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The authors evaluated the contributions of nine genetic (G) variants (selected from 275 single nucleotide polymorphisms in 11 reverse cholesterol transport pathway genes), five environmental (E) factors (selected from 10), and G x G, E x E, and G x E interactions in explaining population variance of blood lipid concentrations. Total cholesterol, triglycerides, and high density lipoprotein (HDL) cholesterol were measured, and low density lipoprotein (LDL) cholesterol and HDL cholesterol/LDL cholesterol ratio were calculated in a population-based random sample of 1,543 men and women in Geneva, Switzerland, aged 35-74 years in 1999-2001. Explained variances (R2) for HDL cholesterol/LDL cholesterol ratio, HDL cholesterol, and LDL cholesterol, respectively, were 34%, 33%, and 19%, decomposed into main effects of G (6%, 4%, and 5%) and E (25%, 28%, and 11%), with just 3%, 2%, and 3% due to G x G, E x E, and G x E interactions, respectively. Risk factor clustering was only moderate: 70% of study subjects had < or =3 variants, 75% had < or =2 environmental exposures, and 69% had < or =5 of both types of factors. Multiple genes with weak associations, together with more dominating environmental factors, are involved in determining blood lipid concentrations. Interactions added little explained variance. Increasing trends in hypercholesterolemia are attributable to environmental changes affecting populations as a whole. Reducing obesity and smoking and moderating alcohol intake in entire populations should remain the primary strategies for lipid control. [ABSTRACT FROM AUTHOR]

Phospholipids are essential components of cell membranes which may also function to mediate some of the behavioural effects of dopamine receptor stimulation caused by psychostimulant drugs. Neuroimaging and pharmacological data suggest that abnormal brain metabolism of phospholipids might explain some of the consequences of chronic exposure to drugs of abuse including drug craving. We previously reported decreased activity of calcium-stimulated phospholipase A(2) (Ca-PLA(2)) in autopsied putamen of human cocaine users. To establish the specificity of this change in phospholipid metabolism and whether decreased Ca-PLA(2) might be a general feature of all abused drugs which enhance dopaminergic neurotransmission, we measured activity of 11 major phospholipid metabolic enzymes in dopamine-rich (putamen) and poor brain areas of chronic users of cocaine and of methamphetamine. Enzyme changes were restricted to the putamen which showed decreased (-21%, as compared with the control subjects) Ca-PLA(2) activity in users of methamphetamine and reduced (-31%) activity of phosphocholine cytidylyltransferase (PCCT), the rate-limiting enzyme of phosphatidylcholine synthesis, in the cocaine users. We suggest that chronic exposure to psychostimulant drugs might cause a compensatory downregulation of Ca-PLA(2) in dopamine-rich brain areas due to excessive dopamine-related stimulation of the enzyme. Decreased striatal Ca-PLA(2) and/or PCCT activity in cocaine users might also help to explain why CDP choline, which enhances phospholipid synthesis, reduces craving in some users of the drug cocaine. [ABSTRACT FROM AUTHOR]

Introduction: The Northern Ontario School of Medicine University seeks to address rural physician shortages in Northern Ontario. One key strategy the school employs is the use of experiential learning placements embedded throughout its undergraduate curriculum. In second year, students embark on two 4-week placements in rural and remote communities. This study sought to explore the factors that contribute to a positive learning experience from the preceptor's perspective., Methods: Semi-structured interviews were conducted with five community preceptors who have participated in these placements. Using the information from these interviews a survey was created and sent to another 15 preceptors. Data were analyzed using qualitative methods and frequencies., Results: Three key themes were identified from both the interviews and survey data: the role of early rural and remote placements; the risks of these placements; and the need for a reciprocal relationship between institutions, preceptors, and students to create a positive learning environment., Conclusion: Preceptors value the opportunity to teach students, but the aims of these placements are not clear and preceptors and local hospitals need more workforce resources to make these experiences positive.

Introduction: Rural communities have poorer health compared to urban populations due partly to having lesser healthcare access. Rural placements during medical education can equip students with the knowledge and skills to work in rural communities, and, it is hoped, increase the supply of rural physicians. It is unclear how students gain knowledge of rural generalism during placements, and how this can be understood in terms of place-based and/or sociocultural educational theories. To gain insight into these questions we considered the experiences of pre-clerkship medical students who completed two mandatory four-week rural placements during their second year of medical school., Methods: Data was collected using semi-structured interviews or focus groups, followed by thematic analysis of the interview transcripts., Results: Rural placements allowed students to learn about rural generalism such as breadth of practice, and boundary issues. This occurred mainly by students interacting with rural physician faculty, with the effectiveness of precepting being key to students acquiring knowledge and skills and reporting a positive regard for the placement experience., Discussion: Our data show the central role of generalist physician preceptors in how and what students learn while participating in rural placements. Sociocultural learning theory best explains student learning, while place-based education theory helps inform the curriculum. Effective training and preparation of preceptors is likely key to positive student placement experiences., Competing Interests: The authors declare no conflict of interest., (© 2024 Ross, Taylor, Button, Kilbertus, Cameron; licensee Synergies Partners.)

Background: Students are selected for admission to the Northern Ontario School of Medicine University (NOSM U) MD degree program using criteria aiming to maximize access of persons thought most likely to practice in the region, including use of a geographic context score (GCS) which ranks those with lived experience in northern Ontario and/or rurality most highly. This study investigates the effect of this admissions process upon medical school academic performance., Methods: We used a retrospective cohort design combined with multiple linear regression analysis to investigate the relationship between admission scores and performance on pre-clerkship courses, and the Medical Council of Canada Qualifying Exam Part 1 (MCCQE1).The GCS did not significantly explain performance variance on any pre-clerkship course, nor on the MCCQE1, while the undergraduate Grade Point Average correlated with most assessment scores. The number of prior undergraduate biomedical courses predicted science and clinical skills performance, particularly in Year 1, but not with MCCQE1 scores. Performance on Year 2 courses, particularly foundational sciences and clinical skills, significantly predicted MCCQE1 scores., Results: Our data suggest that admission geographic context scoring is unrelated to future academic performance. Further, students with fewer prior undergraduate biomedical courses may benefit from increased support and/or a modified program during the early years., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 Ross, Acharya, Welch, Biasiol, Prowse, Hogard; licensee Synergies Partners.)

