Comparative Lipidomics of Oral Commensal and Opportunistic Bacteria.

The oral cavity contains a vast array of microbes that contribute to the balance between oral health and disease. In addition, oral bacteria can gain access to the circulation and contribute to other diseases and chronic conditions. There are a limited number of publications available regarding the comparative lipidomics of oral bacteria and fungi involved in the construction of oral biofilms, hence our decision to study the lipidomics of representative oral bacteria and a fungus. We performed high-resolution mass spectrometric analyses (<2.0 ppm mass error) of the lipidomes from five Gram-positive commensal bacteria: Streptococcus oralis, Streptococcus intermedius, Streptococcus mitis, Streptococcus sanguinis, and Streptococcus gordonii; five Gram-positive opportunistic bacteria: Streptococcus mutans, Staphylococcus epidermis, Streptococcus acidominimus, Actinomyces viscosus, and Nanosynbacter lyticus; seven Gram-negative opportunistic bacteria: Porphyromonas gingivalis. Prevotella brevis, Proteus vulgaris, Fusobacterium nucleatum, Veillonella parvula, Treponema denticola, and Alkermansia muciniphila; and one fungus: Candida albicans. Our mass spectrometric analytical platform allowed for a detailed evaluation of the many structural modifications made by microbes for the three major lipid scaffolds: glycerol, sphingosine and fatty acyls of hydroxy fatty acids (FAHFAs).

Pilot Lipidomics Study of Copepods: Investigation of Potential Lipid-Based Biomarkers for the Early Detection and Quantification of the Biological Effects of Climate Change on the Oceanic Food Chain.

Maintenance of the health of our oceans is critical for the survival of the oceanic food chain upon which humanity is dependent. Zooplanktonic copepods are among the most numerous multicellular organisms on earth. As the base of the primary consumer food web, they constitute a major biomass in oceans, being an important food source for fish and functioning in the carbon cycle. The potential impact of climate change on copepod populations is an area of intense study. Omics technologies offer the potential to detect early metabolic alterations induced by the stresses of climate change. One such omics approach is lipidomics, which can accurately quantify changes in lipid pools serving structural, signal transduction, and energy roles. We utilized high-resolution mass spectrometry (≤2 ppm mass error) to characterize the lipidome of three different species of copepods in an effort to identify lipid-based biomarkers of copepod health and viability which are more sensitive than observational tools. With the establishment of such a lipid database, we will have an analytical platform useful for prospectively monitoring the lipidome of copepods in a planned long-term five-year ecological study of climate change on this oceanic sentinel species. The copepods examined in this pilot study included a North Atlantic species (Calanus finmarchicus) and two species from the Gulf of Mexico, one a filter feeder (Acartia tonsa) and one a hunter (Labidocerca aestiva). Our findings clearly indicate that the lipidomes of copepod species can vary greatly, supporting the need to obtain a broad snapshot of each unique lipidome in a long-term multigeneration prospective study of climate change. This is critical, since there may well be species-specific responses to the stressors of climate change and co-stressors such as pollution. While lipid nomenclature and biochemistry are extremely complex, it is not essential for all readers interested in climate change to understand all of the various lipid classes presented in this study. The clear message from this research is that we can monitor key copepod lipid families with high accuracy, and therefore potentially monitor lipid families that respond to environmental perturbations evoked by climate change.

Construction of a Bacterial Lipidomics Analytical Platform: Pilot Validation with Bovine Paratuberculosis Serum.

Lipidomics analyses of bacteria offer the potential to detect and monitor infections in a host since many bacterial lipids are not present in mammals. To evaluate this omics approach, we first built a database of bacterial lipids for representative Gram-positive and Gram-negative bacteria. Our lipidomics analysis of the reference bacteria involved high-resolution mass spectrometry and electrospray ionization with less than a 1.0 ppm mass error. The lipidomics profiles of bacterial cultures clearly distinguished between Gram-positive and Gram-negative bacteria. In the case of bovine paratuberculosis (PTB) serum, we monitored two unique bacterial lipids that we also monitored in Mycobacterium avian subspecies PTB. These were PDIM-B C82, a phthiodiolone dimycocerosate, and the trehalose monomycolate hTMM 28:1, constituents of the bacterial cell envelope in mycolic-containing bacteria. The next step will be to determine if lipidomics can detect subclinical PTB infections which can last 2-to-4 years in bovine PTB. Our data further suggest that it will be worthwhile to continue building our bacterial lipidomics database and investigate the further utility of this approach in other infections of veterinary and human clinical interest.

