Emersion and Terrestrial Locomotion of the Northern Snakehead (Channa argus) on Multiple Substrates.

Most fishes known for terrestrial locomotion are small and/or elongate. Northern snakeheads (Channa argus) are large, air-breathing piscivores anecdotally known for terrestrial behaviors. Our goals were to determine their environmental motivations for emersion, describe their terrestrial kinematics for fish 3.0-70.0 cm and compare kinematics among four substrates. For emersion experiments, C. argus was individually placed into aquatic containers with ramps extending through the surface of the water, and exposed to 15 ecologically-relevant environmental conditions. For kinematic experiments, fish were filmed moving on moist bench liner, grass, artificial turf, and a flat or tilted rubber boat deck. Videos were digitized for analysis in MATLAB and electromyography was used to measure muscular activity. Only the low pH (4.8), high salinity (30 ppt), and high dCO2 (10% seltzer solution) treatments elicited emersion responses. While extreme, these conditions do occur in some of their native Asian swamps. Northern snakeheads >4.5 cm used a unique form of axial-appendage-based terrestrial locomotion involving cyclic oscillations of the axial body, paired with near-simultaneous movements of both pectoral fins. Individuals ≤3.5 cm used tail-flip jumps to travel on land. Northern snakeheads also moved more quickly on complex, three-dimensional substrates (e.g., grass) than on smooth substrates (e.g., bench liner), and when moving downslope. Release of snakeheads onto land by humans or accidentally by predators may be more common than voluntary emersion, but because northern snakeheads can respire air, it may be necessary to factor in the ability to spread overland into the management of this invasive species.

Emersión y locomoción terrestre de la cabeza de serpiente del norte (Channa argus) en múltiples sustratos (Emersion and terrestrial locomotion of the northern snakehead (Channa argus) on multiple substrates) La mayoría de los peces conocidos por locomoción terrestre son pequeños y/o alargados. Las cabezas de serpiente del norte (Channa argus) son grandes pesces piscívoros que respiran aire, anecdóticamente conocidos por sus comportamientos terrestres. Nuestros objetivos fueron determinar sus motivaciones ambientales para la emersión, describir su cinemática terrestre para peces de 3, 0 a 70, 0 cm y comparar la cinemática entre cuatro sustratos. Para los experimentos de emersión, C. argus se colocó individualmente en contenedores acuáticos con rampas que se extienden a través de la superficie del agua y fueron expuesto a quince condiciones ambientales ecológicamente pertinentes. Para los experimentos cinemáticos, los peces se filmaron moviéndose sobre un revestimiento de banco húmedo, césped, césped artificial y una cubierta de bote de goma plana o inclinada. Los videos se digitalizaron para su análisis en MATLAB y se usó electromiografía para medir la actividad muscular. Solo los tratamientos de bajo pH (4, 8), alta salinidad (30 partes por mil) y alto dCO2 (solución de agua de Seltz 10%) provocaron respuestas de emersión. Aunque son extremas, estas condiciones si ocurren en algunos de sus pantanos asiáticos nativos. Las cabezas de serpiente del norte >4, 5 cm usaron una forma única de locomoción terrestre basada en movimientos apéndiculares-axiales que involucra oscilaciones cíclicas del cuerpo axial, junto con movimientos casi simultáneos de ambas aletas pectorales. Los individuos de ≤3, 5 cm usaron saltos de cola para moverse en tierra. Las cabezas de serpiente del norte también se movían más rápidamente en sustratos tridimensionales complejos (ej., césped) que en sustratos lisos (ej., revestimiento de banco), y al moverse cuesta abajo. La liberación de cabezas de serpiente en la tierra por humanos o accidentalmente por depredadores puede ser más común que la emersión voluntaria, pero debido a que las cabezas de serpiente del norte pueden respirar aire, puede ser necesario tener en cuenta la capacidad de propagarse por tierra en el manejo de esta especie invasora. Translated to Spanish by YE Jimenez (yordano_jimenez@brown.edu).

DAP12 deficiency in liver allografts results in enhanced donor DC migration, augmented effector T cell responses and abrogation of transplant tolerance.

