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Articles by J. Luke Meador in JoVE

 JoVE General

توصيف المظهري والوظيفي للخلايا غشائي مستعمرة تشكيل المستمدة من الإنسان دم الحبل السري


JoVE 3872 4/13/2012

Herman B Wells Center for Pediatric Research, Indiana University School of Medicine

الخلايا البطانية التي تشكل مستعمرة (ECFCs) تنتشر الخلايا البطانية مع احتمال قوي التكاثري نسيلي التي تعرض جوهري

Other articles by J. Luke Meador on PubMed

Job Search and Employment-related Issues in Athletic Training Education Programs

To investigate the amount of classroom instruction appropriated for employment-related issues and how career service centers were used by students in National Athletic Trainers' Association (NATA)-approved/Commission on Accreditation of Allied Health Education Programs (CAAHEP)-accredited undergraduate athletic training curriculums.

Acute Renal Failure Can Occur with Inappropriate Use of a Coxib

Pilot Investigation of Hyaluronate Injections for First Metacarpal-carpal (MC-C) Osteoarthritis

Hyaluronate intraarticular injections are widely used for treatment of pain associated with osteoarthritis of the knee, but there is no published literature on its use in osteoarthritis of the hand. We describe an open-label, baseline-controlled pilot study in which 5 weekly injections of 10 mg sodium hyaluronate (molecular weight 500-730 kDa) in 1 mL was used to treat 16 patients with osteoarthritic first metacarpal-carpal (MC-C) joints. The injections were performed easily and were well tolerated. Mean pain score at 5 months after the last injection, on a 10-point visual analog scale, decreased from 4.74 to 2.56 at rest. Pain on use decreased from 5.91 to 4.33. Pinch strength and a short questionnaire on hand function did not significantly change. The results of this small pilot study suggest that intraarticular injections into the first MC-C joint are easily administered, well tolerated, and could be an effective treatment option for patients with osteoarthritis of this joint. Further investigation using larger, blind controlled clinical studies are warranted.

Impact of Major Co-morbidities on Mortality and Complications After Gastric Bypass

We hypothesized that major co-morbidities affect survival and complications after gastric bypass.

Relating Results of Chronic Toxicity Responses to Population-level Effects: Modeling Effects on Wild Chinook Salmon Populations

Standard toxicity tests assess the physiological responses of individual organisms to exposure to toxic substances under controlled conditions. Time and space restrictions often prohibit the assessment of population-level responses to a toxic substance. Compounds affecting various toxicity endpoints, such as growth, fecundity, behavior, or immune function, alter different demographic traits and produce different impacts on the population. Chronic effects of immune suppression, reproductive impairment, and growth reduction were examined using life history models for Chinook salmon (Oncorhynchus tshawytscha). Modeled immune suppression acted through reductions in age-specific survival, with first- and second-year survival producing the greatest changes in the population growth rate (lamda). A 10% reduction in various reproductive parameters all produced a similar lamda, but different sensitivity and stable age distributions. Growth reduction models incorporated effects to both survival and reproduction and produced additive effects. Overall, model output indicated that for Chinook salmon, alteration of first-year survival has the greatest relative impact on lamda. Results support the importance of linking toxicity endpoints to the demographic traits that they influence and help generate toxicity tests that are more relevant for the species. Life history modeling provides a useful tool to develop testable hypotheses regarding specific and comparative population-level impacts.

Distinct Cognitive Neurophysiologic Profiles for Lamotrigine and Topiramate

To contrast the effects of lamotrigine (LTG) and topiramate (TPM) on cognitive task-related and resting-state EEG and evoked potential (EP) measures.

Knowledge and Risks of Human Immunodeficiency Virus Transmission Among Veterans with Severe Mental Illness

This study is among the first to examine knowledge about human immunodeficiency virus (HIV) and behavioral risks for HIV transmission among veterans with severe mental illness (SMI), a group at high risk for HIV infection. This study examined associations between accuracy of HIV knowledge, risk behaviors, and clinical and demographic characteristics in a sample of male veteran psychiatric inpatients diagnosed with SMI (N = 353). Results showed high rates of inaccurate HIV knowledge, with > 40% of patients demonstrating some inaccuracies, particularly those related to the progression and symptoms of acquired immunodeficiency syndrome. Inaccurate HIV knowledge was associated with older age, minority status, education level, marital status, no homelessness within the previous 6 months, and no reported history of illicit intranasal drug use. There is a need for more effective HIV prevention interventions for persons with SMI.

Co-infections of Adenovirus Species in Previously Vaccinated Patients

Despite the success of the adenovirus vaccine administered to US military trainees, acute respiratory disease (ARD) surveillance still detected breakthrough infections (respiratory illnesses associated with the adenovirus serotypes specifically targeted by the vaccine). To explore the role of adenoviral co-infection (simultaneous infection by multiple pathogenic adenovirus species) in breakthrough disease, we examined specimens from patients with ARD by using 3 methods to detect multiple adenoviral species: a DNA microarray, a polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay, and a multiplex PCR assay. Analysis of 52 samples (21 vaccinated, 31 unvaccinated) collected from 1996 to 2000 showed that all vaccinated samples had co-infections. Most of these co-infections were community-acquired serotypes of species B1 and E. Unvaccinated samples primarily contained only 1 species (species E) associated with adult respiratory illness. This study highlights the rarely reported phenomenon of adenoviral co-infections in a clinically relevant environment suitable for the generation of new recombinational variants.

Modulation of the Turnover of Formamidopyrimidine DNA Glycosylase

In recent years, significant progress has been made in determining the catalytic mechanisms by which base excision repair (BER) DNA glycosylases and glycosylase-abasic site (AP) lyases cleave the glycosyl bond. While these investigations have identified active site residues and active site architectures, few investigations have analyzed postincision turnover events. Previously, we identified a critical residue (His16) in the T4-pyrimidine dimer glycosylase (T4-Pdg) that, when mutated, interferes with enzyme turnover [Meador et al. (2004) J. Biol. Chem. 279, 3348-3353]. To test whether comparable residues and mechanisms might be operative for other BER glycosylase:AP-lyases, molecular modeling studies were conducted comparing the active site regions of T4-Pdg and the Escherichia coli formamidopyrimidine DNA glycosylase (Fpg). These analyses revealed that His71 in Fpg might perform a similar function to His16 in T4-Pdg. Site-directed mutagenesis of the Fpg gene and analyses of the reaction mechanism of the mutant enzyme revealed that the H71A enzyme retained activity on a DNA substrate containing an 8-oxo-7,8-dihydroguanine (8-oxoG) opposite cytosine and DNA containing an AP site. The H71A Fpg mutant was severely compromised in enzyme turnover on the 8-oxoG-C substrate but had turnover rates comparable to that of wild-type Fpg on AP-containing DNA. The similar mutant phenotypes for these two enzymes, despite a complete lack of structural or sequence homology between them, suggest a common mechanism for the rate-limiting step catalyzed by BER glycosylase:AP-lyases.

Physical Activity and Quality of Life Improvements Before Obesity Surgery

To examine quality of life (QOL), physical activity (PA), and physical activity readiness (PAR) among gastric-bypass surgery (GBS) candidates.

Academic Medical Centers and Conflicts of Interest

Antiepileptic Drugs and Neurodevelopment

Clinical studies have documented the teratogenic potential of antiepileptic drugs (AEDs). More recent cohort studies have been trying to sort out which AEDs impose the highest risk of teratogenicity. Currently, there is evidence demonstrating an increased risk of major congenital malformations (MCMs) for valproate, phenobarbital, and polytherapy during pregnancy. Based on the current data from multiple studies, the risk for valproate is the highest. Additional studies are needed to fully delineate if differences exist for other AEDs, especially the newer AEDs. However, although MCMs are easy to recognize and have been shown to be more common after in utero exposure to AEDs, there are insufficient data regarding their long-term effects on cognition and behavior in exposed children. Although most children born to women with epilepsy are healthy, in recent years there has been increasing awareness of the long-term effects of in utero exposure to AEDs. Recent discovery of neuronal apoptosis following in utero AED exposure in animals during a period that corresponds to the third trimester and early infancy in humans raises further concerns. Prospective clinical studies seem necessary in order to better understand the long-term neurodevelopmental effects of in utero exposure to AEDs.

Structured Cueing on a Semantic Fluency Task Differentiates Patients with Temporal Versus Frontal Lobe Seizure Onset

Patients with frontal lobe dysfunction (e.g., Huntington's disease) reportedly benefit more from cueing on measures of semantic fluency than do patients with damage to temporal lobe structures (e.g., Alzheimer's disease). This differential benefit from cueing suggests that different neurocognitive functions are impaired in these two groups. Patients with frontal lobe dysfunction are presumed to have difficulty with the executive aspects of this generative fluency task, whereas patients with temporal lobe impairment are limited by deficits in semantic memory. We studied the performance of patients with complex partial seizures of frontal or temporal lobe onset, as determined by video/EEG monitoring, on standard and cued measures of semantic fluency administered in a counterbalanced sequence across groups. These groups did not differ significantly in terms of age, education, gender, age at seizure onset, total number of antiepileptic drugs, or IQ, and all patients subsequently underwent surgery for intractable epilepsy. Patients with frontal lobe dysfunction (FL group) performed significantly worse than patients with temporal lobe impairment (TL group) on the standard semantic fluency paradigm (TL group: M=18.4, SD=4.7; FL group: M=11.1, SD=5.3), t(27)=-3.75, P<0.001. Nevertheless, results of an ANCOVA demonstrated that the FL group showed significantly greater performance improvement than the TL group when provided with a cued semantic fluency format, even after controlling for baseline differences in ability on the standard semantic fluency task (TL group: M=0.45, SD=3.8; FL M=9.4, SD=5.1), F(1,29)=12.37, P=0.002. These findings support previous research suggesting that frontal and temporal structures contribute uniquely to semantic generative fluency and suggest that using a combination of standard and cued semantic fluency tasks may help confirm localization of seizure onset in partial epilepsy by localizing the associated cognitive dysfunction.

Cognitive Effects of Lamotrigine Compared with Topiramate in Patients with Epilepsy

To compare the cognitive effects of lamotrigine vs topiramate as adjunctive therapy in adults with epilepsy.

In Utero Antiepileptic Drug Exposure: Fetal Death and Malformations

Pregnancy outcomes following in utero exposure to antiepileptic drugs (AEDs) are uncertain, limiting an evidenced-based approach.

Using the PRECEDE Model to Plan Men's Health Programs in a Managed Care Setting

Managed care organizations represent an important venue for delivering health promotion programs. However, most health plans do not employ public health strategies that match peoples' needs and preferences to effective behavior change techniques. This article focuses on the planning efforts by Blue Cross and Blue Shield of North Carolina (BCBSNC) to address the problem of underutilization of preventive health care services among adult male members--an issue that has received comparatively little attention in the health behavior arena. BCBSNC planners used the PRECEDE planning process to define issues relevant to the target population and determine appropriate intervention strategies. Increasing perceived susceptibility and severity to disease, perceived benefits of screening, physician recommendation for screening, and health knowledge/awareness emerged as intervention priorities. The PRECEDE planning process yielded important evidence-based information and strategies to address men's underuse of preventive services and led BCBSNC to adopt new systems for planning interventions to promote the health of its members.

Memory Loss After Left Anterior Temporal Lobectomy in Patients with Mesial Temporal Lobe Sclerosis

Fluorescent Signal Amplification of Carbocyanine Dyes Using Engineered Viral Nanoparticles

We report enhancement in the fluorescent signal of the carbocyanine dye Cy5 by using an engineered virus as a scaffold to attach >40 Cy5 reporter molecules at fixed locations on the viral capsid. Although cyanine dye loading is often accompanied by fluorescence quenching, our results demonstrate that organized spatial distribution of Cy5 reporter molecules on the capsid obviates this commonly encountered problem. In addition, we observe energy transfer from the virus to adducted dye molecules, resulting in a highly fluorescent viral nanoparticle. We have used this enhanced fluorescence for the detection of DNA-DNA hybridization. When compared with the most often used detection methods in a microarray-based genotyping assay for Vibrio cholerae O139, these viral nanoparticles markedly increased assay sensitivity, thus demonstrating their applicability for existing DNA microarray protocols.

Rapid Detection of Major Depression in Epilepsy: a Multicentre Study

Depression is a common comorbid disorder in epilepsy but is not routinely assessed in neurology clinics. We aimed to create a rapid yet accurate screening instrument for major depression in people with epilepsy.

Twisted, Z-shaped Perylene Bisimide

The first derivative of a new class of perylene bisimide chromophores, N,N'-bis(octyl)-3,9-bis(phenyl)perylene-1,2,7,8-tetracarboxyl bisimide, 1, has been synthesized and its fundamental photophysical and electrochemical properties assessed. The extended, Z-shaped structure was achieved by use of the classic photoenolization of an o-methylbenzophenone analogue, 1,5-dibenzoyl-9,10-dihydroanthracene, and in situ Diels-Alder trapping of the resulting o-xylylenol intermediates with N-octylmaleimide. Subsequent dehydration and aromatization of the resulting bisadduct afforded 1. In dichloromethane, bisimide 1 has an absorption lambdamax at 491 nm (epsilon = 29,600 M-1 cm-1), a fluorescence lambdamax at 517 nm with a high quantum yield (Phi = 0.70), and a single-exponential fluorescence decay (tau = 5.01 ns). Pure crystals of 1 have red emission, suggesting exciplex formation in the solid state. X-ray crystallographic analysis of 1 revealed significant twisting of its perylene core.

Phenacenes from Diels-Alder Trapping of Photogenerated O-xylylenols: Phenanthrenes and Benzo[e]pyrene Bisimide

[structure: see text] The synthesis of phenanthrene and benzo[e]pyrene bisimides, 1 and 2, was accomplished via the Diels-Alder trapping of sterically congested o-xylylenols photochemically generated from 3,6-dibenzoyl-o-xylene and 1,4-dibenzoyl-9,10-dihydroanthracene, respectively. Absorption and emission from 2 are red-shifted from 1 and unsubstituted benzo[e]pyrene. The fluorescence quantum yield for 2 is an order of magnitude lower than that of 1 and comparable to that of the parent benzo[e]pyrene.

Health Care System Accessibility. Experiences and Perceptions of Deaf People

People who are deaf use health care services differently than the general population; little research has been carried out to understand the reasons.

Assessment of Depressive Symptoms in Deaf Persons

Evidence suggests that Deaf people may have a greater prevalence of depressive symptoms. However, it is unclear whether commonly used written screening instruments are accurate with this population because of their unique cultural and linguistic factors. Setting: Deaf persons (n = 71) residing in southeastern Michigan.

The Finished DNA Sequence of Human Chromosome 12

Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.

How to Image Memory in Epilepsy

Insurance-mandated Preoperative Dietary Counseling Does Not Improve Outcome and Increases Dropout Rates in Patients Considering Gastric Bypass Surgery for Morbid Obesity

Preoperative dietary counseling (PDC) before bariatric surgery is mandated by a growing number of insurance payers. Their claim is that PDC improves outcomes and postoperative compliance. We compared outcomes of GBP patients undergoing a mandatory 13 weeks of PDC (n = 72) to a contemporaneous group of patients with no such requirement (no-PDC; n = 252) who underwent operation between January 2000 and December 2002.

Physical Activity Stage of Readiness Predicts Moderate-vigorous Physical Activity Participation Among Morbidly Obese Gastric Bypass Surgery Candidates

Despite the ever-growing body of literature linking stage of physical activity readiness (PAR) with physical activity (PA) participation in overweight and obese populations, this relationship has not been examined among individuals seeking gastric bypass surgery (GBS). Furthermore, little is known about the specific intensity of activities undertaken by GBS candidates. Therefore, this study sought to determine whether greater PAR was associated with greater moderate-vigorous physical activity (MVPA) participation among GBS candidates.

Induction of Micronuclei in Human Fibroblasts Across the Bragg Curve of Energetic Heavy Ions

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LEpsilonTau gamma or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. The dose delivered by the charged particle increases sharply as the particle approaches the end of its range, a position known as the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the "biological Bragg curve" is dependent on the energy and the type of the primary particle and may vary for different biological end points. Here we report measurements of the biological response across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. A quantitative biological response curve generated for micronuclei per binucleated cell across the Bragg curve did not reveal an increased yield of micronuclei at the location of the Bragg peak. However, the ratio of mono- to binucleated cells, which indicates inhibition of cell progression, increased at the Bragg peak location. These results confirm the hypothesis that severely damaged cells at the Bragg peak are more likely to go through reproductive death and not be evaluated for micronuclei.

Spirituality and Care at the End of Life

The CITRA Research-practice Consensus-workshop Model: Exploring a New Method of Research Translation in Aging

On the basis of the experience of an extensive community-based research partnership in New York City, we developed an innovative process for bridging the gap between aging-related research and practice, using a consensus-workshop model.

Neurons of the Rostral Ventrolateral Medulla Contribute to Obesity-induced Hypertension in Rats

Activation of the sympathetic nervous system contributes to the pathogenesis of obesity-induced hypertension. The present study sought to determine whether sympathetic regulatory neurons of the rostral ventrolateral medulla contribute to the elevated blood pressure in obese rats. Male Sprague-Dawley rats (350 to 425 g) were placed on a moderately high-fat diet (32% kcal as fat) or a low-fat (LF) diet (10.6% kcal as fat). After 13 weeks, rats fed the moderately high-fat diet segregated into obesity-prone (OP) and obesity-resistant (OR) groups based on their body weight (OP: 839+/-22 g; OR: 668+/-15 g; LF: 680+/-18 g; n=15 for all groups; P<0.01). Under isoflurane anesthesia, baseline mean arterial blood pressure was significantly elevated in the OP rats versus the OR and LF rats (OP: 108+/-2 mm Hg; OR: 100+/-2 mm Hg; LF: 97+/-3 mm Hg; n=7; P<0.05). Inhibition of the rostral ventrolateral medulla with bilateral microinjection of the GABA(A) receptor agonist muscimol (200 pmol/100 nL) decreased mean arterial blood pressure to similar levels across the groups (OP: 49+/-1 mm Hg; OR: 50+/-2 mm Hg; LF: 49+/-1 mm Hg), but the magnitude of this decrease was significantly greater in the OP versus the OR and LF rats (OP: -58+/-2 mm Hg; OR: -49+/-1 mm Hg; LF: -48+/-3 mm Hg; P<0.01). These differences in mean arterial blood pressure cannot be explained by changes in vascular reactivity as the ED(50) in response to phenylephrine and norepinephrine was similar across the groups. The present findings suggest that the elevated sympathetic nerve activity and arterial blood pressure in obese rats depends on the tonic activity of rostral ventrolateral medulla sympathetic neurons.

Congregational Health Ministries: a National Study of Pastors' Views

Since the 1980s, there has been a growing, but little studied, movement that organizes church-based health services under the direction of a coordinator, usually a registered nurse. These Congregational Health Ministries (CHMs) emphasize health promotion and disease prevention. We compared the perceptions of pastors with and without organized CHMs and the characteristics of their congregations' health ministries.