Sphingolipidomics of Bovine Pink Eye: A Pilot Study.

Sphingolipids are essential structural components of tear film that protect the surface of the eye from dehydration. A detailed analysis of the effects of pink eye infections on the sphingolipidome in cattle has not previously been undertaken. We recently published a new assay utilizing high-resolution mass spectrometric monitoring of the chloride adducts of sphingolipids that provides enhanced sensitivity and specificity. Utilizing this assay, we monitored decreases in the levels of tear film ceramides with short-chain fatty acids, hydroxy-ceramides, phytoceramides, and hydroxy-phytoceramides. Dihydroceramide levels were unaltered and increased levels of ceramides with long-chain fatty acids (24:0 and 24:1) were monitored in cattle with pink eye. The data from this pilot study (n = 8 controls and 8 pink eye) demonstrate a major disruption of the lipid tear film layer in pink eye disease, that can result in severe eye irritation and damage.

Serine ether glycerophospholipids: Decrements in the frontal cortex associated with mild cognitive impairment and Alzheimer's disease.

Ether glycerophospholipids (GPL) are involved in membrane fluidity and fusion. Vinyl-ether GPL are also conjectured to provide antioxidant capacity in the brain. The roles of these lipids in the processes involved in the development of dementia are not understood but choline and ethanolamine vinyl-ether GPL (i.e., plasmalogens) are decreased in the brains of subjects with dementia. In contrast, serine ether and vinyl-ether GPL have not been investigated in human brain. We therefore undertook an evaluation of these lipids, utilizing high-resolution mass spectrometry (HR-MS), in tissues from control and dementia subjects that we had previously characterized in-depth. We can report for the first time that a number of serine ether GPL and a more limited number of serine plasmalogens are present in human frontal cortex. In addition, we found that some of these frontal cortex lipids are decreased in Mild Cognitive Impairment (MCI), early-onset Alzheimer's disease (EOAD), and late-onset AD (LOAD). In contrast no alterations in serine ether GPL were monitored in the frontal cortex of donors with schizophrenia, demonstrating disease specificity. These data suggest that further studies of the roles of ether GPL, including serine ether GPL, in brain function are worthy of undertaking.

Human Brain Lipidomics: Investigation of Formalin Fixed Brains.

Human brain lipidomics have elucidated structural lipids and lipid signal transduction pathways in neurologic diseases. Such studies have traditionally sourced tissue exclusively from brain bank biorepositories, however, limited inventories signal that these facilities may not be able to keep pace with this growing research domain. Formalin fixed, whole body donors willed to academic institutions offer a potential supplemental tissue source, the lipid profiles of which have yet to be described. To determine the potential of these subjects in lipid analysis, the lipid levels of fresh and fixed frontal cortical gray matter of human donors were compared using high resolution electrospray ionization mass spectrometry. Results revealed commensurate levels of specific triacylglycerols, diacylglycerols, hexosyl ceramides, and hydroxy hexosyl ceramides. Baseline levels of these lipid families in human fixed tissue were identified via a broader survey study covering six brain regions: cerebellar gray matter, superior cerebellar peduncle, gray and subcortical white matter of the precentral gyrus, periventricular white matter, and internal capsule. Whole body donors may therefore serve as supplemental tissue sources for lipid analysis in a variety of clinical contexts, including Parkinson's disease, Alzheimer's disease, Lewy body dementia, multiple sclerosis, and Gaucher's disease.

Lipidomic analysis of surfactant and plasma from horses with asthma and age-matched healthy horses.