Liver interstitial dendritic cells (DC) have been implicated in immune regulation and tolerance induction. We found that the transmembrane immuno-adaptor DNAX-activating protein of 12 kDa (DAP12) negatively regulated conventional liver myeloid (m) DC maturation and their in vivo migratory and T cell allostimulatory ability. Livers were transplanted from C57BL/6(H2(b) ) (B6) WT or DAP12(-/-) mice into WT C3H (H2(k) ) recipients. Donor mDC (H2-K(b+) CD11c(+) ) were quantified in spleens by flow cytometry. Anti-donor T cell reactivity was evaluated by ex vivo carboxyfluorescein diacetate succinimidyl ester-mixed leukocyte reaction and delayed-type hypersensitivity responses, while T effector and regulatory T cells were determined by flow analysis. A threefold to fourfold increase in donor-derived DC was detected in spleens of DAP12(-/-) liver recipients compared with those given WT grafts. Moreover, pro-inflammatory cytokine gene expression in the graft, interferon gamma (IFNγ) production by graft-infiltrating CD8(+) T cells and systemic levels of IFNγ were all elevated significantly in DAP12(-/-) liver recipients. DAP12(-/-) grafts also exhibited reduced incidences of CD4(+) Foxp3(+) cells and enhanced CD8(+) T cell IFNγ secretion in response to donor antigen challenge. Unlike WT grafts, DAP12(-/-) livers failed to induce tolerance and were rejected acutely. Thus, DAP12 expression in liver grafts regulates donor mDC migration to host lymphoid tissue, alloreactive T cell responses and transplant tolerance.

Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury.

Mononuclear phagocyte recognition of apoptotic cells triggering suppressive cytokine signaling is a key event in inflammation resolution from injury. Mice deficient in thrombospondin (TSP)-1 (thbs1⁻/⁻), an extracellular matrix glycoprotein that bridges cell-cell interactions, are prone to lipopolysaccharide-induced lung injury and show defective macrophage interleukin (IL)-10 production during the resolution phase of inflammation. Reconstitution of IL-10 rescues thbs1⁻/⁻ mice from persistent neutrophilic lung inflammation and injury and thbs1⁻/⁻ alveolar macrophages show defective IL-10 production following intratracheal instillation of apoptotic neutrophils despite intact efferocytosis. Following co-culture with apoptotic neutrophils, thbs1⁻/⁻ macrophages show a selective defect in IL-10 production, whereas prostaglandin E2 and transforming growth factor beta 1 responses remain intact. Full macrophage IL-10 responses require the engagement of TSP-1 structural repeat 2 domain and the macrophage scavenger receptor CD36 LIMP-II Emp sequence homology (CLESH) domain in vitro. Although TSP-1 is not essential for macrophage engulfment of apoptotic neutrophils in vivo, TSP-1 aids in the curtailment of inflammatory responses during the resolution phase of injury in the lungs by providing a means by which apoptotic cells are recognized and trigger optimal IL-10 production by macrophages.

Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs.

I/R injury is a major deleterious factor of successful kidney transplantation (KTx). Carbon monoxide (CO) is an endogenous gaseous regulatory molecule, and exogenously delivered CO in low concentrations provides potent cytoprotection. This study evaluated efficacies of CO exposure to excised kidney grafts to inhibit I/R injury in the pig KTx model. Porcine kidneys were stored for 48 h in control UW or UW supplemented with CO (CO-UW) and autotransplanted in a 14-day follow-up study. In the control UW group, animal survival was 80% (4/5) with peak serum creatinine levels of 12.0 +/- 5.1 mg/dL. CO-UW showed potent protection, and peak creatinine levels were reduced to 6.9 +/- 1.4 mg/dL with 100% (5/5) survival without any noticeable adverse event or abnormal COHb value. Control grafts at 14 days showed significant tubular damages, focal fibrotic changes and numerous infiltrates. The CO-UW group showed significantly less severe histopathological changes with less TGF-beta and p-Smad3 expression. Grafts in CO-UW also showed significantly lower early mRNA levels for proinflammatory cytokines and less lipid peroxidation. CO in UW provides significant protection against renal I/R injury in the porcine KTx model. Ex vivo exposure of kidney grafts to CO during cold storage may therefore be a safe strategy to reduce I/R injury.

Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy.