Background: Medical education can help alleviate the chronic undersupply of physicians to rural communities. Providing students with early rural clinical experiences may allow the gaining of necessary knowledge and skills to practice and live rurally, as well as the desire to do so., Purpose: This study aims to provide a detailed understanding of Remote and Rural Community Placements (RRCPs) which occur in the second year of a Doctor of Medicine programme., Methodology/approach: Using a thematic analysis approach, we examined the experiences of students and preceptors in the RRCP. Data were collected using semi-structured interviews and focus groups., Findings/conclusions: Students valued RRCPs as a formative clinical experience and preceptors gained professionally from participating. The RRCPs enhanced students regard for, and knowledge of, rural medicine. Yet, contrary to the stated aims of the placement, students spent very little time in activities outside of the clinic, neither learning about the community nor about the life of a physician as a community member., Implications: Medical educators should recognise that students and preceptors will inevitably place different value on the different sociocultural and perceptual aspects of placements, namely clinical and non-clinical. As such, the curriculum should draw clearly articulated links between each., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Schizophrenia is a serious mental illness of unclear aetiology. The reduced ability of methylnicotinate to induce a topical vasodilatory response in patients with the disorder is well established. Methylnicotinate causes vasodilation via stimulating the release of prostaglandins (including prostaglandin D 2 ) in the skin which in turn leads to relaxation of vascular smooth muscle. To determine whether the abnormality is likely to be due to decreased prostaglandin production, or a decreased effect of prostaglandins upon the vessels, topical methylnicotinate was applied to the forearms of patients with schizophrenia or healthy controls, followed by rating of the resulting erythema. The concentration of prostaglandin D 2 and its metabolite 11β-prostaglandin F 2α in the blood draining the arm was also measured. Although erythema was reduced in the patient group, this was not correlated with plasma prostaglandin concentrations. This data suggests the abnormality underlying the reduced potency of methylnicotinate to produce vasodilation in the disorder occurs downstream of prostaglandin synthesis possibly within the vasculature itself., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Occupational health nurses motivate employees to engage in healthy behaviors. Both clinicians and researchers need strong theories on which to base decisions for health programs (e.g., healthy diet) and experimental interventions (e.g., workplace walking). The self-determination theory could be useful as it includes concepts of individual autonomy, competence to perform healthy behaviors, and relationships as predictors of health behaviors and outcomes. In this article, the self-determination theory is described and evaluated using Walker and Avant's criteria. The theory is applied to a population of federal employees who smoke. By increasing employees' ability to autonomously choose smoking cessation programs, support their competence to stop smoking, and improve their relationships with both others who smoke and employee health services, smoking cessation should increase.

Kainate receptors (KARs) are glutamate receptors with peak expression during late embryonic and early postnatal periods. Altered KAR-mediated neurotransmission and subunit expression are observed in several brain disorders, including epilepsy. Here, we examined the role of KARs in regulating seizures in neonatal C57BL/6 mice exposed to a hypoxic insult. We found that knockout of the GluK2 subunit, or blockade of KARs by UBP310 reduced seizure susceptibility during the period of reoxygenation. Following the hypoxic insult, we observed an increase in excitatory neurotransmission in hippocampal CA3 pyramidal cells, which was blocked by treatment with UBP310 prior to hypoxia. Similarly, we observed increased excitatory neurotransmission in CA3 pyramidal cells in an in vitro hippocampal slice model of hypoxic-ischemia. This increase was absent in slices from GluK2 -/- mice and in slices treated with UBP310, suggesting that KARs regulate, at least in part, excitatory synaptic neurotransmission following in vivo hypoxia in neonatal mice. Data from these hypoxia models demonstrate that KARs, specifically those containing the GluK2 subunit, contribute to alterations in excitatory neurotransmission and seizure susceptibility, particularly during the reoxygenation period, in neonatal mice. Therapies targeting KARs may prove successful in treatment of neonates affected by hypoxic seizures.

Breath analysis is a form of metabolomics that utilises the identification and quantification of volatile chemicals to provide information about physiological or pathological processes occurring within the body. An inherent assumption of such analyses is that the concentration of the exhaled gases correlates with the concentration of the same gas in the tissue of interest. In this study we have investigated this assumption by quantifying some volatile compounds in peripheral venous blood headspace, and in nasal breath collected in Tedlar bags obtained at the same time from 30 healthy volunteers, prior to analysis by selected ion flow tube mass spectrometry. Some endogenous compounds were significantly correlated between blood headspace and nasal breath, such as isoprene (r p  = 0.63) and acetone (r p  = 0.68), however many, such as propanol (r p  = -0.26) and methanol (r p  = 0.23), were not. Furthermore, the relative concentrations of volatiles in blood and breath varied markedly between compounds, with some, such as isoprene and acetone, having similar concentrations in each, while others, such as acetic acid, ammonia and methanol, being significantly more abundant in breath, and others, such as methanal, being detectable only in breath. We also observed that breath propanol and acetic acid concentrations were higher in male compared to female participants, and that the blood headspace methanol concentration was negatively correlated to body mass index. No relationship between volatile concentrations and age was observed. Our data suggest that breath concentrations of volatiles do not necessarily give information about the same compound in the blood stream. This is likely due to the upper airway contributing compounds over and above that originating in the circulation. An investigation of the relationship between breath volatile concentrations and that in the tissue(s) of interest should therefore become a routine part of the development process of breath-based biomarkers.