OBJECTIVE: To perform lipidomic analysis of surfactant and plasma from asthmatic and healthy horses. ANIMALS: 30 horses with clinical signs of asthma and 30 age-matched control horses. PROCEDURES: Detailed history, physical examination, CBC, and bronchoalveolar lavage fluid (BALF) cytologies were obtained. Asthmatic horses were grouped based on their BALF inflammatory profile: severe equine asthma (SEA), mild equine asthma with neutrophilic airway inflammation (MEA-N), or mild equine asthma with eosinophilic airway inflammation (MEA-E). Each asthma group was assigned its own age-matched control group. Lipidomic analysis was completed on surfactant and plasma. Surfactant protein D (SP-D) concentrations were measured in serum and BALF. RESULTS: SEA surfactant was characterized by a phospholipid deficit and altered composition (increased ceramides, decreased phosphatidylglycerol, and increased cyclic phosphatidic acid [cPA]). In comparison, MEA-N surfactant only had a decrease in select phosphatidylglycerol species and increased cPA levels. The plasma lipidomic profile was significantly different in all asthma groups compared to controls. Specifically, all groups had increased plasma phytoceramide. SEA horses had increased plasma cPA and diacylglycerol whereas MEA-N horses only had increased cPA. MEA-E horses had increases in select ceramides and dihydrocermides. Only SEA horses had significantly increased serum SP-D concentrations. CLINICAL RELEVANCE: The most significant surfactant alterations were present in SEA (altered phospholipid content and composition); only mild changes were observed in MEA-N horses. The plasma lipidomic profile was significantly altered in all groups of asthmatic horses and differed among groups. Data from a larger population of asthmatic horses are needed to assess implications for diagnosis, prognosis, and treatment.

Advanced Meditation and Vegan Diet Increased Acylglycines and Reduced Lipids Associated with Improved Health: A Prospective Longitudinal Study.

Introduction: Samyama is an Isha Yoga 8-day residential meditation/yoga retreat combined with 60 days of preparation with vegan diet. We showed earlier Samyama retreat was associated with lower systemic inflammation and favorable lipid profiles along with other physical and mental health benefits. There is no mechanistic study on the impact of an advanced meditative process on multiple blood lipids and their implications on meditation-related improved physical and mental wellbeing. Methods: Sixty-four Samyama participants on vegan diet had blood sampled immediately before and immediately after the 8-day retreat for lipidomic analysis. The complex plasma lipidome was characterized using high-resolution mass spectrometric analysis and tandem mass spectrometry. Results: Pre- and post-Samyama blood samples of 64 Samyama participants were analyzed. Acylglycines (acetyl, propionyl, butyryl, and valeryl) were increased in the plasma post-Samyama compared with pre-Samyama (p < 0.001). Levels of glycerophosphocholines, glycerophosphoethanolamines, di-unsaturated ethanolamine plasmalogens, cholesterol esters, acylcarnitines, and acylgylcerines (triacylglycerols and diacylglycerols) decreased after the Samyama meditation. Plasma levels of glycerophosphoserines or glycerophosphoinositols were unchanged. Conclusion: An 8-day advanced meditation retreat resulted in increased acylglycines, an endocannabinoid-like fatty acid amide associated with increased cellular anandamide levels, anti-inflammation, analgesia, and vascular relaxation. Other serum lipid levels, including some that are associated with increased risk of atherosclerosis, were reduced following the Samyama program. ClinicalTrials.gov Registration: Identifier: NCT04366544.

Human Brain Lipidomics: Pilot Analysis of the Basal Ganglia Sphingolipidome in Parkinson's Disease and Lewy Body Disease.

