Cognitive and motor function in developmental coordination disorder.

AIM: To analyse the development of motor skill and executive function in school-aged children with and without developmental coordination disorder (DCD). METHOD: Using a longitudinal design, 186 children (86 males, 100 females) aged 6 to 11 years at Time 1 were tested over a 2-year period, 52 of whom were diagnosed with DCD at Time 1 (27 males, 25 females; mean age 8y 5mo, SD 1y 6mo) using DSM-5 criteria. The McCarron Assessment of Neuromuscular Development assessed motor status at Time 1 and at 2-year follow-up (Time 2). Executive function was assessed using a well-validated measure, the Groton Maze Learning Test. RESULTS: The DCD cohort at Time 1 had moderate incidence of executive function deficit (41%). Most importantly, at a group level, children with persisting DCD (across Times 1 and 2) also showed significantly lower levels of executive function than children with typical motor development at both time points. At an individual level, around 26% of children in this group had persisting executive function deficits relative to normal ranges of performance. INTERPRETATION: Children with persisting DCD are at significant risk of executive function issues. The combination of motor and cognitive issues as a potential risk factor in the longer-term development of children is discussed. WHAT THIS PAPER ADDS: Around half of children initially diagnosed with developmental coordination disorder (DCD) had the same diagnosis at 2-year follow-up. 41% of children with DCD have impaired executive function. Children with persisting DCD show poorer executive function than those with typical motor development or remitting DCD.

International clinical practice recommendations on the definition, diagnosis, assessment, intervention, and psychosocial aspects of developmental coordination disorder.

AIM: These international clinical practice recommendations (CPR) for developmental coordination disorder (DCD), initiated by the European Academy of Childhood Disability (EACD), aim to address key questions on the definition, diagnosis, assessment, intervention, and psychosocial aspects of DCD relevant for clinical practice. METHOD: Key questions in five areas were considered through literature reviews and formal expert consensus. For recommendations based on evidence, literature searches on 'mechanisms', 'assessment', and 'intervention' were updated since the last recommendations in 2012. New searches were conducted for 'psychosocial issues' and 'adolescents/adults'. Evidence was rated according to the Oxford Centre for Evidence-Based Medicine (level of evidence [LOE] 1-4) and transferred into recommendations. For recommendations based on formal consensus, two meetings of an international, multidisciplinary expert panel were conducted with a further five Delphi rounds to develop good clinical practice (GCP) recommendations. RESULTS: Thirty-five recommendations were made. Eight were based on the evidence from literature reviews (three on 'assessment', five on 'intervention'). Twenty-two were updated from the 2012 recommendations. New recommendations relate to diagnosis and assessment (two GCPs) and psychosocial issues (three GCPs). Additionally, one new recommendation (LOE) reflects active video games as adjuncts to more traditional activity-oriented and participation-oriented interventions, and two new recommendations (one GCP, one LOE) were made for adolescents and adults with DCD. INTERPRETATION: The CPR-DCD is a comprehensive overview of DCD and current understanding based on research evidence and expert consensus. It reflects the state of the art for clinicians and scientists of varied disciplines. The international CPR-DCD may serve as a basis for national guidelines. WHAT THIS PAPER ADDS: Updated international clinical practice guidelines on developmental coordination disorder (DCD). Refined and extended recommendations on clinical assessment and intervention for DCD. A critical synopsis of current research on mechanisms of DCD. A critical synopsis of psychosocial issues in DCD, with implications for clinical practice. The first international recommendations to consider adolescents and adults with DCD.

Randomised controlled trial comparing uptake of NHS Health Check in response to standard letters, risk-personalised letters and telephone invitations.