A large body of evidence suggests that dietary supplementation with omega-3 fatty acids may ameliorate depressed mood. The magnitude of the effect varies between studies, however, ranging from none at all to being of clinical significance. Given that substantial comorbidity occurs between mood and anxiety disorders, suggesting that they have one or more pathophysiological mechanisms in common, we hypothesized that omega-3 fatty acids may be acting primarily to reduce anxiety rather than depression per se, a possibility which could underlie their variable effects on mood. To test this hypothesis rats were fed for 8 weeks with diets containing one of three types of omega-3 fatty acids, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, as well as a low omega-3 fatty acid control diet. Although brain omega-3 fatty acid concentrations were altered by dietary supplementation with eicospentaenoic acid and docosahexaenoic acid, no significant change in anxiety related behaviors were observed compared to the control group as assessed by the elevated-plus maze test. Our data therefore do not support an anxiolytic effect of omega-3 fatty acids and suggest that any effect of these lipids on mood likely occurs by a mechanism unrelated to reducing anxiety., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Virtual reality (VR) offers immersive, realistic, three-dimensional experiences that "transport" users to novel environments. Because VR is effective for acute pain and anxiety, it may have benefits for hospitalized patients; however, there are few reports using VR in this setting., Objective: The aim was to evaluate the acceptability and feasibility of VR in a diverse cohort of hospitalized patients., Methods: We assessed the acceptability and feasibility of VR in a cohort of patients admitted to an inpatient hospitalist service over a 4-month period. We excluded patients with motion sickness, stroke, seizure, dementia, nausea, and in isolation. Eligible patients viewed VR experiences (eg, ocean exploration; Cirque du Soleil; tour of Iceland) with Samsung Gear VR goggles. We then conducted semistructured patient interview and performed statistical testing to compare patients willing versus unwilling to use VR., Results: We evaluated 510 patients; 423 were excluded and 57 refused to participate, leaving 30 participants. Patients willing versus unwilling to use VR were younger (mean 49.1, SD 17.4 years vs mean 60.2, SD 17.7 years; P=.01); there were no differences by sex, race, or ethnicity. Among users, most reported a positive experience and indicated that VR could improve pain and anxiety, although many felt the goggles were uncomfortable., Conclusions: Most inpatient users of VR described the experience as pleasant and capable of reducing pain and anxiety. However, few hospitalized patients in this "real-world" series were both eligible and willing to use VR. Consistent with the "digital divide" for emerging technologies, younger patients were more willing to participate. Future research should evaluate the impact of VR on clinical and resource outcomes., Clinicaltrial: Clinicaltrials.gov NCT02456987; https://clinicaltrials.gov/ct2/show/NCT02456987 (Archived by WebCite at http://www.webcitation.org/6iFIMRNh3).

The quantification of trace compounds in alcoholic beverages is a useful means to both investigate the chemical basis of beverage flavor and to facilitate quality control during the production process. One compound of interest is methanol which, due to it being toxic, must not exceed regulatory limits. The analysis of headspace gases is a desirable means to do this since it does not require direct sampling of the liquid material. One established means to conduct headspace analysis is selected ion flow tube mass spectrometry (SIFT-MS). The high concentration of ethanol present in the headspace of alcoholic drinks complicates the analysis, however, via reacting with the precursor ions central to this technique. We therefore investigated whether methanol could be quantified in the presence of a large excess of ethanol using SIFT-MS. We found that methanol reacted with ionized ethanol to generate product ions that could be used to quantify methanol concentrations and used this technique to quantify methanol in beverages containing different quantities of ethanol. We conclude that SIFT-MS can be used to quantify trace compounds in alcoholic beverages by determining the relevant reaction chemistry.

Reactive oxygen species react with unsaturated fatty acids to form a variety of metabolites including aldehydes. Many aldehydes are volatile enough to be detected in headspace gases of blood or cultured cells and in exhaled breath, in particular propanal and hexanal which are derived from omega-3 and omega-6 polyunsaturated fatty acids, respectively. Aldehydes are therefore potential non-invasive biomarkers of oxidative stress and of various diseases in which oxidative stress is thought to play a role including cancer, cardiovascular disease and diabetes. It is unclear, however, how changes in the abundance of the fatty acid precursors, for example by altered dietary intake, affect aldehyde concentrations. We therefore fed male Wistar rats diets supplemented with either palm oil or a combination of palm oil plus an n-3 fatty acid (alpha-linolenic, eicosapentaenoic, or docosahexaenoic acids) for 4 weeks. Fatty acid analysis revealed large changes in the abundance of both n-3 and n-6 fatty acids in the liver with smaller changes observed in the brain. Despite the altered fatty acid abundance, headspace concentrations of C1-C8 aldehydes, and tissue concentrations of thiobarbituric acid reactive substances, did not differ between the 4 dietary groups. Our data suggest that tissue aldehyde concentrations are independent of fatty acid abundance, and further support their use as volatile biomarkers of oxidative stress.

Objectives: To determine if the activity-dependent trafficking of γ2 subunit-containing γ-aminobutyric acid type A receptors (GABAA Rs) that has been observed in older animals and posited to contribute to benzodiazepine pharmacoresistance during status epilepticus (SE) is age-dependent, and to evaluate whether blockade of protein phosphatases can inhibit or reverse the activity-dependent plasticity of these receptors., Methods: The efficacy and potency of diazepam 0.2-10 mg/kg administered 3 or 60 min after the onset of a lithium/pilocarpine-induced seizure in postnatal day 15-16 rats was evaluated using video-electroencephalography (EEG) recordings. The surface expression of γ2 subunit-containing GABAA Rs was assessed using a biotinylation assay, and GABAA R-mediated miniature inhibitory postsynaptic currents (mIPSCs) were recorded using whole-cell patch-clamp recording techniques from dentate granule cells in hippocampal slices acutely obtained 60 min after seizure onset (SE-treated). The effect of the protein phosphatase inhibitors FK506 and okadaic acid (OA) on the surface expression of these receptors was determined in organotypic slice cultures exposed to high potassium and N-methyl-d-aspartate (NMDA) or in SE-treated slices., Results: Diazepam terminated seizures of 3 min but not 60 min duration, even at the highest dose. In the SE-treated slices, the surface expression of γ2 subunit-containing GABAA Rs was reduced and the amplitude of the mIPSCs was diminished. Inhibition of protein phosphatases prevented the activity-induced reduction of the γ2 subunit-containing GABAA Rs in organotypic slice cultures. Furthermore, treatment of SE-treated slices with FK506 or OA restored the surface expression of the γ2 subunit-containing GABAA Rs and the mIPSC amplitude., Significance: This study demonstrates that the plasticity of γ2 subunit-containing GABAA Rs associated with the development of benzodiazepine resistance in young and adult animals is similar. The findings of this study suggest that the mechanisms regulating the activity-dependent trafficking of GABAA Rs during SE can be targeted to develop novel adjunctive therapy for the treatment of benzodiazepine-refractory SE., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Objective: To evaluate short- and long-term outcome after medical and surgical management of horses with cecal impaction and to determine reasons for death or euthanasia., Study Design: Retrospective case series., Animals: Horses (n = 150)., Methods: Data collected from medical records (1991-2011) of horses with a diagnosis of cecal impaction, included signalment, history of recent disease/surgical procedure, admission data, management (medical, typhlotomy alone, jejunocolostomy), complications, and outcome. Short-term outcome (alive or dead at discharge) and long-term outcome (alive or dead at ≥1 year) were determined by telephone interview. Data were analyzed using a χ(2) or Fisher's exact test. Level of significance was P < .05., Results: Of 150 horses hospitalized with a diagnosis of cecal impaction, 102 (68%) had a history of recent disease or a surgical procedure. Thirty-eight horses (25%) had cecal perforation at admission and 3 horses (2%) were euthanatized without treatment. Of 109 horses treated, 59 (54%) were managed medically and 50 (46%) surgically (typhlotomy [26]; jejunocolostomy [24]). The proportion of horses alive at hospital discharge was significantly lower for horses managed medically (61%) compared with surgically (82%; P = .02) but there was no difference between horses managed with typhlotomy alone (77%) or with jejunocolostomy (88%; P = .47). There were 57% of horses managed medically alive at 1 year. There was a similar proportion of horses alive at 1 year after typhlotomy alone (73%) and jejunocolostomy (70%; P = .86)., Conclusions: Compared to the recent reports, the proportion of horses alive at hospital discharge was lower for both medically and surgically managed horses with cecal impaction. There was decreased survival for horses treated medically than those treated surgically; however, no significant difference was seen in survival between horses managed with typhlotomy alone versus jejunocolostomy., (© Copyright 2014 by The American College of Veterinary Surgeons.)