Chromosome Aberrations Induced by Dual Exposure of Protons and Iron Ions

During space travel, astronauts will be exposed to protons and heavy charged particles. Since the proton flux is high compared to HZE particles, on average, it is assumed that a cell will be hit by a proton before it is hit by an HZE ion. Although the effects of individual ion species on human cells have been investigated extensively, little is known about the effects of exposure to mixed beam irradiation. To address this, we exposed human epithelial cells to protons followed by HZE particles and analyzed chromosomal damage using the multicolor banding in situ hybridization (mBAND) procedure. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of intra-chromosomal aberrations (inversions and deletions within a single painted chromosome) as well as inter-chromosomal aberrations (translocation to unpainted chromosomes). Our results indicated that chromosome aberration frequencies from exposures to protons followed by Fe ions did not simply decrease as the interval between the two exposures increased, but peak when the interval was 30 min.

Can Basin Land Use Effects on Physical Characteristics of Streams Be Determined at Broad Geographic Scales?

The environmental setting (e.g., climate, topography, geology) and land use affect stream physical characteristics singly and cumulatively. At broad geographic scales, we determined the importance of environmental setting and land use in explaining variation in stream physical characteristics. We hypothesized that as the spatial scale decreased from national to regional, land use would explain more of the variation in stream physical characteristics because environmental settings become more homogeneous. At a national scale, stepwise linear regression indicated that environmental setting was more important in explaining variability in stream physical characteristics. Although statistically discernible, the amount of variation explained by land use was not remarkable due to low partial correlations. At level II ecoregion spatial scales (southeastern USA plains, central USA plains, and a combination of the western Cordillera and the western interior basins and ranges), environmental setting variables were again more important predictors of stream physical characteristics, however, as the spatial scale decreased from national to regional, the portion of variability in stream physical characteristics explained by basin land use increased. Development of stream habitat indicators of land use will depend upon an understanding of relations between stream physical characteristics and environmental factors at multiple spatial scales. Smaller spatial scales will be necessary to reduce the confounding effects of variable environmental settings before the effects of land use can be reliably assessed.

Cognitive/behavioral Teratogenetic Effects of Antiepileptic Drugs

The majority of children of mothers with epilepsy are normal, but they are at increased risk for developmental delay. Antiepileptic drugs (AEDs) appear to play a role. Our current knowledge is reviewed, including research design issues and recommendations for future research. In animals, exposure of the immature brain to some AEDs can produce widespread neuronal apoptosis and behavioral deficits. The risks of AEDs in humans are less clear, but recent studies raise concerns, especially for valproate. There is a critical need for well-designed systematic research to improve our understanding of AED effects on the fetal brain.

Neuropsychological and Neurophysiologic Effects of Carbamazepine and Levetiracetam

The relative effects of levetiracetam (LEV) and carbamazepine (CBZ) on cognitive and neurophysiologic measures are uncertain.

The Basic Science of Memory As It Applies to Epilepsy

The mechanisms of memory delineated by the model of long-term potentiation (LTP) are similar to those underlying epileptogenesis by kindling. Memory is impaired by seizures and epilepsy. High frequency neural activity is important in both memory formation and seizures. Both kindling and LTP are most effectively induced by high-frequency stimuli, involve synaptic facilitation, and share overlapping molecular mechanisms, such as N-methyl-d-aspartate (NMDA) receptor-induced calcium cascade and protein synthesis. The hippocampus contributes to both through its role in memory formation and its low seizure threshold.

"We Never Used to Do Things This Way": Behavioral Health Care Reform in New Mexico

This column describes the first year of efforts in New Mexico to reform the behavioral health system. The process, guided by principles of cultural exchange theory, seeks to establish a "collaborative culture" among all stakeholders involved, including state agencies, consumers, families, advocates, and providers. Challenges have included inadequate system funding; insufficient development of skill sets among state personnel; underestimation of time and labor needed to address complex tasks; varying federal statutory and funder requirements for individual agencies; lack of a solid infrastructure for data collection, management, and dissemination; and clear definitions of the roles and relationships of local stakeholders to the state leadership group.

Religion, Spirituality, and Medicine: Psychiatrists' and Other Physicians' Differing Observations, Interpretations, and Clinical Approaches

This study compared the ways in which psychiatrists and nonpsychiatrists interpret the relationship between religion/spirituality and health and address religion/spirituality issues in the clinical encounter.

The CITRA Pilot Studies Program: Mentoring Translational Research

We developed an innovative pilot studies program to foster partnerships between university researchers and agencies serving older people in New York City. The development of researchers willing to collaborate with frontline service agencies and service agencies ready to partner with researchers is critical for translating scientific research into evidence-based practice that benefits community-dwelling older adults.

Virulence Gene- and Pandemic Group-specific Marker Profiling of Clinical Vibrio Parahaemolyticus Isolates

Vibrio parahaemolyticus is a halophilic bacterium capable of causing food- and waterborne gastroenteritis, wound infections, and septicemia in humans. The organism has recently received increasing attention, as the emergence of a new clone, V. parahaemolyticus O3:K6, has resulted in the first documented pandemic spread of V. parahaemolyticus. We used microarray analyses to explore the presence of known virulence factors and genetic markers thought to be specific for V. parahaemolyticus O3:K6 and its clonal derivatives. Analyses of 48 human clinical isolates collected between 1997 and 2005 revealed that the V. parahaemolyticus chromosome 2 type III secretion system is not specifically associated with pandemic strains and can be found in tdh-negative (i.e., Kanagawa-negative) clinical isolates. These results highlight the genetic dynamism of V. parahaemolyticus and aid in refining the genetic definition of the pandemic group members.

To Drive or Not to Drive: Roles of the Physician, Patient, and State

How Skeptical Should We Be About Industry-sponsored Studies?

Electrical Stimulation Promotes Peripheral Axon Regeneration by Enhanced Neuronal Neurotrophin Signaling

Electrical stimulation of cut peripheral nerves at the time of their surgical repair results in an enhancement of axon regeneration. Regeneration of axons through nerve allografts was used to evaluate whether this effect is due to an augmentation of cell autonomous neurotrophin signaling in the axons or signaling from neurotrophins produced in the surrounding environment. In the thy-1-YFP-H mouse, a single 1 h application of electrical stimulation at the time of surgical repair of the cut common fibular nerve results in a significant increase in the proportion of YFP+ dorsal root ganglion neurons, which were immunoreactive for BDNF or trkB, as well as an increase in the length of regenerating axons through allografts from wild type litter mates, both 1 and 2 weeks later. Axon growth through allografts from neurotrophin-4/5 knockout mice or grafts made acellular by repeated cycles of freezing and thawing is normally very poor, but electrical stimulation results in a growth of axons through these grafts, which is similar to that observed through grafts from wild type mice after electrical stimulation. When cut nerves in NT-4/5 knockout mice were electrically stimulated, no enhancement of axon regeneration was found. Electrical stimulation thus produces a potent enhancement of the regeneration of axons in cut peripheral nerves, which is independent of neurotrophin production by cells in their surrounding environment but is dependent on stimulation of trkB and its ligands in the regenerating axons themselves.

Victoria Symptom Validity Test Performance in a Heterogenous Clinical Sample

We retrospectively reviewed Victoria Symptom Validity Test (VSVT) in 374 patients who underwent neuropsychological assessment in an academic hospital-based practice. Patients were classified as either non-TBI clinically referred (generally patients referred from neurology, neurosurgery, or medicine), clinically referred TBI (no known external financial incentive), and non-clinical referrals (e.g., attorney-referred, Worker's Compensation). Three patients were not classified into any group and considered separately. Intentional response distortion, defined as statistically less than chance performance on hard VST items, was present in only 1/306 (0.3%) clinically referred non-TBI patients, and no clinically referred TBI patient obtained scores significantly less than chance on this measure. One additional clinically referred patient with a non-neurologic diagnosis who was subsequently found to be pursuing a disability claim also performed worse than chance. In contrast, 5/25 patients (20%) referred by attorneys or otherwise deemed a priori to be at-risk for deficit exaggeration performed less than chance. These data suggest that intentional response distortion in patients referred for non-forensic neuropsychological evaluation is rare. Performances by specific diagnosis using different classification criteria are also presented.

Wound Wise: Wounds in Surgical Patients Who Are Obese

The number of surgical patients who are obese in the United States is rising, a trend that's likely to continue. Such patients are at higher risk than nonobese patients are for surgical site infections and other complications such as dehiscence, pressure ulcers, deep tissue injury, and rhabdomyolysis. This article details the factors that can contribute to such complications, including a high number of comorbidities, and offers practical suggestions for preventing them. Nurses should understand that special equipment, precautions, and protocols may be needed at every stage of care, and that obese patients aren't anomalies but rather a part of a growing population with particular needs.

Selective, Versus Routine, Upper Gastrointestinal Series Leads to Equal Morbidity and Reduced Hospital Stay in Laparoscopic Gastric Bypass Patients

The use of routine upper gastrointestinal contrast radiology series (UGIS) after laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) can entail risk, expense, and patient discomfort. We have discontinued routine UGIS in favor of selective UGIS guided by patient symptoms and signs or elevations in the juxta-anastomotic drain amylase. We hypothesized that elimination of routine UGIS would not adversely affect morbidity or mortality.

The Relationship Between Psychiatry and Religion Among U.S. Physicians

This study compared the religious characteristics of psychiatrists with those of other physicians and explored whether nonpsychiatrist physicians who are religious are less willing than their colleagues to refer patients to psychiatrists and psychologists.

A Biomechanical Analysis of Anterior Load Carriage

Front load carriage is a common occupational task in some industries (e.g. agriculture, construction), but, as compared to lifting tasks, relatively little research has been conducted on the biomechanical loading during these activities. The focus of this study was to explore the low back biomechanics during these activities and, specifically, to examine the effects of load height and walking speed on trunk muscle activity and trunk posture. Eleven male participants participated in two separate front load-carriage experiments. The first experiment called for carrying a barbell (with weight corresponding to 20% of elbow flexion strength) at three heights (knuckle height, elbow height and shoulder height) at a constant horizontal distance from the spine. The second experiment called for participants to carry a bucket of potatoes weighing 14 kg at the same three heights, but with no further restrictions in technique. In both experiments, the participants performed this task while either standing still or walking at a self-selected speed. As they performed these tasks, the activity levels of the right-side muscle of the rectus abdominis, external oblique, biceps brachii, anterior deltoid and three levels (T9, T12 and L3) of the erector spinae were sampled. Mid-sagittal plane trunk posture was also quantified using three magnetic field-based motion sensors at T9, T12 and L3. The results showed a significant effect of both walking speed and load height on trunk posture and trunk muscle activity levels in both the barbell and bucket experiments. In the barbell experiment, the walking trials generated 43% more trunk muscle activity than the standing trials. Trials at shoulder height produced 11% more muscle activity than trials at elbow height in the T9 erector spinae muscles and 71% more muscle activity in the anterior deltoid. In the bucket experiment, trunk muscle activity responded in a similar fashion, but the key result here was the quantification of the natural hyperextension posture of the spine used to balance the bucket of potatoes. These results provide insight into muscle activation patterns in dynamic settings, especially (load) carrying biomechanics, and have implications in industrial settings that require workers to carry loads in front of their bodies.

Afterdischarges During Cortical Stimulation at Different Frequencies and Intensities

The occurrence of unwanted afterdischarges (ADs) impedes cortical stimulation for mapping purposes. We investigated the safety of several stimulation paradigms.

Participation in 150 Min/wk of Moderate or Higher Intensity Physical Activity Yields Greater Weight Loss After Gastric Bypass Surgery

The American College of Sports Medicine's position stand on weight loss and prevention of weight regain in adults has suggested that overweight adults should participate in a minimum of 150 min/wk of moderate intensity physical activity (PA). This study compared the 3-, 6-, and 12-month postoperative weight loss between gastric bypass surgery (GBS) patients who met or exceeded the recommended 150 min/wk of moderate or higher PA and those not meeting the recommendation.

Racial Differences in Antidepressant Treatment Preceding Suicide in a Medicaid Population

African Americans have less use of antidepressants than whites, suggesting racial differences in the diagnosis and treatment of mood disorders. This study assessed whether this racial disparity is present among patients with a very high risk of severe mood disorders--that is, those with completed suicides.

What Constitutes High Quality of Care for Adults with Epilepsy?

Providers are increasingly being held accountable for the quality of care provided. While quality indicators have been used to benchmark the quality of care for a number of other disease states, no such measures are available for evaluating the quality of care provided to adults with epilepsy. In order to assess and improve quality of care, it is critical to develop valid quality indicators. Our objective is to describe the development of quality indicators for evaluating care of adults with epilepsy. As most care is provided in primary and general neurology care, we focused our assessment of quality on care within primary care and general neurology clinics.

The Relationship Between Dose of Vitamin E and Suppression of Oxidative Stress in Humans

The oxidation hypothesis of atherogenesis has been the focus of much research over the past 2 decades. However, randomized placebo-controlled trials evaluating the efficacy of vitamin E in preventing cardiovascular events in aggregate have failed to show a beneficial effect. Implicit in these trials is that the dose of vitamin E tested effectively suppressed oxidative stress status but this was never determined. We defined the dose-dependent effects of vitamin E (RRR-alpha-tocopherol) to suppress plasma concentrations of F2-isoprostanes, a biomarker of free radical-mediated lipid peroxidation, in participants with polygenic hypercholesterolemia and enhanced oxidative stress, a population at risk for cardiovascular events. A time-course study was first performed in participants supplemented with 3200 IU/day of vitamin E for 20 weeks. A dose-ranging study was then performed in participants supplemented with 0, 100, 200, 400, 800, 1600, or 3200 IU/day of vitamin E for 16 weeks. In the time-course study, maximum suppression of plasma F2-isoprostane concentrations did not occur until 16 weeks of supplementation. In the dose-ranging study there was a linear trend between the dosage of vitamin E and percentage reduction in plasma F2-isoprostane concentrations which reached significance at doses of 1600 IU (35+/-2%, p<0.035) and 3200 IU (49+/-10%, p<0.005). This study provides information on the dosage of vitamin E that decreases systemic oxidant stress in vivo in humans and informs the planning and evaluation of clinical studies that assess the efficacy of vitamin E to mitigate disease.

Neuropsychological and Behavioral Effects of Antiepilepsy Drugs

Antiepilepsy drugs work by decreasing neuronal irritability, which may also result in the non-desired side effect of decreased neuropsychological function. In addition to cognitive side effects, antiepilepsy drugs (AEDs) may be associated with behavioral effects which may range from irritability and hyperactivity to positive psychotropic effects on mood. There have been many new medications released since the 1990s, and although they tend to have more favorable side effect profiles compared to their older counterparts, there continues to be a risk of decreased cognitive function with the majority of these agents. The effects of in utero antiepilepsy drug exposure are increasingly being investigated, and differential drug risk is beginning to be described for both anatomic and cognitive outcomes. Patients with epilepsy undergoing neuropsychological evaluations are commonly on AEDs, and it is important for the clinician to recognize the potential contribution of AED therapy to neuropsychological profiles. The present article serves to provide an overview of our current understanding regarding the risks of antiepilepsy drug use for both cognitive and behavioral side effects.

Antibody-mediated Protection Against Genital Herpes Simplex Virus Type 2 Disease in Mice by Fc Gamma Receptor-dependent and -independent Mechanisms

The ability of antibody (Ab) to modulate HSV pathogenesis is well recognized but the mechanisms by which HSV-specific IgG antibodies protect against genital HSV-2 disease are not well understood. The requirement for Ab interactions with Fcgamma receptors (FcgammaR) in protection was examined using a murine model of genital HSV-2 infection. IgG antibodies isolated from the serum of HSV-immune mice protected normal mice against HSV-2 disease when administered prior to genital HSV-2 inoculation. However, protection was significantly diminished in recipient mice lacking the gamma chain subunit utilized in FcgammaRI, FcgammaRIII, FcgammaRIV and FcepsilonRI receptors and in normal mice depleted of Gr-1(+) immune cell populations known to express FcgammaR, suggesting protection was largely mediated by an FcgammaR-dependent mechanism. To test whether neutralizing Ab might provide superior protection, a highly neutralizing HSV glycoprotein D (gD)-specific monoclonal antibody (mAb) was utilized. Similar to results with HSV-specific polyclonal IgG, administration of the gD-specific mAb did not prevent initial infection of the genital tract but resulted in lower virus loads in the vaginal epithelium and provided significant protection against disease and acute infection of the sensory ganglia; however, this protection was independent of host FcgammaR expression and was manifest in mice depleted of Gr-1(+) immune cells. Together, these data demonstrate that substantial Ab-mediated protection against genital HSV-2 disease could be achieved by either FcgammaR-dependent or -independent mechanisms. These studies suggest that HSV vaccines might need to elicit multiple, diverse antibody effector mechanisms to achieve optimal protection.

Effects of IL-10 and Age on IL-6, IL-1beta, and TNF-alpha Responses in Mouse Skeletal and Cardiac Muscle to an Acute Inflammatory Insult

Exaggerated proinflammatory cytokine responses can be observed with aging, and reduced levels of the anti-inflammatory cytokine IL-10 may contribute to these responses. IL-10 can reduce IL-6, IL-1beta, and TNF-alpha expression in nonmuscle tissues; however, no studies have examined the combined effects of IL-10 and age on cytokine responses in skeletal and cardiac muscle. These experiments tested the hypothesis that the absence of IL-10, in vivo, is associated with greater IL-6, TNF-alpha, and IL-1beta responses to an inflammatory challenge in skeletal and cardiac muscle and that aging exaggerates these responses. We compared IL-6, IL-1beta, and TNF-alpha mRNA and protein levels in skeletal and cardiac muscle of young (4 mo) and mature (10-11 mo) wild-type (IL-10(+/+)) and IL-10 deficient (IL-10(-/-)) mice following LPS. Skeletal and cardiac IL-6 mRNA and protein were elevated by LPS for IL-10(+/+) and IL-10(-/-) mice with greater responses in the IL-10(-/-) mice (P < 0.01). In skeletal muscle these effects were greater in mature than young mice (P < 0.01). IL-1beta mRNA and protein responses to LPS were greater in cardiac muscle of young but not mature IL-10(-/-) mice compared with IL-10(+/+) (P < 0.01). However, IL-1beta responses were greater in mature than young mice, but only in IL-10(+/+) groups (P < 0.05). The absence of IL-10 was associated with higher TNF-alpha protein levels in cardiac muscle (P < 0.05). The results provide the first in vivo evidence that the absence of IL-10 is associated with a greater IL-6 response to LPS in skeletal and cardiac muscles, and in skeletal muscle aging further exaggerates these responses.

Suicide in Patients with Epilepsy

Using Fluorescent Aromatic Compounds in Bile from Juvenile Salmonids to Predict Exposure to Polycyclic Aromatic Hydrocarbons

We provide data from four different studies in which fish were fed polycyclic aromatic hydrocarbons (PAHs) that were used to develop a predictive relationship between dose (mug/g fish/d) and metabolites of PAHs in bile. Juvenile salmonids were fed various doses of total PAH that were applied as a mixture to fish pellets. The number of PAHs in each mixture ranged from 10 to 21 different low- and high-molecular-weight compounds, and their relative proportions and abundance were based on stomach concentrations observed for field-collected fish. Although we examined both the phenanthrene (PHN) and benzo[a]pyrene signals for the fluorescent aromatic compounds (FACs) in bile, the PHN signal exhibited the highest correlation and was considered to be the better choice for predicting exposure. A large database of PHN FAC values for field-collected fish was examined and used to predict dose by the method of inverse prediction. The goal of the present study was to develop a predictive relationship that would allow estimation of an exposure dose for an observed value of PHN FACs from juvenile salmonids sampled in the field. This dose would then be used to estimate adverse effects based on toxicity results from laboratory studies. Additional analyses were performed to determine ventilation doses from water concentrations of total PAH and then relate those to PHN FAC values.

