readily available biofluid that is sensitive to metabolic changes and can be collected through rapid and non-invasive collection procedures, and it shows great promise for clinical metabolomic studies. This work studied the metabolite composition of, and the differences between, saliva samples collected by unstimulated spitting/drooling, paraffin chewing-stimulated spitting, and parotid gland suction using targeted nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for metabolite quantification. As applied here, these two analytical techniques provide complementary metabolite information and together extend the metabolome coverage with robust NMR quantification of soluble metabolites and sensitive targeted LC-MS/MS analysis of bioactive lipids in specific metabolic pathways. The NMR analysis was performed on ultrafiltrated (3kDa cutoff) saliva samples and resulted in a total of 45 quantified metabolites. The LC-MS/MS analysis was performed on both filtered and unfiltered samples and resulted in the quantification of two endocannabinoids (AEA and PEA) and 22 oxylipins, which at present is the most comprehensive targeted analysis of bioactive lipids in human saliva. Important differences in the metabolite composition were observed between the three saliva sample collection methods, which should be taken into consideration when designing metabolomic studies of saliva. Furthermore, the combined use of the two metabolomics platforms (NMR and LC-MS/MS) proved to be viable for research and clinical studies of the salivary metabolome.