Demethylation of industrial lignin has been for long coveted as a pathway to the production of an abundant natural substitute for fossil-oil derived phenol. In an attempt to possibly identify a novel Kraft lignin-demethylating enzyme, we surveyed a collection of fungi by using selected ion flow tube-mass spectrometry (SIFT-MS). This method readily identifies methanol resulting from lignin demethylation activity. Absidia cylindrospora, and unidentified Cylindrocladium sp. and Aspergillus sp. were shown to metabolize lignin via different pathways, based on the HPLC analysis of lignin fragments. Of these three, Cylindrocladium and Aspergillus were shown to retain most of the lignin intact after 3 weeks in culture, while removing about 40% of the available methoxy groups. Our results demonstrate that after optimization of culture and lignin recovery methods, biological modification of Kraft lignin may be a feasible pathway to obtaining demethylated lignin for further industrial use., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Ethane in human breath derives from lipid peroxidation, specifically the reaction between omega-3 fatty acids and reactive oxygen species. It has been proposed to be a non-invasive marker of oxidative stress, a deleterious process which may play an important role in the pathophysiology of several common diseases. It is unclear, however, whether ethane concentration actually correlates with systemic oxidative stress or whether it is primarily a marker of airway biochemistry. To investigate this possibility the breath ethane concentrations in 24 healthy volunteers were compared to that of a systemic measure of oxidative stress, plasma hydroperoxides, as well as to blood concentrations of the lipophilic anti-oxidant vitamin E, and the abundance of omega-3 fatty acids. Breath ethane concentrations were significantly (p < 0.05) positively correlated with blood hydroperoxide concentrations (rp = 0.60) and negatively with that of vitamin E (rp = -0.65), but were not correlated with either the total omega-3 fatty acid concentration (rp = -0.22) or that of any individual species of this fatty acid class. This data supports the hypothesis that breath ethane is a marker of systemic lipid peroxidation, as opposed to that of omega-3 fatty acid abundance.

Basil (Ocimum basilicum) is an important flavourant plant which constitutes the major ingredient of the pasta sauce 'Pesto alla Genovese'. The characteristic smell of basil stems mainly from a handful of terpenoids (methyl cinnamate, eucalyptol, linalool and estragole), the concentration of which varies according to basil cultivars. The simple and rapid analysis of the terpenoid constituents of basil would be useful as a means to optimise harvesting times and to act as a quality control process for basil-containing foodstuffs. Classical analytical techniques such as gas chromatography/mass spectrometry (GC/MS) are, however, slow, technically demanding and therefore less suitable for routine analysis. A new chemical ionisation technique which allows real-time quantification of traces gases, Selected Ion Flow Tube Mass Spectrometry (SIFT-MS), was therefore utilised to determine its usefulness for the assay of terpenoid concentrations in basil and pesto sauce headspace. Trace gas analysis was performed using the NO(+) precursor ion which minimised interference from other compounds. Character-impacting compound concentration was measured in basil headspace with good reproducibility and statistically significant differences were observed between cultivars. Quantification of linalool in pesto sauce headspace proved more difficult due to the presence of interfering compounds. This was resolved by careful selection of reaction product ions which allowed us to detect differences between various commercial brands of pesto. We conclude that SIFT-MS may be a valid tool for the fast and reproducible analysis of flavourant terpenoids in basil and basil-derived foodstuffs., (Copyright © 2011 John Wiley & Sons, Ltd.)

The disassembly of a core-satellite nanostructured substrate is presented as a colorimetric biosensor observable under dark-field illumination. The fabrication method described herein utilizes thiol-mediated adsorption and streptavidin-biotin binding to self-assemble core-satellite nanostructures with a sacrificial linking peptide. Biosensing functionality is demonstrated with the protease trypsin, and the optical properties of the nanoassemblies are characterized. A figure of merit is presented to determine the optimal core and satellite size for visual detection. Nanoassemblies with 50 nm cores and 30 or 50 nm satellites are superior as these structures achieve an orange to green color shift greater than 70 nm that is easily discernible by the naked eye. This colorimetric substrate may prove to be a favorable alternative to liquid-based colloidal sensors and a useful visual readout mechanism for point-of-care microfluidic diagnostic assays.

Inspired by the natural processes during morphogenesis, we demonstrate the transformation capability of active soft-matter to define nanoscale metal-on-polymer architectures below the resolution limit of conventional lithography. Specifically, using active polymers, we fabricate and characterize ultradense nanoplasmonic antenna arrays with sub-10 nm tip-to-tip nanogaps. In addition, the macroscale morphology can be independently manipulated into arbitrary three-dimensional geometries, demonstrated with the fabrication of an omnidirectional nanoplasmonic optical antenna array.