Chemosensory Deprivation in Juvenile Coho Salmon Exposed to Dissolved Copper Under Varying Water Chemistry Conditions

Dissolved copper is an important nonpoint source pollutant in aquatic ecosystems worldwide. Copper is neurotoxic to fish and is specifically known to interfere with the normal function of the peripheral olfactory nervous system. However,the influence of water chemistry on the bioavailability and toxicity of copper to olfactory sensory neurons is not well understood. Here we used electrophysiological recordings from the olfactory epithelium of juvenile coho salmon (Oncorhynchus kisutch) to investigate the impacts of copper in freshwaters with different chemical properties. In low ionic strength artificial fresh water, a short-term (30 min) exposure to 20 microg/L dissolved copper reduced the olfactory response to a natural odorant (10(-5) M L-serine) by 82%. Increasing water hardness (0.2-1.6 mM Ca) or alkalinity (0.2-3.2 mM HCO3-) only slightly diminished the inhibitory effects of copper. Moreover, the loss of olfactory function was not affected by a change in pH from 8.6 to 7.6. By contrast, olfactory capacity was partially restored by increasing dissolved organic carbon (DOC; 0.1-6.0 mg/L). Given the range of natural water quality conditions in the western United States, water hardness and alkalinity are unlikelyto protect threatened or endangered salmon from the sensory neurotoxicity of copper. However, the olfactory toxicity of copper may be partially reduced in surface waters that have a high DOC content.

Differential Neuropsychological Test Sensitivity to Left Temporal Lobe Epilepsy

We examined the sensitivity of the Rey Auditory Verbal Learning Test (AVLT), California Verbal Learning Test (CVLT), Boston Naming Test (BNT), and Multilingual Aphasia Examination Visual Naming subtest (MAE VN) to lateralized temporal lobe epilepsy (TLE) in patients who subsequently underwent anterior temporal lobectomy. For the AVLT (n = 189), left TLE patients performed more poorly than their right TLE counterparts [left TLE = 42.9 (10.6), right TLE = 47.7 (9.9); p < .002 (Cohen's d = .47)]. Although statistically significant, the CVLT group difference (n = 212) was of a smaller magnitude [left LTE = 40.7 (11.1), right TLE = 43.8 (9.9); (p < .03, Cohen's d = .29)] than the AVLT. Group differences were also present for both measures of confrontation naming ability [BNT: left LTE = 43.1 (8.9), right TLE = 48.1 (8.9); p < .001 (Cohen's d = .56); MAE VN: left TLE = 42.2, right TLE = 45.6, p = .02 (Cohen's d = .36)]. When these data were modeled in independent logistic regression analyses, the AVLT and BNT both significantly predicted side of seizure focus, although the positive likelihood ratios were modest. In the subset of 108 patients receiving both BNT and AVLT, the AVLT was the only significant predictor of seizure laterality, suggesting individual patient variability regarding whether naming or memory testing may be more sensitive to lateralized TLE.

A Test of the Mechanisms of Sensory Extinction to Simultaneous Stimulation

Four Hundred Fifty Consecutive Laparoscopic Roux-en-Y Gastric Bypasses with No Mortality and Declining Leak Rates and Lengths of Stay in a Bariatric Training Program

We reviewed our obesity surgery database for 2 experienced bariatric surgeons since their last patient death in October 2003 through July 2007.

Cognitive Effects of Levetiracetam Versus Topiramate

Histone H2AX is a Critical Factor for Cellular Protection Against DNA Alkylating Agents

Histone H2A variant H2AX is a dose-dependent suppressor of oncogenic chromosome translocations. H2AX participates in DNA double-strand break repair, but its role in other DNA repair pathways is not known. In this study, role of H2AX in cellular response to alkylation DNA damage was investigated. Cellular sensitivity to two monofunctional alkylating agents (methyl methane sulfonate and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)) was dependent on H2AX dosage, and H2AX null cells were more sensitive than heterozygous cells. In contrast to wild-type cells, H2AX-deficient cells displayed extensive apoptotic death due to a lack of cell-cycle arrest at G(2)/M phase. Lack of G(2)/M checkpoint in H2AX null cells correlated well with increased mitotic irregularities involving anaphase bridges and gross chromosomal instability. Observation of elevated poly(ADP) ribose polymerase 1 (PARP-1) cleavage suggests that MNNG-induced apoptosis occurs by PARP-1-dependent manner in H2AX-deficient cells. Consistent with this, increased activities of PARP and poly(ADP) ribose (PAR) polymer synthesis were detected in both H2AX heterozygous and null cells. Further, we demonstrate that the increased PAR synthesis and apoptotic death induced by MNNG in H2AX-deficient cells are due to impaired activation of mitogen-activated protein kinase pathway. Collectively, our novel study demonstrates that H2AX, similar to PARP-1, confers cellular protection against alkylation-induced DNA damage. Therefore, targeting either PARP-1 or histone H2AX may provide an effective way of maximizing the chemotherapeutic value of alkylating agents for cancer treatment.

Pregnancy Outcomes in Women with Epilepsy: a Systematic Review and Meta-analysis of Published Pregnancy Registries and Cohorts

To conduct a systematic review and meta-analysis to quantify the incidence of congenital malformations (CMs) and other pregnancy outcomes as a function of in utero anti-epileptic drug (AED) exposure.

In Vivo Vitamin E Administration Attenuates Interleukin-6 and Interleukin-1beta Responses to an Acute Inflammatory Insult in Mouse Skeletal and Cardiac Muscle

Antioxidants are associated with reduced pro-inflammatory cytokine expression in immune cells and isolated tissues; however, no studies have examined whether short-term vitamin E administration is associated with reduced lipopolysaccharide (LPS)-induced cytokine expression in mouse skeletal and cardiac muscle, in vivo. These experiments tested the hypothesis that vitamin E administration attenuates nuclear factor kappaB (NF-kappaB), IL-6, IL-1beta and tumour necrosis factor alpha (TNFalpha) responses in skeletal and cardiac muscle to an inflammatory challenge induced by systemic LPS. We compared IL-6, IL-1beta and TNFalpha mRNA and protein, activated NF-kappaB and total oxidized proteins in skeletal and cardiac muscle 4 or 24 h after saline or LPS injection in mice receiving vitamin E or placebo for 3 days prior to the insult. Skeletal and cardiac IL-6 mRNA and protein were significantly elevated by LPS in both groups, but responses were significantly lower in vitamin E- compared with placebo-treated mice. In skeletal and cardiac muscle, LPS increased IL-1beta mRNA and protein in placebo- but not vitamin E-treated mice. Lipopolysaccharide-induced levels of cardiac IL-1beta mRNA and protein and skeletal IL-1beta mRNA were lower with vitamin E than placebo. Lipopolysaccharide-induced NF-kappaB activation and increases in total oxidized proteins were attenuated with vitamin E compared with placebo in both tissues. Vitamin E decreased LPS-induced increases in plasma IL-1beta but not IL-6 compared with placebo. The major results provide the first in vivo evidence that short-term vitamin E administration reduces IL-6 and IL-1beta responses to LPS in skeletal and cardiac muscle and prevents LPS-induced increases in NF-kappaB activation and total oxidized proteins.

To Stop or Not to Stop the AED?

Effect of the GC Content of DNA on the Distribution of UVB-induced Bipyrimidine Photoproducts

Solar UV radiation is a major mutagen that damages DNA through the formation of dimeric photoproducts between adjacent thymine and cytosine bases. A major effect of the GC content of the genome is thus anticipated, in particular in prokaryotes where this parameter significantly varies among species. We quantified the formation of UV-induced photolesions within both isolated and cellular DNA of bacteria of different GC content. First, we could unambiguously show the favored formation of cytosine-containing photoproducts with increasing GC content (from 28 to 72%) in isolated DNA. Thymine-thymine cyclobutane dimer was a minor lesion at high GC content. This trend was confirmed by an accurate and quantitative analysis of the photochemical data based on the exact dinucleotide frequencies of the studied genomes. The observation of the effect of the genome composition on the distribution of photoproducts was then confirmed in living cells, using two marine bacteria exhibiting different GC content. Because cytosine-containing photoproducts are highly mutagenic, it may be predicted that species with genomes exhibiting a high GC content are more susceptible to UV-induced mutagenesis.

Comparison of Detection and Signal Amplification Methods for DNA Microarrays

One of the factors limiting the use of DNA microarray technology for the detection of pathogenic organisms from clinical and environmental matrices has been inadequate assay sensitivity. To assess the effectiveness of post-hybridization secondary detection steps to enhance the sensitivity of DNA microarray-based pathogen detection, we evaluated a panel of 11 commercial and novel hybridization detection and signal amplification methods (direct labeling, indirect aminoallyl labeling, antibody, DNA dendrimers, viral particles, internally fluorescent nanoparticles, tyramide signal amplification, resonance light scattering nanoparticles and quantum dots) using a multiplex PCR and spotted long oligonucleotide microarray for Vibrio cholerae. Quantitative parameters such as sensitivity, signal intensity, background, assay complexity, time and cost were assessed and provide comparative criteria to be considered for DNA microarray experimental design. While the most important parameter is likely to vary based on the assay, when weighted equally, the findings suggest that recognition element- and dye-functionalized viral particles provide the most attractive option for microarray detection and signal amplification.

A Facility Specialist Model for Improving Retention of Nursing Home Staff: Results from a Randomized, Controlled Study

This article reports on a randomized, controlled intervention study designed to reduce employee turnover by creating a retention specialist position in nursing homes.

Pregnancy Registries in Epilepsy: a Consensus Statement on Health Outcomes

Most pregnant women with epilepsy require antiepileptic drug (AED) therapy. Present guidelines recommend optimizing treatment prior to conception, choosing the most effective AED for seizure type and syndrome, using monotherapy and lowest effective dose, and supplementing with folate. The Epilepsy Therapy Project established the international Health Outcomes in Pregnancy and Epilepsy (HOPE) forum to learn more about the impact of AEDs on the developing fetus, particularly the role of pregnancy registries in studying AED teratogenicity. The primary outcome of interest in these registries is the occurrence of major congenital malformations, with some data collected on minor malformations. Cognitive and behavioral outcomes are often beyond the timeframe for follow-up of these registries and require independent study. The HOPE consensus report describes the current state of knowledge and the limitations to interpretations of information from the various sources. Data regarding specific risks for both older and newer AEDs need to be analyzed carefully, considering study designs and confounding factors. There is a critical need for investigations to delineate the underlying mechanisms and explain the variance seen in outcomes across AEDs and within a single AED.

[Surgical Wounds in Obese Patients]

What is the Risk of Orofacial Clefts from Lamotrigine Exposure During Pregnancy?

Wrapping of Single-walled Carbon Nanotubes by a Pi-conjugated Polymer: the Role of Polymer Conformation-controlled Size Selectivity

Wrapping of a single-walled carbon nanotube (SWNT) was examined by using a poly[( m-phenylenevinylene)- alt-( p-phenylenevinylene)] (PmPV) derivative. The polymer's intrinsic ability in forming a helical conformation was found to play an essential role in the separation of nanotubes. Among about 15 tubes present in the pure SWNT (HiPcoTM) sample, the polymer was found to selectively pick up the tubes (11,6), (11,7) and (12,6), which correspond to tube diameters of 1.19, 1.25 and 1.24 nm, respectively. The SWNTs of smaller diameters were held loosely by the PmPV, and were gradually dropped out under centrifugation. The suspension solution prepared from the SWNT and PmPV was not permanently stable, with precipitation occurring after a few weeks. Irradiation in the UV-vis region exhibited a catalytic effect to shorten the precipitation time to hours. Those tubes, which were held loosely by PmPV, were quickly separated from the suspension during the irradiation process.

Teratogenicity of Antiepileptic Medications

Antiepileptic drugs (AEDs) are frequently used to treat several conditions that are common in women of childbearing age, including epilepsy, headaches, and mood disorders. Moreover, as in the case of epilepsy and severe psychiatric disease, clinicians frequently do not have the option of stopping these medications or switching to another class of drugs. Overall, AEDs have been associated with an increased risk of major congenital malformations, minor anomalies, specific congenital syndromes, and developmental disorders seen in childhood. However, the differential effects of individual AEDs remain uncertain. Data are accumulating which strongly suggest that these risks are highest in patients receiving polypharmacy and valproate. There is also modest evidence to suggest an increased risk for phenobarbital. While other older AEDs appear to carry some teratogenic risk, there is not adequate evidence to further stratify their risk. Clinical and basic science research regarding newer AEDs suggests equivalent, if not safer, profiles compared with older AEDs, but these data are inconclusive. Management of women with epilepsy should include a discussion of these risks, prophylactic treatment with folic acid, and the minimal use of polypharmacy and valproate needed to maintain optimum seizure control.

Contribution of IL-6 to the Hsp72, Hsp25, and AlphaB-crystallin [corrected] Responses to Inflammation and Exercise Training in Mouse Skeletal and Cardiac Muscle

The heat shock proteins (Hsps) Hsp72, Hsp25, and alphaB-crystallin (alphaB C) [corrected]may protect tissues during exercise and/or inflammatory insults; however, no studies have investigated whether exercise training increases both basal and inflammation-induced expression of these Hsps in skeletal or cardiac muscle. IL-6 is produced by muscle during both exercise and inflammation and has been shown to modulate Hsp expression. These studies tested the hypothesis that voluntary wheel running (RW) increases basal and inflammation-induced Hsp72, Hsp25, and alphaB C [corrected] protein through an IL-6-dependent mechanism. We compared Hsp72, Hsp25, alphaB C, [corrected] and IL-6 protein levels 4 h after systemic inflammation induced by lipopolysaccharide (LPS) in skeletal and cardiac muscles of wild-type (IL-6(+/+)) and IL-6 deficient (IL-6(-/-)) mice after 2 wk of RW or normal cage activity (Sed). LPS significantly increased skeletal Hsp72 and Hsp25 relative to saline in Sed IL-6(+/+), but not IL-6(-/-) mice. LPS increased Hsp72 relative to saline in Sed IL-6(+/+) cardiac muscle. RW increased basal Hsp72, Hsp25, and alphaB C [corrected] in skeletal muscle in IL-6(+/+) and IL-6(-/-) mice. However, LPS was not associated with increases in any Hsp in RW IL-6(+/+) or IL-6(-/-) mice. LPS increased IL-6 protein in skeletal muscle and plasma in Sed and RW groups, with a significantly greater response in RW. The major results provide the first in vivo evidence that the absence of IL-6 is associated with reduced skeletal muscle Hsp72 and Hsp25 responses to LPS, but that IL-6 is not required for exercise-induced Hsp upregulation in skeletal or cardiac muscle.

Applicability of NINDS-sponsored Studies to Community-based Physician Involvement

The National Institute of Neurological Disorders and Stroke (NINDS) Clinical Trials Group established the Clinical Research Collaboration (CRC) Project in 2005 to increase community-based physician involvement in NINDS-sponsored research.

Does Diabetes Affect Weight Loss After Gastric Bypass?

Weight loss in diabetics improves glycemic control. We investigated whether diabetes mellitus (DM) adversely affects postgastric bypass weight loss.

Ethical and Regulatory Issues Related to Pregnancy Registries and Their Outcomes

Pregnancy registries should be devised so that the interests of science, society, and the individual are all considered. For example, there may be ethical issues that relate to how women are chosen to participate in the registry and how informed consent is obtained. In most cases, consent is required for both the mother and the infant. Some institutional review boards will require that consent be obtained by someone other than the woman's physician. Once data are obtained, there may be an issue as to when results should be released. Options are to release data when there is the first indication of a concerning finding, thereby potentially preventing exposure in the largest number of women, versus waiting until the finding is absolutely confirmed. In a related issue, there are questions of when and how regulatory agencies should change labeling based on findings.

Effect of Stratospheric Ozone Depletion and Enhanced Ultraviolet Radiation on Marine Bacteria at Palmer Station, Antarctica in the Early Austral Spring

We investigated the interactions between ozone-depleted air masses and subsequent changes in UVB on marine bacterial abundance and production at Palmer Station, Antarctica from September to November 1999. During periods of low total column ozone (TCO), bacterial cell concentrations declined by 57%. Photoinhibition of bacterial [(3)H]-leucine (Leu) and [(3)H]-thymidine (TdR) incorporation due to UVB was greatest during periods of low TCO in September and early October. During diel ( approximately 28 h) exposure experiments, light treatment samples exhibited >75-100% inhibition of TdR incorporation by mid-afternoon. Leu incorporation exhibited maximum inhibition (50-100%) at sunset and early evening hours. Leu and TdR incorporation in light treatment samples did not exhibit recovery during subsequent periods of darkness. Bacterial Leu and TdR incorporation rates were inversely related to Setlow Dose during a period of recovery from low TCO. These data further suggested a threshold exposure below which bacterial Leu and TdR incorporation recovered rapidly. Recovery of bacterial production after acute Setlow Dose exposures lagged recovery of TCO and was linearly related to TCO measured 2 days previously. This lag in recovery may have resulted from the energetically expensive repair of UVR-induced DNA damage acquired during periods of low TCO.

Impact of Ambulance Crew Configuration on Simulated Cardiac Arrest Resuscitation

Despite the widespread use of both two paramedic and single paramedic ambulance crews, there is little evidence regarding differences between these two staffing configurations in the delivery of patient care.

Hitting the Target: Why Existing Measures of "religiousness" Are Really Reverse-scored Measures of "secularism"

Over 100 measures of religiousness and spirituality are used in research investigating the associations between religion and health. These measures are often used to assess "religiousness in general," but this approach lumps together widely divergent worldviews in ways that can distort religion beyond recognition. The authors suggest that the existing measures of religiousness are perhaps better understood as reverse-coded measures of "secularism." This argument suggests that the existing data regarding religiousness and health might be best interpreted as demonstrating a small, robust health liability associated with a deliberately secular worldview. If true, this conclusion might change the direction of future research, and it would imply that meaningful inferences about the health associations of religious practice will depend on developing tools that measure specific religions in their particularity.

10th Anniversary Critical Review: The Tissue-residue Approach for Toxicity Assessment: Concepts, Issues, Application, and Recommendations

The tissue-residue approach for toxicity assessment (TRA) is simply the use of tissue concentrations as the dose metric for characterizing toxicant potency. There are several advantages to using tissue residues over exposure concentrations (e.g., water, sediment, and diet) to calculate toxicity metrics. These include a large reduction in toxic response variability among all species for a given compound, an improved ability to address mixture toxicity, an increased use of information on modes and mechanisms of toxic action, a likely reduction in the number of species needed to characterize toxicant potency, the potential to improve ecological risk assessments, and the generation of more scientifically defensible tissue, water, and sediment toxicity guidelines or criteria. A keystone concept for the TRA is that the body/tissue residue reflects the target "dose" better than the traditional dose (e.g., water, air, soil/sediment, or diet) because the closer the dose surrogate is to the actual site of toxic action the less it is influenced by myriad modifying factors. Our goal for this review is to present the concepts and issues associated with the TRA and discuss some of the potential applications and expected improvements to the field of environmental toxicology that we believe will promote enhanced protection for species and ecosystems.

