A Multi-level Analysis Examining How Smoking Friends, Parents, and Older Students in the School Environment Are Risk Factors for Susceptibility to Smoking Among Non-smoking Elementary School Youth

Prevention Science : the Official Journal of the Society for Prevention Research. Dec, 2006  |  Pubmed ID: 16823633

The purpose of this study was to examine how social models for smoking are related to smoking susceptibility among a sample of non-smoking elementary school students. The Tobacco Module of the School Health Action, Planning and Evaluation System (SHAPES) was administered to 6,431 students (grades 6 to 8) in 57 elementary schools in the province of Ontario, Canada. Multi-level logistic regression analysis was used to examine how smoking friends, parents, and the prevalence of smoking among grade 8 students at a school were related to smoking susceptibility among the 2,478 non-smoking grade 6 and 7 students. Findings indicate that non-smoking grade 6 and 7 students are more likely to be susceptible to smoking if they have (a) smoking friends, (b) a mother who smokes, or (c) two or more close friends who smoke and attend a school with a relatively high smoking rate among the grade 8 students. Sub-populations of non-smoking youth may be at increased risk for smoking because of the elementary school they attend. Future school-based smoking prevention programs might benefit from targeting prevention programming activities to the schools that are putting students at the greatest risk for smoking.

Perceptions of Tobacco Use in Early Adolescents

The Journal of Primary Prevention. Sep, 2006  |  Pubmed ID: 16897409

In an effort to strengthen tobacco use prevention programs, this study explores early (9- to 13-year-old) adolescent motivations for and perceptions of use. Data were collected, via electronic keypads, from students visiting 12 health education centers in the U.S. (N=1433). Multivariate logistic regression showed that perceptions of frequent peer tobacco use and popularity of adolescent smoking, in addition to absence of family discussion of tobacco use, were associated with greater likelihood for smoking and of reporting past smoking. Even though most participants thought adolescents who smoke are very unpopular, more than 60% said the primary reason for adolescent smoking was that smokers believe it will make them popular. Participants thought the best way to prevent use was to give kids "other fun things to do instead." Recommendations are given for customizing curricula or programs.

Lack of Decay of HIV-1 in Gut-associated Lymphoid Tissue Reservoirs in Maximally Suppressed Individuals

Journal of Acquired Immune Deficiency Syndromes (1999). Sep, 2006  |  Pubmed ID: 16936559

Although peripheral blood mononuclear cells (PBMCs) and lymph nodes represent a principal reservoir, the contribution of gut-associated lymphoid tissue (GALT) has not been evaluated. In 15 HIV-1-infected subjects with maximal suppression of HIV replication by highly active antiretroviral therapy, we quantified HIV-1 DNA and RNA in mucosal biopsy specimens, PBMCs, and plasma with ultrasensitive assays. We also calculated compartmental burdens of HIV-1 DNA-positive cells and characterized the temporal decay of these reservoirs in a period of 1 year (with projections to >50 years). HIV-1 RNA was detected in 20% of the subjects' mucosal biopsy specimens and in 80% of the PBMC samples. Mucosal HIV-1 DNA was detected in 80% of the subjects and in 100% of the PBMC samples. Calculated numbers of lymphoid cells containing "potentially replication-competent" HIV-1 DNA showed that the PBMC compartment contained approximately 70,000 such cells, and GALT contained approximately 160,000 cells. Rates of decay slopes for all 15 subjects in both compartments were not statistically significantly different when compared with each other or with zero slope. Our data indicate that GALT is a quantitatively important reservoir of potentially replicative cells containing HIV-1 DNA, harboring at least as many or more of such cells as the PBMC compartment. In well-suppressed patients on highly active antiretroviral therapy, the GALT compartment showed no clear pattern of HIV-1 decay, similar to that in the PBMCs.

Ultrasound Diagnosis of Mouse Pregnancy and Gestational Staging

Comparative Medicine. Aug, 2006  |  Pubmed ID: 16941953

Phenotypic analysis of mutant mice is limited by lack of accurate, simple, and nondestructive in utero imaging techniques. This study evaluated the usefulness of ultrasound imaging (US) to stage fetal mouse gestational age (GA) and depict morphologic development. We imaged 16 pregnant CD-1 mice and a total of 92 fetuses with a 15-MHz US transducer from 9.5 d postcoitus (DPC) until 20.5 DPC or delivery. Parameters recorded included gestational sac dimensions, crown-rump length (CRL), biparietal diameter (BPD), thoracoabdominal diameter (TAD), onset of cardiac activity, and morphologic development. At 9.5 d DPC, all gestations appeared as rounded sacs, with a diameter (mean +/- standard error) of 4.4 +/- 1 mm. BPD, CRL, and GA were highly correlated. The following structures were first identifiable at the following GA: cardiac activity, 10.5 DPC; major cardiovascular structures, 11.5 DPC; limb buds, 10.5 DPC; spine, 12.5 DPC; face and skull ossification, 13.5 DPC; rib ossification, 15.5 DPC; hind- and forelimb digits, 15.5 DPC; stomach and urinary bladder, 17.5 DPC; visualization of the rhombencephalic vesicle, 13.5 DPC; and visualization of the lateral ventricles, 14.5 DPC. The echogenic lungs were distinct from the liver as early as 12.5 DPC. The circle of Willis was detectable with color Doppler as early as 13.5 DPC and was easily visualized at 15.5 DPC. We found that US provides accurate, simple staging criteria for fetal mouse gestational development after 9.5 DPC and may be a nondestructive means of documenting phenotypic alterations in mutant mice in utero.

Validation of QF-PCR for Prenatal Aneuploidy Screening in the United States

Prenatal Diagnosis. Nov, 2006  |  Pubmed ID: 16952193

QF-PCR is an inexpensive and reliable method for aneuploidy screening; however, despite its obvious advantages, it is not in routine use in the United States. Our objective in the present study was to validate QF-PCR as a means for prenatal aneuploidy screening in our institution.

Gender, Age, and Behavior Differences in Early Adolescent Worry

The Journal of School Health. Oct, 2006  |  Pubmed ID: 16978167

Early adolescents in the United States are increasingly exposed to a culture of worrisome messages. A degree of adolescent worry is normal, but the likelihood of a young person being anxious or depressed increases with the perceived number of worries. This study examined the effect of age, gender, and worry behavior on frequency of 8 adolescent worries. Data were obtained from 1,004 9- to 13-year-old students visiting 10 health education centers in 7 states. Students responded via individual, electronic keypads. Multivariate logistic regression revealed that boys worry more about the future, whereas girls worry more about being liked or being overweight. The oldest adolescents worry most about their appearance, being overweight, their friends, and problems at home. Adolescents who prefer talking to parents when worried are less likely to worry about being liked, while those who keep worries to themselves have more worries about grades. Those who turn to parents for information are less likely to worry about being liked, failure, their future, and their friends than those who turn to other sources (teachers, Internet, and friends). Recommendations are given to assist health educators and other school staff to recognize frequent worriers and plan school-based approaches to address their needs.

Deterioration

Epilepsia. 2006  |  Pubmed ID: 17105454

Intellectual deterioration in epilepsy may be real or apparent. The latter refers to delay in cognitive development such that performance against age-related norms appears to drop. The former, real deterioration can occur due to concomitant degenerative neurological disease of which epilepsy is also a symptom, or it may happen as a consequence of one or more of a number of other factors. These include (1) direct effects of seizures and abnormal electroencephalogram activity on brain function, (2) traumatic brain injury secondary to seizures, including status epilepticus, (3) the influence of antiepileptic therapy, both drugs and surgery, on cognitive function, (4) psychosocial sequelae of diagnosis. Some epilepsy syndromes include intellectual deterioration as a frequent feature, with various causes. Developmental factors may also play a part. Cognitive functioning may be impaired by the presence of an epileptogenic lesion, and also in different ways and at different times by other brain areas involved with partial seizures, including irritative and functional deficit zones. Abnormal activity in these areas at critical periods in development may interact and disrupt pathways necessary for maturation of frontal lobe and limbic system functioning, leading to long-term neurological deficits. Increased understanding of the mechanisms by which this may happen raises intriguing possibilities for prevention and remediation.

Questions About Behavioral Function in Mental Illness (QABF-MI): a Behavior Checklist for Functional Assessment of Maladaptive Behavior Exhibited by Individuals with Mental Illness

Behavior Modification. Nov, 2006  |  Pubmed ID: 17050763

The Questions About Behavioral Function (QABF), a 25-item rating scale, was developed to identify the function(s) of maladaptive behavior in individuals with developmental disabilities. The authors adapted it for use with individuals with serious mental illness who engage in maladaptive behavior and assessed the psychometric characteristics of the new scale (Questions About Behavioral Function in Mental Illness; QABF-MI) in a sample of 135 adults with serious mental illness from three inpatient psychiatric hospitals. Staff most familiar with each person rated each item on a 5-point Likert-type rating scale, and the ratings were subjected to a number of psychometric analyses. The results of factor analyses provided a conceptually meaningful five-factor solution: physical discomfort, social attention, tangible reinforcement, escape, and nonsocial reinforcement. Congruence between the five factors derived with the QABF-MI and the corresponding factors in the original QABF was perfect. The results indicated that the QABF-MI has robust psychometric properties and may be useful as a screening tool for determining the nature of the variables that maintain maladaptive behavior exhibited by individuals with serious mental illness.

Children with Chronic Pain: Impact of Sex and Age on Long-term Outcomes

Pain. Mar, 2007  |  Pubmed ID: 17055163

The present study examined the long-term pain and disability outcomes of a pediatric chronic pain clinic cohort and evaluated whether these outcomes differed by age and sex. Patients were interviewed a mean of 3 years after their last appointment at a pediatric pain clinic. The cohort comprised 95 females and 48 males, aged 5-23 years when interviewed. Of the cohort, 62.2% (67 females, 22 males) reported continuing pain. Females were significantly more likely than males to report continuing pain (OR=2.9, 95% CI=1.4-5.8, p=.005), use of health care (OR=5.1, 95% CI=1.4-18.5, p=.01), medication (OR=4.7, 95% CI=1.3-16.9, p=.02) and non-drug methods of pain control (OR=3.4, 95% CI=1.3-9.2, p=.02). For patients whose pain had associated psychosocial factors, females (76.4%) were significantly more likely than males (21.4%) to report continuing pain (OR=13.8, 95% CI=3.3-58.4, p=.005). Finally, among patients still experiencing pain, the frequency of pain episodes increased significantly with age (OR=1.3, 95% CI=1.0-1.5, p=.02). Results indicate that chronic pain persists for many children despite treatment at specialized clinics. Females may be at higher risk for continuing pain and report greater use of health care, medication, and non-drug methods of pain control.

Risk Perception, Fuzzy Representations and Comparative Optimism

British Journal of Psychology (London, England : 1953). Nov, 2007  |  Pubmed ID: 17931467

Rather than a unitary value, individuals may represent health risk as a fuzzy entity that permits them to make a number of specific possible estimates. Comparative optimism might be explained by people flexibly, using such a set to derive optimistic risk estimates. Student participants were asked to rate the likelihood of eight harmful alcohol-related outcomes occurring to themselves and to an average student. Participants made either unitary estimates or estimates representing the upper and lower bounds of a set denoting 'realistic probability' estimates. Personal risk estimates were lower when they were made as unitary estimates than those calculated from the mid-points of the bounded estimates. Unitary estimates of personal risk made after the bounded estimates were lower than initial unitary estimates. There were no effects for estimates made with regard to the average student. Risk may be internally represented as a fuzzy set, and comparative optimism may exist partly because this set allows people the opportunity to make optimistic unitary estimates for personal risk within what they see as realistic parameters.

An EGR2/CITED1 Transcription Factor Complex and the 14-3-3sigma Tumor Suppressor Are Involved in Regulating ErbB2 Expression in a Transgenic-mouse Model of Human Breast Cancer

Molecular and Cellular Biology. Dec, 2007  |  Pubmed ID: 17938205

Amplification and elevated expression of the ErbB2 receptor tyrosine kinase occurs in 20% of human breast cancers and is associated with a poor prognosis. We have previously demonstrated that mammary tissue-specific expression of activated ErbB2 under the control of its endogenous promoter results in mammary tumor formation. Tumor development was associated with amplification and overexpression of ErbB2 at both the transcript and protein levels. Here we demonstrate that the EGR2/Krox20 transcription factor and its coactivator CITED1 are coordinately upregulated during ErbB2 tumor induction. We have identified an EGR2 binding site in the erbB2 promoter and demonstrated by chromatin immunoprecipitation assays that EGR2 and CITED1 associate specifically with this region of the promoter. EGR2 and CITED1 were shown to associate, and expression from an erbB2 promoter-reporter construct was stimulated by EGR2 and was further enhanced by CITED1 coexpression. Furthermore, expression of the 14-3-3sigma tumor suppressor led to downregulation of ErbB2 protein levels and relocalization of EGR2 from the nucleus to the cytoplasm. Taken together, these observations suggest that, in addition to an increased gene copy number and upregulation of EGR2 and CITED1, an elevated erbB2 transcript level involves the loss of 14-3-3sigma, which sequesters a key transcriptional regulator of the erbB2 promoter.

Effects of a Single-lesson Tobacco Prevention Curriculum on Knowledge, Skill Identification and Smoking Intention

Journal of Drug Education. 2007  |  Pubmed ID: 17982935

One in five students report experimenting with tobacco before the age of 13 and most prevention efforts take place in the school setting. This study measures the effect of a single-lesson tobacco prevention curriculum, conducted by a health education center, focusing on knowledge of tobacco, ability to identify refusal techniques, and intent not to smoke. Data were collected, via electronic keypads, from students visiting a non-school, health education center in Michigan (n = 704 intervention and 85 comparison). Contingency table Chi-squared tests and t-tests demonstrated that a single lesson can improve general knowledge and ability to identify appropriate refusal techniques. Improvement in intent not to smoke was not significant because both groups had very high intent prior to implementation. Similar to results from other programs, multivariate logistic regression of gender, general knowledge, and skill identification revealed that only the skill variable was associated with intent not to smoke at pretest. Recommendations are given for further research and for designing more effective curricula or programs.