BACKGROUND: NHS Health Check is a primary prevention programme offering cardiovascular disease (CVD) risk assessment to adults in England aged 40-74. Uptake remains a challenge and invitation method is a strong predictor of uptake. There is evidence of low uptake when using invitation letters. Telephone invitations might increase uptake, but are not widely used. We explored the potential to improve uptake through personalising letters to patient's CVD risk, and to compare this with generic letters and telephone invitations. METHODS: HEalth Check TRial (HECTR) was a three-arm randomised controlled trial in nine general practices in Staffordshire (UK). Eligible patients were randomised to be invited to a NHS Health Check using one of three methods: standard letter (control); telephone invitation; letter personalised to the patient's CVD risk. The primary outcome was attendance/non-attendance. Data were collected on a range of patient- and practice-level factors (e.g., patient socio-demographics, CVD risk, practice size, Health Checks outside usual working hours). Multi-level logistic regression estimated the marginal effects to explore whether invitation method predicted attendance. Invitation costs were collated from practices to estimate cost benefit. RESULTS: In total, 4614 patients were included in analysis (mean age 50.2 ± 8.0 yr.; 52.4% female). Compared with patients invited by standard letter (30.9%), uptake was significantly higher in those invited by telephone (47.6%, P < .001), but not personalised letter (31.3%, p = .812). In multi-level analysis, compared with the standard letter arm, likelihood of attendance was 18 percentage points higher in the telephone arm and 4 percentage points higher in the personalised letter arm. The effect of telephone calls appeared strongest in patients who were younger and had lower CVD risk. We estimated per 1000 patients invited, risk-personalised letters could result in 40 additional attended Health Checks (at no extra cost) and telephone invitations could result in 180 additional Health Checks at an additional cost of £240. CONCLUSIONS: Telephone invitations should be advocated to address the substantial deficit between current and required levels of NHS uptake, and could be targeted at younger and lower CVD risk adults. Risk-personalised letters should be explored further in a larger sample of high risk individuals. TRIAL REGISTRATION: Registration number: ISRCTN15840751 date of registration: 24/10/2017.

A dynamic early East Antarctic Ice Sheet suggested by ice-covered fjord landscapes.

The first Cenozoic ice sheets initiated in Antarctica from the Gamburtsev Subglacial Mountains and other highlands as a result of rapid global cooling ∼34 million years ago. In the subsequent 20 million years, at a time of declining atmospheric carbon dioxide concentrations and an evolving Antarctic circumpolar current, sedimentary sequence interpretation and numerical modelling suggest that cyclical periods of ice-sheet expansion to the continental margin, followed by retreat to the subglacial highlands, occurred up to thirty times. These fluctuations were paced by orbital changes and were a major influence on global sea levels. Ice-sheet models show that the nature of such oscillations is critically dependent on the pattern and extent of Antarctic topographic lowlands. Here we show that the basal topography of the Aurora Subglacial Basin of East Antarctica, at present overlain by 2-4.5 km of ice, is characterized by a series of well-defined topographic channels within a mountain block landscape. The identification of this fjord landscape, based on new data from ice-penetrating radar, provides an improved understanding of the topography of the Aurora Subglacial Basin and its surroundings, and reveals a complex surface sculpted by a succession of ice-sheet configurations substantially different from today's. At different stages during its fluctuations, the edge of the East Antarctic Ice Sheet lay pinned along the margins of the Aurora Subglacial Basin, the upland boundaries of which are currently above sea level and the deepest parts of which are more than 1 km below sea level. Although the timing of the channel incision remains uncertain, our results suggest that the fjord landscape was carved by at least two iceflow regimes of different scales and directions, each of which would have over-deepened existing topographic depressions, reversing valley floor slopes.

Cognitive and neuroimaging findings in developmental coordination disorder: new insights from a systematic review of recent research.