Measuring Religiousness in Health Research: Review and Critique

Although existing measures of religiousness are sophisticated, no single approach has yet emerged as a standard. We review the measures of religiousness most commonly used in the religion and health literature with particular attention to their limitations, suggesting that vigilance is required to avoid over-generalization. After placing the development of these scales in historical context, we discuss measures of religious attendance, private religious practice, and intrinsic/extrinsic religious motivation. We also discuss measures of religious coping, wellbeing, belief, affiliation, maturity, history, and experience. We also address the current trend in favor of multi-dimensional and functional measures of religiousness. We conclude with a critique of the standard, "context-free" approach aimed at measuring "religiousness-in-general", suggesting that future work might more fruitfully focus on developing ways to measure religiousness in specific, theologically relevant contexts.

Effects of in Utero Antiepileptic Drug Exposure

Recent studies demonstrate an increased teratogenic risk for valproate and a probable increased risk for phenobarbital. Carbamazepine and lamotrigine appear relatively safe; however, results are inconclusive concerning a specific risk for cleft lip/palate for both drugs as well as a dose-dependent effect for malformations associated with lamotrigine. Data regarding teratogenic risks for other antiepileptic drugs are inadequate. Additional studies are needed to delineate further the risks for all antiepileptic drugs and determine the underlying mechanisms.

Subjective Perception of Cognition is Related to Mood and Not Performance

Clinicians monitor cognitive effects of drugs primarily by asking patients to describe their side effects. We examined the relationship of subjective perception of cognition to mood and objective cognitive performance in healthy volunteers and neurological patients.

Cancer Prevention Knowledge of People with Profound Hearing Loss

Deaf persons, a documented minority population, have low reading levels and difficulty communicating with physicians. The effect of these on their knowledge of cancer prevention recommendations is unknown.

Sunlight-induced DNA Damage in Marine Micro-organisms Collected Along a Latitudinal Gradient from 70 Degrees N to 68 Degrees S

We examined ultraviolet radiation (UVR)-induced DNA damage in marine micro-organisms collected from surface seawater along a latitudinal transect in the Central Pacific Ocean from 70 degrees N to 68 degrees S. Samples were collected predawn and incubated under ambient UVR in transparent incubators at in situ temperatures until late afternoon at which time they were filtered into primarily bacterioplankton and eukaryotic fractions. Cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts [(6-4)PDs] were quantified in DNA extracts using radioimmunoassays. UVB was lowest in the polar regions and highest near the equator and correlations between UVB and DNA damage were observed. The eukaryotic fraction showed significant CPDs across the entire transect; (6-4)PDs were detected only in the tropics. The bacterial fraction showed no accumulation of (6-4)PDs at any latitude, although residual (6-4)PDs were observed. Bacterial cell volumes were greatest in the sub-Arctic and northern temperate latitudes and lower in the tropics and southern hemisphere, a unique observation that parallels Bergmann's rule. A strong negative correlation was observed between cell volume and CPDs. The environmental impact of solar UVR on marine micro-organisms in the open ocean is complex and our results suggest that several factors such as DNA repair, cell size, temperature, salinity, nutrients and species composition are important in determining relative sensitivity.

Universal Detection and Identification of Avian Influenza Virus by Use of Resequencing Microarrays

Zoonotic microbes have historically been, and continue to emerge as, threats to human health. The recent outbreaks of highly pathogenic avian influenza virus in bird populations and the appearance of some human infections have increased the concern of a possible new influenza pandemic, which highlights the need for broad-spectrum detection methods for rapidly identifying the spread or outbreak of all variants of avian influenza virus. In this study, we demonstrate that high-density resequencing pathogen microarrays (RPM) can be such a tool. The results from 37 influenza virus isolates show that the RPM platform is an effective means for detecting and subtyping influenza virus, while simultaneously providing sequence information for strain resolution, pathogenicity, and drug resistance without additional analysis. This study establishes that the RPM platform is a broad-spectrum pathogen detection and surveillance tool for monitoring the circulation of prevalent influenza viruses in the poultry industry and in wild birds or incidental exposures and infections in humans.

Glutamine Preserves Skeletal Muscle Force During an Inflammatory Insult

The purpose of this study was to test the hypothesis that acute glutamine (GLN) supplementation can counteract skeletal muscle contractile dysfunction occurring in response to inflammation by elevating muscle heat shock protein (Hsp) expression and reducing inflammatory cytokines. Mice received 5 mg/kg lipopolysaccharide (LPS) concurrently with 1 g/kg GLN or vehicle treatments. Plantarflexor isometric force production was measured at 2 hours post-injection. Blood and gastrocnemius muscles were collected, and serum and muscle tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and muscle Hsp70 and Hsp25 were quantified. Saline/LPS treatment was associated with a 33% reduction in maximal force and elevated serum TNF-alpha and IL-6. GLN completely prevented this force decrement with LPS. GLN was found to reduce muscle Hsp70 and IL-6, but only in the presence of LPS. GLN supplementation provides an effective, novel, clinically applicable means of preserving muscle force during acute inflammation. These data indicate that force preservation is not dependent on reductions in serum cytokines or muscle TNF-alpha, or elevated Hsp levels.

Association Between Obesity and Asthma in US Children and Adolescents

To explore the association between obesity and asthma in US children and adolescents with adjustment of other structural and behavioral factors.

Loss of Somatosensory-evoked Potentials and the Timing of Perception

To determine if patients with brain lesions who have a unilateral loss of their primary somatosensory-evoked potential (SSEP) have altered temporal perception.

A Prospective Study of Cognitive Fluency and Originality in Children Exposed in Utero to Carbamazepine, Lamotrigine, or Valproate Monotherapy

To investigate the differential effects of fetal exposure to antiepileptic drugs (AEDs) on cognitive fluency and flexibility in a prospective sample of children.

Diagnostic Utility of Wada Memory Asymmetries: Sensitivity, Specificity, and Likelihood Ratio Characterization

The authors used logistic regression, dichotomous and multiple level likelihood ratios, and receiver operating characteristic (ROC) analyses to examine Wada Memory Asymmetries (WMAs) in 324 patients who subsequently underwent temporal lobe (TL) surgery (left TL surgery = 172; right TL surgery = 152) using the Medical College of Georgia Wada protocol. Logistic regression correctly classified 84% of left TL patients and 77% of right TL patients using WMA. Corresponding dichotomous likelihood ratios (LRs) were: LR+ = 3.64; LR- = 0.21. The area under the curve using ROC was similarly highly significant (.886, standard error = .018, p < .001). When classifying patients using multiple level LRs, 40 left TL patients (23.3%) obtained asymmetry scores greater than +4, whereas no right TL patients obtained asymmetry scores in this range. No left TL patients obtained a WMA of -8 or less, although 12 right TL patients (7.9%) obtained a difference score of -8. Multiple level LRs indicate impressive diagnostic sensitivity for certain WMA ranges, greatly increasing the probability of undergoing either left or right TL surgery depending on WMA magnitude.

The Essential Neurologic Examination: What Should Medical Students Be Taught?

A Brief Computerized Self-screen for Dementia

Among his many contributions to the field of neuropsychology, Arthur Benton recognized the broad public health significance and unique ability of focused neuropsychological tests to screen for dementia. The need for validated screening tests for the presence of dementia will continue to grow as the cumulative prevalence of dementia grows and as our ability to treat or slow the progression of these diseases improves. We have developed a brief, self-administered computerized screening test for dementia, which is user friendly to the majority of elderly participants, including those with dementia. This test demonstrates comparable discriminant validity to the Mini Mental State Examination (MMSE), and its subscales correlate well with the traditional neuropsychological tests upon which it is based. We discuss its relative merits and limitations in comparison to other current instruments as well as suggesting future directions for this field.

Bariatric Surgery in Medicare Patients: Greater Risks but Substantial Benefits

Recent reports have documented greater mortality for bariatric surgery in Medicare (MC) patients compared with patients from other payors.

Becoming Physically Active After Bariatric Surgery is Associated with Improved Weight Loss and Health-related Quality of Life

The purpose of this study was to determine whether pre- to postoperative increases in physical activity (PA) are associated with weight loss and health-related quality of life (HRQoL) following bariatric surgery. Participants were 199 Roux-en-Y gastric bypass (RYGB) surgery patients. The International Physical Activity Questionnaire (IPAQ) was used to categorize participants into three groups according to their preoperative and /1-year postoperative PA level: (i) Inactive/Active (<200-min/week/>or=200-min/week), (ii) Active/Active (>or=200-min/week/>or=200-min/week) and (iii) Inactive/Inactive (<200-min/week/<200-min/week). The Medical Outcomes Study Short Form-36 (SF-36) was used to assess HRQoL. Analyses of covariance were conducted to examine the effects of PA group on weight and HRQoL changes. Inactive/Active participants, compared with Inactive/Inactive individuals, had greater reductions in weight (52.5 +/- 15.4 vs. 46.4 +/- 12.8 kg) and BMI (18.9 +/- 4.6 vs. 16.9 +/- 4.2 kg/m(2)). Weight loss outcomes in the Inactive/Active and Active/Active groups were similar to each other. Inactive/Active and Active/Active participants reported greater improvements than Inactive/Inactive participants on the mental component summary (MCS) score and the general health, vitality and mental health domains (P < 0.01). Although the direction of causation is not clear, these findings suggest that RYGB patients who become active postoperatively achieve weight losses and HRQoL improvements that are greater than those experienced by patients who remain inactive and comparable to those attained by patients who stay active. Future randomized controlled trials should examine whether assisting patients who are inactive preoperatively to increase their PA postoperatively contributes to optimization of weight loss and HRQoL outcomes.

Re: Conflicts of Interest for Authors of American Academy of Neurology Clinical Practice Guidelines

Cognitive Function at 3 Years of Age After Fetal Exposure to Antiepileptic Drugs

Fetal exposure of animals to antiepileptic drugs at doses lower than those required to produce congenital malformations can produce cognitive and behavioral abnormalities, but cognitive effects of fetal exposure of humans to antiepileptic drugs are uncertain.

Practice Parameter Update: Management Issues for Women with Epilepsy--focus on Pregnancy (an Evidence-based Review): Vitamin K, Folic Acid, Blood Levels, and Breastfeeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society

To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy.

Practice Parameter Update: Management Issues for Women with Epilepsy--focus on Pregnancy (an Evidence-based Review): Teratogenesis and Perinatal Outcomes: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society

To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy.

Practice Parameter Update: Management Issues for Women with Epilepsy--focus on Pregnancy (an Evidence-based Review): Obstetrical Complications and Change in Seizure Frequency: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society

To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy in WWE compared to other women, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy.

Antiepileptic Drug Use in Women of Childbearing Age

Research on antiepileptic drug (AED) teratogenesis has demonstrated an increased risk for valproate. The impact of these findings on current AED prescribing patterns for women of childbearing age with epilepsy is uncertain. The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study is an ongoing prospective multicenter observational investigation that enrolled pregnant women with epilepsy on the most common AED monotherapies from October 1999 to February 2004 (carbamazepine, lamotrigine, valproate, and phenytoin). A 2007 survey of AED use in women of childbearing age at eight NEAD centers found a total of 932 women of childbearing age with epilepsy (6% taking no AED, 53% monotherapy, 41% polytherapy). The most common monotherapies were lamotrigine or levetiracetam. Since 2004, prescriptions of carbamazepine, phenytoin, and valproate have decreased, whereas those for levetiracetam have increased. Except for the top two AED monotherapies, there were marked differences in other monotherapies and in polytherapies between U.S. and UK centers. Future investigations are needed to examine reasons for drug choice.

Drain Amylase Levels Are an Adjunct in Detection of Gastrojejunostomy Leaks After Roux-en-Y Gastric Bypass

Because anastomotic leaks after gastric bypass surgery can have devastating consequences for the patient, early detection is highly desirable. This and many other bariatric surgical centers have discontinued routine use of upper gastrointestinal contrast x-ray because of the lack of cost-effectiveness, discomfort to the patient, and the failure of the study to detect some leaks. We postulated that drain amylase levels from a juxta-anastomotic drain would detect the presence of salivary amylase and be a sensitive test for gastrojejunostomy leak.

Management Issues for Women with Epilepsy-Focus on Pregnancy (an Evidence-based Review): I. Obstetrical Complications and Change in Seizure Frequency: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. The committee evaluated the available evidence according to a structured literature review and classification of relevant articles. For WWE who are taking antiepileptic drugs (AEDs), there is probably no substantially increased risk (>2 times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (>1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. WWE should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84-92%) of remaining seizure-free during pregnancy. WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery.

Management Issues for Women with Epilepsy-Focus on Pregnancy (an Evidence-based Review): II. Teratogenesis and Perinatal Outcomes: Report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurology and the American Epilepsy Society

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including antiepileptic drug (AED) teratogenicity and adverse perinatal outcomes. It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine (CBZ), and possibly compared to phenytoin (PHT) or lamotrigine (LTG). It is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. AED polytherapy probably contributes to the development of MCMs and reduced cognitive outcomes compared to monotherapy. Intrauterine exposure to VPA monotherapy probably reduces cognitive outcomes and monotherapy exposure to PHT or phenobarbital (PB) possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. If possible, avoidance of VPA and AED polytherapy during the first trimester of pregnancy should be considered to decrease the risk of MCMs. If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered and avoidance of PHT and PB throughout pregnancy may be considered to prevent reduced cognitive outcomes.

Management Issues for Women with Epilepsy--focus on Pregnancy (an Evidence-based Review): III. Vitamin K, Folic Acid, Blood Levels, and Breast-feeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast-milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in clinically important amounts. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4 mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of levetiracetam and oxcarbazepine (as MHD) levels may be considered. A paucity of evidence limited the strength of many recommendations.

Cognitive Abilities and Behaviour of Children Exposed to Antiepileptic Drugs in Utero

The last two decades have witnessed a growing concern over the treatment of epilepsy in women of childbearing age, with an increased risk of major congenital malformations and possible cognitive difficulties associated with certain antiepileptic drugs. The aim here is to review the literature regarding the possible cognitive and behavioural impact of exposure to antiepileptic drugs in utero.

Tailoring Elastic Properties of Silica Aerogels Cross-linked with Polystyrene

The effect of incorporating an organic linking group, 1,6-bis(trimethoxysilyl)hexane (BTMSH), into the underlying silica structure of a styrene cross-linked silica aerogel is examined. Vinyltrimethoxysilane (VTMS) is used to provide a reactive site on the silica backbone for styrene polymerization. Replacement of up to 88 mol % of the silicon from tetramethoxyorthosilicate with silicon derived from BTMSH and VTMS during the making of silica gels improves the elastic behavior in some formulations of the cross-linked aerogels, as evidenced by measurement of the recovered length after compression of samples to 25% strain. This is especially true for some higher density formulations, which recover nearly 100% of their length after compression to 25% strain twice. The compressive modulus of the more elastic monoliths ranged from 0.2 to 3 MPa. Although some of these monoliths had greatly reduced surface areas, changing the solvent used to produce the gels from methanol to ethanol increased the surface area in one instance from 6 to 220 m(2)/g with little affect on the modulus, elastic recovery, porosity, or density.

Structure-property Relationships in Porous 3D Nanostructures: Epoxy-cross-linked Silica Aerogels Produced Using Ethanol As the Solvent

Cross-linking silica aerogels with organic groups has been shown to improve the strength over un-cross-linked aerogels by as much as 2 orders of magnitude. Previous cross-linking chemistry has been developed using solvents specifically chosen to dissolve the monomers and accommodate the reaction temperature. Because the process of making the aerogels requires so much solvent, it is of interest to consider less toxic solvents such as ethanol to increase safety and enhance scale up. To this end, two different epoxy precursors with suitable solubility in ethanol were evaluated as cross-linkers for silica gels prepared from (3-aminopropyl)triethoxysilane and tetraethylorthosilicate. In addition, 1,6-bis(trimethoxysilyl)hexane (BTMSH) was used as an additive in the underlying silica structure to add flexibility to the aerogels. It was found that the ethanol-derived aerogels exhibited more shrinkage than those prepared from other solvents but that including BTMSH in the aerogels significantly reduced this shrinkage. Inclusion of BTMSH also imparted the ability of the aerogel monoliths to recover elastically when compressed up to 50% strain. In addition, optimized cross-linked aerogels prepared in this study have mechanical properties comparable to those using other more undesirable solvents and cross-linkers.

Flexible Nanofiber-reinforced Aerogel (xerogel) Synthesis, Manufacture, and Characterization

Silica aerogels are sol-gel-derived materials consisting of interconnected nanoparticle building blocks that form an open and highly porous three-dimensional silica network. Flexible aerogel films could have wide applications in various thermal insulation systems. However, aerogel thin films produced with a pure sol-gel process have inherent disadvantages, such as high fragility and moisture sensitivity, that hinder wider applications of these materials. We have developed synthesis and manufacturing methods to incorporate electrospun polyurethane nanofibers into the cast sol film prior to gelation of the silica-based gel in order to reinforce the structure and overcome disadvantages such as high fragility and poor mechanical strength. In this method, a two-stage sol-gel process was employed: (1) acid-catalyzed tetraethyl orthosilicate hydrolysis and (2) base-catalyzed gelation. By precisely controlling the sol gelation kinetics with the amount of base present in the formulation, nanofibers were electrospun into the sol before the onset of the gelation process and uniformly embedded in the silica network. Nanofiber reinforcement did not alter the thermal conductivity and rendered the final composite film bendable and flexible.

Testing and Validation of High Density Resequencing Microarray for Broad Range Biothreat Agents Detection

Rapid and effective detection and identification of emerging microbiological threats and potential biowarfare agents is very challenging when using traditional culture-based methods. Contemporary molecular techniques, relying upon reverse transcription and/or polymerase chain reaction (RT-PCR/PCR) provide a rapid and effective alternative, however, such assays are generally designed and optimized to detect only a limited number of targets, and seldom are capable of differentiation among variants of detected targets. To meet these challenges, we have designed a broad-range resequencing pathogen microarray (RPM) for detection of tropical and emerging infectious agents (TEI) including biothreat agents: RPM-TEI v 1.0 (RPM-TEI). The scope of the RPM-TEI assay enables detection and differential identification of 84 types of pathogens and 13 toxin genes, including most of the class A, B and C select agents as defined by the Centers for Disease Control and Prevention (CDC, Atlanta, GA). Due to the high risks associated with handling these particular target pathogens, the sensitivity validation of the RPM-TEI has been performed using an innovative approach, in which synthetic DNA fragments are used as templates for testing the assay's limit of detection (LOD). Assay specificity and sensitivity was subsequently confirmed by testing with full-length genomic nucleic acids of selected agents. The LOD for a majority of the agents detected by RPM-TEI was determined to be at least 10(4) copies per test. Our results also show that the RPM-TEI assay not only detects and identifies agents, but is also able to differentiate near neighbors of the same agent types, such as closely related strains of filoviruses of the Ebola Zaire group, or the Machupo and Lassa arenaviruses. Furthermore, each RPM-TEI assay results in specimen-specific agent gene sequence information that can be used to assess pathogenicity, mutations, and virulence markers, results that are not generally available from multiplexed RT-PCR/PCR-based detection assays.