INTRODUCTION: Copper deficiency is an increasingly recognised cause of neurological impairment. This retrospective review highlights clinical and electrodiagnostic findings in patients diagnosed at our institution with copper deficiency. METHODS: Clinical, radiographic and electrodiagnostic findings were reviewed in patients with evidence of copper deficiency. Patients with other potential causes of myelopathy or neuropathy were excluded. RESULTS: The predominant clinical feature in all six patients was a sensory ataxia, resulting in marked gait unsteadiness. Nerve conduction studies and needle EMG were performed in all patients and revealed a mild to moderate distal, axonal, sensorimotor peripheral neuropathy. Median and tibial somatosensory evoked potentials were abnormal in all five patients in which it was performed, showing impaired conduction in central or proximal peripheral somatosensory pathways. CONCLUSIONS: This pattern of electrodiagnostic findings suggests that impairment in somatosensory pathways demonstrated by somatosensory evoked potential testing is the main cause of the sensory ataxia in patients with copper deficiency.

Niacin skin test response in dyslexia.

The niacin skin test reflects a flush and oedema owing to the production of prostaglandin D2 from arachidonic acid. A diminished response may indicate abnormalities in the phospholipid metabolism, which has been shown in schizophrenia. There is evidence that dyslexia might also involve phospholipid abnormalities, therefore we examined the skin response in 51 dyslexics and 45 controls. Four concentrations of aqueous methyl nicotinate were applied topically to the forearm. Flushing was rated using a seven-point scale at 3 min intervals over 21 min. Repeated measures ANOVA for the four concentrations across all seven time-points showed no significant effect of subject group, but when analyses were confined to the first 9 min, flushing was reduced in dyslexics. Significant group differences were also found for the lowest niacin concentration (0.0001M) across six out of seven time-points. The results indicate a slightly reduced and delayed response to niacin in dyslexia.

Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease.

BACKGROUND: Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (or motor neuron disease). A range of antioxidant medications are available, and have been studied. OBJECTIVES: To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (July 2003), MEDLINE (from January 1966 to July 2003), EMBASE (from January 1980 to July 2003) and other sources. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis. DATA COLLECTION AND ANALYSIS: The reviewers independently applied the selection criteria, assessed study quality and two reviewers performed independent data extraction. MAIN RESULTS: The search identified 21 studies for consideration but only eight studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure, (survival at 12 months treatment). Sufficient data were available from three studies to allow analysis of the primary outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed of vitamin E 500 mg twice daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta-analysis of antioxidants in general when combining the results. No significant differences were demonstrated in secondary outcome measures. REVIEWERS' CONCLUSIONS: There is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and patients. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Omega-3 and omega-6 fatty acid concentrations in red blood cell membranes relate to schizotypal traits in healthy adults.

Reduced omega-3 and omega-6 fatty acids in red blood cell (RBC) membranes are often found in patients with schizophrenia. Here we investigated whether membrane concentrations of these fatty acids might vary as a function of schizotypal traits in non-psychotic individuals. Twenty-five healthy adults completed the O-LIFE schizotypal trait inventory and fatty acid composition of their venous blood samples was analysed via gas-liquid chromatography. Correlations between schizotypy measures and RBC fatty acids were examined and comparisons made between groups high and low on fatty acid measures and schizotypy scores. The omega-6 fatty acids arachidonic, adrenic and docosapentaenoic acid were directly related to positive schizotypal trait measures, as were most omega-3 fatty acids, but none were related to a negative, withdrawn form of schizotypy. Our findings of high RBC concentrations of omega-3 and omega-6 fatty acids in healthy adults with positive schizotypal traits clearly contrast with the low levels often found in schizophrenia, but are quite consistent with evidence that omega-3 fatty acids (notably EPA) can be useful in the treatment of schizophrenic illness.

Can we eliminate placebo in ALS clinical trials?

BACKGROUND: Previous studies concluded that the decline in strength in patients with amyotrophic lateral sclerosis (ALS) is a linear function. If so, a patient's natural history might serve as the control, instead of placebo, in a clinical trial. METHODS: A placebo-controlled ALS clinical trial included a natural history phase, followed by a 6-month treatment phase. Each patient's forced vital capacity (FVC) score and maximal voluntary isometric contraction (MVIC) raw scores were measured monthly, standardized, and averaged into megascores. For 138 patients, the arm, leg, FVC, arm+leg combination, and arm+leg+FVC combination megascore slopes during the natural history phase and during the placebo phase were compared. RESULTS: The mean slope of megascores during the natural history phase and the mean slope during the placebo phase were not different for the arm, leg, and arm+leg megascores, but were different for the FVC and arm+leg+FVC combination megascores. CONCLUSIONS: Natural history controls may be useful in ALS exploratory trials that use arm megascore slope as the primary outcome measure. However, there are distinct limitations to the use of natural history controls, so that Phase 3 ALS clinical trials require placebo controls.