AJR Teaching File: Intraventricular Mass

AJR. American Journal of Roentgenology. Dec, 2007  |  Pubmed ID: 18029902

AJR Teaching File: Lumbar Radiculopathy and Intraspinal Mass

AJR. American Journal of Roentgenology. Dec, 2007  |  Pubmed ID: 18029903

Exploring the Geometric and Mechanical Characteristics of the Spine Musculature to Provide Rotational Stiffness to Two Spine Joints in the Neutral Posture

Human Movement Science. Feb, 2007  |  Pubmed ID: 17141904

Joint stiffness is inherently linked to both performance and injury. Muscular activation is the predominant provider of stiffness to the lumbar spine, and is essential to ensure optimal spine performance. The purpose of the current paper was to examine the potential of the trunk muscles to provide rotational joint stiffness at two spine joints in the neutral posture, and to demonstrate the sensitivity of this stiffening potential to various muscle orientation and stiffness assumptions. Two separate anatomical models were utilized to analyze the muscular contributions to the 3-dimensional rotational stiffness about each of the L1-L2 and L4-L5 spine joints. Total muscular stiffening potentials, for both joints in each anatomical model, were found to be highest about the global lateral bend axis, and lowest about the global axial twist axis. The stiffening potential was found to depend highly on both the assumed muscle stiffness coefficient (q value) and the moment arm of the muscle about the joint in question. Analyses of spine stiffness were found to be greatly affected by both the anatomical representation of the surrounding musculature and the selection of the q value in the determination of muscular stiffness. Inappropriate choices of either of these factors could lead to errors in stiffness and subsequently stability estimates, and in the interpretation and possible clinical recommendations stemming from such estimates.

Early Adolescents Perceptions of Health and Health Literacy

The Journal of School Health. Jan, 2007  |  Pubmed ID: 17212754

Health illiteracy is a societal issue that, if addressed successfully, may help to reduce health disparities. It has been associated with increased rates of hospital admission, health care expenditures, and poor health outcomes. Because of this, much of the research in the United States has focused on adults in the health care system. This study investigated the effect of aspects of health literacy on the motivation to practice health-enhancing behaviors among early adolescents.

Five-year Follow-up of Trial of Replication-competent Adenovirus-mediated Suicide Gene Therapy for Treatment of Prostate Cancer

Molecular Therapy : the Journal of the American Society of Gene Therapy. Mar, 2007  |  Pubmed ID: 17228316

Replication-competent adenovirus-mediated suicide gene therapy is an investigational cancer treatment that combines the oncolytic actions of human adenoviruses with the cytotoxic effects of chemo-radiosensitizing genes. Previously, we reported the short-term effects of this therapy in men with local recurrence of prostate cancer after definitive radiotherapy. With a median prostate-specific antigen (PSA) follow-up of 5 years, we report here the effect of the gene therapy on prostate-specific antigen doubling time (PSADT), a surrogate end point with significant prognostic power. When considering all evaluable subjects, the PSADT increased following the gene therapy from a mean of 17 to 31 months (median 16 to 22 months) (P=0.014). Assuming that salvage androgen suppression therapy androgen suppression therapy (AST) was uniformly initiated at a PSA of 15 ng/mL, the gene therapy would have delayed the projected onset of salvage therapy by an average of 2 years. The results indicate that replication-competent adenovirus-mediated suicide gene therapy may provide a potential long-term benefit to patients, as shown by a lengthening of the PSADT, and delay in when salvage therapy is indicated. Given the high morbidity associated with AST, we believe this approach could provide an attractive treatment option for selection of patients experiencing PSA relapse following definitive therapy.

Inhibition of CYP1A Enzymes by Alpha-naphthoflavone Causes Both Synergism and Antagonism of Retene Toxicity to Rainbow Trout (Oncorhynchus Mykiss)

Aquatic Toxicology (Amsterdam, Netherlands). Mar, 2007  |  Pubmed ID: 17257690

Retene (7-isopropyl-1-methyl phenanthrene) is a polycyclic aromatic hydrocarbon (PAH), that causes dioxin-like toxicity to early life stages of fish, including increased rates of mortality, developmental defects characterized as blue sac disease (BSD), and induction of CYP1A enzymes. This study determined whether toxicity is associated with retene, or with its metabolism by CYP1A enzymes to hydroxylated derivatives. Larval rainbow trout (Oncorhynchus mykiss) were co-exposed to four concentrations of waterborne retene and four concentrations of waterborne alpha-naphthoflavone (ANF), a compound that antagonizes CYP1A induction and inhibits oxygenation reactions. The prevalence of mortality and BSD increased in an exposure-dependent manner for larvae exposed to retene alone. Tissue concentrations of CYP1A protein and retene metabolites also increased, but no un-metabolized retene (i.e., the parent compound) was measurable. At low concentrations of ANF, toxicity increased dramatically, while tissue concentrations of polar hydroxylated metabolites of retene decreased, and concentrations of less polar metabolites, and of parent retene, increased. At the highest concentration of ANF, retene toxicity was eliminated, and parent retene was the predominant form in tissue; no concentration of ANF was toxic by itself. The inhibition of retene hydroxylation and toxicity by ANF suggests that toxicity was caused by specific retene metabolites, and not by parent retene. The potentiation of retene toxicity at low concentrations of ANF, and the antagonism at high concentrations is a unique, non-linear interaction based on modulating CYP1A enzyme activity and retene metabolism. It demonstrates that effects on fish of different complex mixtures of hydrocarbons may not be easily predicted.

Issues in Imaging-guided Tumor Ablation in Children Versus Adults

AJR. American Journal of Roentgenology. Sep, 2007  |  Pubmed ID: 17715110

OBJECTIVE: Despite the growing use of percutaneous imaging-guided tumor ablation in adults, few reports describe its use in children except for osteoid osteoma. Our objective is to describe how tumor ablation in children and adults may differ, both to facilitate dialogue on pediatric tumor ablation and to increase awareness and use of this valuable technique. CONCLUSION: There are numerous indications for which various ablative techniques may be safe and effective for treatment of pediatric tumors. Nonetheless, important differences between the pediatric and adult populations warrant consideration.

Magnetically-labeled Sensitized Splenocytes to Identify Glioma by MRI: a Preliminary Study

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Sep, 2007  |  Pubmed ID: 17763342

This study investigated the feasibility of imaging the migration and incorporation of magnetically-labeled sensitized splenocytes in an experimental 9L glioma brain tumor model. Splenocytes collected from tumor-bearing (sensitized splenocytes) or control (nonsensitized splenocytes) host rats were analyzed to determine the population of different cells, labeled with ferumoxides-protamine sulfate (FePro) and injected intravenously to recipient rats (N=4, for each group) bearing intracranial 9L tumors. Day 3 postinjection of splenocytes multiecho T2*-weighted and three-dimensional (3D) gradient echo MRI were obtained using a 7 Tesla MR system. R2* (1/T2*) maps were created from the T2*-weighted images. Signal intensities (SIs) and R2* values in the tumors and contralateral brain were determined by hand drawn regions of interest (ROIs). Brain sections were stained for the evidence of administered cells. Both 3D and T2*-weighted MRI showed low signal intensity areas in and around the tumors in rats that received labeled sensitized splenocytes. Prussian blue (PB), CD45- and CD8-positive cells were present in areas at the corresponding sites of low signal intensities seen on MRI. Rats that received labeled nonsensitized splenocytes did not show low signal intensity areas or PB positive cells in or around the implanted tumors. In conclusion, the immunogenic reaction can be exploited to delineate recurrent glioma using MRI following systemically delivered magnetically labeled sensitized splenocytes or T-cells.

Differential Radiation Effect in Tumor and Normal Tissue After Treatment with Ramipril, an Angiotensin-converting Enzyme Inhibitor

Radiation Research. Oct, 2007  |  Pubmed ID: 17903031

The angiotensin-converting enzyme inhibitor, ramipril, has been shown to mitigate radiation injury in normal tissues. Using A549 cell xenografts grown in athymic mice, we measured the effect of ramipril on radiation damage to tumors. Ramipril did not alter tumor response to radiation despite different times of drug administration with respect to radiation delivery (drug started 2 weeks before or immediately after irradiation). In contrast, using the same dose, ramipril reduced normal tissue radiation injury (30 Gy x 2 or 6 Gy x 10) as assessed by a semi-quantitative scale of skin damage and relative leg contraction. The results indicate that ramipril could offer therapeutic gain due to its different effect on normal tissues and tumors.

Effects of Abdominal Stabilization Maneuvers on the Control of Spine Motion and Stability Against Sudden Trunk Perturbations

Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. Oct, 2007  |  Pubmed ID: 16996278

Much discussion exists about which is the most effective technique to improve spine stability. The purpose of this study was to evaluate the effectiveness of abdominal bracing and abdominal hollowing maneuvers to control spine motion and stability against rapid perturbations. Eleven healthy males were posteriorly loaded in different experimental conditions: resting with no knowledge of the perturbation timing; performing each of the stabilization maneuvers at 10%, 15% and 20% of internal oblique maximum voluntary contraction with no knowledge of the perturbation timing; and naturally coactivating the trunk muscles when perturbation timing was known. An EMG biofeedback system was used to control the pattern and intensity of abdominal coactivation. The muscular preactivation of seven trunk muscles (bilaterally registered), the applied force, and the torso muscular and kinematic responses to loading were measured; and the spine stability and compression were modeled. The hollowing maneuver was not effective for reducing the kinematic response to sudden perturbation. On the contrary, the bracing maneuver fostered torso cocontraction, reduced lumbar displacement, and increased trunk stability, but at the cost of increasing spinal compression. When the timing of the perturbation was known, the participants were able to stabilize the trunk while imposing smaller spine compressive loads.

Mitigation of Radiation-induced Optic Neuropathy in Rats by ACE Inhibitor Ramipril: Importance of Ramipril Dose and Treatment Time

Journal of Neuro-oncology. Apr, 2007  |  Pubmed ID: 17004100

Radiation-induced optic nerve damage was reduced by ramipril, a prodrug angiotensin-converting enzyme inhibitor (ACEI). This study was to determine the optimum dose and administration time of ramipril for mitigating radiation-induced optic neuropathy.

Safety in Pediatric MR and Cardiac CT: Results of a Membership Survey of the Society for Pediatric Radiology-2006

Pediatric Radiology. Apr, 2007  |  Pubmed ID: 17325823

Integrating Public Health Policy, Practice, Evaluation, Surveillance, and Research: the School Health Action Planning and Evaluation System

American Journal of Public Health. Apr, 2007  |  Pubmed ID: 17329662

The Canadian Cancer Society and the National Cancer Institute of Canada have charged their Centre for Behavioral Research and Program Evaluation with contributing to the development of the country's systemic capacity to link research, policy, and practice related to population-level interventions. Local data collection and feedback systems are integral to this capacity. Canada's School Health Action Planning and Evaluation System (SHAPES) allows data to be collected from all of a school's students, and these data are used to produce computer-generated school "health profiles." SHAPES is being used for intervention planning, evaluation, surveillance, and research across Canada. Strong demand and multipartner investment suggest that SHAPES is adding value in all of these domains. Such systems can contribute substantially to evidence-informed public health practice, public engagement, participatory action research, and relevant, timely population intervention research.

False-positive Quadruple Screen Test for Trisomy 18 in a Patient with a Fetus with Bloom's Syndrome

Fetal Diagnosis and Therapy. 2007  |  Pubmed ID: 17361088

In the literature, conflicting reports on the significance of false-positive maternal serum multiple marker testing for trisomy 18 are encountered; however, the biology of this finding is discussed infrequently. We present such a case in association with Bloom's syndrome in the fetus. The fetus had intrauterine growth restriction, seen early in the second trimester, oligohydramnios, and was delivered at 34 weeks of gestation for impending fetal compromise. We propose that the adverse outcome of the pregnancy with false-positive serum analyte testing for trisomy 18 might result from a small-sized placenta and perhaps pathology at receptor level.

Visually Directed High-intensity Focused Ultrasound for Organ-confined Prostate Cancer: a Proposed Standard for the Conduct of Therapy

BJU International. Apr, 2007  |  Pubmed ID: 17378856

The Effect of Reducing the Number of EMG Channel Inputs on Loading and Stiffness Estimates from an EMG-driven Model of the Spine

Ergonomics. May, 2007  |  Pubmed ID: 17454091

Electromyography (EMG)-driven models of the spine routinely require between ten and 14 EMG channels to estimate joint load and stiffness variables. This study was designed to determine the sensitivity of common EMG-driven model outputs to the removal of individual EMG channels, and to test two adapted models driven from eight channels. A total of 11 male participants performed a variety of static exertions designed to resist either an applied trunk flexion or right side trunk lateral bend moment. In this study, 14 channels of EMG were recorded and used to drive a biomechanical model of the spine to predict L4-L5 joint load and stiffness values. The model was subsequently re-run after the removal of individual pairs of bilateral EMG channels, and again with eight-channel models in which the rectus abdominus, latissimus dorsi and multifidus EMG-channels were eliminated. Results showed that the eight-channel model provided estimates for the majority of output variables that did not differ substantially from the 14-channel model, except in instances in which muscle force output was ramped to resist flexion moments. Estimates of the output variables were, in general, improved when multifidus fascicles were re-added to the model and driven from the lumbar erector spinae EMG sites.