No Kidding: High Risk of Cognitive Difficulty in New-onset Pediatric Epilepsy

Field Emission and Radial Distribution Function Studies of Fractal-like Amorphous Carbon Nanotips

The short-range order of individual fractal-like amorphous carbon nanotips was investigated by means of energy-filtered electron diffraction in a transmission electron microscope (TEM). The nanostructures were grown in porous silicon substrates in situ within the TEM by the electron beam-induced deposition method. The structure factor S(k) and the reduced radial distribution function G(r) were calculated. From these calculations a bond angle of 124 degrees was obtained which suggests a distorted graphitic structure. Field emission was obtained from individual nanostructures using two micromanipulators with sub-nanometer positioning resolution. A theoretical three-stage model that accounts for the geometry of the nanostructures provides a value for the field enhancement factor close to the one obtained experimentally from the Fowler-Nordheim law.

Increased Susceptibility of Human Small Airway Epithelial Cells to Apoptosis After Long Term Arsenate Treatment

Inorganic arsenic (arsenate and arsenite) are well known human carcinogens. Apoptosis is a normal biological process that is involved in regulating cell development and differentiation, and is an important protective response to cell injury. The aim of this study was to determine the long term arsenic effect on human small airway epithelial cells (SAEC) by analyzing two distinct apoptosis-inducing agents, Fas ligand (Fas L), which evokes death receptor-mediated apoptosis, and hydrogen peroxide H2O2, which induces apoptosis mediated by reactive oxygen species (ROS). The SAEC were continuously exposed to 0.5 microg/mL arsenic for 28 weeks, and apoptosis was examined after 24 h treatment with either Fas L or H2O2. SAEC displayed decreased cell viability and increased apoptosis after treatment with Fas L and H2O2, compared to non-arsenic treated control cells. Furthermore, treatment of these arsenic-exposed SAEC with Fas L or H2O2 induced cleavage of the DNA damage recognition protein, poly (ADP-ribose) polymerase (PARP), and the 'effector' caspase, Caspase-3, both canonical indicators of apoptosis. We observed increased phosphorylation of p38, a member of the MAP kinase family, following treatment with Fas L or H2O2. To confirm the involvement of p38 in the regulation of apoptosis we pretreated cells with the p38 kinase inhibitor, SB 203580 and observed a significant decrease in apoptosis.

Predicting the Biological Condition of Streams: Use of Geospatial Indicators of Natural and Anthropogenic Characteristics of Watersheds

We developed and evaluated empirical models to predict biological condition of wadeable streams in a large portion of the eastern USA, with the ultimate goal of prediction for unsampled basins. Previous work had classified (i.e., altered vs. unaltered) the biological condition of 920 streams based on a biological assessment of macroinvertebrate assemblages. Predictor variables were limited to widely available geospatial data, which included land cover, topography, climate, soils, societal infrastructure, and potential hydrologic modification. We compared the accuracy of predictions of biological condition class based on models with continuous and binary responses. We also evaluated the relative importance of specific groups and individual predictor variables, as well as the relationships between the most important predictors and biological condition. Prediction accuracy and the relative importance of predictor variables were different for two subregions for which models were created. Predictive accuracy in the highlands region improved by including predictors that represented both natural and human activities. Riparian land cover and road-stream intersections were the most important predictors. In contrast, predictive accuracy in the lowlands region was best for models limited to predictors representing natural factors, including basin topography and soil properties. Partial dependence plots revealed complex and nonlinear relationships between specific predictors and the probability of biological alteration. We demonstrate a potential application of the model by predicting biological condition in 552 unsampled basins across an ecoregion in southeastern Wisconsin (USA). Estimates of the likelihood of biological condition of unsampled streams could be a valuable tool for screening large numbers of basins to focus targeted monitoring of potentially unaltered or altered stream segments.

Hepatic Drug-metabolizing Enzyme Induction and Implications for Preclinical and Clinical Risk Assessment

Hepatic drug metabolizing enzyme (DME) induction complicates the development of new drugs owing to altered efficacy of concomitant treatments, reduction in exposure resulting from autoinduction, and potential generation of toxic metabolites. Risk assessment of DME induction during clinical evaluation is confounded by several uncertainties pertaining to hazard identification and dose response analysis. Hepatic DME induction rarely leads to clinical evidence of altered metabolism and toxicity in the patient, which typically occur only if the DME induction is relatively severe. High drug doses are associated with a greater likelihood of hepatic DME induction and downstream effects; therefore, drugs of low potency requiring higher dosing tend to lead to a greater risk of drug-drug interactions. Vigilance in clinical trials for increased or diminished drug effect and, specifically, pharmacokinetic studies in the presence of other drugs and concomitant diseases are necessary for a drug risk assessment profile. Efforts to remove hepatic DME-inducing drugs from development can be facilitated with current in vitro and in vivo assessments and will improve with the development of newer technologies. A carefully tailored case-by-case approach will lead to the development of efficacious drugs with an acceptable risk/benefit profile available to patients.

In Situ Biomonitoring of Juvenile Chinook Salmon (Onchorhynchus Tshawytscha) Using Biomarkers of Chemical Exposures and Effects in a Partially Remediated Urbanized Waterway of the Puget Sound, WA

In situ biomonitoring has been used to assess the effects of pollution on aquatic species in heavily polluted waterways. In the current study, we used in situ biomonitoring in conjunction with molecular biomarker analysis to determine the effects of pollutant exposure in salmon caged in the Duwamish waterway, a Pacific Northwest Superfund site that has been subject to remediation. The Duwamish waterway is an important migratory route for Pacific salmon and has received historic inputs of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Juvenile pre-smolt Chinook salmon (Oncorhynchus tshawytscha) caged for 8 days in the three contaminated sites in close proximity within the Duwamish were analyzed for steady state hepatic mRNA expression of 7 exposure biomarker genes encompassing several gene families and known to be responsive to pollutants, including cytochrome P4501A (CYP1A) and CYP2K1, glutathione S-transferase pi class (GST-pi), microsomal GST (mGST), glutamylcysteine ligase catalytic subunit (GCLC), UDP-glucuronyltransferase family 1 (UDPGT), and type 2 deiodinase (type 2 DI, or D2). Quantitation of gene expression was accomplished by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in assays developed specifically for Chinook salmon genes. Gill PAH-DNA adducts were assessed as a chemical effects biomarker using (32)P-postlabeling. The biomarkers in the field-caged fish were analyzed with respect to caged animals maintained at the hatchery receiving flow-through water. Chemical analysis of sediment samples from three field sampling sites revealed relatively high concentrations of total PAHs in one site (site B2, 6711ng/g dry weight) and somewhat lower concentrations of PAHs in two adjacent sites (sites B3 and B4, 1482 and 1987ng/g, respectively). In contrast, waterborne PAHs at all of the sampling sites were relatively low (<1ng/L). Sediment PCBs at the sites ranged from a low of 421ng/g at site B3 to 1160ng/g at site B4, and there were no detectable waterborne PCBs at any of the sites (detection limit=10ng/L). There were no significant differences (p<0.05) in biomarker gene expression in the Duwamish-caged fish relative to controls, although there was a pattern of gene expression suppression at site B3, the most heavily PAH-enriched site. The lack of a marked perturbation of mRNA biomarkers was consistent with relatively low levels of gill PAH-DNA adduct levels that did not differ among caged reference and field fish, and which were also consistent with relatively low waterborne concentrations of chemicals. The results of our study suggest a low bioavailability of sediment pollutants in caged juvenile Chinook potentially reflecting low waterborne exposures occurring at contaminated sites within the Duwamish waterway that have undergone partial remediation.

How Localized is Localization-related Epilepsy?

Fall Risk Assessment in the Outpatient Setting

Bradycardia During Induction of Anesthesia with Sevoflurane in Children with Down Syndrome

Bradycardia is a complication associated with inhaled induction of anesthesia with halothane in children with Down syndrome. Although bradycardia has been reported after anesthetic induction with sevoflurane in these children, the incidence is unknown.

Bioaccumulation of Polychlorinated Biphenyls in Juvenile Chinook Salmon (Oncorhynchus Tshawytscha) Outmigrating Through a Contaminated Urban Estuary: Dynamics and Application

A field study was conducted to examine bioaccumulation of polychlorinated biphenyls (PCBs) for hatchery-raised and naturally reared (wild) ocean-type juvenile chinook salmon outmigrating through the Lower Duwamish Waterway (LDW), a contaminated urban estuary in Seattle, WA, USA. These results show differences in bioaccumulation of PCBs over time and space in this estuary, which may also occur for any contaminant that is distributed heterogeneously in this system. Highly mobile, outmigrating salmon accumulated approximately 3-5 times more PCBs on the east side of the LDW than fish on the west side, which is supported by an almost identical difference in mean sediment concentrations. The tPCB concentration data suggest that for most of the spring and early summer, juvenile chinook were likely segregated between the east and west side of the LDW, but may have crossed the channel later in the year as larger fish. Additionally, we used biota-sediment accumulation factors to assess the relative degree of bioaccumulation and explore these factors as potential metrics for predicting adverse sediment concentrations. These results highlight the importance of time and space in sampling design for a highly mobile species in a heterogeneous estuary.

Screening for Chronic Kidney Disease in the Ambulatory HIV Population

In 2005, the Infectious Disease Society of America published a guideline recommending that all patients with human immunodeficiency virus (HIV) be screened for kidney disease. We initiated a screening program for kidney disease in a dedicated HIV clinic that follows 1,631 patients.

Analysis of Factors Associated with Durable Remission of Diabetes After Roux-en-Y Gastric Bypass

Data on the durability of remission of type 2 diabetes mellitus (T2DM) after gastric bypass are limited. Our purpose was to identify the rate of long-term remission of T2DM and the factors associated with durable remission.

Reinforced Thermoplastic Polyimide with Dispersed Functionalized Single Wall Carbon Nanotubes

Molecular pi-complexes were formed from pristine HiPCO single- wall carbon nanotubes (SWCNTs) and 1-pyrene- N-(4-N'-(5-norbornene-2,3-dicarboxyimido)phenyl butanamide, 1. Polyimide films were prepared with these complexes as well as uncomplexed SWCNTs and the effects of nanoadditive addition on mechanical, thermal, and electrical properties of these films were evaluated. Although these properties were enhanced by both nanoadditives, larger increases in tensile strength and thermal and electrical conductivities were obtained when the SWCNT/1 complexes were used. At a loading level of 5.5 wt %, the T(g) of the polyimide increased from 169 to 197 degrees C and the storage modulus increased 20-fold (from 142 to 3045 MPa). The addition of 3.5 wt % SWCNT/1 complexes increased the tensile strength of the polyimide from 61.4 to 129 MPa; higher loading levels led to embrittlement and lower tensile strengths. The electrical conductivities (DC surface) of the polyimides increased to 1 x 10(-4) Scm(-1) (SWCNT/1 complexes loading level of 9 wt %). Details of the preparation of these complexes and their effects on polyimide film properties are discussed.

Thioether Benzenesulfonamide Inhibitors of Carbonic Anhydrases II and IV: Structure-based Drug Design, Synthesis, and Biological Evaluation

A novel series of potent thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV was discovered using structure-based drug design. Synthesis, structure-activity relationship, and optimization of physicochemical properties are described. Low nanomolar potency was achieved, and selected compounds with improved thermodynamic solubility showed promising in vitro inhibition of carbonic anhydrase activity in rabbit iris ciliary body homogenate.

Elastic Behavior of Methyltrimethoxysilane Based Aerogels Reinforced with Tri-isocyanate

The elastic properties and/or flexibility of polymer reinforced silica aerogels having methyltrimethoxysilane (MTMS) and bis(trimethoxysilylpropyl)amine (BTMSPA) making up the silica structure are examined. The dipropylamine spacer from BTMSPA is used both to provide a flexible linking group in the silica structure, and as a reactive site via its secondary amine for reaction with a tri-isocyanate, Desmodur N3300A. The tri-isocyanate provides an extended degree of branching or reinforcement, resulting in increased compressive strength of the aerogel monoliths while the overall flexibility arising from the underlying silica structure is maintained. The compressive moduli of the reinforced aerogel monoliths in this study range from 0.001 to 158 MPa. Interestingly, formulations across this entire range of modulus recover nearly all of their length after two compressions to 25% strain. Differences in pore structure of the aerogels due to processing conditions and solvent are also discussed.

Electroencephalographic Seizures After Neonatal Cardiac Surgery with High-flow Cardiopulmonary Bypass

Postoperative electroencephalographic (EEG) seizures are reported to occur in 14% to 20% of neonates after cardiac surgery with cardiopulmonary bypass (CPB). EEG seizures are associated with prolonged deep hypothermic circulatory arrest and with adverse long-term neurodevelopmental outcomes. We performed video/EEG monitoring before and for 72 hours after neonatal cardiac surgery, using a high-flow CPB protocol and cerebral oxygenation monitoring, to ascertain incidence, severity, and factors associated with EEG seizures.

Emotional Indifference in Alzheimer's Disease

One of the most common and disabling symptoms of Alzheimer's disease is apathy. Patients with Alzheimer's disease might appear apathetic for several reasons, including deficits in emotional communication, presence of depression, perceptual-semantic-cognitive deficits, and a degeneration of areas of the brain important in experiencing emotions. The purpose of this study was to learn if patients with Alzheimer's disease have a reduction in the depth of their emotional experiences. Participants with Alzheimer's disease and healthy comparison subjects were asked to view pleasant and unpleasant pictures and to rate these pictures by making a mark on pieces of paper that had a happy face on one end (proximal or distal) and a sad face at the other end. The more pleasant they found this picture, the closer their mark should be to the happy face and vice versa. Patients with Alzheimer's disease judged these pictures' emotional valence as less intense than did the comparison subjects and also made more valence-inconsistent responses. These results might have been induced by impaired picture comprehension or a reduction of emotional experiences induced by degeneration of the limbic-cortical-reticular networks.

Anxiety Disorders, Subsyndromic Depressive Episodes, and Major Depressive Episodes: Do They Differ on Their Impact on the Quality of Life of Patients with Epilepsy?

To compare the impact of anxiety disorders, major depressive episodes (MDEs), and subsyndromic depressive episodes (SSDEs) on the quality of life of patients with epilepsy (PWEs), and to identify the variables predictive of poor quality of life.

Influence of Growth Temperature and Starvation State on Survival and DNA Damage Induction in the Marine Bacterium Sphingopyxis Alaskensis Exposed to UV Radiation

Despite the considerable volume of literature describing the individual effects of temperature or UV light on aquatic bacteria, little is known about their combined effects. The current study was conducted to learn about the effects of growth temperature and duration of starvation on the response of a marine bacterium, Sphingopyxis alaskensis to UV-B or simulated solar radiation. Cells grown at 12 degrees C or 24 degrees C, and harvested at early or late stationary phase, were exposed to UV-B or simulated solar radiation (>290 nm). The predominant forms of UV-induced DNA damage, namely cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts (6-4PP s), were quantified using a HPLC-mass spectrometry. While the commonly accepted view that DNA damage induced by UV-B radiation is temperature-independent, we observed in S. alaskensis that the yield of photoproducts for 12 degrees C was generally lower than for cells grown at 24 degrees C. The relative distribution of DNA photoproducts also varied with growth temperature, with an increased formation of TC 6-4PP for late compared to early stationary phase cells. In contrast, with the exception of cultures grown at 12 degrees C exposed to simulated solar radiation, the duration of stationary phase had no effect on total photoproduct formation. Collectively, these data indicate that growth temperature has more effect than duration of starvation on the formation of photoproducts in S. alaskensis.

Public's View of Mental Health Services for the Elderly: Responses to Dear Abby

The need for adequate mental health services for older adults is an increasingly urgent issue as the life expectancy of Americans continues to extend; yet there are unresolved questions regarding the public's perception of service needs. The Group for the Advancement of Psychiatry collaborated with advice columnist Jeannie Phillips of "Dear Abby" to invite public feedback on mental health services for the elderly. Feedback was invited on access to services as well as perceived need for improvement in the quality or quantity of those services. The effort resulted in 800 responses that identified three primary issues: problems in accessing care, inadequate detection of mental health conditions by general practitioners, and a need for more psychotherapy services. It is hoped that this Open Forum will stimulate discussion throughout the country for the benefit of older persons with mental health needs as the country grapples with changes to come after the passage of health care reform.

Human RecQL4 Helicase Plays Critical Roles in Prostate Carcinogenesis

Prostate cancer is the second leading cause of cancer-associated deaths among men in the western countries. Here, we report that human RecQL4 helicase, which is implicated in the pathogenesis of a subset of cancer-prone Rothmund-Thomson syndrome, is highly elevated in metastatic prostate cancer cell lines. Increased RecQL4 expression was also detected in human prostate tumor tissues as a function of tumor grade with the highest expression level in metastatic tumor samples, suggesting that RecQL4 may be a potential prognostic factor for advanced stage of prostate cancer. Transient and stable suppression of RecQL4 by small interfering RNA and short hairpin RNA vectors drastically reduced the growth and survival of metastatic prostate cancer cells, indicating that RecQL4 is a prosurvival factor for prostate cancer cells. RecQL4 suppression led to increased poly(ADP-ribose) polymerase (PARP) synthesis and RecQL4-suppressed prostate cancer cells underwent an extensive apoptotic death in a PARP-1-dependent manner. Most notably, RecQL4 knockdown in metastatic prostate cancer cells drastically reduced their cell invasiveness in vitro and tumorigenicity in vivo, showing that RecQL4 is essential for prostate cancer promotion. Observation of a direct interaction of retinoblastoma (Rb) and E2F1 proteins with RecQL4 promoter suggests that Rb-E2F1 pathway may regulate RecQL4 expression. Collectively, our study shows that RecQL4 is an essential factor for prostate carcinogenesis.

Chinese Hamster Ovary Cells Can Produce Galactose-α-1,3-galactose Antigens on Proteins

How Have Electronic Medical Records Impacted Patient Care?

Effects of Breastfeeding in Children of Women Taking Antiepileptic Drugs

Breastfeeding is known to have beneficial effects, but there is concern that breastfeeding during antiepileptic drug (AED) therapy may be harmful to cognitive development. Animal and human studies have demonstrated that some AEDs can adversely affect the immature brain. However, no investigation has examined effects of breastfeeding during AED therapy on subsequent cognitive abilities in children.

Auditory Responsive Naming Versus Visual Confrontation Naming in Dementia

Dysnomia is typically assessed during neuropsychological evaluation through visual confrontation naming. Responsive naming to description, however, has been shown to have a more distributed representation in both fMRI and cortical stimulation studies. While naming deficits are common in dementia, the relative sensitivity of visual confrontation versus auditory responsive naming has not been directly investigated. The current study compared visual confrontation naming and auditory responsive naming in a dementia sample of mixed etiologies to examine patterns of performance across these naming tasks. A total of 50 patients with dementia of various etiologies were administered visual confrontation naming and auditory responsive naming tasks using stimuli that were matched in overall word frequency. Patients performed significantly worse on auditory responsive naming than visual confrontation naming. Additionally, patients with mixed Alzheimer's disease/vascular dementia performed more poorly on auditory responsive naming than did patients with probable Alzheimer's disease, although no group differences were seen on the visual confrontation naming task. Auditory responsive naming correlated with a larger number of neuropsychological tests of executive function than did visual confrontation naming. Auditory responsive naming appears to be more sensitive to effects of increased of lesion burden compared to visual confrontation naming. We believe that this reflects more widespread topographical distribution of auditory naming sites within the temporal lobe, but may also reflect the contributions of working memory and cognitive flexibility to performance.