AIM: To better understand the neural and performance factors that may underlie developmental coordination disorder (DCD), and implications for a multi-component account. METHOD: A systematic review of the experimental literature published between June 2011 and September 2016 was conducted using a modified PICOS (population, intervention, comparison, outcomes, and study type) framework. A total of 106 studies were included. RESULTS: Behavioural data from 91 studies showed a broad cluster of deficits in the anticipatory control of movement, basic processes of motor learning, and cognitive control. Importantly, however, performance issues in DCD were often shown to be moderated by task type and difficulty. As well, we saw new evidence of compensatory processes and strategies in several studies. Neuroimaging data (15 studies, including electroencephalography) showed reduced cortical thickness in the right medial orbitofrontal cortex and altered brain activation patterns across functional networks involving prefrontal, parietal, and cerebellar regions in children with DCD than those in comparison groups. Data from diffusion-weighted magnetic resonance imaging suggested reduced white matter organization involving sensorimotor structures and altered structural connectivity across the whole brain network. INTERPRETATION: Taken together, results support the hypothesis that children with DCD show differences in brain structure and function compared with typically developing children. Behaviourally, these differences may affect anticipatory planning and reduce automatization of movement skill, prompting greater reliance on slower feedback-based control and compensatory strategies. Implications for future research, theory development, and clinical practice are discussed.

Coupling of online control and inhibitory systems in children with atypical motor development: A growth curve modelling study.

INTRODUCTION: Previous research indicates that children with Developmental Coordination Disorder (DCD) show deficits performing online corrections, an issue exacerbated by adding inhibitory constraints; however, cross-sectional data suggests that these deficits may reduce with age. Using a longitudinal design, the aim of the study presented here was to model the coupling that occurs between inhibitory systems and (predictive) online control in typically developing children (TDC) and in those with Developmental Coordination Disorder (DCD) over an extended period of time, using a framework of interactive specialization. We predicted that TDC would show a non-linear growth pattern, consistent with re-organisation in the coupling during the middle childhood period, while DCD would display a developmental lag. METHOD: A group of 196 children (111 girls and 85 boys) aged between 6 and 12years participated in the study. Children were classified as DCD according to research criteria. Using a cohort sequential design, both TDC and DCD groups were divided into age cohorts. Predictive (online) control was defined operationally by performance on a Double-Jump Reaching Task (DJRT), which was assessed at 6-month intervals over two years (5 time points in total). Inhibitory control was examined using an anti-jump condition of the DJRT paradigm whereby children were instructed to touch a target location in the hemispace opposite a cued location. RESULTS: For the TDC group, model comparison using growth curve analysis revealed that a quadratic trend was the most appropriate fit with evidence of rapid improvement in anti-reach performance up until middle childhood (around 8-9years of age), followed by a more gradual rate of improvement into late childhood and early adolescence. This pattern was evident on both chronometric and kinematic measures. In contrast, for children with DCD, a linear function provided the best to fit on the key metrics, with a slower rate of improvement than controls. CONCLUSION: We conclude that children with DCD require a more extended period of development to effectively couple online motor control and executive systems when completing anti-reach movements, whereas TDC show rapid improvement in early and middle childhood. These group differences in growth curves are likely to reflect a maturational lag in the development of motor-cognitive networks in children with DCD.

The Gamburtsev mountains and the origin and early evolution of the Antarctic Ice Sheet.

Ice-sheet development in Antarctica was a result of significant and rapid global climate change about 34 million years ago. Ice-sheet and climate modelling suggest reductions in atmospheric carbon dioxide (less than three times the pre-industrial level of 280 parts per million by volume) that, in conjunction with the development of the Antarctic Circumpolar Current, led to cooling and glaciation paced by changes in Earth's orbit. Based on the present subglacial topography, numerical models point to ice-sheet genesis on mountain massifs of Antarctica, including the Gamburtsev mountains at Dome A, the centre of the present ice sheet. Our lack of knowledge of the present-day topography of the Gamburtsev mountains means, however, that the nature of early glaciation and subsequent development of a continental-sized ice sheet are uncertain. Here we present radar information about the base of the ice at Dome A, revealing classic Alpine topography with pre-existing river valleys overdeepened by valley glaciers formed when the mean summer surface temperature was around 3 degrees C. This landscape is likely to have developed during the initial phases of Antarctic glaciation. According to Antarctic climate history (estimated from offshore sediment records) the Gamburtsev mountains are probably older than 34 million years and were the main centre for ice-sheet growth. Moreover, the landscape has most probably been preserved beneath the present ice sheet for around 14 million years.