Orthognathic surgery is frequently accompanied by intermaxillary fixation. Intermaxillary fixation impedes the maintenance of effective oral hygiene and prolonged fixation can result in periodontal disease. A potential shorter term effect is the generation of oral malodour. It is unclear, however, as to how the production of malodorous compounds in the oral cavity is altered post-surgery. Oral air concentration of sulphur containing compounds, short chain organic acids, ammonia, isoprene and acetone were measured using selected ion flow tube-mass spectrometry in a patient who had undergone orthognathic surgery with subsequent intermaxillary fixation. Total sulphide levels rose approximately 5-fold during fixation with metal ties, with smaller increases recorded for the other compounds measured with the exception of isoprene which remained close to baseline levels. Organic acid levels declined markedly once elastic ties had replaced metal ties, with a lesser reduction being observed in sulphide levels, with both declining further after the commencement of a chlorhexidine-containing mouthwash. These data suggest that bacterial generation of a variety of malodorous compounds increases markedly following intermaxillary fixation. This single case also suggests that the use of elastic ties and effective oral hygiene techniques, including the use of chlorhexidine mouthwash, may help ameliorate such post-surgical effects.

Oxidative stress has been reported to be elevated in mental illness. Preliminary evidence suggests this phenomenon can be assessed non-invasively by determining breath levels of the omega-3 polyunsaturated fatty acid (PUFA) oxidation product ethane. This study compares alkane levels in chronic, medicated, patients with schizophrenia or bipolar disorder with those in healthy controls. Both ethane and butane levels were significantly increased in patients with schizophrenia or bipolar disorder, although elevated butane levels were likely due to increased ambient gas concentrations. Ethane levels were not correlated with symptom severity or with erythrocyte omega-3 PUFA levels. Our results support the hypothesis that oxidative stress is elevated in patients with schizophrenia and bipolar disorder leading to increased breath ethane abundance. This does not appear to be caused by increased abundance of omega-3 PUFA, but rather is likely due to enhanced oxidative damage of these lipids. As such, breath hydrocarbon analysis may represent a simple, non-invasive means to monitor the metabolic processes occurring in these disorders., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We present a self-powered integrated microfluidic blood analysis system (SIMBAS) that does not require any external connections, tethers, or tubing to deliver and analyze a raw whole-blood sample. SIMBAS only requires the user to place a 5 μL droplet of whole-blood at the inlet port of the device, whereupon the stand-alone SIMBAS performs on-chip removal of red and white cells, without external valving or pumping mechanisms, followed by analyte detection in platelet-containing plasma. Five complete biotin-streptavidin sample-to-answer assays are performed in 10 min; the limit of detection is 1.5 pM. Red and white blood cells are removed by trapping them in an integral trench structure. Simulations and experimental data show 99.9% to 100% blood cell retention in the passive structure. Powered by pre-evacuation of its PDMS substrate, SIMBAS' guiding design principle is the integration of the minimal number of components without sacrificing effectiveness in performing rapid complete bioassays, a critical step towards point-of-care molecular diagnostics.

The reactions of H(3) O(+) , NO(+) and O 2+ with twelve terpenoids and one terpene, all of which occur naturally in plants and which possess important smell and flavourant properties, were characterized using Selected Ion Flow Tube Mass Spectrometry (SIFT-MS). The H(3) O(+) reactions resulted primarily in the formation of the proton transfer product and occasionally in a water elimination product. The NO(+) reactions instead generated the charge transfer product or NO(+) adducts, and occasionally alkyl fragments, or resulted in hydride abstraction. Reaction with O 2+ caused a higher fragmentation of the terpenoids with the molecular ion being the minor product of most reactions. Identification and quantification of each compound in complex mixtures are probably possible in most cases using the H(3) O(+) and/or NO(+) precursors while O 2+ may be useful for isomer discrimination. Our data suggests that SIFT-MS may be a useful tool for the rapid analysis of these compounds in plants and derived foodstuffs., (Copyright © 2010 John Wiley & Sons, Ltd.)

The cognitive profile of early onset Parkinson's disease (EOPD) has not been clearly defined. Mutations in the parkin gene are the most common genetic risk factor for EOPD and may offer information about the neuropsychological pattern of performance in both symptomatic and asymptomatic mutation carriers. EOPD probands and their first-degree relatives who did not have Parkinson's disease (PD) were genotyped for mutations in the parkin gene and administered a comprehensive neuropsychological battery. Performance was compared between EOPD probands with (N = 43) and without (N = 52) parkin mutations. The same neuropsychological battery was administered to 217 first-degree relatives to assess neuropsychological function in individuals who carry parkin mutations but do not have PD. No significant differences in neuropsychological test performance were found between parkin carrier and noncarrier probands. Performance also did not differ between EOPD noncarriers and carrier subgroups (i.e., heterozygotes, compound heterozygotes/homozygotes). Similarly, no differences were found among unaffected family members across genotypes. Mean neuropsychological test performance was within normal range in all probands and relatives. Carriers of parkin mutations, whether or not they have PD, do not perform differently on neuropsychological measures as compared to noncarriers. The cognitive functioning of parkin carriers over time warrants further study.

Objective: To assess the frequency and clinical characteristics of carriers of previously identified mutations in 6 genes associated with early-onset Parkinson disease (PD) and provide empirical data that can be used to inform genetic counseling., Design: Cross-sectional observational study., Setting: Thirteen movement disorders centers., Patients: Nine hundred fifty-three individuals with early-onset PD defined as age at onset (AAO) younger than 51 years. Participants included 77 and 139 individuals of Hispanic and Jewish ancestry, respectively. Intervention Mutations in SNCA, PRKN, PINK1, DJ1, LRRK2, and GBA were assessed. A validated family history interview and the Unified Parkinson Disease Rating Scale were administered. Demographic and phenotypic characteristics were compared among groups defined by mutation status. Main Outcome Measure Mutation carrier frequency stratified by AAO and ethnic background., Results: One hundred fifty-eight (16.6%) participants had mutations, including 64 (6.7%) PRKN, 35 (3.6%) LRRK2 G2019S, 64 (6.7%) GBA, and 1 (0.2%) DJ1. Mutation carriers were more frequent in those with an AAO of 30 years or younger compared with those with AAO between 31 and 50 years (40.6% vs 14.6%, P < .001), in individuals who reported Jewish ancestry (32.4% vs 13.7%, P < .001), and in those reporting a first-degree family history of PD (23.9% vs 15.1%, P = .01). Hispanic individuals were more likely to be PRKN carriers than non-Hispanic individuals (15.6% vs 5.9%, P = .003). The GBA L444P mutation was associated with a higher mean Unified Parkinson Disease Rating Scale III score after adjustment for covariates., Conclusion: Individuals of Jewish or Hispanic ancestry with early-onset PD, those with AAO of 30 years or younger, and those with a history of PD in a first-degree relative may benefit from genetic counseling.