Analysis of Ionizing Radiation-induced DNA Damage and Repair in Three-dimensional Human Skin Model System

Knowledge of cellular responses in tissue microenvironment is crucial for the accurate prediction of human health risks following chronic or acute exposure to ionizing radiation (IR). With this objective, we investigated the radio responses for the first time in three-dimensional (3D) artificial human skin tissue microenvironment after gamma-rays radiation. IR-induced DNA damage/repair response was assessed by immunological analysis of well-known DNA double strand break (DSB) repair proteins, i.e. 53BP1 and phosphorylated ataxia telangiectasia mutated(ser1981) (ATM(ser1981)). Efficient 53BP1 and phosphorylated ATM foci formation was observed in human EpiDerm tissue constructs after low and high doses of gamma-rays. Interestingly, EpiDerm tissue constructs displayed less 53BP1 and ATM foci number at all radiation doses (0.1, 1, 2.5 and 5 Gy) than that observed for 2D human fibroblasts. DSB repair efficiency judged by the disappearance of 53BP1 foci declined with increasing doses of gamma-rays and tissue constructs irradiated with 2.5 and 5 Gy of gamma-rays displayed 53BP1 foci persisting up to 72 h of analysis. Pretreatment of EpiDerm tissue constructs with LY294002, [an inhibitor of phosphatidylinositol-3 kinase and PI-3 kinase like kinases (PIKK)] completely abolished IR-induced 53BP1 foci formation and increased the apoptotic death. This observation indicates the importance of PIKK signalling pathway for efficient radiation responses in intact tissue constructs. In summary, we have successfully demonstrated the feasibility of monitoring the DNA damage response in human skin tissue microenvironment. In this system, 53BP1 can be used as a useful marker for monitoring the DSB repair efficiency.

Infantile Form of Scimitar Syndrome with Contralateral Pulmonary Vein Stenosis

Infantile scimitar syndrome (SS) carries significant mortality. Consistent management guidelines have not been well established, and outcomes continue to be disappointing. We present our experience managing an SS patient with complex anatomy who developed stenosis of the pulmonary veins contralateral to the hypoplastic lung.

Brain Function and Anatomy in Juvenile Myoclonic Epilepsy

Cognition Across the Lifespan: Antiepileptic Drugs, Epilepsy, or Both?

Cognitive problems in persons with epilepsy manifest over a lifetime; however, whether abnormal cognition in an individual with epilepsy is a result of comorbid brain substrate, the epilepsy itself or its underlying etiology, the antiepileptic agents used to control it, or a combination of these and other factors remains controversial. There is a continuing need for improved therapies to control seizures and reduce the incidence of adverse events, especially those involving the central nervous system that compromise attention, intelligence, language skills, verbal and nonverbal memory, executive function, and psychomotor speeds. Although cognitive decline typically occurs among patients with more severe epilepsy, physicians must judiciously select therapy with an eye toward not only controlling seizures but also ensuring that all patients retain as much function as possible throughout their lives.

DNA-dependent Protein Kinase (DNA-PK)-deficient Human Glioblastoma Cells Are Preferentially Sensitized by Zebularine

Brain tumor cells respond poorly to radiotherapy and chemotherapy due to inherently efficient anti-apoptotic and DNA repair mechanisms. This necessitates the development of new strategies for brain cancer therapy. Here, we report that the DNA-demethylating agent Zebularine preferentially sensitizes the killing of human glioblastomas deficient in DNA-dependent protein kinase (DNA-PK). In contrast to DNA-PK-proficient human glioblastoma cells (MO59K), cytotoxicity assay with increasing Zebularine concentrations up to 300 microM resulted in a specific elevation of cell killing in DNA-PK-deficient MO59J cells. Further, an elevated frequency of polyploid cells observed in MO59J cells after Zebularine treatment pointed out a deficiency in mitotic checkpoint control. Existence of mitotic checkpoint deficiency in MO59J cells was confirmed by the abnormal centrosome number observed in Zebularine-treated MO59J cells. Although depletion of DNA methyltransferase 1 by Zebularine occurred at similar levels in both cell lines, MO59J cells displayed increased extent of DNA demethylation detected both at the gene promoter-specific level and at the genome overall level. Consistent with increased sensitivity, deoxy-Zebularine adduct level in the genomic DNA was 3- to 6-fold higher in MO59J than in MO59K cells. Elevated micronuclei frequency observed after Zebularine treatment in MO59J cells indicates the impairment of DNA repair response in MO59J cells. Collectively, our study suggests that DNA-PK is the major determining factor for cellular response to Zebularine.

Theta Oscillations Mediate Interaction Between Prefrontal Cortex and Medial Temporal Lobe in Human Memory

The medial temporal lobe (MTL) and the prefrontal cortex (PFC) are known to be critical structures for human memory processes. Furthermore, it has been suggested that they are part of a memory network. Although memory-modulated interaction between PFC and MTL has been observed at the hemodynamic level, it remains unclear what the neuronal process is that mediates the communication between these 2 areas. Experiments in rodents suggest that field oscillations in the theta band (4-8 Hz) facilitate PFC-MTL interaction. No such evidence has been reported in humans. To address this problem, cortical electrical activity from MTL, PFC, and lateral temporal lobe was recorded from implanted electrode grids in 3 epilepsy patients performing a verbal free recall task. The data were analyzed using a parametric spectral method to obtain estimates of power, coherence, and Granger causality. A task-modulated increase in coherence values between PFC and MTL was seen during free recall as opposed to a baseline condition. Concurrently, the number of coherent PFC-MTL site pairs was significantly increased during recall. Granger causality analysis further revealed that the increased coherence is a consequence of higher bidirectional information flow between the 2 regions, with a generally greater driving from MTL to PFC, namely, (MTL-->PFC) > (PFC-->MTL).

Episcopal Measure of Faith Tradition: a Context-specific Approach to Measuring Religiousness

Precise measurement of religiousness remains a vexing problem. In addition to relying almost exclusively on self-report, existing measures of religiousness pay little attention to the specific context of religious belief, and this may override distinctive norms of particular faith traditions and potentially confound the conclusions drawn from such research. To address these limitations, the authors describe a modified form of narrative content analysis that could eventually sort respondents into distinct theological traditions. A pilot test among Episcopalians demonstrates encouraging reliability (kappa 0.74, 95% LCI 0.47, P < 0.0002), and tests for convergent and discriminate validity suggest that the context of religious belief is both relevant and insufficiently assessed by the existing paradigm of religious measurements. If validated in a religiously diverse sample, this approach could be combined with existing, context-free measures of religiousness to generate more meaningful findings.

Spirituality in Medical School Curricula: Findings from a National Survey

No systematic information exists on what U.S. medical schools are teaching on spirituality and health or on the attitudes of faculty toward inclusion of this subject in the medical curriculum. We systematically surveyed U.S. medical school deans and assessed both attitudes about and the extent to which spirituality is addressed in medical school curricula.

Statin-associated Myopathy and Its Exacerbation with Exercise

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are a common and effective treatment for hypercholesterolemia, with a low overall rate of side-effects. The most common complication is some degree of skeletal muscle myopathy, ranging from painless serum creatine kinase elevations to rhabdomyolysis. Unfortunately, the likelihood and/or severity of complications increases with the combination of statin treatment and physical activity. The specific pathways that mediate statin-associated myopathy are unclear, and research directly addressing the exacerbation with exercise is limited. Potential mechanisms include the induction of skeletal muscle fiber apoptosis, alterations in ubiquitin-proteasome pathway activity, mitochondrial dysfunction, and terpenoid depletion. In this review we provide an overview of research that specifically addresses the combination of statin-associated myopathy and physical activity and highlight some deficiencies in the available literature, as well as future directions for this important subset of statin-associated myopathy.

Is Antiepileptic Drug Use Related to Depression and Suicidal Ideation Among Patients with Epilepsy?

Depression and suicide are increased in patients with epilepsy. The U.S. Food and Drug Administration warns that antiepileptic drugs (AEDs) are associated with increased risk of suicidality. This study examines the relationship among depression, suicidal ideation, and AEDs in a prospective cohort of 163 patients with epilepsy from a registry at the University of Florida (January 2006 to August 2008). The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was used to measure mood and suicidal ideation across two time points (median = 154 days). Groups included: (1) No AED Change, (2) New AED Added, (3) AED Dose Increased, (4) AED Reduced/Stopped, (5) Multiple AED Changes, and (6) Combined Any AED Change (groups 2-5 combined). No group had worsening mood or suicidal ideation. Significant improvements in proportions of depression and suicidal ideation were seen only for the No AED Change group, which differed only with the AED Dose Increased group with respect to suicidal ideation.

Neurocognitive Effects of Brivaracetam, Levetiracetam, and Lorazepam

Brivaracetam (BRV) is a new anticonvulsant under development. Although BRV is an analog of levetiracetam (LEV), in addition to being an SV2A ligand, it also inhibits sodium channels in a voltage-dependent manner. The cognitive effects of BRV are uncertain.

The Clergy Occupational Distress Index (CODI): Background and Findings from Two Samples of Clergy

This study demonstrates the reliability and validity of the Clergy Occupational Distress Index (CODI). The five-item index allows researchers to measure the frequency that clergy, who traditionally have not been the subject of occupational health studies, experience occupational distress. We assess the reliability and validity of the index using two samples of clergy: a nationally representative sample of clergy and a sample of clergy from nine Protestant denominations. Exploratory factor analysis and Cronbach's scores are generated. Construct validity is measured by examining the association between CODI scores and depressive symptoms while controlling for demographic, ministerial, and health variables. In both samples, the five items of the CODI load onto a single factor and the Cronbach's alpha scores are robust. The regression model indicates that a high score on the CODI (i.e., more frequent occupational distress) is positively associated with having depressive symptoms within the last 4 weeks. The CODI can be used to identify clergy who frequently experience occupational distress and to understand how occupational distress affects clergy's health, ministerial career, and the functioning of their congregation.

Going Home: Identifying and Overcoming Barriers to Nursing Home Discharge

This article describes barriers to nursing home discharge encountered in an intervention designed to transition nursing home residents to the community. Staff in the intervention ("Project Home") provided intensive case management and discharge planning services to nursing home residents who expressed a desire to return to community-based living arrangements. Sixty program participants took part in the program evaluation that informs this article. With the exception of Medicaid status, no differences were found between the social, demographic, and health characteristics of individuals who remained in the nursing home and those who were discharged. A qualitative analysis was conducted to describe barriers to discharge and strategies intervention staff used to leverage each client's strengths and work around obstacles. Three main barriers to discharge were found: having an unstable or complex medical condition, lacking family or social support, and being unable to obtain suitable housing. Intervention staff advocated on the behalf of clients, encouraged clients to build skills toward independent living. and contributed extensive knowledge of local resources to advance client goals. Cases of successful transition suggest that a person-centered approach from intervention staff combined with a flexible organizational structure is a promising model for future interventions.

Abnormal Interictal Gamma Activity May Manifest a Seizure Onset Zone in Temporal Lobe Epilepsy

Even though recent studies have suggested that seizures do not occur suddenly and that before a seizure there is a period with an increased probability of seizure occurrence, neurophysiological mechanisms of interictal and pre-seizure states are unknown. The ability of mathematical methods to provide much more sensitive tools for the detection of subtle changes in the electrical activity of the brain gives promise that electrophysiological markers of enhanced seizure susceptibility can be found even during interictal periods when EEG of epilepsy patients often looks 'normal'. Previously, we demonstrated in animals that hippocampal and neocortical gamma-band rhythms (30-100 Hz) intensify long before seizures caused by systemic infusion of kainic acid. Other studies in recent years have also drawn attention to the fast activity (>30 Hz) as a possible marker of epileptogenic tissue. The current study quantified gamma-band activity during interictal periods and seizures in intracranial EEG (iEEG) in 5 patients implanted with subdural grids/intracranial electrodes during their pre-surgical evaluation. In all our patients, we found distinctive (abnormal) bursts of gamma activity with a 3 to 100 fold increase in power at gamma frequencies with respect to selected by clinicians, quiescent, artifact-free, 7-20 min "normal" background (interictal) iEEG epochs 1 to 14 hours prior to seizures. Increases in gamma activity were largest in those channels which later displayed the most intensive electrographic seizure discharges. Moreover, location of gamma-band bursts correlated (with high specificity, 96.4% and sensitivity, 83.8%) with seizure onset zone (SOZ) determined by clinicians. Spatial localization of interictal gamma rhythms within SOZ suggests that the persistent presence of abnormally intensified gamma rhythms in the EEG may be an important tool for focus localization and possibly a determinant of epileptogenesis.

Antiepileptic Drugs and Neurodevelopment: an Update

In utero exposure to some antiepileptic drugs (AEDs) is associated with an increased risk of impaired cognitive development. Specifically, valproate and polytherapy exposure are each associated with an increased risk of cognitive impairment in children compared with other antiepileptic medications. The data regarding the risk to neurocognitive development imposed by maternal use of other AEDs are conflicting or insufficient at this time to draw definitive conclusions. Behavioral dysfunction including autistic spectrum disorder is also associated with maternal use of AEDs during pregnancy. Whether treatment with AEDs during childhood permanently affects cognitive neurodevelopment is yet to be determined.

Synthesis, Optical Characterization, and Electrochemical Properties of Isomeric Tetraphenylbenzodifurans Containing Electron Acceptor Groups

Isomeric tetraphenylbenzodifuran systems, benzo[1,2-b:5,4]difuran and benzo[1,2-b:4,5]difuran, containing electron acceptor groups (CF(3), CN, and NO(2)) have been synthesized and studied. Their electronic absorption, fluorescence, two-photon absorption cross sections, and electrochemical properties were investigated. The absorption and emission maxima are red-shifted for the linear-conjugated systems in comparison with the corresponding isomer. Dual fluorescence was observed and the existence of a twisted intramolecular charge transfer state was confirmed by low-temperature emission experiments. Wide HOMO-LUMO energy gaps were obtained ranging from 2.53 to 3.28 eV. HOMO levels were found in the energy range of -6.03 to -6.63 eV while LUMO are within -2.55 to -3.52 eV.

P53-independent Downregulation of Histone Gene Expression in Human Cell Lines by High- and Low-let Radiation

Using microarrays to analyze differential gene expression as a function of p53 status and radiation quality, we observed downregulation of a large set of histone genes in p53 wild-type TK6 cells 24 h after exposure to equitoxic doses of high-LET (1.67 Gy 1 GeV/amu (56)Fe ions) or low-LET (2.5 Gy γ rays) radiation. Quantitative real-time PCR of specific subtypes of core (H2A, H2B, H3 and H4) and linker (H1) histones confirmed this result. DNA synthesis and histone gene expression are tightly coordinated during the S phase of the cell cycle, and both processes are regulated by cell cycle checkpoints in response to DNA damage caused by ionizing radiation. However, we observed similar repression of histone gene expression in both TK6 cells and their p53-null derivative NH32 after radiation exposure, although the histone gene expression was not decreased to the same extent in NH32 cells as it was in TK6 cells. We also found decreased histone gene expression that was dose- and time-dependent in the colon cancer cell line HCT116 and its p53-null derivative. These results show that both high- and low-LET radiation exposure negatively regulate histone gene expression in human lymphoblastoid and colon cancer cell lines independent of p53 status.

Relationship of Child IQ to Parental IQ and Education in Children with Fetal Antiepileptic Drug Exposure

Clinical trial designs need to control for genetic and environmental influences when examining cognitive outcomes in children for whom clinical considerations preclude randomization. However, the contributions of maternal and paternal IQ and education to pediatric cognitive outcomes are uncertain in disease populations. The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study is an ongoing prospective observational multicenter study in the United States and United Kingdom, which enrolled pregnant women with epilepsy to determine if differential long-term neurodevelopmental effects exist across four commonly used antiepileptic drugs. Here, we examined the relationship of IQ and education in both parents to child IQ at age 3 years. IQ and education for both parents were statistically correlated to child IQ. However, paternal IQ and education were not significant after accounting for maternal IQ effects. Because maternal IQ and education are independently related to child cognitive outcome, both should be assessed in studies investigating the effects of fetal drug exposures or other environmental factors that could affect the child's cognitive outcome.

Rethinking Professionalism in Medical Education Through Formation

BACKGROUND: Contemporary educational approaches to professionalism do not take into account the dominant influence that the culture of academic medicine has on the nascent professional attitudes, beliefs, and behaviors of medical learners. This article examines formation as an organizing principle for professionalism in medical education. Virtue, the foundation to understanding professionalism, is the habits and dispositions that are fostered in individuals but that are embedded in learning environments. Formation, the ongoing integration of an individual, growing in self-awareness and in recognition of a life of service, with others who share in the common mission of a larger group, depicts this process. One model of formation considers a continuum from novice to more advance stages that is predicated on rules that must be applied in greater contextually shaped situations. Within medical education, formation is the process by which lives of service are created and sustained by learning communities that promote human capacities for intuition, empathy, and compassion. An imagined curriculum in formation would link the lived experiences of mentors and learners with an interdisciplinary set of didactic materials in an intentionally progressive fashion.

Squeezing the Middleman: Ending Underhanded Dealing in the Pharmacy Benefit Management Industry Through Regulation

Pharmacy benefit management (PBM) companies are the middlemen of the pharmaceutical industry, designing plans for sponsors and insurers and pushing the products of manufacturers. Their unique position can often create conflicts of interest, which has been the basis of much litigation. This article reviews the structure of the PBM industry and analyzes concerns arising from its handling of prescription drug pricing, manufacturer rebates and discounts, and mail order pharmacies. After surveying several legislative proposals, it concludes with a comprehensive outline for legislation to eliminate underhanded dealing in the industry and lower the cost of prescription drugs.

Cognitive and Neurodevelopmental Effects of Antiepileptic Drugs

This article primarily represents the contributions of two young investigators to the understanding of the neuropsychological consequences of epilepsy and its treatment. The authors have reviewed two key areas of importance: the complex relationship between cognitive dysfunction and epilepsy and the risks of cognitive dysfunction in children as a consequence of in utero exposure to antiepileptic drug treatment. The work of two young investigators is presented and future research needs are outlined.

