Inhibitory Control in Children with Autism Spectrum Disorder

Impairments in executive abilities such as cognitive flexibility have been identified in individuals with autism spectrum disorder (ASD). It remains unclear, however, whether such individuals also experience impairments in another executive ability: inhibitory control. In the present study, we administered three inhibitory tasks to 18 children with ASD, 23 siblings of children with ASD, and 25 typically developing children. After controlling for individual differences in age, overall IQ, and processing speed, children with ASD demonstrated impaired performance on two of the three inhibitory tasks. Results suggest that children with ASD experience circumscribed deficits in some but not all aspects of inhibitory control. More generally, the findings underscore the importance of using multiple measures to assess a putative single cognitive ability.     

Down-regulation of early ionotrophic glutamate receptor subunit developmental expression as a mechanism for observed plasticity deficits following gestational exposure to benzo(a)pyrene

The focus of this study was to characterize the impact of gestational exposure to benzo(a)pyrene [B(a)P] on modulation of glutamate receptor subunit expression that is critical for the maintenance of synaptic plasticity mechanisms during hippocampal or cortical development in offspring. Previous studies have demonstrated that hippocampal and/or cortical synaptic plasticity (as measured by long-term potentiation and S1-cortex spontaneous/evoked neuronal activity) and learning behavior (as measured by fixed-ratio performance operant testing) is significantly impaired in polycyclic aromatic or halogenated aromatic hydrocarbon-exposed offspring as compared to controls. These previous studies have also revealed that brain to body weight ratios are greater in exposed offspring relative to controls indicative of intrauterine growth retardation which has been shown to manifest as low birth weight in offspring. Recent epidemiological studies have identified an effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 years of life among inner-city children [Perera FP, Rauh V, Whyatt RM, Tsai WY, Tang D, Diaz D, et al. Effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 years of life among inner-city children. Environ Health Perspect 2006;114:1287-92]. The present study utilizes a well-characterized animal model to test the hypothesis that gestational exposure to B(a)P causes dysregulation of developmental ionotropic glutamate receptor subunit expression, namely the N-methyl-d-aspartate receptor (NMDAR) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptor (AMPAR) both critical to the expression of synaptic plasticity mechanisms. To mechanistically ascertain the basis of B(a)P-induced plasticity perturbations, timed pregnant Long-Evans rats were exposed in an oral subacute exposure regimen to 0, 25 and 150mug/kg BW B(a)P on gestation days 14-17. The first sub-hypothesis tested whether gestational exposure to B(a)P would result in significant disposition in offspring. The second sub-hypothesis tested whether gestational exposure to B(a)P would result in down-regulation of early developmental expression of NMDA and AMPA receptor subunits in the hippocampus of offspring as well as in primary neuronal cultures. The results of these studies revealed significant: (1) disposition to the hippocampus and cortex, (2) down-regulation of developmental glutamate receptor mRNA and protein subunit expression and (3) voltage-dependent decreases in the amplitude of inward currents at negative potentials in B(a)P-treated cortical neuronal membranes. These results suggest that plasticity and behavioral deficits produced as a result of gestational B(a)P exposure are at least, in part, a result of down-regulation of early developmental glutamate receptor subunit expression and function at a time when excitatory synapses are being formed for the first time in the developing central nervous system. The results also predict that in B(a)P-exposed offspring with reduced early glutamate receptor subunit expression, a parallel deficit in behaviors that depend on normal hippocampal or cortical functioning will be observed and that these deficits will be present throughout life.     

Civil affairs augmentation of Special Forces units greatly enhance MEDRETE impact

Medical readiness education and training exercises (MEDRETEs) provide acute, primary, and preventative medicine services to populations in countries other than the United States. MEDRETEs provide training in deployment, redeployment, austere environment medicine, supply, security, and defense for our active duty and reserve component personnel. MEDRETEs also improve public relations, advance U.S. foreign policy, and build confidence in the partner nation services. This article documents the great increase in ability to see multiple patients provided when a Special Forces unit is augmented by assistance from Civil Affairs attachments.     