Background: Mutations in the parkin gene are the most common genetic cause of early-onset Parkinson disease (PD). Results from a multicenter study of patients with PD systematically sampled by age at onset have not been reported to date., Objective: To determine risk factors associated with carrying parkin mutations., Design: Cross-sectional observational study., Setting: Thirteen movement disorders centers., Participants: A total of 956 patients with early-onset PD, defined as age at onset younger than 51 years., Main Outcome Measures: Presence of heterozygous, homozygous, or compound heterozygous parkin mutations., Results: Using a previously validated interview, 14.7% of patients reported a family history of PD in a first-degree relative. Sixty-four patients (6.7%) had parkin mutations (3.9% heterozygous, 0.6% homozygous, and 2.2% compound heterozygous). Copy number variation was present in 52.3% of mutation carriers (31.6% of heterozygous, 83.3% of homozygous, and 81.0% of compound heterozygous). Deletions in exons 3 and 4 and 255delA were common among Hispanics (specifically Puerto Ricans). Younger age at onset (<40 years) (odds ratio [OR], 5.0; 95% confidence interval [CI], 2.8-8.8; P = .001), Hispanic race/ethnicity (OR compared with white non-Hispanic race/ethnicity, 2.7; 95% CI, 1.3-5.7; P = .009), and family history of PD in a first-degree relative (OR compared with noncarriers, 2.8; 95% CI, 1.5-5.3; P = .002) were associated with carrying any parkin mutation (heterozygous, homozygous, or compound heterozygous). Hispanic race/ethnicity was associated with carrying a heterozygous mutation (OR compared with white non-Hispanic race/ethnicity, 2.8; 95% CI, 1.1-7.2; P = .03) after adjustment for covariates., Conclusions: Age at onset, Hispanic race/ethnicity, and family history of PD are associated with carrying any parkin mutation (heterozygous, homozygous, or compound heterozygous) and heterozygous mutations alone. The increased odds of carrying a parkin mutation among Hispanics warrants further study.

The reactions of H(3)O(+), NO(+), and O(2) (+) with nineteen ester compounds occurring naturally in plants, and having important flavourant properties, were examined using selected ion flow tube mass spectrometry (SIFT-MS). The H(3)O(+) reactions primarily generate [R(1)COOR(2).H](+), and may also produce [R(2)](+) fragment ions and/or fragmentation within the ester linkage. Collisional association/adduct ions, [R(1)COOR(2).NO](+), are the main products formed in the NO(+) reactions, although the carboxyl fragment ion is also detected frequently. The identification of the parent compound may be made more easily in the H(3)O(+) and NO(+) reactions. The inclusion of O(2) (+) reactions in the analysis provides additional information, which may be applied when the identity of a parent compound cannot be determined solely from the H(3)O(+) and NO(+) analysis. Consideration of the product ions generated with the three precursors suggests that SIFT-MS can differentiate between many of the esters investigated, including isomers, although the product ions generated in the reactions with some esters are too similar to allow independent quantification. Our data therefore suggest that SIFT-MS may be a useful tool to rapidly analyse and quantify flavourant esters in complex gas mixtures., (Copyright (c) 2010 John Wiley & Sons, Ltd.)

Background and Aims: Breath diagnostics, the measurement of volatile chemicals in human breath, is currently receiving attention as a technique for the detection of disease which, being non-invasive in nature, is particularly suited to screening for pre-symptomatic disease in healthy populations. A disorder in which more effective screening would be beneficial is celiac disease (CD), an under-diagnosed autoimmune disease of the small intestine characterized by nutritional malabsorption, which presents with diverse, and sometimes serious, symptoms. We aimed to determine whether breath analyses could be used to screen for the presence of CD., Methods: Based on our hypotheses that malabsorption of dietary carbohydrates would lead to over production of alcohol fermentation products in the large intestine, we investigated levels of alcohols in the breath of 10 patients with CD compared to that in 10 healthy controls using selected ion flow tube mass spectrometry (SIFT-MS)., Results: No differences were found in the breath levels of methanol, propanol, butanol, heptanol or hexanol investigated using chemical ionization of breath air with H3O+ and/or NO+ precursor ions. In one patient, diagnosed within days of our study and not currently in receipt of any therapeutic intervention, a relatively high production of three product ions was detected compared to all other study patients., Conclusion: Our data suggest that breath alcohol levels are unlikely to be of diagnostic use in CD, although further investigation of those recently diagnosed with the disorder may be warranted.

Objective: To determine the motor phenotype of LRRK2 G2019S mutation carriers. LRRK2 mutation carriers were previously reported to manifest the tremor dominant motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared with the postural instability and gait difficulty (PIGD) phenotype., Design: Cross-sectional observational study., Setting: Thirteen movement disorders centers., Participants: Nine hundred twenty-five early-onset Parkinson disease cases defined as age at onset younger than 51 years., Main Outcome Measures: LRRK2 mutation status and Parkinson disease motor phenotype: tremor dominant or PIGD. Demographic information, family history of Parkinson disease, and the Unified Parkinson's Disease Rating Scale score were collected on all participants. DNA samples were genotyped for LRRK2 mutations (G2019S, I2020T, R1441C, and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish ancestry, levodopa dose, and family history of Parkinson disease., Results: Thirty-four cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be Ashkenazi Jewish (55.9% vs 11.9%; P < .001) but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (P = .03) and were more likely to have a PIGD phenotype (92.3% vs 58.9%; P = .003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and Ashkenazi Jewish ancestry (odds ratio, 17.7; P < .001)., Conclusion: Early-onset Parkinson disease G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course.