A Multi-dimensional High Performance Liquid Chromatographic Method for Fingerprinting Polycyclic Aromatic Hydrocarbons and Their Alkyl-homologs in the Heavy Gas Oil Fraction of Alaskan North Slope Crude

Journal of Chromatography. A. Jul, 2007  |  Pubmed ID: 17482627

We report an offline multi-dimensional high performance liquid chromatography (HPLC) technique for the group separation and analysis of PAHs in a heavy gas oil fraction (boiling range 287-481 degrees C). Waxes present in the heavy gas oil fraction were precipitated using cold acetone at -20 degrees C. Recovery studies showed that the extract contained 93% (+/-1%; n=3) of the PAHs that were originally present while the wax residue contained only 6% (+/-0.5%; n=3). PAHs present in the extract were fractionated, based on number of rings, into five fractions using a semi-preparative silica column (normal-phase HPLC). These fractions were analyzed using reverse-phase HPLC (RP-HPLC) coupled to a diode array detector (DAD). The method separated alkyl and un-substituted PAHs on two reverse-phase columns in series using an acetonitrile/water mobile phase. UV spectra of the chromatographic peaks were used to differentiate among PAH groups. Further characterization of PAHs within a given group to determine the substituent alkyl carbon number used retention time matching with a suite of alkyl-PAH standards. Naphthalene, dibenzothiophene, phenanthrene and fluorene and their C1-C4 alkyl isomers were quantified. The concentrations of these compounds obtained using the current method were compared with that of a GC-MS analysis obtained from an independent oil chemistry laboratory.

Replication-competent Adenovirus-mediated Suicide Gene Therapy with Radiation in a Preclinical Model of Pancreatic Cancer

Molecular Therapy : the Journal of the American Society of Gene Therapy. Sep, 2007  |  Pubmed ID: 17551507

In preparation for a Phase I trial, we evaluated the efficacy and toxicity of replication-competent adenovirus-mediated suicide gene therapy in combination with radiation in a preclinical model of pancreatic cancer. Human MiaPaCa-2 and PANC-1 pancreatic adenocarcinoma cells were found to be sensitive to the oncolytic effects of the Ad5-yCD/mutTK(SR39)rep-ADP adenovirus and also to the cytotoxic effects of the yeast cytosine deaminase (yCD) and herpes simplex virus thymidine kinase (HSV-1 TK(SR39)) genes in vitro. Combining Ad5-yCD/mutTK(SR39)rep-ADP-mediated suicide gene therapy with radiation significantly increased tumor control beyond that of either modality alone. Injection of Ad5-yCD/mutTK(SR39)rep-ADP in the dog pancreas at doses (10(12) virus particle (vp)) to be used in humans resulted in mild pancreatitis but not peritonitis or hepatotoxicity. Following administration of 9-(4-[(18)F]-fluoro-3-hydroxymethylbutyl)guanine ([(18)F]-FHBG), a positron-emitting substrate of HSV-1 TK, Ad5-yCD/mutTK(SR39)rep-ADP activity could be monitored non-invasively by positron emission tomography (PET). [(18)F]-FHBG uptake was readily detected in the pancreas but not in other major abdominal organs, indicating that little of the injected adenovirus disseminates to collateral tissues. These results demonstrate that Ad5-yCD/mutTK(SR39)rep-ADP-mediated suicide gene therapy has the potential to augment the effectiveness of pancreatic radiotherapy without resulting in excessive toxicity. Hence they provide the scientific basis for an ongoing Phase I trial in pancreatic cancer.

Recombinant Human Growth Hormone to Treat HIV-associated Adipose Redistribution Syndrome: 12 Week Induction and 24-week Maintenance Therapy

Journal of Acquired Immune Deficiency Syndromes (1999). Jul, 2007  |  Pubmed ID: 17592343

HIV-associated adipose redistribution syndrome (HARS) is an HIV-associated disorder characterized by excess truncal fat, including visceral adipose tissue (VAT).

A Model for Optimizing Adenoviral Delivery in Human Cancer Gene Therapy Trials

Human Gene Therapy. Jun, 2007  |  Pubmed ID: 17594241

Optimization of adenoviral delivery to the target volume is required for adenovirus-mediated cancer gene therapy to reach its maximal potential. The purpose of these studies was to develop a model of gene expression to improve adenovirus-mediated cancer gene therapy in the clinic. We measured the distribution of gene expression after a single deposit of a replication-competent adenovirus carrying the human sodium iodide symporter (hNIS) reporter gene was delivered to naive canine prostate and to human tumor xenografts. We generated hypothetical treatment plans for two prospective prostate cancer patients, using standard brachytherapy algorithms. In both models, the gene expression distribution from a single adenoviral deposit could be accurately described by a Gaussian function. In the naive canine prostate, a 0.1-ml deposit of 3 x 10(11) viral particles (VP) resulted in a gene expression volume of 1.14 +/- 0.70 cm(3), indicating that a minimum of 40 adenoviral deposits would be required to cover a 40-cm(3) prostate with therapeutic gene expression. On a viral particle basis, the gene expression volume obtained in human tumor xenografts (7 x 10(-12) cm(3)/VP) was twice that (3.5 x 10(-12) cm(3)/VP) measured in the naive canine prostate. Hypothetical treatment plans for two prostates indicated that 26 and 57 0.1-ml adenoviral deposits would be required to cover, respectively, 24- and 49-cm(3) prostates with gene expression. Although our studies focused on prostate, we believe the methodology to model gene expression presented here has much broader application to optimize treatment plans in other solid tumor sites; this assertion should be confirmed experimentally.

Anxiety Sensitivity, Fear of Pain and Pain-related Disability in Children and Adolescents with Chronic Pain

Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur. 2007  |  Pubmed ID: 18080045

Converging lines of evidence suggest that anxiety sensitivity and fear of pain may be important vulnerability factors in the development of avoidance behaviours and disability in adults with chronic pain. However, these factors have not been evaluated in children with chronic pain.

Metabolic Effects of a Growth Hormone-releasing Factor in Patients with HIV

The New England Journal of Medicine. Dec, 2007  |  Pubmed ID: 18057338

Visceral adipose tissue accumulates during antiretroviral therapy in many patients who are infected with the human immunodeficiency virus (HIV); this process is associated with an increased cardiovascular risk. We assessed the use of a growth hormone-releasing factor analogue, tesamorelin, to decrease visceral adiposity.

Coronary Artery In-stent Stenosis Persists Despite Inhibition of the Von Willebrand Factor--collagen Interaction in Baboons

Thrombosis and Haemostasis. Dec, 2007  |  Pubmed ID: 18064334

Revascularization techniques, such as angioplasty and stent implantation, frequently lead to restenosis due to the formation of neointima after platelet activation and the concomitant release of various smooth muscle cell mitogenic and attractant factors. We here investigate whether inhibition of initial platelet adhesion after stent implantation can decrease neointima formation in a clinically relevant baboon model of in-stent stenosis using standard treatment with aspirin, clopidogrel and heparin. Inhibition of platelet adhesion was established by administration of the anti-von Willebrand factor (VWF) monoclonal antibody 82D6A3, which inhibits VWF binding to collagen. Administration of 82D6A3 resulted in a complete inhibition of VWF binding to collagen during the first three days after stent implantation. No thrombocytopenia or prolongation of the bleeding time was observed. Our results show that the formation of neointima was not affected in the group of baboons where primary platelet adhesion was abolished with 82D6A3 when compared to the control group. Vascular injury scores were the same in both groups. Inhibition of platelet adhesion during the first three days after stenting, on top of standard treatment with aspirin, clopidogrel and heparin, had no effect on neo-intima formation in a baboon model of in-stent stenosis. During the last decade, attempts to translate seemingly effective therapies based on smaller animal experimentation to the clinic have consistently failed. This study, using a non-human primate model that more closely resembles the clinical situation, presents a model that may be of further clinical interest for studying the prevention of restenosis.

Phase I Trial of Replication-competent Adenovirus-mediated Suicide Gene Therapy Combined with IMRT for Prostate Cancer

Molecular Therapy : the Journal of the American Society of Gene Therapy. May, 2007  |  Pubmed ID: 17375076

Replication-competent adenovirus-mediated suicide gene therapy is an investigational cancer treatment in which an oncolytic adenovirus armed with chemo-radiosensitizing genes is used to destroy tumor cells. Previously, we evaluated the toxicity and efficacy of this approach in two clinical trials of prostate cancer using a first-generation adenovirus. Here, we report the toxicity and preliminary efficacy of this approach in combination with intensity-modulated radiotherapy (IMRT) in patients with newly diagnosed prostate cancer using an improved, second-generation adenovirus. The investigational therapy was associated with low toxicity, and there were no dose-limiting toxicities or treatment-related serious adverse events. Relative to a previous trial using a first-generation adenovirus, there was no increase in hematologic, hepatic, gastrointestinal (GI), or genitourinary (GU) toxicities. Post-treatment prostate biopsies yielded provocative preliminary results. When the results of two similar trials were combined, 22% of evaluable patients were positive for adenocarcinoma at their last biopsy, which is better than expected (>or=40%) for this cohort of patients (P=0.038). When the results were categorized by prognostic risk, most of the treatment effect was observed in the intermediate-risk group, with 0 of 12 patients (0%) being positive for cancer at their last biopsy (P<0.01). These results further demonstrate the safety of this investigational approach and raise the possibility that it may have the potential to improve the outcome of conformal radiotherapy in select patient groups.

Design Considerations for Incorporating Sodium Iodide Symporter Reporter Gene Imaging into Prostate Cancer Gene Therapy Trials

Human Gene Therapy. Apr, 2007  |  Pubmed ID: 17408358

This study was done to aid in the design of a phase I gene therapy trial in patients with prostate cancer. We determined the dosimetric characteristics of our reporter gene system when coupled with intravenous administration of radioactive sodium pertechnetate (Na(99m) TcO(4)) and determined the feasibility of using human sodium iodide symporter (hNIS) as a reporter gene to study the dynamics of adenoviral transgene expression in a large animal tumor. A replication-competent Ad5-yCD/mutTK(SR39) rep-hNIS adenovirus was injected into the prostate gland of dogs for dosimetry purposes, and into a canine soft tissue sarcoma (STS) for imaging purposes. After resection of the prostate, the amount of (99m)TcO(4)() sequestered in the prostate was determined, the radiation dose absorbed by the prostate and nontarget critical organs was calculated, and hNIS reporter gene expression was imaged in the STS by single-photon emission computed tomography (SPECT). On the basis of the findings from 25 dogs, the amount of (99m)TcO (4)() sequestered in the prostate ranged from 13 to 276 muCi. Using the highest value observed, absorbed radiation dose to critical organs was calculated and found to be below U.S. Food and Drug Administration limits for diagnostic imaging. Also, (99m)TcO (4)() uptake was readily detected by SPECT and found to persist in vivo for at least 4 days. On the basis of our dosimetry calculations, up to five imaging procedures can be safely performed in humans after intraprostatic injection of the Ad5-yCD/mutTK(SR39)rep-hNIS adenovirus and the hNIS reporter gene system can be used to study the dynamics of adenoviral gene therapy vectors in large animal tumors.

Relative Distribution of Plasma Flow Markers and Red Blood Cells Across BBB Openings in Acute Cerebral Ischemia

Neurological Research. Jan, 2007  |  Pubmed ID: 17427280

Acute blood-brain barrier (BBB) opening in cerebral ischemia is an often observed but seldom studied phenomenon. Increased permeability has been implicated with several consequences including exacerbating ischemic injury, leading to hemorrhagic transformation (HT) and also predictive of chronic damage and a way of delivering therapeutics to the diseased parts of brain. Very few studies have investigated the 'size' of such acute openings. Herein the blood-brain distribution of fluorescent isothiocyanate (FITC)- labeled red blood cells (RBCs; approximately 5 tm in diameter) and two different sized plasma flow markers in cerebral microvessels was studied by laser scanning confocal microscopy (LSCM) 6 and 24 hours after the onset of a 3 hour period of focal ischemia. At hour 6, Evans blue-tagged albumin [EB-Alb; molecular weight (MW)= 68 kDa, Stokes-Einstein radius=37 A], a marker of both plasma flow and BBB opening, was seen both inside and around microvessels whereas the RBCs were only intravascular. FITC-labeled dextran (FITC-dextran; MW=2000 kDa, Stokes-Einstein radius = approximately 150 A), another plasma flow tracer, had not leaked across the BBB into the tissue at this time. At hour 24, both RBCs and FITC-dextran were found extravascularly along with EB-Alb. We postulate that smaller sized openings in BBB at hour 6 limited the leaking of the two large tracers (RBCs and FITC-dextran) and that such size-dependency was lost by 24 hours with the progression of the ischemic injury.

Reporter Gene Imaging Using Radiographic Contrast from Nonradioactive Iodide Sequestered by the Sodium-iodide Symporter

Contrast Media & Molecular Imaging. Sep-Oct, 2007  |  Pubmed ID: 18058866

The hypothesis that the human sodium-iodide symporter, NIS, can be used to detect NIS expression using standard radiological techniques was tested using adenoviral transduced NIS expression in human tumor xenografts grown in mice and in a naive dog prostate. Nonradioactive iodide was administered systemically to animals that 1-3 days previously had received a local injection of a replication-competent adenovirus expressing NIS under the control of the CMV promoter. The distribution of radiopacity was assessed in mouse tumors using micro-CT and a clinical X-ray machine and in the prostate of an anesthetized dog using a clinical spiral CT. Iodide sequestration and NIS expression were measured using X-ray spectrochemical analysis and fluorescence microscopy, respectively. Radiographic contrast due to NIS gene expression that was observed indicates the technique has potential for use in preclinical rodent tumor studies but probably lacks sensitivity for human use.