Sphingolipids constitute a complex class of bioactive lipids with diverse structural and functional roles in neural tissue. Lipidomic techniques continue to provide evidence for their association in neurological diseases, including Parkinson's disease (PD) and Lewy body disease (LBD). However, prior studies have primarily focused on biological tissues outside of the basal ganglia, despite the known relevancy of this brain region in motor and cognitive dysfunction associated with PD and LBD. Therefore electrospray ionization high resolution mass spectrometry was used to analyze levels of sphingolipid species, including ceramides (Cer), dihydroceramides (DHC), hydoxyceramides (OH-Cer), phytoceramides (Phyto-Cer), phosphoethanolamine ceramides (PE-Cer), sphingomyelins (SM), and sulfatides (Sulf) in the caudate, putamen and globus pallidus of PD (n = 7) and LBD (n = 14) human subjects and were compared to healthy controls (n = 9). The most dramatic alterations were seen in the putamen, with depletion of Cer and elevation of Sulf observed in both groups, with additional depletion of OH-Cer and elevation of DHC identified in LBD subjects. Diverging levels of DHC in the caudate suggest differing roles of this lipid in PD and LBD pathogenesis. These sphingolipid alterations in PD and LBD provide evidence for biochemical involvement of the neuronal cell death that characterize these conditions.

Plasma lipidome of healthy and Rhodococcus equi-infected foals over time.

BACKGROUND: Many foals that develop thoracic ultrasonographic lesions as a result of Rhodococcus equi infection heal on their own. However, most of these foals receive antimicrobials because foals at risk of developing clinical pneumonia cannot be identified. Untargeted lipidomics is useful to identify candidate biomarkers. OBJECTIVES: (a) To describe the changes that occur in foal lipidomics as a result of ageing (birth to 8 weeks) and (b) To compare these results with those observed in foals after experimental infection with R. equi. STUDY DESIGN: Experimental study. METHODS: Healthy newborn foals (n = 9) were challenged with R. equi intratracheally the first week of life. Foals were treated with antimicrobials if they developed clinical pneumonia (n = 4, "clinical group") or were closely monitored if they showed no signs of disease (n = 5 "subclinical group"). An unchallenged group (n = 4) was also included. All foals were free of disease (transtracheal wash fluid evaluation and culture as well as thoracic ultrasonography) by 8 weeks of life. Plasma lipidomics was determined by LC-MS weekly for the study duration (8 weeks). RESULTS: Both ageing and experimental infection altered the foal's plasma lipidome as demonstrated by multivariate statistical analysis. The intensities of 31 lipids were altered by ageing and 12 by infection (P < .05). Furthermore, nine lipids changed by more than twofold between clinical and subclinical groups. MAIN LIMITATIONS: The number of foals is limited. Foals were experimentally challenged with R. equi. CONCLUSIONS: Ageing and R. equi infection induced changes in the plasma lipidome of foals. These experimental results provide the background for future work in the discovery of earlier biomarkers of R. equi pneumonia. Early identification of foals at risk of developing clinical pneumonia is key in order to decrease antimicrobial use and development of antimicrobial resistance.

Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine.

Phenelzine (PLZ) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. This multifaceted drug has a number of pharmacological and neurochemical effects in addition to inhibition of MAO, and findings on these effects have contributed to a body of evidence indicating that PLZ also has neuroprotective/neurorescue properties. These attributes are reviewed in this paper and include catabolism to the active metabolite ß-phenylethylidenehydrazine (PEH) and effects of PLZ and PEH on the GABA-glutamate balance in brain, sequestration of reactive aldehydes, and inhibition of primary amine oxidase. Also discussed are the encouraging findings of the effects of PLZ in animal models of stroke, spinal cord injury, traumatic brain injury, and multiple sclerosis, as well other actions such as reduction of nitrative stress, reduction of the effects of a toxin on dopaminergic neurons, potential anticonvulsant actions, and effects on brain-derived neurotrophic factor, neural cell adhesion molecules, an anti-apoptotic factor, and brain levels of ornithine and N-acetylamino acids.

Dynamics of DHA and EPA supplementation: incorporation into equine plasma, synovial fluid, and surfactant glycerophosphocholines.