Views of older people on cataract surgery options: an assessment of preferences by conjoint analysis.

BACKGROUND: Key issues in the quality of care for people with cataracts in the UK include hospital waiting lists, complication rates from surgery, and the use of junior surgeons. The main objective of this study was to investigate the relative importance that older people attach to these factors when given theoretical choices over options for cataract surgery. METHOD: A systematic sample of 194 individuals aged 60-84 years on a general practice register in Nottingham were invited to take part in an interview based survey. Respondents ranked 11 "cataract surgery packages" containing different waiting list lengths, complication risks, and surgeon grades. Conjoint analysis was performed to determine the relative importance of these factors for individuals and for the group as a whole. RESULTS: Of the 194 subjects invited to participate, 146 (72%) completed the interview. For the group as a whole the "averaged importance" of the factors was: complication risk 45.8%; waiting time 41.1%, surgeon grade 13.1%. Analysis of importance scores for individuals showed that some were particularly concerned about complication risk while others were more concerned about waiting times. There was a strong negative correlation between importance scores for these factors (Spearman's rho -0.78, p<0.001). CONCLUSIONS: Most respondents thought that either risk of damage to sight and/or waiting time were important, while surgeon grade was relatively unimportant. The findings show that some potential cataract patients prefer a greater risk of complication combined with a short wait than a low complication rate and a longer wait.

The effect of fiber-type heterogeneity on optimized work and power output of hindlimb muscles of the salamander Ambystoma tigrinum.

Most vertebrate muscles are composed of a mixture of fiber types. However, studies of muscle mechanics have concentrated on homogeneous bundles of fibers. Hindlimb muscles of the tiger salamander, Ambystoma tigrinum, present an excellent system to explore the consequences of fiber heterogeneity. Isometric twitches and work loops were obtained in vitro from two muscles, the m. iliotibialis pars posterior (heterogeneous, containing types I, IIa and IIb fibers) and the m. iliofibularis (nearly homogeneous for type IIa fibers). Maximal isometric twitch and tetanic stresses in m. iliotibialis posterior were significantly greater than in iliofibularis. Work loops were obtained over a range of frequencies (0.5-3.0 Hz) and strains (2-6% muscle length) that encompassed the observed ranges in vivo. Work per cycle from the homogeneous iliofibularis declined from 1.5-3.0 Hz, while that from the heterogeneous m. iliotibialis posterior increased from 0.5 Hz to 2.5 Hz and declined at 3.0 Hz. Power output from the iliofibularis rose with frequency to at least 3 Hz; power from the iliotibialis posterior rose with frequency to 2.5 Hz and declined thereafter. Mass-specific work per cycle and power output were higher in iliofibularis than iliotibialis posterior over most frequencies and strains tested.

Fetlock joint kinematics differ with age in Thoroughbred [was thoroughbred] racehorses.

Fetlock joint kinematics during galloping in 2-, 3-, 4-, and 5-year-old Thoroughbreds in race training were quantified to determine if differences due to age could account for the observation that 2-year old Thoroughbred racehorses incur a high number of injuries to the bones and soft tissues in the distal forelimbs during training and at the outset of racing. Twelve Thoroughbred racehorses were videotaped in the sagittal plane at 250 frames/s during their daily galloping workout on a 7/8 mile sand-surface training track. Four galloping strides were recorded for each horse and subsequently digitized to determine fetlock joint angles of the leading forelimb during the limb support period of a stride. Four kinematic variables were measured from each stride's angular profile: angle of fetlock joint dorsi-flexion at mid-stance, negative angular velocity, positive angular velocity and time from hoof impact to mid-stance phase of limb support. The 2-year old Thoroughbreds had significantly quicker rates of dorsi-flexion of their fetlock joints than 3- (p=0.01), 4- (p=0.01), and 5-year old (p<0.01) Thoroughbreds following impact of the leading forelimb during moderate galloping (avg. 14 m/s). Higher rates of dorsi-flexion in young Thoroughbreds may reflect immaturity (lack of stiffness) of the suspensory apparatus tissues.