Circadian changes in long noncoding RNAs in the pineal gland.

Long noncoding RNAs (lncRNAs) play a broad range of biological roles, including regulation of expression of genes and chromosomes. Here, we present evidence that lncRNAs are involved in vertebrate circadian biology. Differential night/day expression of 112 lncRNAs (0.3 to >50 kb) occurs in the rat pineal gland, which is the source of melatonin, the hormone of the night. Approximately one-half of these changes reflect nocturnal increases. Studies of eight lncRNAs with 2- to >100-fold daily rhythms indicate that, in most cases, the change results from neural stimulation from the central circadian oscillator in the suprachiasmatic nucleus (doubling time = 0.5-1.3 h). Light exposure at night rapidly reverses (halving time = 9-32 min) levels of some of these lncRNAs. Organ culture studies indicate that expression of these lncRNAs is regulated by norepinephrine acting through cAMP. These findings point to a dynamic role of lncRNAs in the circadian system.

Adaptation and Extension of the European Recommendations (EACD) on Developmental Coordination Disorder (DCD) for the UK context.

BACKGROUND: Developmental Coordination Disorder (DCD) affects the learning and performance of everyday motor skills. It commonly co-occurs with other developmental disorders and a range of associated psycho-social impairments. Recent evidence-based guidelines on diagnosis, assessment, and intervention provide valuable information for practitioners. However these are directed primarily at German-speaking countries and focus on work with children. AIM: The aim of this project was to consider the application of these guidelines in the UK and to extend them for use with adults with DCD. METHODS: Individuals with DCD, parents, and professionals from a wide range of disciplines were invited to two workshops to discuss and debate the guidelines, to adapt them for the UK and produce dissemination materials. RESULTS: A working definition of DCD was agreed, minor revisions were made to the guidelines to reflect the UK context, an extension for adults was compiled and a series of leaflets was produced to disseminate this information to health and education professionals, parents, and employers. CONCLUSIONS: This work will raise awareness of the condition across different professional groups. It provides information to help those working with children and adults with DCD in the UK to assist in the process of diagnosis, assessment, and intervention.

International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors.

The hormone melatonin (5-methoxy-N-acetyltryptamine) is synthesized primarily in the pineal gland and retina, and in several peripheral tissues and organs. In the circulation, the concentration of melatonin follows a circadian rhythm, with high levels at night providing timing cues to target tissues endowed with melatonin receptors. Melatonin receptors receive and translate melatonin's message to influence daily and seasonal rhythms of physiology and behavior. The melatonin message is translated through activation of two G protein-coupled receptors, MT(1) and MT(2), that are potential therapeutic targets in disorders ranging from insomnia and circadian sleep disorders to depression, cardiovascular diseases, and cancer. This review summarizes the steps taken since melatonin's discovery by Aaron Lerner in 1958 to functionally characterize, clone, and localize receptors in mammalian tissues. The pharmacological and molecular properties of the receptors are described as well as current efforts to discover and develop ligands for treatment of a number of illnesses, including sleep disorders, depression, and cancer.

Mapping the Melatonin Receptor. 8. Selective MT2 Agonists Derived from 5,6-Dihydroindolo[2,1-a]isoquinolines and Related Systems.