Correlates of Resilience in the Face of Adversity for Korean Women Immigrating to the US

Journal of Immigrant and Minority Health / Center for Minority Public Health. Oct, 2008  |  Pubmed ID: 18066717

To explore the association between resilience and psychosocial variables of theoretical relevance such as self-esteem, optimism, religiousness, cultural interdependency, and belief in higher education in a population of elderly Korean women and their daughters who experienced great adversity.

MRI Measurement of Change in Vascular Parameters in the 9L Rat Cerebral Tumor After Dexamethasone Administration

Journal of Magnetic Resonance Imaging : JMRI. Jun, 2008  |  Pubmed ID: 18504732

To demonstrate in the rat 9L cerebral tumor model that repeated MRI measurements can quantitate acute changes in the blood-brain distribution of Gadomer after dexamethasone administration.

Glucagon is Absorbed from the Rectum but Does Not Hasten Recovery from Hypoglycaemia in Patients with Type 1 Diabetes

British Journal of Clinical Pharmacology. Jul, 2008  |  Pubmed ID: 18507661

A failure to secrete glucagon during hypoglycaemia is near universal in patients with type 1 diabetes 5 years after disease onset and may contribute to delayed counter-regulation during hypoglycaemia. Rectal glucagon delivery may assist glucose recovery following insulin-induced hypoglycaemia in such patients and has not been previously studied.

The '2-week Wait' Rule for Referrals for Suspected Urological Cancers--urgent Need for Refinement of Criteria

Annals of the Royal College of Surgeons of England. Sep, 2008  |  Pubmed ID: 18765032

All NHS-suspected cancers should be seen within 2 weeks of referral and are referred under government guidelines (Health Service Circular 205; HSC 205). This policy will be subject to review in 2009. Review is vital to allow the appropriate detection of malignancy without overburdening the premium clinic slots with the healthy.

Self-injurious Behaviour, Traumatic Life Events and Alexithymia Among Treatment-seeking Opiate Addicts: Prevalence, Pattern and Correlates

Drug and Alcohol Dependence. Dec, 2008  |  Pubmed ID: 18639391

Aim of this study was to determine the prevalence and pattern of self-injurious behaviour (SIB) and identify the predictors of SIB among treatment-seeking opiate addicts.

Long-term Safety and Effects of Tesamorelin, a Growth Hormone-releasing Factor Analogue, in HIV Patients with Abdominal Fat Accumulation

AIDS (London, England). Sep, 2008  |  Pubmed ID: 18690162

Treatment of HIV patients with daily tesamorelin, a growth hormone-releasing factor analogue, for 26 weeks resulted in a significant decrease in visceral adipose tissue (VAT) and improvement in lipids. The objective of the 26-week extension phase was to evaluate long-term safety and effects of tesamorelin.

Recombinant Production of Hyaluronic Acid

Current Pharmaceutical Biotechnology. Aug, 2008  |  Pubmed ID: 18691082

Presently, the two main commercial sources of hyaluronic acid (HA) are rooster combs and streptococci. Harvesting from rooster combs is complex and costly. Streptococci are difficult to genetically manipulate and require complex media for growth. Both sources have potential problems with unwanted by-products, such as allergens and toxins. These problems can be solved by producing the HA with safe bacilli that are expressing a recombinant HA synthase (HAS).

Southside Medical Homes Network: Linking Emergency Department Patients to Community Care

Prehospital and Disaster Medicine. May-Jun, 2008  |  Pubmed ID: 18702276

BBACKGROUND The 14 neighborhoods surrounding University of Chicago Hospitals (UCH) have both Chicago's highest "ambulatory-care-sensitive condition" hospitalization rates and lack of community-based care. To address these problems, in 2004, the Southside Medical Homes (SMH) Network began linking emergency department (ED) patients with 18 community providers. The ED-based patient navigator (patient advocate) is an integral component of this network, and both their current and developing roles will be discussed. MMETHODS Six navigators worked in the UCH-ED approached eligible patients that are flagged by the ED electronic tracking system. Patients were offered the services provided by primary-care referral and appropriate dental, mental health, and substance abuse facilities. Appointments were scheduled, and pertinent ED medical data was faxed to the outlying sites. Navigator roles were expanding with SMH to include: (1) focus on frequent user/chronic disease populations such as sickle cell disease where advocates will expedite a multidisciplinary clinic referral; (2) navigator training to better inform patients of the specific benefits a "medical home" provides for preventive and psychosocial care; (3) and improving navigator, and secondarily, patient knowledge, of community resources: health-education sites, vocational programs, advocacy agencies, support groups, etc. RRESULTS/CONCLUSIONS Data through 01 July 2007 show a monthly average of 950 ED patients surveyed and 80% of these accepting follow-up referral services. Of those patients with ED-scheduled appointments (43%) in community clinics, network data shows patients returning to their referred providers: 39% of patients have been -> or = times. The navigator role is evolving with the expansion of SMH to include: (1) frequent-user population referrals; (2) preventive health education; and (3) utilization of community resources.

Phase I Study of Noninvasive Imaging of Adenovirus-mediated Gene Expression in the Human Prostate

Molecular Therapy : the Journal of the American Society of Gene Therapy. Oct, 2008  |  Pubmed ID: 18714306

To monitor noninvasively potentially therapeutic adenoviruses for cancer, we have developed a methodology based on the sodium iodide symporter (NIS). Men with clinically localized prostate cancer were administered an intraprostatic injection of a replication-competent adenovirus, Ad5-yCD/utTK(SR39)rep-hNIS, armed with two suicide genes and the NIS gene. NIS gene expression (GE) was imaged noninvasively by uptake of Na(99 m)TcO(4) in infected cells using single photon emission-computed tomography (SPECT). The investigational therapy was safe with 98% of the adverse events being grade 1 or 2. GE was detected in the prostate in seven of nine (78%) patients at 1 x 10(12) virus particles (vp) but not at 1 x 10(11) vp. Volume and total amount of GE was quantified by SPECT. Following injection of 1 x 10(12) vp in 1 cm(3), GE volume (GEV) increased to a mean of 6.6 cm(3), representing, on average, 18% of the total prostate volume. GEV and intensity peaked 1-2 days after the adenovirus injection and was detectable in the prostate up to 7 days. Whole-body imaging demonstrated intraprostatic gene expression, and there was no evidence of extraprostatic dissemination of the adenovirus by SPECT imaging. The results demonstrate that noninvasive imaging of adenovirus-mediated gene therapy in humans is feasible and safe.

An Ultrasound Investigation into the Morphology of the Human Abdominal Wall Uncovers Complex Deformation Patterns During Contraction

European Journal of Applied Physiology. Dec, 2008  |  Pubmed ID: 18726611

The abdominal wall components, specifically muscle and connective tissue, must meet and accommodate a wide range of force demands for torso movement, spine stabilization, and respiration. It has a composite laminate nature that may lend itself to facilitating the required tissue responses. The purpose of this exploratory study was to examine the deformations of the abdominal wall connective tissues, with a special focus on both the internal oblique aponeurosis and the tendinous intersections of the rectus abdominis, using ultrasound imaging, during relatively simple contractions of the abdominal musculature. There were two main findings of this study: (1) deformations occurred in nearly 50% of contractions that would be characterized by a simultaneous expansion in multiple planes; (2) the laterally generated forces of the oblique and transverse muscles transfer a great deal of force across the rectus abdominis muscle and sheath, leading to a lateral movement of the rectus muscle during abdominal contraction.

Chronic Nicotine in Utero Selectively Suppresses Hypoxic Sensitivity in Neonatal Rat Adrenal Chromaffin Cells

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. May, 2008  |  Pubmed ID: 18070822

Nicotine in cigarette smoke has been linked to several deleterious side effects on the offspring of smoking mothers, including impaired development of the sympathoadrenal system, abnormal arousal reflexes, and sudden infant death syndrome. Catecholamine (CA) release from adrenomedullary chromaffin cells (AMCs) in response to asphyxial stressors, e.g., low O(2) (hypoxia) and elevated CO(2) (hypercapnia), is critical for adaptation to extrauterine life and occurs before splanchnic innervation. Here, we investigated the effects of prenatal nicotine bitartrate exposure on the ability of neonatal (P0) rat AMCs to respond appropriately to asphyxial stressors. Control AMCs isolated from pups born to saline-treated dams displayed typical responses to hypoxia and hypercapnia, including inhibition of outward K(+) current, membrane depolarization, increased cytosolic calcium, and CA secretion. In contrast, P0 AMCs from pups born to nicotine-treated dams showed a marked suppression or loss of hypoxic sensitivity, although hypercapnic sensitivity and the expression of CO(2) markers (i.e., carbonic anhydrase I and II) appeared normal. Moreover, isolated saline-treated P0 AMCs lost their hypoxic sensitivity when grown in culture for approximately 1 wk in the presence of a subsaturating concentration of nicotine base (50 microM), and this effect was abolished by the nicotinic acetylcholine receptor (nAChR) blocker mecamylamine (100 microM). Taken together, these data suggest that the adverse effects of maternal smoking on sympathoadrenal function in the offspring are due in part to a loss or suppression of acute hypoxic sensitivity in adrenal chromaffin cells, triggered by the direct action of nicotine on endogenous nicotinic acetylcholine receptors.

Safety and Immunogenicity of a Replication-incompetent Adenovirus Type 5 HIV-1 Clade B Gag/pol/nef Vaccine in Healthy Adults

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Jun, 2008  |  Pubmed ID: 18433307

The safety and immunogenicity of the MRK adenovirus type 5 human immunodeficiency virus type 1 clade B gag/pol/nef vaccine, a replication-incompetent adenovirus type 5-vectored vaccine designed to elicit cell-mediated immunity against conserved human immunodeficiency virus proteins, was assessed in a phase 1 trial.

Epinephrine/Lidocaine Injection Vs. Saline During Endoscopic Sinus Surgery

The Laryngoscope. Jul, 2008  |  Pubmed ID: 18438267

To assess the safety and effectiveness of an epinephrine/lidocaine mixture administered by injection versus epinephrine administered topically and to learn its pharmacokinetics following administration to the nasal mucosa.

Glucosensing in an Immortalized Adrenomedullary Chromaffin Cell Line: Role of ATP-sensitive K+ Channels

Neuroscience Letters. Nov, 2008  |  Pubmed ID: 18786611

Using an immortalized adrenal chromaffin cell line (MAH cells), we investigated the cellular mechanisms underlying sensitivity to glucose-free solution (aglycemia) using ratiometric Ca2+ imaging and whole-cell recording. Though few cells (< 15%) responded to aglycemia with an increase in intracellular-free Ca2+ concentration ([Ca2+]i), in most cells (approximately 75%), aglycemia caused > 50% suppression of the Delta[Ca2+]i induced by the depolarizing stimulus, high (10 mM) K+. Moreover, in normal K+, the average aglycemia-induced rise in Cai2+ as well as the proportion of aglycemia-responsive cells increased in the presence of the K(ATP) channel blocker, glibenclamide. During membrane potential (Vm) measurements, aglycemia induced either hyperpolarization (6/20), depolarization (4/20) or no change in Vm. RT-PCR and Western blotting confirmed the presence of K(ATP) channel subunits Kir6.2 and SUR1 in MAH cells. These findings suggest a dual inhibitory and excitatory action of aglycemia in MAH cells, where activation of K(ATP) channels effectively inhibits or blunts the Delta[Ca2+]i due to the excitatory effect. Thus, this cell line appears as an attractive model for studying the molecular mechanisms of glucosensing.

Miscarriage and Its Associations

Seminars in Reproductive Medicine. Sep, 2008  |  Pubmed ID: 18825607

Despite many years of study, abnormal chromosome number remains the most common and well-documented cause of miscarriage. Nonchromosomal factors that have been associated with miscarriage are many and include endocrine abnormalities, anatomic abnormalities, inherited and acquired thrombophilia, environmental exposures, immunologic factors, and others. This article attempts to provide a brief overview and critique of the frequently reported factors. In addition, we call attention to the fact that, to be most helpful, modern studies of miscarriage need to provide details about the sonographically determined gestational age and fetal anatomic development prior to or at the time of pregnancy loss. Such information will be critical in helping to sort out which miscarriage-associated factors are more relevant at which stage of fetal development.

Mechanisms of Radiation-induced Brain Toxicity and Implications for Future Clinical Trials

Journal of Neuro-oncology. May, 2008  |  Pubmed ID: 18209952

Radiation therapy is widely used in the treatment of primary malignant brain tumors and metastatic tumors of the brain with either curative or palliative intent. The limitation of cancer radiation therapy does not derive from the inability to ablate tumor, but rather to do so without excessively damaging the patient. Among the varieties of radiation-induced brain toxicities, it is the late delayed effects that lead to severe and irreversible neurological consequences. Following radiation exposure, late delayed effects within the CNS have been attributable to both parenchymal and vascular damage involving oligodendrocytes, neural progenitors, and endothelial cells. These reflect a dynamic process involving radiation-induced death of target cells and subsequent secondary reactive neuroinflammatory processes that are believed to lead to selective cell loss, tissue damage, and functional deficits. The progressive, late delayed damage to the brain after high-dose radiation is thought to be caused by radiation-induced long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines. Experimental studies suggest that radiation-induced brain injury can be successfully mitigated and treated with several well established drugs in wide clinical use which exert their effects by blocking pro-inflammatory cytokines and reactive oxygen species. This review highlights preclinical and early clinical data that are translatable for future clinical trials.