Spatiotemporal expression of angiogenesis growth factor receptors during the revascularization of regenerating rat liver.

Regenerating liver was evaluated for the spatiotemporal expression of angiogenic growth factor receptors on endothelial cell (EC) membranes during revascularization resulting from 70% partial hepatectomy (PHx). Fractions enriched in EC membranes were examined by Western blot for angiogenic growth factor receptor expression from 1 to 14 days after PHx. Increases in vascular endothelial growth factor (VEGF) receptors Flt-1 and Flk-1/KDR, angiopoietin receptors Tie-1, Tie-2, and platelet-derived growth factor receptor beta (PDGF-Rbeta), modest increases in epidermal growth factor receptor (EGF-R), and no increase in hepatocyte growth factor receptor (c-Met) or fibroblast growth factor receptors (FGF-R) were observed in isolated membranes during EC proliferation. All receptors were tyrosine phosphorylated, and therefore activated, during peak expression. Immunofluorescence staining of regenerating liver identified populations with increased receptor expression, indicating cells receptive to ligand signaling. EGF-R was upregulated evenly throughout the sinusoidal membrane, whereas c-Met was observed on hepatocyte canaliculae, bile duct epithelium, and large vessel EC. Tie-2 and PDGF-Rbeta were increased on sinusoidal and large vessel EC, whereas Tie-1 was expressed in EC surrounding avascular hepatic islands. Flk-1/KDR was increased on large vessels with slight increases on sinusoidal EC, whereas Flt-1 was increased in arterioles, sinusoidal EC as well as in hepatocytes. Although Flt-1 was phosphorylated on isolated hepatocytes, vascular endothelial growth factor(165) (VEGF(165)) did not induce a proliferative or motogenic response. Proliferation assays on isolated EC indicated responsiveness to VEGF(165), but synergism among several growth factors including PDGF-BB was also observed. The data identify novel autocrine and paracrine interactions and indicate that each growth factor acts on a specific set of EC at specific times during revascularization of regenerating liver.

Principles of observation medicine.

The defining characteristic of emergency medicine is "time," or the acuity of disease presentation. Observation, like resuscitation, involves the management of time-sensitive conditions. In the ED there is a continuum of time-sensitive conditions. This continuum extends from resuscitation on one end to observation on the other. When performed well, observation services have been shown to improve diagnostic accuracy, improve treatment outcomes, decrease costs, and improve patient satisfaction. For the subset of ED patients who would have been inappropriately discharged or unnecessarily admitted, the OU has become a safety net of the ED itself. Like EDs, OUs have progressed from being poorly managed areas of the hospital to the cutting edge of acute health care. The principles developed through past experience and research provide a framework for future developments in emergency medicine.

Cardiac markers protocols in a chest pain observation unit.

The use of cardiac markers to identify high-risk patients in the observation unit is undeniable. As the literature reviewed here reveals, the history and ECG miss a significant portion of patients with acute cardiac ischemia. It appears that acute MI and some high-risk "unstable angina" observation unit patients can be identified within 6 hours of hospital presentation using a combination of cardiac markers. Testing these patients soon after symptom onset or on arrival in the ED for myoglobin, CK-MB subforms, or CK-MB delta appears to provide the best diagnostic usefulness. For testing later in the clinical course, CK-MB troponin I, or troponin T are of clear diagnostic and prognostic value. The markers currently used are unable to identify the significant subset of patients with "non-AMI" coronary syndromes, however. These patients require further testing with appropriate noninvasive or invasive diagnostic studies.

Maximizing use of the emergency department observation unit: a novel hybrid design.