A series of substituted indolo[2,1-a]isoquinolines and indolo[1,2-a]benzoxazines have been prepared, as melatonin analogues, to investigate the nature of the binding site of the melatonin receptor. Agonist and antagonist potency of all the analogues was measured using the [35S]GTPγS binding assay protocol. The binding affinity of the analogues were measured by competition binding studies against the human MT1 (hMT1) and MT2 (hMT2) receptors stably transfected in Chinese Hamster Ovarian (CHO) cells, using 2-[125 I]-iodomelatonin, as a ligand. N-Acetyl 2-(10-methoxy-5,6-dihydroindolo[2,1-a]isoquinolin-12-yl)propyl-1-amine (12 a) binds strongly to both the hMT1 and hMT2 receptors, and shows a preference for the hMT2, as does its propanamido counterpart 12 b. The introduction of two methyl groups into their side chain, analogues 15 a and 15 b, leads to antagonism, in the case of the former, and drastically diminishes its hMT1 binding; an analogous profile is seen for 15 b, which, however, is a partial agonist. Introduction of chlorine or methoxy groups into ring 4 gives compounds, that are weakly binding, with a preference for MT2. Substitution of oxygen for carbon at position 5 gives the indolo[1,2-c]benzoxazines 33, 36 a and b, that bind strongly to the human receptors, 33, 36 b being potent agonists at the melatonin receptors, but do not discriminate between hMT1 and hMT2.

Transcriptomic profiles of Wnt3a and insulin in primary cultured rat cortical neurones.

Glycogen synthase kinase 3 (GSK3) is a widely expressed, constitutively active, serine/threonine kinase that is negatively regulated by both Wnt and insulin via two independent signalling pathways. GSK3 is an important mediator in many physiological processes including glycogen metabolism, apoptosis and gene transcription. In addition, GSK3 is implicated in diseases such as Alzheimer's, schizophrenia and cancer, where it exhibits deregulated activity. In this study, we sought to determine the neuronal genes regulated by both Wnt and insulin in an in vitro cell culture model to further elucidate the signalling roles GSK3 plays in the CNS. Affymetrix Rat Genome 230 2.0 whole genome microarrays were used to explore the expression profiles of rat primary cortical neurones treated with recombinant Wnt3a (10 nM) or insulin (50 nM) for 2 h. Following a conservative correction (Bonferroni) for multiple testing, seven genes were identified to be differentially expressed from controls; four of these genes were regulated by insulin and three genes were regulated by both insulin and Wnt3a. The data were also analysed using a false discovery rate cut off, which is a less stringent correction for multiple testing. This approach yielded 105 genes that were differentially regulated from controls; 72 of the gene changes were attributable to insulin treatment, 11 were because of Wnt3a treatment and 22 genes were altered by both insulin and Wnt3a. These data demonstrate that the Wnt and insulin pathways exhibit both divergent and overlapping signalling activities in neuronal cells. The overlapping transcriptional response was not attributable to Wnt3a activating Akt. These findings have ramifications for neurodevelopment and neurological diseases, in which the Wnt and insulin signalling pathways are implicated.

Global daily dynamics of the pineal transcriptome.

Transcriptome profiling of the pineal gland has revealed night/day differences in the expression of a major fraction of the genes active in this tissue, with two-thirds of these being nocturnal increases. A set of over 600 transcripts exhibit two-fold to >100-fold daily differences in abundance. These changes appear to be primarily attributable to adrenergic-cyclic-AMP-dependent mechanisms, which are controlled via a neural pathway that includes the suprachiasmatic nucleus, the master circadian oscillator. In addition to melatonin synthesis, night/day differences in gene expression impact genes associated with several specialized functions, including the immune/inflammation response, photo-transduction, and thyroid hormone/retinoic acid biology. The following nonspecialized cellular features are also affected: adhesion, cell cycle/cell death, cytoskeleton, DNA modification, endothelium, growth, RNA modification, small molecule biology, transcription factors, vesicle biology, signaling involving Ca(2+), cyclic nucleotides, phospholipids, mitogen-activated protein kinases, the Wnt signaling pathway, and protein phosphorylation.

A comparison of characteristics, developmental disorders and motor progression between children with and without developmental coordination disorder.