INTRODUCTION: Horses with asthma or osteoarthritis frequently receive ω-3 fatty acid supplements. Docosahexaenoic (DHA; 22:6) and eicosapentaenoic (EPA; 20:5) acids are essential ω-3 fatty acid precursors of anti-inflammatory mediators and components of structural glycerophospholipids (GPL) that act as reservoirs of these fatty acids. Analysis of the incorporation of dietary DHA + EPA into GPL pools in different body compartments has not been undertaken in horses. OBJECTIVES: We undertook a detailed study of dietary supplementation with DHA + EPA in horses and monitored incorporation into DHA- and EPA-containing glycerophosphocholines (GPC) 38:5, 38:6, 40:5, and 40:6 in plasma, synovial fluid (SF), and surfactant. METHODS: Horses (n = 20) were randomly assigned to the supplement or control group and evaluated on days 0, 30, 60, and 90. GPC in plasma, SF, and surfactant were measured by high-resolution mass spectrometry with less than 3 ppm mass error. Validation of DHA and EPA incorporation into these GPC was conducted utilizing MS2 of the [M + Cl]- adducts of GPC. RESULTS: Dietary supplementation resulted in augmented levels of GPC 38:5, 38:6, 40:5, and 40:6 in all compartments. Maximum incorporation into GPCs was delayed until 60 days. Significant increases in the levels of GPC 38:5, 40:5, and 40:6, containing docosapentaenoic acid (DPA; 22:5), also was noted. CONCLUSIONS: DHA and EPA supplementation results in augmented storage pools of ω-3 essential fatty acids in SF and surfactant GPC. This has the potential to improve the ability of anti-inflammatory mechanisms to resolve inflammatory pathways in these critical compartments involved in arthritis and asthma.

Human Brain Lipidomics: Utilities of Chloride Adducts in Flow Injection Analysis.

Ceramides have been implicated in a number of disease processes. However, current means of evaluation with flow infusion analysis (FIA) have been limited primarily due to poor sensitivity within our high-resolution mass spectrometry lipidomics analytical platform. To circumvent this deficiency, we investigated the potential of chloride adducts as an alternative method to improve sensitivity with electrospray ionization. Chloride adducts of ceramides and ceramide subfamilies provided 2- to 50-fold increases in sensitivity both with analytical standards and biological samples. Chloride adducts of a number of other lipids with reactive hydroxy groups were also enhanced. For example, monogalactosyl diacylglycerols (MGDGs), extracted from frontal lobe cortical gray and subcortical white matter of cognitively intact subjects, were not detected as ammonium adducts but were readily detected as chloride adducts. Hydroxy lipids demonstrate a high level of specificity in that phosphoglycerols and phosphoinositols do not form chloride adducts. In the case of choline glycerophospholipids, the fatty acid substituents of these lipids could be monitored by MS2 of the chloride adducts. Monitoring the chloride adducts of a number of key lipids offers enhanced sensitivity and specificity with FIA. In the case of glycerophosphocholines, the chloride adducts also allow determination of fatty acid substituents. The chloride adducts of lipids possessing electrophilic hydrogens of hydroxyl groups provide significant increases in sensitivity. In the case of glycerophosphocholines, chloride attachment to the quaternary ammonium group generates a dominant anion, which provides the identities of the fatty acid substituents under MS2 conditions.

Lipidomics of the chicken egg yolk: high-resolution mass spectrometric characterization of nutritional lipid families.

While previous studies have characterized the fatty acids and global lipid families of the chicken egg yolk, there have been no publications characterizing the individual lipids in these lipid families. Such an in-depth characterization of egg yolk lipids is essential to define the potential benefits of egg yolk consumption for the supply of structural and anti-inflammatory lipids. Historically, the major focus has been on the cholesterol content of eggs and the potential negative health benefits of this lipid, while ignoring the essential roles of cholesterol in membranes and as a precursor to other essential sterols. A detailed analysis of egg yolk lipids, using high-resolution mass spectrometric analyses and tandem mass spectrometry to characterize the fatty acid substituents of complex structural lipids, was used to generate the first in-depth characterization of individual lipids within lipid families. Egg yolks were isolated from commercial eggs (Full Circle Market) and lipids extracted with methyl-t-butylether before analyses via high-resolution mass spectrometry. This analytical platform demonstrates that chicken egg yolks provide a rich nutritional source of complex structural lipids required for lipid homeostasis. These include dominant glycerophosphocholines (GPC) (34:2 and 36:2), plasmalogen GPC (34:1, 36:1), glycerophosphoethanolamines (GPE) 38:4 and 36:2), plasmalogen GPE (36:2 and 34:1), glycerophosphoserines (36:2 and 38:4), glycerophosphoinositols (38:4), glycerophosphoglycerols (36:2), N-acylphosphatidylethanolamines (NAPE) (56:6), plasmalogen NAPE (54:4 and 56:6), sphingomyelins (16:0), ceramides (22:0 and 24:0), cyclic phosphatidic acids (16:0 and 18:0), monoacylglycerols (18:1 and 18:2), diacylglycerols (36:3 and 36:2), and triacylglycerols (52:3). Our data indicate that the egg yolk is a rich source of structural and energy-rich lipids. In addition, the structural lipids possess ω-3 and ω-6 fatty acids that are essential precursors of endogenous anti-inflammatory lipid mediators. These data indicate that eggs are a valuable nutritional addition to the diets of individuals that do not have cholesterol issues.