Polyamines are a class of aliphatic compounds which include putrescine, cadaverine, spermine and spermidine. They are involved in a variety of cellular processes and have been implicated in a number of different pathophysiological mechanisms. Polyamines are volatile compounds having a distinctive odour normally perceived as being unpleasant. The measurement of their abundance has, however, been restricted to compounds present in the aqueous phase. Using selected ion flow tube mass spectrometry (SIFT-MS) we have shown that the polyamines react with the ions H3O+, NO+ and O2+ to form distinctive product ions allowing their levels to be quantified in the vapour phase. The low volatility of spermine did not allow extensive analysis of this compound by SIFT-MS while the adherent properties of cadaverine and putrescine required the use of PTFE transfer lines and couplers. Our data suggested the presence of cadaverine and putrescine in both oral air and the headspace of putrefying bovine muscle, while product ions corresponding to putrescine and spermidine were found in the headspace of human semen. SIFT-MS therefore appears to be a practical means of measuring vapour-phase polyamine levels, having applications in biology, medicine and dentistry, and food science., (Copyright 2009 John Wiley & Sons, Ltd.)

We present a systematic theoretical study of core-satellite gold nanoparticle assemblies using the Generalized Multiparticle Mie formalism. We consider the importance of satellite number, satellite radius, the core radius, and the satellite distance, and we present approaches to optimize spectral shift due to satellite attachment or release. This provides clear strategies for improving the sensitivity and signal-to-noise ratio for molecular detection, enabling simple colorimetric assays. We quantify the performance of these strategies by introducing a figure of merit. In addition, we provide an improved understanding of the nanoplasmonic interactions that govern the optical response of core-satellite nanoassemblies.

Anxiety disorders are a common group of psychiatric illnesses which have significant personal, family and societal costs. Current treatments have limited efficacy in many patients highlighting a need for new therapeutic approaches to be explored. Anxiety disorders exhibit marked comorbity with mood disorders suggesting the existence of mechanistic similarities. Such a notion is supported by observations that some conventional pharmacotherapies are both effective antidepressants and anxiolytics. As such, given that omega-3 PUFA supplementation may be effective in the treatment of major depressive disorder it is reasonable to propose that they may also possess anxiolytic properties. Experimental data in support of such a hypothesis is currently lacking although reduced abundance of omega-3 PUFA have been reported in patients with anxiety, while supplementation with omega-3 PUFA appears to inhibit activation of the HPA axis and can ameliorate some of the symptoms of anxiety. Clinical investigations carried out to date have, however, involved small numbers of participants. Larger trials using a variety of omega-3 PUFA species in clinically well-defined patients with anxiety will be required to demonstrate a therapeutic role for omega-3 PUFA in these disorders. Given the excellent side effect profile of omega-3 PUFA as well as their strong theoretical rationale, such future trials appear justified.

Background: Mutations in the glucocerebrosidase (GBA) gene are associated with Lewy body (LB) disorders., Objective: To determine the relationship of GBA mutations and APOE4 genotype to LB and Alzheimer disease (AD) pathological findings., Design: Case-control study., Setting: Academic research., Participants: The 187 subjects included patients with primary neuropathological diagnoses of LB disorders with or without AD changes (95 cases), randomly selected patients with AD (without significant LB pathological findings; 60 cases), and controls with neither LB nor AD pathological findings (32 cases)., Main Outcome Measures: GBA mutation status, APOE4 genotype, LB pathological findings (assessed according to the third report of the Dementia With Lewy Body Consortium), and Alzheimer plaque and tangle pathological findings (rated by criteria of Braak and Braak, the Consortium to Establish a Registry for Alzheimer Disease, and the National Institute on Aging-Reagan Institute)., Results: GBA mutations were found in 18% (34 of 187) of all subjects, including 28% (27 of 95) of those with primary LB pathological findings compared with 10% (6 of 60) of those with AD pathological findings and 3% (1 of 32) of those without AD or LB pathological findings (P=.001). GBA mutation status was significantly associated with the presence of cortical LBs (odds ratio, 6.48; 95% confidence interval, 2.45-17.16; P<.001), after adjusting for sex, age at death, and presence of APOE4. GBA mutation carriers were significantly less likely to meet AD pathological diagnostic (National Institute on Aging-Reagan Institute intermediate or high likelihood) criteria (odds ratio, 0.35; 95% confidence interval, 0.15-0.79; P=.01) after adjustment for sex, age at death, and APOE4., Conclusion: GBA mutations may be associated with pathologically "purer" LB disorders, characterized by more extensive (cortical) LB, and less severe AD pathological findings and may be a useful marker for LB disorders.

We present the first optical study of large-area random arrays of crescent-shaped nanoholes. The crescent-shaped nanohole antennae, fabricated using wafer-scale nanosphere lithography, provide a complement to crescent-shaped nanostructures, called nanocrescents, which have been established as powerful plasmonic biosensors. With both systematic experimental and computational analysis, we characterize the optical properties of crescent-shaped nanohole antennae and demonstrate tunability of their optical response by varying all key geometric parameters. Crescent-shaped nanoholes have reproducible sub-10-nm tips and are sharper than corresponding nanocrescents, resulting in higher local field enhancement, which is predicted to be |E|/|E(0)| = 1500. In addition, the crescent-shaped nanohole hole-based geometry offers increased integratability and the potential to nanoconfine analyte in "hot-spot" regions, increasing biomolecular sensitivity and allowing localized nanoscale optical control of biological functions.

We propose a new solution for high hot-spot density creation by coupling a particle and a cavity in a structure dubbed a plasmonic enhanced particle-cavity (PEP-C) antenna. In comparison to analogous particle-based dimer antenna structures, the PEP-C allows both a higher maximum field and an order-of-magnitude higher hot-spot density. In addition, the hot-spots of the PEP-C antenna can be precisely controlled, resulting in increased reliability. We elucidate the photonic characteristics of the PEP-C antenna and show tuning and optimization through choice of geometric parameters. These properties make the PEP-C antenna an excellent candidate for plasmonic-based biomolecular sensors.

With a systematic comparison of the near- and far-field measures of plasmon resonance, we show that significant differences arise between the measures for both gold and silver spherical particles. The difference of the peak wavelengths between the near- and far-field measures increases with increasing particle size, reaching over 200 nm for a particle radius of 100 nm for both gold and silver. We physically explain these results by applying radiation damping to the quasi-static approximation, and we provide simple phenomenonological fits, which readily convert between the peak wavelengths for each measure. We expect that taking into account these differences can provide improvement in understanding and optimizing surface-enhanced spectroscopies.