Transparent Large-strain Thermoplastic Polyurethane Magnetoactive Nanocomposites

Organically modified superparamagnetic MnFe(2)O(4)/thermoplastic polyurethane elastomer (TPU) nanocomposites (0.1-8 wt %) were prepared by solvent mixing followed by solution casting. Linear aliphatic alkyl chain modification of spherical MnFe(2)O(4) provided compatibility with the TPU containing a butanediol extended polyester polyol-MDI. All MnFe(2)O(4)/TPU nanocomposite films were superparamagnetic and their saturation magnetization, σ(s), increased with increasing MnFe(2)O(4) content. All nanocomposite films exhibited large deformations (>10 mm) under a magneto-static field. This is the first report of large actuation of magnetic nanoparticle nanocomposites at low-loading levels of 0.1 wt % (0.025 vol %). The maximum actuation deformation of the MnFe(2)O(4)/TPU nanocomposite films increased exponentially with increasing nanoparticle concentration. An empirical correlation between the maximum displacement, saturation magnetization, and magnetic nanoparticle loading is proposed. The cyclic deformation actuation of a 6 wt % surface modified MnFe(2)O(4)/TPU, in a low magnetic field 151 < B(y) < 303 Oe, exhibited excellent reproducibility and controllability. MnFe(2)O(4)/TPU nanocomposite films (0.1-2 wt %) were transparent and semitransparent over the wavelengths from 350 to 700 nm.

The α7β1-integrin Accelerates Fiber Hypertrophy and Myogenesis Following a Single Bout of Eccentric Exercise

The α(7)β(1)-integrin is a heterodimeric transmembrane protein that adheres to laminin in the extracellular matrix, representing a critical link that maintains structure in skeletal muscle. In addition to preventing exercise-induced skeletal muscle injury, the α(7)-integrin has been proposed to act as an intrinsic mechanosensor, initiating cellular growth in response to mechanical strain. The purpose of this study was to determine the extent to which the α(7)-integrin regulates muscle hypertrophy following eccentric exercise. Wild-type (WT) and α(7)-integrin transgenic (α(7)Tg) mice completed a single bout of downhill running exercise (-20°, 17 m/min, 60 min), and gastrocnemius-soleus complexes were collected 1, 2, 4, and 7 days (D) postexercise (PE). Maximal isometric force was maintained and macrophage accumulation was suppressed in α(7)Tg muscle 1D PE. Mean fiber cross-sectional area was unaltered in WT mice but increased 40% in α(7)Tg mice 7D PE. In addition, a rapid and striking fivefold increase in embryonic myosin heavy chain-positive fibers appeared in α(7)Tg mice 2D PE. Although Pax7-positive satellite cells were increased in α(7)Tg muscle 1D PE, the number of nuclei per myofiber was not altered 7D PE. Phosphorylation of mammalian target of rapamycin (mTOR) was significantly elevated in α(7)Tg 1D PE. This study provides the first demonstration that the presence of the α(7)β(1)-integrin in skeletal muscle increases fiber hypertrophy and new fiber synthesis in the early time course following a single bout of eccentric exercise. Further studies are necessary to elucidate the precise mechanism by which the α(7)-integrin can enhance muscle hypertrophy following exercise.

Lorazepam Effects on Word Memory Test Performance: a Randomized, Double-blind, Placebo-controlled, Crossover Trial

The Word Memory Test (WMT) is a common measure of symptom validity. To investigate the effects of acute benzodiazepines on WMT scores, oral lorazepam 2 mg (LOR) and placebo were administered 1 week apart in a randomized, double-blind, placebo-controlled, crossover study. A total of 28 participants completed the study and were administered the WMT during each drug condition. Within-participant comparisons of LOR vs placebo revealed significant LOR effects for Immediate Recognition (p = .007) and Consistency (p = .019), but not Delayed Recognition (p = .085). Significant LOR effects were present for Reaction Time Measures (Immediate Recognition RT, p = .013; Delayed Recognition RT, p = .001; Multiple Choice RT, p = .011) and Delayed Memory scores (Multiple Choice, p = .007; Paired Associates, p = .029; Free Recall, p = .001). A pattern similar to crossover results was detected for LOR vs placebo between-group differences for initial test assessment scores. When examined using publisher recommended cut scores for the principal WMT measures, there were six participants failing the WMT during initial LOR testing; all six subsequently performed in the normal range upon retesting with placebo. One participant failed WMT during placebo and obtained passing scores during LOR. These data indicate that multiple WMT measures may be affected by acute LOR dosing, and provide additional evidence that potential latent variables and their effects on both SVT performance and cognitive function should be part of the clinical decision-making process.

Fetal Antiepileptic Drug Exposure: Motor, Adaptive, and Emotional/behavioral Functioning at Age 3 Years

The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study is an ongoing prospective observational multicenter study in the United States and United Kingdom that enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study seeks to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, valproate). In this article, we examine fetal AED exposure effects on motor, adaptive, and emotional/behavioral functioning in 229 children who completed at least one of these tests at 3 years of age. Adjusted mean scores for the four AED groups were in the low average to average range for motor functioning, parental ratings of adaptive functioning, and parental ratings of emotional/behavioral functioning. A significant dose-related performance decline in motor functioning was seen for both valproate and carbamazepine. A significant dose-related performance decline in parental ratings of adaptive functioning was also seen for valproate, with a marginal performance decline evident for carbamazepine. Further, parents endorsed a significant decline in social skills for valproate that was dose related. Finally, on the basis of parent ratings of attention span and hyperactivity, children of mothers who took valproate during their pregnancy appear to be at a significantly greater risk for a future diagnosis of attention-deficit/hyperactivity disorder. Additional research is needed to confirm these findings, examine risks of other AEDs, define the risks in the neonate associated with AEDs for treatment of seizures, and determine the underlying mechanisms of adverse AED effects on the immature brain.

The {alpha}7{beta}1 Integrin Increases Muscle Hypertrophy Following Multiple Bouts of Eccentric Exercise

Mechanical stimuli increase skeletal muscle growth in an mTOR- and p70S6K-dependent manner. It has been proposed that costameric proteins at Z bands may sense and transfer tension to these initiators of protein translation, but few candidates have been identified. The purpose of this study was to determine if a role exists for the α7 integrin in the activation of hypertrophic signaling and growth following eccentric exercise training. Five wk old, wild type (WT) and α7BX2 integrin transgenic (α7Tg) mice were randomly assigned to one of two groups: 1) sedentary (SED) or 2) exercise training (EX). Exercise training consisted of downhill running 3 sessions/wk for 4 wk (-20(°), 17 m/min, 30 min). Downhill running was used to induce physiological mechanical strain. Twenty-four hr following the final training session, maximal isometric hindlimb plantarflexor force was measured. Gastrocnemius-soleus complexes were collected for further analysis of signaling changes, which included AKT, mTOR and p70S6K, and muscle growth. Despite increased p70S6K activity in WT/EX, no significant changes in CSA or force were observed in WT/EX compared to WT/SED. AKT, mTOR and p70S6K activation was higher, and whole muscle hypertrophy, relative muscle weight, myofibrillar protein, and force were significantly elevated in α7Tg/EX compared to α7Tg/SED. A marked increase in average myofiber CSA was observed in α7Tg/EX compared to all groups. Our findings demonstrate that the α7β1 integrin sensitizes skeletal muscle to mechanical strain and subsequent growth. Thus, the α7β1 integrin may represent a novel molecular therapy for the treatment of disuse muscle atrophy.

Networks, Cognition, and Epilepsy

Cognitive Effects of Carisbamate in Randomized, Placebo-controlled, Healthy-volunteer, Multidose Studies

Adverse cognitive effects are an important concern for drugs that influence the central nervous system. Carisbamate is a novel drug in development for treatment of seizures and neuropathic pain. Information on its cognitive effects is limited. Three controlled, multiple-dose, crossover studies with treatment durations of 5-9 days were designed to examine the cognitive effects of carisbamate on healthy volunteers. In one study, apparent dose-dependent effects on response, vigilance, and recognition speed were observed (1000 mg and 1500 mg/day). Carisbamate did not differ from placebo for most variables in the other two studies, but increased reaction time and reduced Sternberg memory were seen at higher dosages. Carisbamate did not produce clinically significant adverse effects on cognitive performance at doses <1000 mg/day. Effects were mild to modest at the higher doses tested.

Religiosity is an Important Part of Coping with Grief in Pregnancy After a Traumatic Second Trimester Loss

Women (n = 15) who were pregnant after a traumatic late pregnancy loss (termination because of fetal death or serious anomalies) completed psychometric screening tests and scales, including the Perinatal Grief Scale (PGS), the Impact of Event Scale (IES), the Duke Depression Inventory (DDI), the Generalized Anxiety Disorder-7 (GAD), and the Hoge Scale for Intrinsic Religiosity (IR). Despite a mean elapsed time since the prior loss of 27 (range, 7-47) months, half (7/15, 47%) of the combined groups had high levels of grief on the PGS. Multiple positive scores on psychometric tests were frequent: Sixty percent (9/15) had high scores on the PGS Active Grief subscale or on the IES. Forty percent (6/15) had a high score on the DDI, and 17% (3/15) on the GAD. IR scores significantly and negatively correlated with scores on the Despair subscale of the PGS. The results from this pilot study suggest that high levels of grief and PTS symptoms are significant problems for pregnant women who have suffered late loss of a wanted pregnancy. Religiosity may play an important part in maternal coping during these stressful pregnancies.

Modeling Training Effects Using a Human Performance Taxonomy

The aim of this study was to characterize skill acquisition during training and skill retention as a function of training strategy, retention period, and task type in the form of a numerical model and then apply that model to make predictions of performance on an unknown task.

In Situ Biomonitoring of Caged, Juvenile Chinook Salmon (Oncorhynchus Tshawytscha) in the Lower Duwamish Waterway

Contaminated sediments may have wide-ranging impacts on human and ecological health. A series of in situ caged exposure studies using juvenile Chinook salmon was conducted in the Lower Duwamish Waterway (LDW). Chemical analysis of sediment, water, and fish tissue were completed. Additionally, in 2004, DNA adducts in hepatic and gill tissues were measured. Gills contained significantly higher DNA adducts at stations B2 and B4, prompting further analysis of gills in 2006 and 2007. Fluorescent aromatic compounds (FACs) in bile, and CYP1A1 in hepatic tissue were also measured during 2006 and 2007, respectively. FACs in field-caged fish were comparable or significantly higher than wild-caught fish LDW fish and significantly higher than lab fish after only 8-10 days, demonstrating the equivalency of exposure to that of migrating salmon. Furthermore, selected biomarkers appear to be capable of detecting spikes in contamination between sampling years, emphasizing the need for multiple year data collection.

Spiritual Needs of Couples Facing Pregnancy Termination Because of Fetal Anomalies

The spiritual needs of couples (9 mothers and 5 fathers) who were planning to terminate wanted second trimester pregnancies because of serious fetal anomalies were surveyed. Their greatest needs were for a "guidance from a higher power" and for "someone to pray for them." Unlike other reported groups of patients, they did not want or expect their healthcare team to discuss their faith, or to pray with them. Most would prefer support from their own pastors, but their religious community was involved to only a small extent. They would welcome support from hospital chaplains, who could play a substantive and unique pastoral role in this clinical context.

Disparities in NIH Funding for Epilepsy Research

Using data from NIH Research Portfolio Online Reporting Tools (RePORT) and recently assembled prevalence estimates of 6 major neurologic diseases, we compared the relative prevalences and the annual NIH support levels for 6 major neurologic disorders: Alzheimer disease, amyotrophic lateral sclerosis (ALS), epilepsy, multiple sclerosis, Parkinson disease, and stroke. Compared to these other major neurologic disorders, epilepsy research is funded at a persistently lower rate based on relative disease prevalences. Relative NIH funding for these other disorders in 2010 adjusted for prevalence ranged from 1.7x (stroke) to 61.1x (ALS) greater than epilepsy. The disparity cannot be explained by differences in the overall impact of these diseases on US citizens. Greater transparency in the review and funding process is needed to disclose the reason for this disparity.

Surface Oxidation Study of Single Wall Carbon Nanotubes

Functionalization of single wall carbon nanotubes (SWCNTs) is desirable to enhance their ability to be incorporated into polymers and enhance their bonding with the matrix. One approach to carbon nanotube functionalization is by oxidation via a strong oxidizing agent or refluxing in strong acids. However, this approach can damage the nanotubes, leading to the introduction of defects and/or shorter nanotubes. Such damage can adversely affect the mechanical, thermal, and electrical properties. A more benign approach to nanotube functionalization has been developed involving photo-oxidation. Chemical analysis by XPS revealed that the oxygen content of the photo-oxidized SWCNTs was 11.3 at.% compared to 6.7 at.% for SWCNTs oxidized by acid treatment. The photo-oxidized SWCNTs produced by this method can be used directly in various polymer matrices or can be further modified by additional chemical reactions.

Statin-associated Changes in Skeletal Muscle Function and Stress Response After Novel or Accustomed Exercise

The most common side effect of statins, myopathy, is more likely in exercisers. We investigated the interaction of statin treatment with novel vs. accustomed exercise on muscle function, heat shock protein (Hsp) expression, and caspase activation.

Erratum To: Bioaccumulation of Polychlorinated Biphenyls in Juvenile Chinook Salmon (Oncorhynchus Tshawytscha) Outmigrating Through a Contaminated Urban Estuary: Dynamics and Application

"It's Medically Proven!": Assessing the Dissemination of Religion and Health Research

The recent proliferation of research on the connection between religion and health has raised concerns among some scholars about how these studies affect people's understanding of that connection. However, such concerns assume that religion and health research reaches religious audiences and informs their understanding of the connection between religion and health. We explore the veracity of these assumptions, asking two questions: (1) Is religion and health research disseminating into the American public? (2) Do religious persons incorporate religion and health research into their understanding of the connection between religion and health? We conduct two studies to answer these questions. First, we search three newspapers (The New York Times, The Los Angeles Times, and The Atlanta Journal-Constitution) and three news magazines (Newsweek, Time, and U. S. News and World Report) for articles that mention religion and health research. In the second study, we analyze interview transcripts for respondents' mentions of religion and health research when discussing the relationship between religion and health. Our results indicate substantial growth over time in media reporting on religion and health research but reveal that only a limited portion of religious persons cite such research in explaining their conceptualizations of the connection between religion and health.

A Method to Combine Cognitive and Neurophysiological Assessments of the Elderly

The development of better treatments for brain diseases of the elderly will necessitate more sensitive and efficient means of repeatedly assessing an individual's neurocognitive status.

Topiramate Dose Effects on Cognition: a Randomized Double-blind Study

Topiramate (TPM), a broad-spectrum antiepileptic drug, has been associated with neuropsychological impairment in patients with epilepsy and in healthy volunteers.

Using the Dynamic Bond to Access Macroscopically Responsive Structurally Dynamic Polymers

New materials that have the ability to reversibly adapt to their environment and possess a wide range of responses ranging from self-healing to mechanical work are continually emerging. These adaptive systems have the potential to revolutionize technologies such as sensors and actuators, as well as numerous biomedical applications. We will describe the emergence of a new trend in the design of adaptive materials that involves the use of reversible chemistry (both non-covalent and covalent) to programme a response that originates at the most fundamental (molecular) level. Materials that make use of this approach - structurally dynamic polymers - produce macroscopic responses from a change in the material's molecular architecture (that is, the rearrangement or reorganization of the polymer components, or polymeric aggregates). This design approach requires careful selection of the reversible/dynamic bond used in the construction of the material to control its environmental responsiveness.

Tributyltin and the Obesogen Metabolic Syndrome in a Salmonid

We conducted a dietary feeding study with juvenile chinook salmon (Oncorhynchus tshawytscha) to assess the potential for tributyltin (TBT) to elicit the obesogen response that has been described for mammals. The results show increases in whole-body lipid content, which is consistent with the obesogen response; however, we also observed associated parameters that were dissimilar. We found increases in body mass and alterations to several physiological parameters at doses between 0.4 and 3.5 ng/g fish/day (1.4-12 pmol/g fish/day) and reduced body mass at the highest dose after 55 days of exposure. Lipid related plasma parameters (plasma triacylglycerols, cholesterol, and lipase) exhibited monotonic increases over all doses while other values (glucose and insulin-like growth factor (IGF)) exhibited increases only for the low-dose treatments. The increases noted for several parameters in fish were opposite to those reported for the obesogen metabolic syndrome, which is characterized by a reduction in serum glucose, free fatty acids, and triglycerides. This is the first report of growth stimulation resulting from low-dose exposure to this pesticide, which is an unusual response for any animal exposed to an organic or organometallic xenobiotic. Because a number of environmental contaminants act as metabolic disruptors at very low doses, these results are noteworthy for a variety of species. Intuitively, enhanced growth and lipid storage may appear beneficial; however, for salmonids there are numerous potentially negative consequences for populations.

The Tissue Residue Approach for Toxicity Assessment: Findings and Critical Reviews from a Society of Environmental Toxicology and Chemistry Pellston Workshop

Over the past few years, the "critical body residue" approach for assessing toxicity based on bioaccumulated chemicals has evolved into a more expansive consideration of tissue residues as the dose metric when defining dose-response relationships, evaluating mixtures, developing protective guidelines, and conducting risk assessments. Hence, scientists refer to "tissue residue approach for toxicity assessment" or "tissue residue-effects approach" (TRA) when addressing ecotoxicology issues pertaining to tissue (or internal) concentrations. This introduction provides an overview of a SETAC Pellston Workshop held in 2007 to review the state of the science for using tissue residues as the dose metric in environmental toxicology. The key findings of the workshop are presented, along with recommendations for research to enhance understanding of toxic responses within and between species, and to advance the use of the TRA in assessment and management of chemicals in the environment.

Advancing Environmental Toxicology Through Chemical Dosimetry: External Exposures Versus Tissue Residues

The tissue residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in tissue residue terms, the relationship between external exposure concentration, body and/or tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the tissue residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of residue-effect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating residue-based testing and interpretation approaches, essential in various jurisdictions.

Crucial Role of Mechanisms and Modes of Toxic Action for Understanding Tissue Residue Toxicity and Internal Effect Concentrations of Organic Chemicals

This article reviews the mechanistic basis of the tissue residue approach for toxicity assessment (TRA). The tissue residue approach implies that whole-body or organ concentrations (residues) are a better dose metric for describing toxicity to aquatic organisms than is the aqueous concentration typically used in the external medium. Although the benefit of internal concentrations as dose metrics in ecotoxicology has long been recognized, the application of the tissue residue approach remains limited. The main factor responsible for this is the difficulty of measuring internal concentrations. We propose that environmental toxicology can advance if mechanistic considerations are implemented and toxicokinetics and toxicodynamics are explicitly addressed. The variability in ecotoxicological outcomes and species sensitivity is due in part to differences in toxicokinetics, which consist of several processes, including absorption, distribution, metabolism, and excretion (ADME), that influence internal concentrations. Using internal concentrations or tissue residues as the dose metric substantially reduces the variability in toxicity metrics among species and individuals exposed under varying conditions. Total internal concentrations are useful as dose metrics only if they represent a surrogate of the biologically effective dose, the concentration or dose at the target site. If there is no direct proportionality, we advise the implementation of comprehensive toxicokinetic models that include deriving the target dose. Depending on the mechanism of toxicity, the concentration at the target site may or may not be a sufficient descriptor of toxicity. The steady-state concentration of a baseline toxicant associated with the biological membrane is a good descriptor of the toxicodynamics of baseline toxicity. When assessing specific-acting and reactive mechanisms, additional parameters (e.g., reaction rate with the target site and regeneration of the target site) are needed for characterization. For specifically acting compounds, intrinsic potency depends on 1) affinity for, and 2) type of interaction with, a receptor or a target enzyme. These 2 parameters determine the selectivity for the toxic mechanism and the sensitivity, respectively. Implementation of mechanistic information in toxicokinetic-toxicodynamic (TK-TD) models may help explain time-delayed effects, toxicity after pulsed or fluctuating exposure, carryover toxicity after sequential pulses, and mixture toxicity. We believe that this mechanistic understanding of tissue residue toxicity will lead to improved environmental risk assessment.