BACKGROUND AND AIM: Children with Developmental Coordination Disorder (DCD) have difficulty in the development of motor coordination and with learning new motor skills. Studies demonstrate that children with DCD differ in terms of the nature and severity of their motor difficulties, the incidence of co occurring conditions and family background. However, little is known whether these profiles may relate to motor progression over time. The aim of this study was to describe the profiles of children with and without DCD and track motor progression over time. METHOD: The characteristics of thirty-four 7-14 year old children (M = 10.07, 85.3% boys) with and without DCD were compared and their motor progression monitored over a two academic years. DCD was identified using DSM5 criteria. The Movement Assessment Battery for Children-2 (MABC-2) was used to classify children as TD (≥25th percentile), having moderate motor coordination difficulties (6-16th percentile) or severe motor coordination difficulties (≤ 5th percentile). The Kaufman Brief Intelligence Test - 2 (KBIT-2) was used to measure full scale IQ. Parent questionnaires were used to gather information on socio economic status and co occurrence of other developmental disorders. We used ANOVA to assess whether there were differences in characteristics between the TD children, children with severe motor coordination difficulties and children with moderate motor coordination difficulties. Linear mixed effect modelling was used to estimate any change in motor performance over time and whether this differed between the three groups of children. RESULTS: Children with severe motor coordination difficulties had distinct profiles in motor and non-motor domains, lower IQ and a greater likelihood of having associated characteristics of 2 or more developmental disorders. We found significant differences between the poor motor performance of the severe group compared to the other two groups. Longitudinal analyses revealed stable, persistent and lower motor competence for the severe group. The rate of change in motor proficiency for the typical and severe groups was similar. However, the group with moderate motor difficulties gained on average more points per week compared to the typical group and achieved motor scores in the typically developing range over time. CONCLUSIONS: This is one of the first studies to compare the characteristics and rate of motor progression of children with and without DCD using different motor proficiency cut off scores. The children with severe motor coordination difficulties progressed at the same rate as typically developing peers but remained in the severe group over time, whereas the children with moderate motor coordination difficulties caught up to TDC. The results indicate that different intervention may be required according to the nature and severity of the characteristics in both the motor and non-motor domains of children with DCD.

NCS Assessments of the Motor, Sensory, and Physical Health Domains.

As part of the National Children's Study (NCS) comprehensive and longitudinal assessment of the health status of the whole child, scientific teams were convened to recommend assessment measures for the NCS. This manuscript documents the work of three scientific teams who focused on the motor, sensory, or the physical health aspects of this assessment. Each domain team offered a value proposition for the importance of their domain to the health outcomes of the developing infant and child. Constructs within each domain were identified and measures of these constructs proposed. Where available extant assessments were identified. Those constructs that were in need of revised or new assessment instruments were identified and described. Recommendations also were made for the age when the assessments should take place.

Endogenous melatonin is not obligatory for the regulation of the rat sleep-wake cycle.

STUDY OBJECTIVES: Though melatonin and melatonin receptor agonists are in clinical use and under development for treating insomnia, the role of endogenous melatonin in the regulation of the sleep-wake cycle remains uncertain. Some clinical case reports suggest that reduced nocturnal melatonin secretion is linked to sleep disruption, but pineal-gland removal in experimental animals has given variable results. DESIGN: The present study examined the effects of pinealectomy on the diurnal sleep-wake cycle of rats implanted with a radiotransmitter to allow continuous measurement of cortical electroencephalogram, electromyogram, and core temperature (Tc) without restraint in their home cages. MEASUREMENTS AND RESULTS: Tc was slightly (0.2 degrees C) but significantly lower after pineal removal. The total amount and diurnal distribution of locomotor activity, wake, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were unaltered in pinealectomized rats compared to sham-operated controls. Sleep consolidation measured by determining wake, NREM sleep, and REM sleep bout length and frequency was also unchanged. The EEG power spectrum during NREM sleep was unchanged, but a significant decrease in theta power (5-8 Hz) during REM sleep episodes was found. CONCLUSIONS: Our data provide no evidence that endogenous circulating melatonin plays a role in regulating the sleep-wake cycle in rats. However, because cortical theta oscillations are generated in the CA1-3 layer of the hippocampus, neurons known to express melatonin receptors, this suggests that a lack of melatonin following pineal removal influences the function of these neurons and is consistent with previous work suggesting that endogenous melatonin is an important regulator of hippocampal physiology.