STUDY OBJECTIVE: We sought to determine whether sharing an observation unit with scheduled procedure patients would maintain a more consistent unit census and patient/nurse ratio. A secondary objective was to determine the effect of this model on patient length of stay and discharge rates. METHODS: This retrospective, descriptive study was conducted in a high-volume suburban teaching hospital, using a "before-and-after" study design. A "pure" postprocedure unit became a "hybrid" observation postprocedure unit by displacing specific postprocedure patients to inpatient locations. Subsequently, the displaced patients were returned to the unit. On weekends, the unit operated as a pure observation unit. Hourly unit occupancy and census data were prospectively collected, and hourly patient/nurse ratios were calculated. Patient length of stay and discharge data were collected and compared in different settings. RESULTS: The 2 services showed a complementary census pattern that allowed the hybrid unit to maintain an average hourly patient/nurse ratio of 3.7 compared with the ratio of 2.5 for a pure observation unit. There was no difference in observation patient length of stay (14.8 hours versus 14.7 hours) or discharge rate (20.4% versus 18.1%) between weekdays and weekends. However, scheduled procedure patients experienced significantly shorter lengths of stay in the hybrid unit setting (4.3 hours) than in alternative inpatient locations (9.4 hours). CONCLUSION: The hybrid model showed better hourly census and nurse resource use rates, with no adverse effect on observation patients. However, scheduled procedure patient length of stay was shorter in this setting.

Sinusoidal ultrastructure evaluated during the revascularization of regenerating rat liver.

Sinusoidal endothelial cell (SEC) porosities were compared between the periportal (zone 1) and pericentral (zone 3) regions of the rat liver during regeneration following partial hepatectomy (PHx). SEC porosities and fenestration diameters were measured in control livers, as well as at 5 minutes, 24, 48, 72, 96, 120 hours, and 14 days following PHx. Bimodal maximums in both porosity and fenestration diameters were observed in both zones at 5 minutes and 5 days following PHx. SEC porosities increased significantly in both zones 1 and 3 within 5 minutes following PHx, but the increase was maintained only in zone 1 at 24 hours after resection. Following the initial rise, both zones displayed a gradual decrease to less than half their porosity values at 72 hr post-PHx. After 72 hours, porosities increased to over control levels and remained elevated until 14 days after PHx. The decrease in porosity at 72 hr post-PHx is accompanied by ultrastructural changes within the sinusoid at this time. Vascular corrosion casting and transmission electron microscopy (TEM) show sinusoid compression resulting from increased hepatic plate widths due to hepatocyte proliferation in the absence of SEC proliferation. Also at this time, we observed many SEC completely enveloped by stellate cells. The zonal variations observed for porosities throughout regeneration did not correlate with changes in laminin, collagen I and IV, or fibronectin deposition within the space of Disse. Taken together, the data reveal that SEC are dynamic regulators of porosity that respond rapidly and locally to environmental zonal stimuli during liver regeneration.

Fatty acid metabolism in neurodevelopmental disorder: a new perspective on associations between attention-deficit/hyperactivity disorder, dyslexia, dyspraxia and the autistic spectrum.

There is increasing evidence that abnormalities of fatty acid and membrane phospholipid metabolism play a part in a wide range of neurodevelopmental and psychiatric disorders. This proposal is discussed here in relation to attention-deficit/hyperactivity disorder (ADHD), dyslexia, developmental coordination disorder (dyspraxia) and the autistic spectrum. These are among the most common neurodevelopmental disorders of childhood, with significant implications for society as well as for those directly affected. However, controversy still surrounds both the identification and management of these conditions, and while their aetiology is recognized as being complex and multifactorial, little progress has yet been made in elucidating predisposing factors at the biological level. An overview is provided here of the contents of this Special Issue, which contains a selection of reports from a unique multidisciplinary workshop involving both researchers and clinicians. Its purpose was to explore the possibility that ADHD, dyslexia, dyspraxia and autism fall within a phospholipid spectrum of disorders. This proposal could explain the high degree of co-morbidity between these conditions, their aggregation within families and relation to other psychiatric disorders, and a range of associated features that are already well known at a clinical level. The existing evidence for fatty acid abnormalities in these disorders is summarized, and new approaches are outlined that have the potential to improve both the identification and the management of these and related neurodevelopmental and psychiatric conditions.

Could oxidative stress be a factor in neurodevelopmental disorders?

There is evidence of co-morbidity in the neurodevelopmental disorders and they display depletion of polyunsaturated fatty acids (PUFAs) in their plasma and red cell membranes. This suggests an abnormal fatty acid metabolism, which may affect cell signalling and synthesis of eicosanoids. This common feature in the neurodevelopmental disorders may be genetic in origin: however, oxidative stress may also contribute to decreased PUFAs found in these disorders.