A Review of the Tissue Residue Approach for Organic and Organometallic Compounds in Aquatic Organisms

This paper reviews the tissue residue approach (TRA) for toxicity assessment as it applies to organic chemicals and some organometallic compounds (Sn, Hg, and Pb) in aquatic organisms. Specific emphasis was placed on evaluating key factors that influence interpretation of critical body residue (CBR) toxicity metrics including data quality issues, lipid dynamics, choice of endpoints, processes that alter toxicokinetics and toxicodynamics, phototoxicity, species- and life stage-specific sensitivities, and biotransformation. The vast majority of data available on TRA is derived from laboratory studies of acute lethal responses to organic toxicants exhibiting baseline toxicity. Application of the TRA to various baseline toxicants as well as substances with specific modes of action via receptor-mediated processes, such as chlorinated aromatic hydrocarbons, pesticides, and organometallics is discussed, as is application of TRA concepts in field assessments of tissue residues. In contrast to media-based toxicity relationships, CBR values tend to be less variable and less influenced by factors that control bioavailability and bioaccumulation, and TRA can be used to infer mechanisms of toxic action, evaluate the toxicity of mixtures, and interpret field data on bioaccumulated toxicants. If residue-effects data are not available, body residues can be estimated, as has been done using the target lipid model for baseline toxicants, to derive critical values for risk assessment. One of the primary unresolved issues complicating TRA for organic chemicals is biotransformation. Further work on the influence of biotransformation, a better understanding of contaminant lipid interactions, and an explicit understanding of the time dependency of CBRs and receptor-mediated toxicity are all required to advance this field. Additional residue-effects data on sublethal endpoints, early life stages, and a wider range of legacy and emergent contaminants will be needed to improve the ability to use TRA for organic and organometallic compounds.

Application of the Tissue Residue Approach in Ecological Risk Assessment

The objective of this work is to present a critical review of the application of the tissue residue approach (TRA) in ecological risk and/or impact assessment (ERA) of chemical stressors and environmental criteria development. A secondary goal is to develop a framework for integrating the TRA into ecological assessments along with traditional, exposure concentration-based assessment approaches. Although widely recognized for its toxicological appeal, the utility of the TRA in specific applications will depend on numerous factors, such as chemical properties, exposure characteristics, assessment type, availability of tissue residue-response data, and ability to quantify chemical exposure. Therefore, the decision to use the TRA should include an evaluation of the relative strengths, limitations, and uncertainties among exposure and residue-based methods for characterizing toxicological effects. Furthermore, rather than supplanting exposure concentration-based toxicity assessments, the TRA can be highly effective for evaluating and reducing uncertainty when used in a complementary manner (e.g., when evaluating multiple lines of evidence in field studies). To address limitations with the available tissue residue-response data, approaches for extrapolating residue-based toxicity data across species, tissues, and exposure durations are discussed. Some of these approaches rely on predicted residue-response relationships or toxicological models that have an implicit residue-response basis (e.g., biotic ligand model). Because risk to an organism is a function of both its exposure potential and inherent sensitivity (i.e., on a residue basis), bioaccumulation models will be required not only for translating tissue residue criteria into corresponding water and sediment criteria, but also for defining the most vulnerable species in an assemblage (i.e., highly exposed and highly sensitive species). Application of the TRA in ecological assessments and criteria development are summarized for bioaccumulative organic chemicals, TBT, and in situ bioassays using bivalve molluscs.

Foetal Antiepileptic Drug Exposure and Verbal Versus Non-verbal Abilities at Three Years of Age

We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled pregnant females with epilepsy on monotherapy from 1999 to 2004. The study seeks to determine if differential long-term neurodevelopmental effects exist across four commonly used drugs (carbamazepine, lamotrigine, phenytoin and valproate). This report compares verbal versus non-verbal cognitive outcomes in 216 children who completed testing at the age of three years. Verbal and non-verbal index scores were calculated from the Differential Ability Scales, Preschool Language Scale, Peabody Picture Vocabulary Test and Developmental Test of Visual-Motor Integration. Verbal abilities were lower than non-verbal in children exposed in utero to each drug. Preconceptional folate use was associated with higher verbal outcomes. Valproate was associated with poorer cognitive outcomes. Performance was negatively associated with valproate dose for both verbal and non-verbal domains and negatively associated with carbamazepine dose for verbal performance. No dose effects were seen for lamotrigine and phenytoin. Since foetal antiepileptic drug exposure is associated with lower verbal than non-verbal abilities, language may be particularly susceptible to foetal exposure. We hypothesize that foetal drug exposure may alter normal cerebral lateralization. Further, a dose-dependent relationship is present for both lower verbal and non-verbal abilities with valproate and for lower verbal abilities with carbamazepine. Preconceptional folate may improve cognitive outcomes. Additional research is needed to confirm these findings, extend the study to other drugs, define the risks associated with drug treatment for seizures in the neonates, and understand the underlying mechanisms.

Polyimide Aerogels Cross-linked Through Amine Functionalized Polyoligomeric Silsesquioxane

We report the first synthesis of polyimide aerogels cross-linked through a polyhedral oligomeric silsesquioxane, octa(aminophenyl)silsesquioxane (OAPS). Gels formed from polyamic acid solutions of 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA), bisaniline-p-xylidene (BAX) and OAPS were chemically imidized and dried using supercritical CO(2) extraction to give aerogels having density around 0.1 g/cm(3). The aerogels are greater than 90 % porous, have high surface areas (230 to 280 m(2)/g) and low thermal conductivity (14 mW/m-K at room temperature). Notably, the polyimide aerogels cross-linked with OAPS have higher modulus than polymer reinforced silica aerogels of similar density and can be fabricated as both monoliths and thin films. Thin films of the aerogel are flexible and foldable making them an ideal insulation for space suits, and inflatable structures for habitats or decelerators for planetary re-entry, as well as more down to earth applications.

Biomarker Responses and Disease Susceptibility in Juvenile Rainbow Trout Oncorhynchus Mykiss Fed a High Molecular Weight PAH Mixture

Juvenile rainbow trout were fed a diet containing an environmentally relevant mixture of 10 high molecular weight polycyclic aromatic hydrocarbons (PAHs) at a dose of 0.66 or 7.82 µg PAH · g fish(-1) · d(-1). At 3, 7, 14, and 28 d, biomarkers of aryl hydrocarbon receptor activation (AHR), hepatic microsomal ethoxyresorufin-O-deethylase (EROD) activity, and cytochrome P4501A (CYP1A)-associated staining increased 14- to 26-fold and 6- to 14-fold, respectively, in fish fed 7.82 µg PAH · g fish (-1) · d(-1). Cytochrome P4501A-associated staining increased 2- to 9-fold on days 3, 7, and 28 in fish fed 0.66 µg PAH · g fish(-1) · d(-1). Bile fluorescent aromatic compounds served as a biomarker of exposure and confirmed that PAH exposure was consistent over 50 d. DNA damage in blood cells, protein oxidation, and lipid peroxidation in the kidney were biomarkers of oxidative stress and all increased in fish fed 7.82 µg PAH · g fish(-1) · d(-1). Fish fed 0.66 µg PAH · g fish(-1) · d(-1) had elevated DNA damage in blood cells but increased protein oxidation or lipid peroxidation in the kidney were not observed. Challenge with Aeromonas salmonicida, at lethal concentration (LC) 20, decreased survival in fish previously fed either 0.66 µg PAH · g fish(-1) · d(-1) or 7.82 µg PAH · g fish(-1) · d(-1) relative to fish fed the control diet. In general, biomarkers of both AHR activation and oxidative stress peaked at 3 to 14 d then declined at 28 to 50 d of PAH exposure and an increase in susceptibility to disease was observed at 50 d. These results link PAH exposure to biomarker responses that may be useful as early indicators of population level responses, such as mortality resulting from an increase in disease susceptibility.

Epilepsy: Five New Things

Effect of Osmolality and Selected Ions on Retraction of the Distome Body into the Cercaria Tail Chamber of Proterometra Macrostoma (Trematoda: Azygiidae)

The furcocystocercous cercariae of the digenetic trematode, Proterometra macrostoma , possess a tail chamber into which their distome body withdraws prior to emergence from their snail intermediate host. The process of distome retraction and the conditions that trigger it in this species are not clear. The objectives of the present study were (1) to describe the retraction process in P. macrostoma; (2) to assess whether osmolality affects cercarial retraction; (3) to evaluate the effect of selected ions on retraction; and (4) to compare the swimming effectiveness of naturally ( =  in vivo) retracted versus in vitro retracted cercariae. Retraction of the cercaria body into its tail chamber required only 2 min or less once initiated. The process began with the development of a chamber within the anterior end of the worm's tail. The chamber's lip advanced in a pulsating motion over the stationary distome. Retraction was completed with the constriction and fusion of the chamber lip once it passed over the anterior end of the distome, sealing the latter within the tail chamber. There was a significant difference in the proportions of cercariae with bodies retracted into tails, bodies not retracted, and bodies separated from tails in artificial pond water (APW) versus artificial snail water (ASW). A greater number of cercariae withdrew into their tail chambers in ASW (59/124; 47.6%) than in APW (21/124; 16.9%). In APW, more bodies separated from their tails (24/124; 19.4%) than in ASW (3/124; 2.4%). In both solutions (APW: 63.7%  =  79/124; ASW: 50%  =  62/124), a majority of cercariae never retracted. In APW, 76.2% of distomes retracting into their tails did so within the first 5 min compared to only 30.5% in ASW. There was no significant difference in the proportions of cercariae with bodies retracted into tails, bodies not retracted, and bodies separated from tails based on isosmotic replacement of individual ions, i.e., Na(+), K(+), Ca(++), or Mg(++), in ASW with Li(+). There was also no significant difference in the vertical swimming burst distance in cercariae whose bodies were initially retracted into their tails in vitro versus in vivo.

Tailoring Mechanical Properties of Aerogels for Aerospace Applications

Silica aerogels are highly porous solid materials consisting of three-dimensional networks of silica particles and are typically obtained by removing the liquid in silica gels under supercritical conditions. Several unique attributes such as extremely low thermal conductivity and low density make silica aerogels excellent candidates in the quest for thermal insulation materials used in space missions. However, native silica aerogels are fragile at relatively low stresses. More durable aerogels with higher strength and stiffness are obtained by proper selection of silane precursors and by reinforcement with polymers. This paper first presents a brief review of the literature on methods of silica aerogel reinforcement and then discusses our recent activities in improving not only the strength but also the elastic response of polymer-reinforced silica aerogels. Several alkyl-linked bis-silanes were used in promoting flexibility of the silica networks in conjunction with polymer reinforcement by epoxy.

Environmental Sustainability in an Aging Society: a Research Agenda

This article presents the results of a multidisciplinary consensus conference held to recommend a research agenda on the relationship between aging and environmental sustainability and conservation. The intersection of these two topics has important implications for the health and well-being of older persons but it has thus far received little scientific attention.

Mechanically Strong, Flexible Polyimide Aerogels Cross-linked with Aromatic Triamine

Polyimide gels are produced by cross-linking anhydride capped polyamic acid oligomers with aromatic triamine in solution and chemically imidizing. The gels are then supercritically dried to form nanoporous polyimide aerogels with densities as low as 0.14 g/cm(3) and surface areas as high as 512 m(2)/g. To understand the effect of the polyimide backbone on properties, aerogels from several combinations of diamine and dianhydride, and formulated oligomer chain length are examined. Formulations made from 2,2'-dimethylbenzidine as the diamine shrink the least but have among the highest compressive modulus. Formulations made using 4,4'-oxydianiline or 2,2'dimethylbenzidine can be fabricated into continuous thin films using a roll to roll casting process. The films are flexible enough to be rolled or folded back on themselves and recover completely without cracking or flaking, and have tensile strengths of 4-9 MPa. Finally, the highest onset of decomposition (above 600 °C) of the polyimide aerogels was obtained using p-phenylene diamine as the backbone diamine with either dianhydride studied. All of the aerogels are suitable candidates for high-temperature insulation with glass transition temperatures ranging from 270-340 °C and onsets of decomposition from 460-610 °C.

The Impact of Vasculitis on Patients' Social Participation and Friendships

OBJECTIVES: Our objective is to explore how vasculitis affects patients' friendships and social participation. METHODS: Vasculitis patients (n=221) completed an online questionnaire that asked if, and how, relationships with friends have changed since receiving a vasculitis diagnosis. Participants' written responses were imported into Atlas.ti, and two independent researchers used both structured and unstructured coding to identify themes. After reaching 100% consensus on the themes present in each participant's responses, the coders determined how themes were interrelated across participants. RESULTS: Over half of patients (52%) expressed that vasculitis negatively impacted their friendships and 25% noted a negative impact on their social participation. At times, this negative impact was related to structural changes in patients' social networks due to loss of friendships. Reduced social participation was also associated with friends' inability to understand vasculitis and its effects, vasculitis-related fatigue, and lifestyle changes such as not being able to drink alcohol and avoiding infection-prone events. Additionally, patients withdrew from social engagements due to fatigue or because of physical symptoms and side effects. CONCLUSIONS: The unique circumstances associated with a rare chronic illness like vasculitis can create significant barriers to friendships, including loss of these relationships. Interventions designed to help patients cope with the social impact of vasculitis are implicated, especially if they increase patients' ability to engage in dialogue about their illness with their friends.

Religious Service Attendance and Major Depression: a Case of Reverse Causality?

Although previous studies have found a protective association between attendance at religious services and depression, the extent to which this association is driven by depressed persons' dropping out of religious activities is not clear. The authors examined whether early onset of a major depressive episode (MDE) predicted a subsequent decrease in religious service attendance. Data came from 3 follow-up studies of the National Collaborative Perinatal Project birth cohort (mean age = 37 years at last follow-up; n = 2,097; 1959-2001). The generalized estimating equations method was used to calculate the impact of an early MDE diagnosis (before age 18 years) on the likelihood of change in level of religious service attendance from childhood to adulthood. Twenty-seven percent of study participants met the criteria for lifetime MDE (n = 567), of whom 31% had their first onset prior to age 18 years. Women with early MDE onset were 1.42 times more likely (95% confidence interval: 1.19, 1.70) than women with adult-onset MDE or no lifetime MDE to stop attending religious services by the time of the first adult follow-up wave. No significant associations were observed among men. These findings suggest that women are more likely to stop attending religious services after onset of depression. Selection out of religious activities could be a significant contributor to previously observed inverse correlations between religious service attendance and psychopathology during adulthood.

Preface: Forum on Polymers for Aerospace Applications

Physicians' Beliefs About Faith-Based Treatments for Alcoholism

OBJECTIVE: The study examined physicians' beliefs about faith-based alcohol treatments vis-à-vis Alcoholics Anonymous, pharmacologic treatment, and residential treatment. METHODS: A survey was mailed to a national sample of U.S. primary care physicians and psychiatrists. It included a brief vignette of a nominally religious 47-year-old man hospitalized for acute alcohol poisoning who requested addiction treatment. Physicians rated the likely effectiveness of three treatment methods: Alcoholics Anonymous, pharmacological therapy by an addiction specialist, and a residential program. Physicians were asked whether they would refer the patient to a faith-based program (beyond Alcoholics Anonymous) and whether an emphasis on spirituality is critical to 12-step program success. RESULTS: The response rate was 896 of 1,427 (63%) for primary care physicians and 312 of 487 (64%) for psychiatrists. Psychiatrists were more likely to rate Alcoholics Anonymous as very effective (64% versus 57% of primary care physicians), more likely to rate residential treatment as very effective (47% versus 38% of primary care physicians), and more likely to rate pharmacologic therapy as very effective (31% versus 22% of primary care physicians). Psychiatrists and primary care physicians were equally likely to consider referring the patient to a faith-based program (71% and 79%) and equally likely to believe that "an emphasis on spirituality is critical to the success of 12-step programs" (81% and 85%). CONCLUSIONS: Psychiatrists were more optimistic than primary care physicians about all three treatments. Physicians in both specialties would refer even nominally religious patients to explicitly faith-based programs (beyond Alcoholics Anonymous). Physicians' enthusiasm for faith-based treatments highlights the need for scientific study of these treatments to determine which elements are most helpful for patients seeking recovery. (Psychiatric Services in Advance, April 1, 2012; doi: 10.1176/appi.ps.201100315).

Effects of Fetal Antiepileptic Drug Exposure: Outcomes at Age 4.5 Years

OBJECTIVE:To examine outcomes at age 4.5 years and compare to earlier ages in children with fetal antiepileptic drug (AED) exposure. METHODS:The NEAD Study is an ongoing prospective observational multicenter study, which enrolled pregnant women with epilepsy on AED monotherapy (1999-2004) to determine if differential long-term neurodevelopmental effects exist across 4 commonly used AEDs (carbamazepine, lamotrigine, phenytoin, or valproate). The primary outcome is IQ at 6 years of age. Planned analyses were conducted using Bayley Scales of Infant Development (BSID at age 2) and Differential Ability Scale (IQ at ages 3 and 4.5). RESULTS:Multivariate intent-to-treat (n = 310) and completer (n = 209) analyses of age 4.5 IQ revealed significant effects for AED group. IQ for children exposed to valproate was lower than each other AED. Adjusted means (95% confidence intervals) were carbamazepine 106 (102-109), lamotrigine 106 (102-109), phenytoin 105 (102-109), valproate 96 (91-100). IQ was negatively associated with valproate dose, but not other AEDs. Maternal IQ correlated with child IQ for children exposed to the other AEDs, but not valproate. Age 4.5 IQ correlated with age 2 BSID and age 3 IQ. Frequency of marked intellectual impairment diminished with age except for valproate (10% with IQ <70 at 4.5 years). Verbal abilities were impaired for all 4 AED groups compared to nonverbal skills. CONCLUSIONS:Adverse cognitive effects of fetal valproate exposure persist to 4.5 years and are related to performances at earlier ages. Verbal abilities may be impaired by commonly used AEDs. Additional research is needed.

Effects of Electronic Health Information Technology Implementation on Nursing Home Resident Outcomes

To examine the effects of electronic health information technology (HIT) on nursing home residents.

Different Structural Correlates for Verbal Memory Impairment in Temporal Lobe Epilepsy with and Without Mesial Temporal Lobe Sclerosis

Memory impairment is one of the most prominent cognitive deficits in temporal lobe epilepsy (TLE). The overall goal of this study was to explore the contribution of cortical and hippocampal (subfield) damage to impairment of auditory immediate recall (AIMrecall), auditory delayed recall (ADMrecall), and auditory delayed recognition (ADMrecog) of the Wechsler Memory Scale III (WMS-III) in TLE with (TLE-MTS) and without hippocampal sclerosis (TLE-no). It was hypothesized that volume loss in different subfields determines memory impairment in TLE-MTS and temporal neocortical thinning in TLE-no.

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