The prevalence of airflow obstruction in rural primary care

Spirometry has been reported to be under-utilized, and airflow obstruction may be under-diagnosed, in primary care practice. STUDY OBJECTIVES: The objective of this study was to determine the prevalence and severity of airflow obstruction in rural primary care settings and the degree to which it can be predicted by clinical characteristics. Spirometry was performed in patients 35 years and older who had smoked, presenting for any reason to one of eight rural primary care practices. Obstruction was defined as an FEV(1)/FVC<0.70. A total of 1046 subjects were recruited of whom 1034 had acceptable and reproducible spirometry. Airflow obstruction was detected in 17.4% (180 patients). Of those with obstruction, 77.2% (se 3.1%) had at least one respiratory symptom versus 62.4% (se 1.6%) without obstruction (P=0.0002). Only 44.9% (se 3.7%) of those with airflow obstruction had been previously diagnosed with obstructive lung disease. Of those with an FEV(1)<50% of predicted, 85% (se 5.6%) were breathless on exertion; however, only 63% (se 7.6%) were being treated with respiratory medications. We conclude that airflow obstruction is common in rural primary care practice and cannot be accurately predicted by symptoms. It is undiagnosed half of the time, and often not treated even when symptomatic.     

Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection

Background

There are currently no accurate serum markers for detecting early risk of colorectal cancer (CRC). We therefore developed a non-targeted metabolomics technology to analyse the serum of pre-treatment CRC patients in order to discover putative metabolic markers associated with CRC. Using tandem-mass spectrometry (MS/MS) high throughput MS technology we evaluated the utility of selected markers and this technology for discriminating between CRC and healthy subjects.

Methods

Biomarker discovery was performed using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Comprehensive metabolic profiles of CRC patients and controls from three independent populations from different continents (USA and Japan; total n = 222) were obtained and the best inter-study biomarkers determined. The structural characterization of these and related markers was performed using liquid chromatography (LC) MS/MS and nuclear magnetic resonance technologies. Clinical utility evaluations were performed using a targeted high-throughput triple-quadrupole multiple reaction monitoring (TQ-MRM) method for three biomarkers in two further independent populations from the USA and Japan (total n = 220).

Results

Comprehensive metabolomic analyses revealed significantly reduced levels of 28-36 carbon-containing hydroxylated polyunsaturated ultra long-chain fatty-acids in all three independent cohorts of CRC patient samples relative to controls. Structure elucidation studies on the C28 molecules revealed two families harbouring specifically two or three hydroxyl substitutions and varying degrees of unsaturation. The TQ-MRM method successfully validated the FTICR-MS results in two further independent studies. In total, biomarkers in five independent populations across two continental regions were evaluated (three populations by FTICR-MS and two by TQ-MRM). The resultant receiver-operator characteristic curve AUCs ranged from 0.85 to 0.98 (average = 0.91 ± 0.04).

Conclusions

A novel comprehensive metabolomics technology was used to identify a systemic metabolic dysregulation comprising previously unknown hydroxylated polyunsaturated ultra-long chain fatty acid metabolites in CRC patients. These metabolites are easily measurable in serum and a decrease in their concentration appears to be highly sensitive and specific for the presence of CRC, regardless of ethnic or geographic background. The measurement of these metabolites may represent an additional tool for the early detection and screening of CRC.     

Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory,coagulation and endothelial activation marker profiles in severe traumatic brain injured patients

Background  

Traumatic brain injury (TBI) initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial hypertension and has immunomodulatory properties that may confer neuroprotection. This study examined the impact of hypertonic fluids on inflammatory/coagulation cascades in isolated head injury.     

Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury

Background  

Activated complement system is known to mediate neuroinflammation and neurodegeneration following exposure to hypoxic-ischemic insults. Therefore, inhibition of the complement activation cascade may represent a potential therapeutic strategy for the management of ischemic brain injury. Decay-accelerating factor (DAF, also known as CD55) inhibits complement activation by suppressing the function of C3/C5 convertases, thereby limiting local generation or deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured neuronal cells subjected to sodium cyanide (NaCN)-induced hypoxia from degeneration and apoptosis.