Radiation Mitigation Effect of Cultured Mushroom Fungus Hirsutella Sinensis (CorImmune) Isolated from a Chinese/Tibetan Herbal Preparation -Cordyceps Sinensis

International Journal of Radiation Biology. Feb, 2008  |  Pubmed ID: 18246482

This study was carried out to test the hypothesis that the anti-oxidant and growth promoting properties of the cultured mushroom fungus Hirsutella sinensis (CorImmune) of Cordyceps sinensis mitigate radiation injury in mice.

Safety, Pharmacokinetics, and Antiviral Activity of HGS004, a Novel Fully Human IgG4 Monoclonal Antibody Against CCR5, in HIV-1-infected Patients

The Journal of Infectious Diseases. Mar, 2008  |  Pubmed ID: 18266604

HGS004 is a fully human immunoglobulin (Ig) G4 monoclonal antibody against CC chemokine receptor 5 (CCR5) with robust in vitro activity against a diverse panel of CCR5-tropic human immunodeficiency virus type 1 (HIV-1) isolates.

The Red Flour Beetle's Large Nose: an Expanded Odorant Receptor Gene Family in Tribolium Castaneum

Insect Biochemistry and Molecular Biology. Apr, 2008  |  Pubmed ID: 18342245

The Tribolium castaneum genome sequence reveals a large number of odorant receptor (Or) genes compared to those found in other insects whose olfactory genomes have been studied-341 Or genes and pseudogenes, encoding 259 intact odorant receptor proteins. An RT-PCR study of larvae and adults revealed that only 145 (64%) of 233 genes with successful genomic DNA amplifications were expressed. No expression of the other 87 genes was detected at any age, suggesting either that these genes are not expressed in this particular strain, or that they are induced only in certain environmental or developmental conditions. TcOR1, the ortholog of the Drosophila Or83b (DmOr83b) gene, which is required for the function of olfactory receptor proteins in Drosophila, was expressed in extracts from adult and larval heads and in extracts from adult bodies. Expression of 41 TcOr genes was detected in extracts from larval head tissue and 111 in extracts from adult head tissue (both figures exclude TcOr1). Twenty-eight TcOrs were detected only in adult bodies. Beetle pupae were injected with TcOr1 dsRNA; unlike sham-injected and control beetles, these knock-down beetles showed no significant response to the Tribolium aggregation pheromone, supporting the hypothesis that TcOr1 plays a similar decisive role in olfaction to DmOr83b. The substantial number of Ors poses the question of why Tribolium has such a large olfactory receptor repertoire, and underlines the need for more studies of the natural history of this species.

Induction of HIF-2alpha is Dependent on Mitochondrial O2 Consumption in an O2-sensitive Adrenomedullary Chromaffin Cell Line

American Journal of Physiology. Cell Physiology. Jun, 2008  |  Pubmed ID: 18353899

During low O2 (hypoxia), hypoxia-inducible factor (HIF)-alpha is stabilized and translocates to the nucleus, where it regulates genes critical for survival and/or adaptation in low O2. While it appears that mitochondria play a critical role in HIF induction, controversy surrounds the underlying mechanism(s). To address this, we monitored HIF-2alpha expression and oxygen consumption in an O2-sensitive immortalized rat adrenomedullary chromaffin (MAH) cell line. Hypoxia (2-8% O2) caused a concentration- and time-dependent increase in HIF-2alpha induction, which was blocked in MAH cells with either RNA interference knockdown of the Rieske Fe-S protein, a component of complex III, or knockdown of cytochrome-c oxidase subunit of complex IV, or defective mitochondrial DNA (rho0 cells). Additionally, pharmacological inhibitors of mitochondrial complexes I, III, IV, i.e., rotenone (1 microM), myxothiazol (1 microM), antimycin A (1 microg/ml), and cyanide (1 mM), blocked HIF-2alpha induction in control MAH cells. Interestingly, the inhibitory effects of the mitochondrial inhibitors were dependent on O2 concentration such that at moderate-to-severe hypoxia (6% O2), HIF-2alpha induction was blocked by low inhibitor concentrations that were ineffective at more severe hypoxia (2% O2). Manipulation of the levels of reactive oxygen species (ROS) had no effect on HIF-2alpha induction. These data suggest that in this O2-sensitive cell line, mitochondrial O2 consumption, rather than changes in ROS, regulates HIF-2alpha during hypoxia.

Histone Deacetylase Inhibitors Protect Against and Mitigate the Lethality of Total-body Irradiation in Mice

Radiation Research. Apr, 2008  |  Pubmed ID: 18363436

It was hypothesized that histone deacetylase (HDAC) inhibitors may increase survival after total-body irradiation (TBI) based on previous reports demonstrating that HDAC inhibitors stimulate the proliferation of bone marrow stem cells. Using the time for mice to lose 20% or more of their weight as the end point, two HDAC inhibitors, valproic acid and trichostatin-A, were found to reduce lethality in a dose-dependent manner. HDAC inhibitors were effective at reducing lethality when given either 24 h before or 1 h after TBI. The results indicate that HDAC inhibitors have potential for protecting against and mitigating radiation-induced lethality.

Mitigation of Radiation-induced Skin Injury by AAV2-mediated MnSOD Gene Therapy

The Journal of Gene Medicine. Sep, 2008  |  Pubmed ID: 18613255

Radiation-induced, long-lived free radicals, reactive oxygen species and pro-inflammatory cytokines have been implicated in the resultant tissue injury after exposure to ionizing radiation.

My First Drug Information Question: Should My Wife and Baby Be Participants in an Uncontrolled Clinical Trial?

Journal of the American Pharmacists Association : JAPhA. Jul-Aug, 2008  |  Pubmed ID: 18653414

Editorial. JAK/STAT Signaling in Development and Disease

Seminars in Cell & Developmental Biology. Aug, 2008  |  Pubmed ID: 18722541

The "fetus As Patient": a Critique

The American Journal of Bioethics : AJOB. Jul, 2008  |  Pubmed ID: 18759188

Chemical Sensor Based on a Long-period Fibre Grating Modified by a Functionalized Polydimethylsiloxane Coating

The Analyst. Nov, 2008  |  Pubmed ID: 18936831

A chemical sensor based on a coated long-period grating has been prepared and characterized. Designer coatings based on polydimethylsiloxane were prepared by the incorporation of diphenylsiloxane and titanium cross-linker in order to provide enhanced sensitivity for a variety of key environmental pollutants and optimal refractive index of the coating. Upon microextraction of the analyte into the polymer matrix, an increase in the refractive index of the coating resulted in a change in the attenuation spectrum of the long-period grating. The grating was interrogated using ring-down detection as a means to amplify the optical loss and to gain stability against misalignment and power fluctuations. Chemical differentiation of cyclohexane and xylene was achieved and a detection limit of 300 ppm of xylene vapour was realized.

Paediatrics-based Fetal Care: Unanswered Ethical Questions

Acta Paediatrica (Oslo, Norway : 1992). Dec, 2008  |  Pubmed ID: 18976356

Efficient Screening of Current Smoking Status in Recruitment of Smokers for Population-based Research

Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Nov, 2008  |  Pubmed ID: 18988079

Population-based samples of smokers are necessary for tobacco behavior monitoring and surveillance and for evaluating tobacco control programs and policies. We evaluated the sensitivity and specificity of a simple, one-question screener as a tool to maximize efficiency of obtaining a population representative sample of current smokers. This analysis was based on 5,002 respondents from the Ontario Tobacco Survey (OTS), a regionally stratified longitudinal survey of adult smokers and cross-sectional survey of nonsmokers in Ontario, Canada. Overall, the question "Have you smoked one or more cigarettes in the past six months?" achieved at least 99.7% sensitivity and 87.1% specificity when compared with several standard definitions of current smoking status. The brief screening question minimized respondent burden and data collection costs, and may have had a positive influence on response rate. Having a more conservative measure of smoking status permitted atypical smokers to be included in the survey which will allow us to track their behavior change and evaluate the performance of accepted smoking status definitions. We recommend that studies, which specifically sample smokers, utilize any past 6-month smoking as a brief screener for smoking status.

Radiation-induced Skin Injury in the Animal Model of Scleroderma: Implications for Post-radiotherapy Fibrosis

Radiation Oncology (London, England). 2008  |  Pubmed ID: 19025617

Radiation therapy is generally contraindicated for cancer patients with collagen vascular diseases (CVD) such as scleroderma due to an increased risk of fibrosis. The tight skin (TSK) mouse has skin which, in some respects, mimics that of patients with scleroderma. The skin radiation response of TSK mice has not been previously reported. If TSK mice are shown to have radiation sensitive skin, they may prove to be a useful model to examine the mechanisms underlying skin radiation injury, protection, mitigation and treatment.

Unphosphorylated STATs Go Nuclear

Current Opinion in Genetics & Development. Oct, 2008  |  Pubmed ID: 18840523

The JAK/STAT signal transduction pathway has traditionally been viewed as a cytokine-stimulated activator of gene expression consisting of a straightforward receptor/JAK kinase/STAT transcription factor cascade. Recent studies in Drosophila, have, however consistently identified a range of chromatin-remodelling factors as regulators of in vivo JAK/STAT signalling. Now, the detailed analysis of one of these, heterochromatin protein 1 (HP1), has provided an insight into an unexpected non-canonical in vivo role for STAT. In this model, unphosphorylated STATs associate with and maintain the stability of transcriptionally repressed heterochromatin--an effect countered by the recruitment of STAT to the canonical pathway. We examine the background of this new model and its implications for JAK/STAT pathway requirements in stem cell maintenance and cancer.

Vertebral End-plate Fractures As a Result of High Rate Pressure Loading in the Nucleus of the Young Adult Porcine Spine

Journal of Biomechanics. 2008  |  Pubmed ID: 17706227

In a healthy spine, end-plate fractures occur from excessive pressurization of the intervening nucleus. Younger spines are most susceptible to such type of injury due to the highly hydraulic nature of their intervertebral discs. The purpose of this paper was to confirm this fracture mechanism of the healthy spine through the pressurization of the nucleus in the absence of external compressive loading. Sixteen functional porcine spine units were dissected and both injection and pressure transducer needles were inserted into the nucleus of the intervertebral disc. Hydraulic fluid was rapidly injected into the nucleus until failure occurred. Peak pressure and rate of pressure development were monitored. Spine units were dissected to determine the type and location of fracture. Fifteen of the 16 spine units fractured (the remaining unit had a degenerated disc). Of the 15 fractures, 13 occurred at the posterior margin of the end-plate along the lines of the growth plates. A slightly exponential relationship was found between peak pressure and its rate of development (R(2) = 0.544). Also, in each of the growth-plate fractured specimens, nuclear material was forcefully emitted, during fracture, from the intervertebral disc into the vertebral foramen. The posterior end-plate fractures produced here are similar to those often seen in young adult humans. This provides insight into a mechanism of fracture development through pressurization of the nucleus that might be seen in older adolescents and younger adults during athletic events or mild trauma.

How the Inherent Stiffness of the in Vivo Human Trunk Varies with Changing Magnitudes of Muscular Activation

Clinical Biomechanics (Bristol, Avon). Jan, 2008  |  Pubmed ID: 17910898

The abdominal muscles provide stiffness to the torso in a manner that is not well understood. Their unique anatomical arrangement may modify their stiffening ability with respect to the more commonly studied long strap-like muscles of the limbs. The purpose of this study was to examine stiffness inherent to the trunk, as modified by different torso, and in particular, abdominal muscle activation levels.

Predictors of Injurious Assault Committed During or After Drinking Alcohol: a Case-control Study of Young Offenders

Aggressive Behavior. Mar-Apr, 2008  |  Pubmed ID: 17922526

Studies of causal links between alcohol and aggression are often handicapped by threats to internal and external validity. Case-control methods employ an event-level analysis that can reduce some of these validity threats by the use of within-subject controls. This study used a case-control approach, asking 39 male inmates in a Young Offenders' Institution to compare drinking behaviour before incidents where they reported commission of an injurious assault and a matched incident where they did not. After controlling contextual differences, participants reported personally drinking more heavily and heavier drinking within their group, but not being more impaired when an assault was committed. The assault incidents were more likely to involve spontaneous, rather than planned, drinking and a higher proportion of males in the group. They were less likely to involve drinking in a pub. Our confirmation of previous findings using a case-control methodology strengthens those findings. Limitations of this methodology are also discussed.

Trunk Muscle Responses to Suddenly Applied Loads: Do Individuals Who Develop Discomfort During Prolonged Standing Respond Differently?

Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. Jun, 2008  |  Pubmed ID: 17270465

Individuals with low back pain or injury (LBP/LBI) have been shown to display altered muscle responses to trunk perturbations; however it is unclear whether these observations are a cause or a result of the LBP/LBI. In this study, a 6.78 kg load was suddenly applied to the hands to perturb the trunk prior to and following a 2-h standing period, during which trunk and hip electromyography (EMG) and centre of pressure (CoP) at the feet were recorded. Seven of the 13 participants developed substantial low back discomfort (LBDiscomfort) during the standing period. These individuals, both pre- and post-standing, showed a greater average number of responsive extensor muscles (3.8 compared to 3.1 in those who did not develop discomfort) and a greater occurrence of extensor muscle response (95-100% of trials) as compared to those who did not develop LBDiscomfort (73-86% of trials). Also, after discomfort developed, these individuals displayed an increased response in their abdominal muscles. This overall increase in trunk musculature activity could either be detrimental by potentially increasing spinal loading leading to LBDiscomfort, or beneficial in that this increased musculature responsiveness may reduce one's likelihood of developing a future LBI through a pathway of increased spine stability. In either case, these responses indicate motor control characteristics that can distinguish the likelihood of an individual developing LBDiscomfort during common tasks such as prolonged standing.