Fluorine substituted methoxyphenylalkyl amides as potent melatonin receptor agonists.

A series of fluorine substituted methoxyphenylalkyl amides were prepared with different orientations of the fluorine and methoxy groups with respect to the alkylamide side chain and with alkyl sides of differing lengths (n = 1-3). ß-Dimethyl and α-methyl derivatives were also synthesised. The compounds were tested as melatonin agonists and antagonists using the pigment aggregation of Xenopus melanophores as the biological assay. A number of these compounds were potent melatonin agonists, the potency depending on the length of the alkyl chain, the orientation of the methoxy and fluorine substituents, the amide chain length and, for the ethyl side-chain analogues, the presence of ß-substituents.

An evaluation of the Movement ABC-2 Test for use in Italy: A comparison of data from Italy and the UK.

BACKGROUND: The standardized test within the Movement Assessment Battery for Children-2nd edition (MABC-2) is used worldwide to assess motor problems in children. Ideally, any country using a test developed in another country should produce national norms to ensure that it functions effectively in the new context. AIM: The first objective of this study was to explore the differences in motor performance between Italian and British children. The second was to examine the structural validity of the test for the Italian sample. METHOD: A total of 718 Italian (IT) and 765 British (UK) children, aged 3-10 years, were individually tested on the age-appropriate items of the MABC-2 Test. RESULTS: Developmental trends emerged on every task and differences between IT and UK children were obtained on 11 of 27 task comparisons. Interactions between age and country indicated that differences were not consistently in favor of one culture. Confirmatory factor analysis generally supported the proposed structure of the MABC-2 Test. CONCLUSION: Although the differences between the IT and the UK children were relatively few, those that did emerge emphasize the need for population specific norms and suggest that cultural diversity in motor experiences should be considered when evaluating motor abilities in children.

The transient receptor potential vanilloid 1 (TRPV1) receptor protects against the onset of sepsis after endotoxin.

Transient potential vanilloid 1 (TRPV1) receptor is an ion channel receptor primarily localized on sensory nerves and activated by specific stimuli to initiate and amplify pain and inflammation, as typified by murine models of scald and arthritis. Little is known of the role of TRPV1 in sepsis, an infective disease associated with inflammation. Through use of a sublethal murine model of lipopolysaccharide-induced peritoneal sepsis, we provide novel evidence that genetic deletion of TRPV1 leads to an enhanced onset of various pathological components of systemic endotoxemia. Paired studies of TRPV1 knockout (KO) and wild-type mice demonstrate significantly enhanced hypotension (56+/-2% vs. 38+/-6% decrease in blood pressure, n=12), hypothermia (13+/-3% vs. 7+/-1% decrease in core temperature, n=6), and peritoneal exudate mediator levels (TNF-alpha, 0.78+/-0.2 vs. 0.38+/-0.1 ng/ml; nitrite, for NO, 35+/-10 vs. 15+/-3 microM; n=8) in TRPV1 KO mice, indicating loss of protective effect. Findings correlated with liver edema and raised plasma levels of aspartate aminotransferase in TRPV1 KO mice. These data suggest that TRPV1 may play an important regulatory role in sepsis independent of the major sensory neuropeptide substance P. The findings are relevant to developing strategies that increase the beneficial, and reduce the harmful, components of sepsis to prevent and treat this often fatal condition.