Background: The topical application of methylnicotinate results in a localized vasodilatatory response which has been found to differ from that observed to occur in healthy controls in a variety of medical conditions. The stability of the drug in aqueous solution is unclear while difficulties can be encountered when preparing methylnicotinate solutions for this purpose. To aid in the determination of how long solutions of the drug should be stored before discarding we have used a collection of aged batches of methylnicotinate to determine the stability of the drug in aqueous solution., Findings: The degradation of methylnicotinate was determined in batches which had been stored at 4 degrees C for between 5 and 1062 days prior to analysis by High Performance Liquid Chromatography. The major degradation product of methylnicotinate was nicotinic acid which formed at an approximate rate of 0.5% of the starting methylnicotinate concentration per annum. Furthermore, the ability of methylnicotinate solutions of different ages to induce vasodilatation was assessed in healthy volunteers. No significant difference in vasodilatatory response was apparent between batches which had been stored for between zero and 1057 days., Conclusion: Methylnicotinate exhibits excellent chemical and biological stability in solution facilitating its use in clinical applications.

Background: Selected ion flow tube mass spectrometry (SIFT-MS) allows the real time quantification of trace gases in air. Due to its tolerance of high humidity levels the technique is particularly suited to the chemical analysis of breath. The detection limit of SIFT-MS has previously reported to be approximately 5 - 10 PPBV which is insufficient for the measurement of some low abundance constituents of breath. Recent developments in the design of SIFT-MS instruments have increased the ion precursor count rates. It is, however, unclear as to how these advances will affect instrument sensitivity for breath analysis., Findings: Standard gases were prepared by adding known quantities of compounds present at zero or very low levels in breath (xylene and toluene) to either humidified bottled air or actual human breath. These were then analysed by SIFT-MS to calculate the limits of detection for each compound under conditions which mimic a single breath exhalation. For xylene and toluene the limits of detection was approximately 0.5 PPBV per 10 seconds of analysis time. Results gained using this level of sensitivity suggested the presence of low levels of the compounds indole and methylindole in human alveolar and static oral air, although further studies are necessary to confirm these findings., Conclusion: Recent advances in SIFT-MS have increased the techniques sensitivity for breath analysis into the sub PPBV range enabling the real time quantification of low level trace gases in human breath.

We present a systematic numerical study of plasmon resonance of the nanocrescent. We show that by varying the nanocrescent geometry, the plasmon resonance peak can be tuned into the near-infrared and local field enhancement can be increased significantly, with maximum enhancement of the electric field amplitude of approximately 100 for realistic geometric parameters. Because of its wide tunability, high local field enhancement, and geometry which utilizes both sharp features and intra-particle coupling, the nanocrescent is a structure well suited for in vivo cellular imaging as well as in vitro diagnostic applications.

Background: This study tested the hypothesis that exhaled ethane is a biomarker of cerebral n-3 polyunsaturated fatty acid peroxidation in humans. Ethane is released specifically following peroxidation of n-3 polyunsaturated fatty acids. We reasoned that the cerebral source of ethane would be the docosahexaenoic acid component of membrane phospholipids. Breakdown of the latter also releases phosphorylated polar head groups, giving rise to glycerophosphorylcholine and glycerophosphorylethanolamine, which can be measured from the 31-phosphorus neurospectroscopy phosphodiester peak. Schizophrenia patients were chosen because of evidence of increased free radical-mediated damage and cerebral lipid peroxidation in this disorder., Methods: Samples of alveolar air were obtained from eight patients and ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30). Cerebral 31-phosphorus spectra were obtained from the same patients at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 x 70 x 70 mm3 voxel). The quantification of the 31-phosphorus signals using prior knowledge was carried out in the temporal domain after truncating the first 1.92 ms of the signal to remove the broad component present in the 31-phosphorus spectra., Results: The ethane and phosphodiester levels, expressed as a percentage of the total 31-phosphorus signal, were positively and significantly correlated (rs = 0.714, p < 0.05)., Conclusion: Our results support the hypothesis that the measurement of exhaled ethane levels indexes cerebral n-3 lipid peroxidation. From a practical viewpoint, if human cerebral n-3 polyunsaturated fatty acid catabolism can be measured by ethane in expired breath, this would be more convenient than determining the area of the 31-phosphorus neurospectroscopy phosphodiester peak.

Background: Cigarette smoking is believed to cause oxidative stress by several mechanisms, including direct damage by radical species and the inflammatory response induced by smoking, and would therefore be expected to cause increased lipid peroxidation. The aim was to carry out the first study of the relationship of smoking in humans to the level of n-3 lipid peroxidation indexed by the level of ethane in exhaled breath., Methods: Samples of alveolar air were obtained from 11 smokers and 18 non-smokers. The air samples were analyzed for ethane using mass spectrometry., Results: The two groups of subjects were matched with respect to age and gender. The mean cumulative smoking status of the smokers was 11.8 (standard error 2.5) pack-years. The mean level of ethane in the alveolar breath of the group of smokers (2.53 (0.55) ppb) was not significantly different from that of the group of non-smokers (2.59 (0.29) ppb; p = 0.92). With all 29 subjects included, the Spearman rank correlation coefficient between ethane levels and cumulative smoking status was -0.11 (p = 0.58), while an analysis including only the smokers yielded a corresponding correlation coefficient of 0.11 (p = 0.75)., Conclusion: Our results show no evidence that cigarette smoking is related to increased n-3 lipid peroxidation as measured by expired ethane.

This study directly assessed whether there was a change in the level of exhaled ethane, which provides a non-invasive, quantitative, direct measure of n-3 lipid peroxidation, in the breath of patients with schizophrenia. Samples of alveolar air were obtained from 20 subjects with schizophrenia and 23 age- and sex-matched healthy control subjects. The air samples were analyzed for ethane using mass spectrometry. The mean level of ethane in the schizophrenia sample [5.15 (S.E. 0.56) ppb] was significantly higher than that of the healthy controls [2.63 (S.E. 0.31) ppb; p<0.0005]. A further sub-analysis showed that nicotine dependence was unlikely to be the cause of this difference. These results suggest that the measurement of exhaled ethane levels may offer a non-invasive direct biomarker of increased n-3 lipid peroxidation in schizophrenia.