Two-year Prospective Study of Major Depressive Disorder in HIV-infected Men

Journal of Affective Disorders. Jun, 2008  |  Pubmed ID: 18045694

The risks and factors contributing to major depressive episodes in HIV infection remain unclear. This 2-year prospective study compared cumulative rates and predictors of a major depressive episode in HIV-infected (HIV+) men (N=297) and uninfected (HIV-) risk-group controls (N=90).

Co-activation Alters the Linear Versus Non-linear Impression of the EMG-torque Relationship of Trunk Muscles

Journal of Biomechanics. 2008  |  Pubmed ID: 18054943

The use of electromyographic signals in the modeling of muscle forces and joint loads requires an assumption of the relationship between EMG and muscle force. This relationship has been studied for the trunk musculature and been shown to be predominantly non-linear, with more EMG producing less torque output at higher levels of activation. However, agonist-antagonist muscle co-activation is often substantial during trunk exertions, yet has not been adequately accounted for in determining such relationships. The purpose of this study was to revisit the EMG-moment relationship of the trunk recognizing the additional moment requirements necessitated due to antagonist muscle activity. Eight participants generated a series of isometric ramped trunk flexor and extensor moment contractions. EMG was recorded from 14 torso muscles, and the externally resisted moment was calculated. Agonist muscle moments (either flexor or extensor) were estimated from an anatomically detailed biomechanical model of the spine and fit to: the externally calculated moment alone; the externally calculated moment combined with the antagonist muscle moment. When antagonist activity was ignored, the EMG-moment relationship was found to be non-linear, similar to previous work. However, when accounting for the additional muscle torque generated by the antagonist muscle groups, the relationships became, in three of the four conditions, more linear. Therefore, it was concluded that antagonist muscle co-activation must be included when determining the EMG-moment relationship of trunk muscles and that previous impressions of non-linear EMG-force relationships should be revisited.

An Open-label Pilot Study of High-concentration Capsaicin Patch in Painful HIV Neuropathy

Journal of Pain and Symptom Management. Mar, 2008  |  Pubmed ID: 17959343

Peripheral neuropathy is the most frequent neurological complication of human immunodeficiency virus (HIV)-1 infection and is commonly associated with the development of chronic pain. This open-label, 12-week pilot study assessed the efficacy, tolerability, and safety of a high-concentration capsaicin dermal patch (NGX-4010; capsaicin, 640microg/cm2, 8% w/w) to treat painful HIV-associated distal sensory polyneuropathy (DSP). Eligible patients had moderate-to-severe pain in both feet due to HIV-associated DSP or antiretroviral toxic neuropathy. Patients received a single 60-minute application of the investigational high-concentration capsaicin patch to the affected areas. The primary outcome measure was the mean percent change in numeric pain rating scale (NPRS) during weeks two to 12 postadministration. After a single 60-minute NGX-4010 application, the mean percent change from baseline in "average pain for past 24 hours" NPRS scores during weeks two to 12 was -40% (95% CI: -61%, -19%; P=0.0020). Similar results were observed for "worst pain for past 24 hours" and "pain now" scores. Eight of 12 patients (67%) were treatment responders (> or =30% pain decrease). Four of 12 patients (33%) experienced a > or =50% reduction in pain. Treatment was generally well tolerated. Treatment-associated pain was self-limited and could be managed with short-acting opioids. This study demonstrates that treatment of painful HIV-associated neuropathy with a single application of NGX-4010, a high-concentration capsaicin patch, was feasible, well tolerated, and associated with significant reduction in pain over the 12 weeks studied. No safety concerns were identified. Controlled studies of NGX-4010 for the treatment of painful HIV-associated neuropathy are warranted.

Controlled Trial of High-concentration Capsaicin Patch for Treatment of Painful HIV Neuropathy

Neurology. Jun, 2008  |  Pubmed ID: 18541884

HIV-associated distal sensory polyneuropathy (HIV-DSP) is a painful condition with limited effective treatment. Capsaicin desensitizes cutaneous nociceptors resulting in reduced pain. We report a placebo-controlled study of a high-concentration capsaicin dermal patch (NGX-4010) for the treatment of painful HIV-DSP.

Stem Cell Regulation by JAK/STAT Signaling in Drosophila

Seminars in Cell & Developmental Biology. Aug, 2008  |  Pubmed ID: 18603010

Stem cells have become one of the "buzz" topics in the last decade or so. One of the best systems to study adult stem cells in vivo is in the model organism, Drosophila melanogaster. One hundred years of genetic analysis, a sequenced and highly annotated genome and genomics makes this a difficult organism to avoid. The JAK/STAT pathway has been shown to regulate stem cells during haematopoiesis and gametogenesis in Drosophila. In this review we cover the current literature and contrast each group of stem cells with respect to JAK/STAT signaling.

Strength Limitations to Proper Child Safety Seat Installation: Implications for Child Safety

Applied Ergonomics. Jul, 2009  |  Pubmed ID: 18620335

A majority of child safety restraints are misused in some manner, often leading to an increased risk of serious injury or death. It is possible that at least some instances of misuse are the result of biomechanical limitations during the installation process. Twenty-seven adult participants were trained and then monitored in three stages of child safety seat installation. All installations were done with an identical restraint system in the rear bench seat of a mocked-up minivan. EMG of 10 muscles, as well as trunk, shoulder, and wrist postures were analyzed. Peak maximum efforts were often required of the trunk extensor, forearm, and anterior shoulder muscles during the installation process. Routing and tightening of the seatbelt, as well as placing and securing the child into the seat were observed to be particularly difficult tasks. Many portions of the child safety seat installation process were found to be very physically demanding; some individuals may not be capable of performing these tasks correctly, thereby putting the child at greater risk in the motor vehicle.

Defensive Responses to an Emotive Anti-alcohol Message

Psychology & Health. Jun, 2009  |  Pubmed ID: 20205009

We investigated the idea that emotive imagery used in health promotion advertising can facilitate a defensive response that adversely affects risk perceptions. One hundred student drinkers were exposed to either a printed message accompanied by images designed to maximise emotional distress or the same message presented using less emotive images. A three-way interaction was found, whereby the presentation of distressing images caused lower personal risk estimates in participants higher in denial and vulnerability to alcohol-related problems. This effect may have been mediated by lower reading times, suggesting that participants avoided the messages. Moderation by denial suggests that the effect is attributable to defensiveness, whilst moderation by vulnerability suggests that it is threat specific. These findings suggest that emotive images might trigger defensive avoidance responses that reduce risk estimates in some audience sub-populations.

Transmission of Muscularly Generated Force and Stiffness Between Layers of the Rat Abdominal Wall

Spine. Jan, 2009  |  Pubmed ID: 19139656

In situ testing of the rat abdominal wall.

Comparison of Different Rowing Exercises: Trunk Muscle Activation and Lumbar Spine Motion, Load, and Stiffness

Journal of Strength and Conditioning Research / National Strength & Conditioning Association. Mar, 2009  |  Pubmed ID: 19197209

The objective of this study was to investigate 3 different rowing exercises and quantify the muscle activation of the torso and the hip musculature, together with the corresponding spinal loading and stiffness. Seven healthy men from a university population were instrumented to obtain surface electromyography of selected trunk and hip muscles and to obtain spine position using an electromagnetic spine position sensor, together with video analysis to calculate joint moments. The 3 rowing exercises investigated were the inverted row, standing bent-over row, and standing 1-armed cable row. The inverted row elicited the highest activation of the latissimus dorsi muscles, upper-back, and hip extensor muscles. The lower activation of the lumbar erector spinae muscles during the inverted row corresponded to the lower spine load measured. The standing bent-over row produced large activation symmetrically across the back, but it produced the largest lumbar spine load. The 1-armed cable row challenged the torsional capabilities of the trunk musculature. Some core exercises may be better for rehabilitation (e.g., having the training goals of modest muscle activation with low spine load), whereas other exercises may be better for athletic training (e.g., resulting in higher muscle activation and larger spine load). When prescribing core exercises, those wishing to spare the low back may choose the inverted row, given the lowest spine load exercise. The standing bent-over row elicited large muscle activation symmetrically from the upper to lower back; it induced larger spine loads but also, not surprisingly, the highest spine stiffness. If torsional endurance or strength is the training goal, the 1-armed cable row might be considered.

Radiation Sensitization of Glioblastoma by Cilengitide Has Unanticipated Schedule-dependency

International Journal of Cancer. Journal International Du Cancer. Jun, 2009  |  Pubmed ID: 19199360

We investigated whether cilengitide could amplify the antitumor effects of radiotherapy in an orthotopic rat glioma xenograft model. Cilengitide is a specific inhibitor of alphav series integrins, and acts as an antiangiogenic. U251 human glioma cells express alphavbeta3 and alphavbeta5 integrins. We used in vitro assays of adhesion and growth of tumor and endothelial cells to evaluate cytotoxicity and the potential for cilengitide to enhance radiation toxicity. Treatment was then evaluated in an orthotopic model to evaluate synergy with therapeutic radiation in vivo. In vitro, cilengitide blocked cell adhesion, but did not influence the effects of radiation on U251 cells; cilengitide strongly amplified radiation effects on endothelial cell survival. In vivo, radiotherapy prolonged the survival of U251 tumor-bearing rats from 50 to over 110 days. Cotreatment with cilengitide and radiation dramatically amplified the effects of radiation, producing survival over 200 days and triggering an enhanced apoptotic response and suppression of tumor growth by histology at necropsy. Signaling pathways activated in the tumor included NFkappab, a documented mediator of cellular response to radiation. Because cilengitide has a short plasma half-life (t((1/2)) approximately 20 min), antiangiogenic scheduling typically uses daily injections. We found that a single dose of cilengitide (4 mg/kg) given between 4 and 12 hr prior to radiation was sufficient to produce the same effect. Our results demonstrate that blockade of alphav integrins mediates an unanticipated rapid potentiation of radiation, and suggests possible clinical translation for glioma therapy.

Activation of Peripheral Delta2 Opioid Receptors Increases Cardiac Tolerance to Ischemia/reperfusion Injury Involvement of Protein Kinase C, NO-synthase, KATP Channels and the Autonomic Nervous System

Life Sciences. May, 2009  |  Pubmed ID: 19245818

This study aims to investigate the role of peripheral delta(2) opioid receptors in cardiac tolerance to ischemia/reperfusion injury and to examine the contribution of PKC, TK, K(ATP) channels and the autonomic nervous system in delta(2) cardioprotection.

Exercises for the Torso Performed in a Standing Posture: Spine and Hip Motion and Motor Patterns and Spine Load

Journal of Strength and Conditioning Research / National Strength & Conditioning Association. Mar, 2009  |  Pubmed ID: 19258883

The purpose of this study was to document the muscle activity, spine motion, spine load, and stiffness during several movement-based or "functional" exercises and to assess the effect of technique change. Eight subjects, all healthy men from a university population, were instrumented to obtain surface electromyography of selected trunk and hip muscles, together with video analysis and electromagnetic lumbar spine position sensor to track spine posture. Exercises included a walkout in the sagittal plane that compared an upright form against a wall with those performed on the floor, overhead cable pushes, lateral cable walkouts, the good morning exercise, and the bowler's squat. Generally, muscle activation levels were quite modest even though the tasks were quite strenuous in many cases. Even though similar joint moments were required in different exercises, the pattern of activity between muscles was different. Abdominal bracing increased spine stiffness at the expense of more spine load. Thus, muscle activity seems to be constrained in "functional" exercises. There are several possible reasons for this. Single muscles cannot be activated to 100% of the maximum voluntary contraction in functional exercises because this would upset the balance of moments about the 3 orthopedic axes of the spine, or it would upset the balance of stiffening muscles around the spine required to ensure stability of the spinal column. The one exception was the floor walkout, which resulted in full activation of the rectus abdominis; however, this was a sagittal plane task without the joint moment constraints of multiplanar exercise. Therefore, maximal muscle activity is observed during single-plane tasks, but muscle activation levels were constrained during functional tasks. Thus, strength training muscles may not help in "functional multiplanar" tasks. These data can be used to assist decisions regarding the selection of exercises, specifically choices regarding the starting challenge, progression, exercise form, and possibly corrective technique for those who have spine concerns, or those simply looking for performance enhancement.

Recurrent Cystic Hygroma with Hydrops

Fetal Diagnosis and Therapy. 2009  |  Pubmed ID: 19276638

A patient whose 5 fetuses, including a set of twins, were affected by cystic hygroma (CH) and hydrops is presented.

Torso and Hip Muscle Activity and Resulting Spine Load and Stability While Using the ProFitter 3-D Cross Trainer

Journal of Applied Biomechanics. Feb, 2009  |  Pubmed ID: 19299832

The ProFitter 3-D Cross Trainer is a labile surface device used in the clinic and claimed to train spine stability. The purpose of this study was to quantify the spine mechanics (compression and shear forces and stability), together with muscle activation mechanics (surface electromyography) of the torso and hip, during three ProFitter exercises. Trunk muscle activity was relatively low while exercising on the device (<25%MVC). Gluteus medius activity was phasic with the horizontal sliding position, especially for an experienced participant. Sufficient spinal stability was achieved in all three exercise conditions. Peak spinal compression values were below 3400 N (maximum 3188 N) and peak shear values were correspondingly low (under 500 N). The exercises challenge whole-body dynamic balance while producing very conservative spine loads. The motion simultaneously integrates hip and torso muscles in a way that appears to ensure stabilizing motor patterns in the spine. This information will assist with clinical decision making about the utility of the device and exercise technique in rehabilitation and training programs.