Surfactant protein D concentrations in serum and bronchoalveolar lavage fluid from young healthy horses on pasture and in a barn environment.

OBJECTIVE: To evaluate surfactant protein D (SP-D) concentrations in serum and bronchoalveolar lavage fluid (BALF) from young healthy horses on pasture or housed in a typical barn. ANIMALS: 20 young healthy horses. PROCEDURES: Horses were randomly assigned to 1 of 2 groups (pasture, n = 10; barn, 10), and serum and BALF samples were collected for SP-D determination at baseline (all horses on pasture) and 2 weeks and 4 weeks after the barn group of horses was relocated from the pasture to the barn. Other evaluations included physical and tracheoscopic examinations. Findings were compared within and between groups. RESULTS: Physical and tracheoscopic examinations, CBC, and serum biochemical analysis did not reveal evidence of respiratory disease, and no significant differences were present within and between groups. Serum SP-D concentrations did not significantly differ within and between groups, but BALF SP-D concentrations were significantly lower for the barn group at 2 weeks but not at 4 weeks, compared with baseline. The BALF SP-D concentration-to-BALF total protein concentration ratio was < 1.5 and did not significantly differ within and between groups. CONCLUSIONS AND CLINICAL RELEVANCE: A mild decrease was evident in the concentration of SP-D in the BALF collected from young healthy horses after 2 weeks of exposure to a barn environment. The clinical importance of this finding remains to be determined.

The new pan-European post-specialty training curriculum in Paediatric and Adolescent Gynaecology.

Interest in the field of Paediatric and Adolescent Gynaecology (PAG) has increased substantially over the last decade. Currently there is minimal consensus on how to interpret and validate professional experience, medical knowledge and surgical skills for doctors (accredited in Obstetrics and Gynaecology) who have an interest in and wish to achieve sub-specialisation in PAG. The challenge for the future of PAG is to create a framework of guidelines and references which in turn culminates in improvement and harmonisation in PAG healthcare delivery. The development of a post-specialty training curriculum in PAG for accredited practitioners was a logical next step after EBCOG introduced the PACT curriculum for OBGYN trainees. The guiding principle in the development of the PAG curriculum has been to strive for harmonisation in teaching and training in PAG within Europe. The new EURAPAG curriculum is divided in 17 chapters which in turn have been subdivided into medical and surgical sections plus a baseline skills section. The content has been determined through a consensus procedure amongst European gynaecologists and trainees. The medical chapters involve pathology that requires conservative treatment, prevention, education or lifestyle adjustment. The chapters that are both medical and surgical have a surgical (alternative) treatment ranging from vaginal procedures to advanced hysteroscopic and laparoscopic procedures and laparotomy. Currently, the framework for any medical education is workplace based competency training. Specific tools have been developed for workplace based assessments, such as direct observation (DO) of clinical task performance, Objective Structured Assessment of Technical Skills (OSATS), mini-clinical evaluation exercise (Mini-CEX) or case-based discussion (CBD). To measure progress in this PAG post-specialty training curriculum, the subspecialty trainee will be required to maintain and update a portfolio of experience and competency.

Fatty Acyl Esters of Hydroxy Fatty Acid (FAHFA) Lipid Families.