Best Clinical and Research Practice in Adults with an Intellectual Disability

Epilepsy & Behavior : E&B. Jun, 2009  |  Pubmed ID: 19303944

Though the prevalence of epilepsies is substantially higher in people with intellectual disability (ID) compared with the general population, little is known of the psychosocial burden of epilepsy and adjustment and their respective determinants in this important population. In most modern societies, adult life with an ID is characterized by diminished self-determination, autonomous function, and life choices. These factors alone are known to be critically linked to the individual's overall quality of life. The task is to identify additional burdens attributable to coexisting epilepsy. This article addresses the significance, for people with ID who have epilepsy, of the many different factors, including seizure or epilepsy-related parameters, antiepileptic medication, coexisting motor and sensory impairments, and psychopathological and behavioral disorders, that can impact their quality of life. Discussion also covers the methodological difficulties in published studies, and, finally, proposals are outlined for future research in this field.

Use of a Microcatheter in a Telescopic System to Reach Difficult Targets in Complex Congenital Heart Disease

Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. Apr, 2009  |  Pubmed ID: 19309713

Some lesions can be very difficult to reach, especially if acute angles and/or multiple turns "protect" access. Once reached, the guiding system needs to give sufficient support for balloons or stents to be deployed.

Hybrid Approach As Bridge to Biventricular Repair in a Neonate with Critical Aortic Stenosis and Borderline Left Ventricle

European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery. Jun, 2009  |  Pubmed ID: 19324570

A newborn presented with severe aortic valve stenosis and a borderline hypoplastic left ventricle due to disproportionate left ventricular hypertrophy (maternal diabetes). The aortic valve was balloon dilated and the infant tolerated a biventricular circulation. However, severe retrograde pulmonary hypertension and mitral regurgitation developed, indicating that biventricular circulation was not possible at that stage. A hybrid approach with ductal stenting, atrial septostomy and bilateral dilatable pulmonary artery band placement was followed on day 25. This allowed the left ventricle several months to adapt to lower pressure and normoglycemic conditions. At re-evaluation after 8 months biventricular repair appeared possible: the ductus was closed with Amplatzer occluders and the pulmonary artery bands were opened up with bilateral balloon angioplasty of the dilatable bands. At the age of 3 years, the infant is doing well with a biventricular circulation and normal pulmonary artery pressure. The hybrid approach allowed adequate time (months) for careful consideration and acted as a bridge to biventricular repair in this infant.

Acute Systemic Erythropoietin Therapy to Reduce Delayed Ischemic Deficits Following Aneurysmal Subarachnoid Hemorrhage: a Phase II Randomized, Double-blind, Placebo-controlled Trial. Clinical Article

Journal of Neurosurgery. Jul, 2009  |  Pubmed ID: 19344224

Delayed ischemic deficits (DIDs), a major source of disability following aneurysmal subarachnoid hemorrhage (aSAH), are usually associated with severe cerebral vasospasm and impaired autoregulation. Systemic erythropoietin (EPO) therapy has been demonstrated to have neuroprotective properties acting via EPO receptors on cerebrovascular endothelia and ischemic neurons. In this trial, the authors explored the potential neuroprotective effects of acute EPO therapy following aSAH.

Perforation of the Aortic Sinus After Closure of Atrial Septal Defects with the Atriasept Occluder

Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. Aug, 2009  |  Pubmed ID: 19360869

Percutaneous atrial septal defect closure is routinely performed nowadays because of the ease of implantation as well as the low complication rate. The Atriasept ASD occluder is a low profile, double disc device; over the years several modifications have been made. We report two cases of aortic sinus perforation by the Atriasept ASD occluder (model 2007). Two asymptomatic patients, in whom the device was implanted, were noticed to have metal projecting into the aorta. Real-time fluoroscopy showed fractures of the outer metal ring with abnormal movement of one of the struts of the device. One patient is being conservatively managed and in the other the device was surgically removed due to the presence of a second ASD, which needed closure. Transesophageal echocardiography and fluoroscopy may be necessary to identify this potentially life-threatening complication of this device.

Effects of Orally Administered Lavender Essential Oil on Responses to Anxiety-provoking Film Clips

Human Psychopharmacology. Jun, 2009  |  Pubmed ID: 19382124

Lavender odour is commonly used to alleviate mild anxiety. Double blind studies are difficult to conduct with odours, and there are few reliable investigations of lavender's efficacy.

High-intensity Focused Ultrasound for Prostate Cancer: Comparative Definitions of Biochemical Failure

BJU International. Oct, 2009  |  Pubmed ID: 19388986

To compare the specificity and sensitivity of different definitions of biochemical failure in patients treated with high-intensity focused ultrasound (HIFU) for prostate cancer, to identify the most accurate predictor of clinical failure after HIFU.

Premature Foetal Closure of the Arterial Duct: Clinical Presentations and Outcome

European Heart Journal. Jun, 2009  |  Pubmed ID: 19389789

The prevalence of intra-uterine ductal dysfunction is unknown and the clinical consequences are poorly understood. The aim of this study was to investigate the echocardiographic (ECHO) abnormalities and outcomes of this rare phenomenon.

Coronary Compression Caused by Stenting a Right Pulmonary Artery Conduit

Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. Jul, 2009  |  Pubmed ID: 19405155

Extrinsic compression of the left main coronary artery is a rare and life-threatening complication of endovascular stenting of pulmonary artery conduits. This case report describes fatal myocardial infarction caused by compression of the left main coronary artery due to stent placement in a stenosed right pulmonary artery conduit.

Does Hyperthermia Increase Adenoviral Transgene Expression or Dissemination in Tumors?

International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. Jun, 2009  |  Pubmed ID: 19452300

Viral vectors used for cancer gene therapy are usually delivered by direct intratumoral administration. We studied the role of hyperthermia (HT) in vitro and in vivo in an attempt to achieve higher transfection rates (especially, larger volume of spread).

Hypoxia Inducible Factor (HIF)-2 Alpha is Required for the Development of the Catecholaminergic Phenotype of Sympathoadrenal Cells

Journal of Neurochemistry. Jul, 2009  |  Pubmed ID: 19457096

The basic helix-loop-helix transcription factor, hypoxia inducible factor (HIF)-2alpha has been implicated in the development of the catecholaminergic phenotype in cells of the sympathoadrenal (SA) lineage; however, the underlying mechanisms and HIF-2alpha targets remain unclear. Using an immortalized rat adrenomedullary chromaffin cell line (MAH cells) derived from a fetal SA progenitor, we examined the role of HIF-2alpha in catecholamine biosynthesis. Chronic hypoxia (2% O(2), 24 h) induced HIF-2alpha in MAH cells but expression of the rate-limiting enzyme, tyrosine hydroxylase (TH) and catecholamine levels were unaltered. Interestingly, HIF-2alpha depleted MAH cells showed dramatically lower (5-12 times) levels of dopamine and noradrenaline compared with wild-type and scrambled controls, even in normoxia (21% O(2)). This was correlated with a marked reduction in the expression of DOPA decarboxylase (DDC) and dopamine beta hydroxylase (DbetaH) but not TH. Chromatin immunoprecipitation assays revealed that HIF-2alpha was bound to the DDC gene promoter which contains two putative hypoxia response elements. These data suggest that a basal level of HIF-2alpha function is required for the normal developmental expression of DDC and DbetaH in SA progenitor cells, and that loss of this function leads to impaired catecholamine biosynthesis.

The Active Straight Leg Raise Test and Lumbar Spine Stability

PM & R : the Journal of Injury, Function, and Rehabilitation. Jun, 2009  |  Pubmed ID: 19627942

To determine the utility of the active straight leg raise (ASLR) test as a screen of lumbar spine stability and abdominal bracing (AB) ability.

Post-publication Sharing of Data and Tools

Nature. Sep, 2009  |  Pubmed ID: 19741686

Despite existing guidelines on access to data and bioresources, good practice is not widespread. A meeting of mouse researchers in Rome proposes ways to promote a culture of sharing.

Anomalous Origin of the Right Pulmonary Artery from the Ascending Aorta: a Surgical Case Study in an Adult Patient with "irreversible" Pulmonary Vascular Disease

Journal of Cardiac Surgery. Mar-Apr, 2009  |  Pubmed ID: 19040403

An adult patient presented with an anomalous right pulmonary artery arising from the ascending aorta with severe unilateral pulmonary vascular disease of the left lung due to a large left-sided patent ductus arteriosus. A stenosis in the right pulmonary artery protected the right pulmonary vasculature. Right ventricular pressure was suprasystemic. After ductal ligation and surgical repair, pulmonary artery pressures fell dramatically. An immediate postoperative angiography confirmed extremely poor perfusion of the left lung. At four-and-a-half years of follow-up, the patient's quality of life had improved dramatically, main pulmonary artery pressure was one-sixth of systemic pressures, and there was vastly improved perfusion of the left lung at this lower perfusion pressure. The calculated pulmonary vascular resistance of the left lung was within normal limits. These findings suggested a significant degree of reversal of pulmonary hypertensive disease in the left lung sustained to 54 months postoperatively.

Process and Impact Evaluation of a Legal Assistance and Health Care Community Partnership

Health Promotion Practice. Jul, 2009  |  Pubmed ID: 18408120

Community health partnerships have increased in popularity, but their effectiveness is often not evaluated. Through secondary data analysis, this study evaluates a program that offered access to legal services to address health-related issues, such as Medicaid reimbursement, Social Security benefits, medication coverage, and divorce. Based on the analysis reimbursements to expenditures, the health and law program appears to be cost-effective and thereby economically sustainable. The cost-effectiveness of this program increases the likelihood that it will be institutionalized and/or expanded. This program evaluation is used to exemplify how community stakeholders could partner to leverage resources to establish a sustainable community health and law program to address the needs of people living in medically underserved areas.

Australian Firefighters' Exposure to Air Toxics During Bushfire Burns of Autumn 2005 and 2006

Environment International. Feb, 2009  |  Pubmed ID: 18829114

Bushfire fighting is a hazardous occupation and control strategies are generally in place to minimize the hazards. However, little is known regarding firefighters' exposure to bushfire smoke, which is a complex mixture of toxic gases and particles. In Australia, during the prescribed burning season, firefighters are likely to be exposed on a regular basis to bushfire smoke, but whether these exposures affect health has yet to be determined. There are a number of factors that govern whether exposure to smoke will result in short-term and/or long-term health problems, including the concentrations of air pollutants within the breathing zone of the firefighter, the exposure duration, and health susceptibility of the individual, especially for pre-existing lung or heart disease. This paper presents measurements of firefighters' personal exposure to bushfire smoke, the first step within a risk management framework. It provides crucial information on the magnitude, extent and frequency of personal exposure to bushfire smoke for a range of typical scenarios. It is found that the primary air toxics of concern are carbon monoxide (CO), respirable particles and formaldehyde. Also, work activity is a major factor influencing exposure with exposure standards (both average and short-term limits) likely to be exceeded for activities such as suppression of spot fires, holding the fireline, and patrolling at the edge of a burn area in the urban-rural interface.

Zic2 is Expressed in Pluripotent Cells in the Blastocyst and Adult Brain Expression Overlaps with Makers of Neurogenesis

Gene Expression Patterns : GEP. Jan, 2009  |  Pubmed ID: 18755297

Members of the zic family of transcription factors are widely understood to act during neural patterning and neural crest development. In particular, studies in mice and humans have shown that Zic2 has a role in forebrain patterning, while studies in Xenopus and zebrafish have shown that Zic2 acts during gastrulation. Expression of Zic2 prior to gastrulation has not been reported in the mouse. In the adult, Zic2 is known to be strongly expressed in cerebellar granule cells, but expression elsewhere in the adult brain has not been reported. We present data showing that Zic2 is expressed in pluripotent cells during very early mouse development. Further, in the adult brain, Zic2 expression is broad and overlaps with markers of neurogenesis. The presence of Zic2 in pluripotent cells of the embryo as well as in dividing neural cells in the adult suggests that this transcription factor may have a role in maintaining pluripotency.

School Smoking Policy Characteristics and Individual Perceptions of the School Tobacco Context: Are They Linked to Students' Smoking Status?

Journal of Youth and Adolescence. Nov, 2009  |  Pubmed ID: 19779813

The purpose of this study was to explore individual- and school-level policy characteristics on student smoking behavior using an ecological perspective. Participants were 24,213 (51% female) Grade 10-11 students from 81 schools in five Canadian provinces. Data were collected using student self-report surveys, written policies collected from schools, interviews with school administrators, and school property observations to assess multiple dimensions of the school tobacco policy. The multi-level modeling results revealed that the school a student attended was associated with his/her smoking behavior. Individual-level variables that were associated with student smoking included lower school connectedness, a greater number of family and friends who smoked, higher perceptions of student smoking prevalence, lower perceptions of student smoking frequency, and stronger perceptions of the school tobacco context. School-level variables associated with student smoking included weaker policy intention indicating prohibition and assistance to overcome tobacco addiction, weaker policy implementation involving strategies for enforcement, and a higher number of students smoking on school property. These findings suggest that the school environment is important to tobacco control strategies, and that various policy dimensions have unique relationships to student smoking. School tobacco policies should be part of a comprehensive approach to adolescent tobacco use.