Fatty Acyl esters of Hydroxy Fatty Acids (FAHFA) encompass three different lipid families which have incorrectly been classified as wax esters. These families include (i) Branched-chain FAHFAs, involved in the regulation of glucose metabolism and inflammation, with acylation of an internal branched-chain hydroxy-palmitic or -stearic acid; (ii) ω-FAHFAs, which function as biosurfactants in a number of biofluids, are formed via acylation of the ω-hydroxyl group of very-long-chain fatty acids (these lipids have also been designated as o-acyl hydroxy fatty acids; OAHFA); and (iii) Ornithine-FAHFAs are bacterial lipids formed by the acylation of short-chain 3-hydroxy fatty acids and the addition of ornithine to the free carboxy group of the hydroxy fatty acid. The differences in biosynthetic pathways and cellular functions of these lipid families will be reviewed and compared to wax esters, which are formed by the acylation of a fatty alcohol, not a hydroxy fatty acid. In summary, FAHFA lipid families are both unique and complex in their biosynthesis and their biological actions. We have only evaluated the tip of the iceberg and much more exciting research is required to understand these lipids in health and disease.

Targeted lipidomics and metabolomics evaluations of cortical neuronal stress in schizophrenia.

BACKGROUND: Cortical neuronal dysfunction has been proposed to underlie the psychopathology and cognitive dysfunction of schizophrenia. Previously we have reported altered sphingolipid and N-acylphosphatidylserine (NAPS) metabolism in the frontal cortex in schizophrenia. We continue to expand these investigations to define the biochemical basis for these critical neuropathologies. METHODS: We undertook a targeted high resolution mass spectrometric analysis to validate our previous reports of elevated sphingolipids and NAPS in the frontal cortex of a new cohort of schizophrenia subjects. Furthermore we expanded these analyses to include ceramides, N-acylphosphatidylethanolamines (NAPE), and N-acylethanolamines (NAE). In the same tissue samples we examined N-acetylaspartylglutamate (NAAG), a modulator of excitatory amino acid transmission, hypothesized to be involved in the pathology of schizophrenia. RESULTS: We repeated our observations of elevated sulfatides in the frontal cortex in schizophrenia. An in-depth analysis of other sphingolipids revealed decrements in ceramide levels and increased levels of lactosylceramides. NAPS also were found to be augmented in schizophrenia as we previously reported. In addition, levels of NAPES, established biomarkers of neuronal stress, were elevated while their metabolites, NAEs were decreased. With regard to excitatory amino acid neurotransmission, NAAG levels were decreased by 50% while the metabolic precursor, N-acetylaspartate was unaltered. CONCLUSIONS: Our data support the concept of cortical neuronal dysfunction in schizophrenia as indicated by altered metabolism of structural sphingolipids and NAAG, a modulator of excitatory amino acid neurotransmission.

Provision of paediatric and adolescent gynaecology in Europe today: A joint review by the European Association of Paediatric and Adolescent Gynaecology (EURAPAG) and European Board and College of Obstetrics and Gynaecology (EBCOG).

Paediatric and Adolescent Gynaecology (PAG) is a multidisciplinary field combining aspects of gynaecology but also includes paediatrics, endocrinology, genetics, radiology, psychology and urology. Specialist knowledge is warranted for the care of these youngsters, and it is important that doctors attending to the gynaecological needs of children must understand that they are not just "little women". Their needs and accompanying clinical approaches required are very different from those of adults in this sensitive area, as is the spectrum of diseases and problems. A multidisciplinary collaboration is as important as the establishment and adoption of standards in education, training and management. The situation in Europe in PAG is varied, reflecting the relative youth of this area of special interest and thereby allowing for earlier consolidation of standards and services across Europe. This article summarises the background to PAG in Europe, inequitable current provision of care and issues relating to education and training all of which are relevant in providing a common approach to PAG problems and endeavouring to obtain the best outcomes. There remains huge diversity how the services for "young women" are currently delivered across different countries within Europe. A concerted European approach is urgently required to streamline standards of training and clinical care, to ensure high quality care by using agreed national and European pathways.