Regulation of Oxygen Sensitivity in Adrenal Chromaffin Cells

Annals of the New York Academy of Sciences. Oct, 2009  |  Pubmed ID: 19845615

Adrenomedullary chromaffin cells (AMC) possess a direct hypoxia-sensing mechanism that promotes a vital catecholamine surge at birth. This mitochondria-dependent adaptive mechanism is suppressed postnatally as AMC acquire cholinergic innervation, and it is mediated by K+ channel inhibition, membrane depolarization, and voltage-gated Ca2+ entry. We hypothesized that nicotinic ACh receptor (AChR) activation might contribute to this postnatal loss of O2 sensitivity. Following in utero nicotinic AChR activation, via maternal administration of nicotine bitartrate, hypoxic sensitivity was suppressed in neonatal AMC. Similarly, when neonatal AMC or immortalized chromaffin (MAH) cells were cultured for approximately 7 d with nicotine base (50 muM), hypoxic sensitivity was suppressed. This effect required alpha7 nAChR stimulation, and involved upregulation of K(ATP) channels, which are activated during hypoxia. Thus, nicotinic AChR activation may contribute to the suppression of hypoxic sensitivity in AMC, and this pathway could provide the basis for the loss of hypoxia tolerance in the offspring of smoking mothers.

Aging and the Neuroeconomics of Decision Making: A Review

Cognitive, Affective & Behavioral Neuroscience. Dec, 2009  |  Pubmed ID: 19897790

Neuroeconomics refers to a combination of paradigms derived from neuroscience, psychology, and economics for the study of decision making and is an area that has received considerable scientific attention in the recent literature. Using realistic laboratory tasks, researchers seek to study the neurocognitive processes underlying economic decision making and outcome-based decision learning, as well as individual differences in these processes and the social and affective factors that modulate them. To this point, one question has remained largely unanswered: What happens to decision-making processes and their neural substrates during aging? After all, aging is associated with neurocognitive change, which may affect outcome-based decision making. In our study, we use the subjective expected utility model-a well-established decision-making model in economics-as a descriptive framework. After a short survey of the brain areas and neurotransmitter systems associated with outcome-based decision making-and of the effects of aging thereon-we review a number of decision-making studies. Their general data pattern indicates that the decision-making process is changed by age: The elderly perform less efficiently than younger participants, as demonstrated, for instance, by the smaller total rewards that the elderly acquire in lab tasks. These findings are accounted for in terms of age-related deficiencies in the probability and value parameters of the subjective expected utility model. Finally, we discuss some implications and suggestions for future research.

T10B9 Monoclonal Antibody: a Short-acting Nonstimulating Monoclonal Antibody That Spares Gammadelta T-cells and Treats and Prevents Cellular Rejection

Drug Design, Development and Therapy. 2009  |  Pubmed ID: 19920935

T10B9.1A-31/MEDI-500 is a nonmitogenic immunoglobulin M kappa murine monoclonal antibody (mAb) directed against the alpha-beta (alphabeta) heterodimer of the T-lymphocyte receptor complex. The hybridoma was first produced by fusing spleen cells from BALB/C mice immunized with human peripheral blood T-lymphocytes with SP2/O-Ag14 mutant myeloma cells. The mAb is produced and purified using multistep ion exchange and molecular sieve chromatography protocols. T10B9 has been used successfully to treat acute cellular rejection in renal transplantation and as an immunosuppression induction agent in heart and simultaneous kidney-pancreas transplantation. Because T10B9 is nonmitogenic and causes minimal cytokine release, both treatment of rejection and induction of immunosuppression were accomplished with significantly fewer and milder untoward effects (cytokine release syndrome) than its comparator OKT3. Since T10B9 is directed against the alphabeta heterodimer of the CD3 epitope, it spares the gamma delta (gammadelta) region. These gamma delta (gammadelta) T cells have a unique role in the immune response controlling many serious human diseases and perhaps facilitating the development of immunologic tolerance. T10B9 has a relatively short duration of action, depleting T cells for only 10 to 14 days, unlike the protracted depletion seen with thymoglobulin and Campath-1H. There is no B-lymphocyte depletion with T10B9 as there is with both of the aforementioned reagents. The lack of prolonged lymphocyte depletion may account for less infection observed with T10B9 treatment.

Chronic Nicotine Blunts Hypoxic Sensitivity in Perinatal Rat Adrenal Chromaffin Cells Via Upregulation of KATP Channels: Role of Alpha7 Nicotinic Acetylcholine Receptor and Hypoxia-inducible Factor-2alpha

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Jun, 2009  |  Pubmed ID: 19494136

Fetal nicotine exposure blunts hypoxia-induced catecholamine secretion from neonatal adrenomedullary chromaffin cells (AMCs), providing a link between maternal smoking, abnormal arousal responses, and risk of sudden infant death syndrome. Here, we show that the mechanism is attributable to upregulation of K(ATP) channels via stimulation of alpha7 nicotinic ACh receptors (AChRs). These K(ATP) channels open during hypoxia, thereby suppressing membrane excitability. After in utero exposure to chronic nicotine, neonatal AMCs show a blunted hypoxic sensitivity as determined by inhibition of outward K(+) current, membrane depolarization, rise in cytosolic Ca(2+), and catecholamine secretion. However, hypoxic sensitivity could be unmasked in nicotine-exposed AMCs when glibenclamide, a blocker of K(ATP) channels, was present. Both K(ATP) current density and K(ATP) channel subunit (Kir 6.2) expression were significantly enhanced in nicotine-exposed cells relative to controls. The entire sequence could be reproduced in culture by exposing neonatal rat AMCs or immortalized fetal chromaffin (MAH) cells to nicotine for approximately 1 week, and was prevented by coincubation with selective blockers of alpha7 nicotinic AChRs. Additionally, coincubation with inhibitors of protein kinase C and CaM kinase, but not protein kinase A, prevented the effects of chronic nicotine in vitro. Interestingly, chronic nicotine failed to blunt hypoxia-evoked responses in MAH cells bearing short hairpin knockdown (>90%) of the transcription factor, hypoxia-inducible factor-2alpha (HIF-2alpha), suggesting involvement of the HIF pathway. The therapeutic potential of K(ATP) channel blockers was validated in experiments in which hypoxia-induced neonatal mortality in nicotine-exposed pups was significantly reduced after pretreatment with glibenclamide.

Beyond Substance Abuse: Stress, Burnout, and Depression As Causes of Physician Impairment and Disruptive Behavior

Journal of the American College of Radiology : JACR. Jul, 2009  |  Pubmed ID: 19560063

Disruptive physician behavior may diminish productivity, lead to medical errors, and compromise patient safety. The purpose of this paper is to review how common psychological conditions such as depression, stress, and burnout may drive disruptive behavior in the workplace and result in impaired patterns of professional conduct similar to what is seen with substance abuse. Problems related to these psychological morbidities may be more effectively managed with improved understanding of the conditions and behaviors, their associated risk factors, and the barriers that exist to reporting them. Further research and educational programs are warranted to address how these conditions might affect radiology.

Point/Counterpoint. Hypofractionation is a Proven Safe and Effective Modality for Postoperative Whole-breast Radiotherapy for Early Breast Cancer Patients

Medical Physics. Jun, 2009  |  Pubmed ID: 19610281

Comparison of Different Rowing Exercises: Trunk Muscle Activation and Lumbar Spine Motion, Load, and Stiffness

Journal of Strength and Conditioning Research / National Strength & Conditioning Association. Aug, 2009  |  Pubmed ID: 19620925

The objective of this study was to investigate 3 different rowing exercises and quantify the muscle activation of the torso and the hip musculature, together with the corresponding spinal loading and stiffness. Seven healthy male subjects from a university population were instrumented to obtain surface electromyography of selected trunk and hip muscles and to obtain spine position using an electromagnetic spine position sensor, together with video analysis to calculate joint moments. The 3 rowing exercises investigated are the inverted row, standing bent-over row, and the standing 1-armed cable row. The inverted row elicited the highest activation of the latissimus dorsi muscles, upper back, and hip extensor muscles. The lower activation of the lumbar erector spinae muscles during the inverted row corresponded to the lower-spine load measured. The standing bent-over row produced large activation symmetrically across the back but produced the largest lumbar spine load. The 1-armed cable row challenged the torsional capabilities of the trunk musculature. Some "core" exercises may be better for rehabilitation (e.g., having the training goals of modest muscle activation with low spine load), while other exercises may be better for athletic training (e.g., resulting in higher muscle activation and larger spine load). When prescribing "core" exercises, those wishing to spare the low back may choose the inverted row given the lowest spine load exercise. The standing bent-over row elicited large muscle activation symmetrically from the upper to lower back, however induced larger spine loads, but not surprisingly the highest spine stiffness. If torsional endurance or strength is the training goal, the 1-armed cable row might be considered.

Reducing Distress for Children During Invasive Procedures: Randomized Clinical Trial of Effectiveness of the PediSedate

Paediatric Anaesthesia. Aug, 2009  |  Pubmed ID: 19624359

Procedural pain control remains problematic for young children, especially during anxiety-causing procedures for which children should not be deeply sedated. The PediSedate was designed to address this problem by delivering nitrous oxide in oxygen through a simple nosepiece, combined with an interactive video component, so that children can use attention and distraction with drug delivery.

Skewed X Chromosome Inactivation and Trisomic Spontaneous Abortion: No Association

American Journal of Human Genetics. Aug, 2009  |  Pubmed ID: 19646676

Several studies suggest that highly skewed X chromosome inactivation (HSXI) is associated with recurrent spontaneous abortion. We hypothesized that this association reflects an increased rate of trisomic conceptions due to anomalies on the X chromosome that lead both to HSXI and to a diminished oocyte pool. We compared the distribution of X chromosome inactivation (XCI) skewing percentages (range: 50%-100%) among women with spontaneous abortions in four karyotype groups-trisomy (n = 154), chromosomally normal male (n = 43), chromosomally normal female (n = 38), nontrisomic chromosomally abnormal (n = 61)-to the distribution for age-matched controls with chromosomally normal births (n = 388). In secondary analyses, we subdivided the nontrisomic chromosomally abnormal group, divided trisomies by chromosome, and classified women by reproductive history. Our data support neither an association of HSXI with all trisomies nor an association of HSXI with chromosomally normal male spontaneous abortions. We also find no association between HSXI and recurrent abortion (n = 45).

The Intrinsic Stiffness of the in Vivo Lumbar Spine in Response to Quick Releases: Implications for Reflexive Requirements

Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. Oct, 2009  |  Pubmed ID: 18513993

Torso muscles contribute both intrinsic and reflexive stiffness to the spine; recent modeling studies indicate that intrinsic stiffness alone is sometimes insufficient to maintain stability in dynamic situations. The purpose of this study was to experimentally test this idea by limiting muscular reflexive responses to sudden trunk perturbations. Nine healthy males lay on a near-frictionless apparatus and were subjected to quick trunk releases from the neutral position into flexion or right-side lateral bend. Different magnitudes of moment release were accomplished by having participants contract their musculature to create a range of moment levels. EMG was recorded from 12 torso muscles and three-dimensional lumbar spine rotations were monitored. A second-order linear model of the trunk was employed to estimate trunk stiffness and damping during each quick release. Participants displayed very limited reflex responses to the quick load release paradigms, and consequently underwent substantial trunk displacements (>50% flexion range of motion and >70% lateral bend range of motion in the maximum moment trials). Trunk stiffness increased significantly with significant increases in muscle activation, but was still unable to prevent the largest trunk displacements in the absence of reflexes. Thus, it was concluded that the intrinsic stiffness of the trunk was insufficient to adequately prevent the spine from undergoing potentially harmful rotational displacements. Voluntary muscular responses were more apparent than reflexive responses, but occurred too late and of too low magnitude to sufficiently make up for the limited reflexes.

Dilatable Pulmonary Artery Banding in Infants with Low Birth Weight or Complex Congenital Heart Disease Allows Avoidance or Postponement of Subsequent Surgery

European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery. Feb, 2010  |  Pubmed ID: 19692268

This study evaluated the efficiency and feasibility of dilatable bands in selected patients.

High-pass Filtering Surface EMG in an Attempt to Better Represent the Signals Detected at the Intramuscular Level

Muscle & Nerve. Feb, 2010  |  Pubmed ID: 19722252

Surface electromyography (EMG) is often used to represent activation profiles of the underlying musculature. The purpose of this study was to assess the potential of high-pass (HP) filtering to improve the matching of surface EMG signals to those signals recorded intramuscularly. EMG was recorded at the skin surface over the infraspinatus and supraspinatus muscles as well as from fine-wire electrodes placed in the infraspinatus, supraspinatus, and teres minor muscles. The surface EMG signals were HP-filtered at 18 cutoff frequencies (0-510 HZ in 30 HZ increments), and the time-histories were correlated with the signals from the wire electrodes. HP filtering did not significantly alter the correlated muscle activation waveform relationship between the surface and wire signals until cutoffs reached 240 HZ. HP filtering of the surface signals did not improve the representation of the muscle fiber-level activation profile, but the results suggest that enough information resides in the high-frequency components of the signal to reproduce the activation time-history profile of the muscle.

Childhood Loneliness As a Predictor of Adolescent Depressive Symptoms: an 8-year Longitudinal Study

European Child & Adolescent Psychiatry. Jun, 2010  |  Pubmed ID: 19777287

Childhood loneliness is characterised by children's perceived dissatisfaction with aspects of their social relationships. This 8-year prospective study investigates whether loneliness in childhood predicts depressive symptoms in adolescence, controlling for early childhood indicators of emotional problems and a sociometric measure of peer social preference. 296 children were tested in the infant years of primary school (T1 5 years of age), in the upper primary school (T2 9 years of age) and in secondary school (T3 13 years of age). At T1, children completed the loneliness assessment and sociometric interview. Their teachers completed externalisation and internalisation rating scales for each child. At T2, children completed a loneliness assessment, a measure of depressive symptoms, and the sociometric interview. At T3, children completed the depressive symptom assessment. An SEM analysis showed that depressive symptoms in early adolescence (age 13) were predicted by reports of depressive symptoms at age 8, which were themselves predicted by internalisation in the infant school (5 years). The interactive effect of loneliness at 5 and 9, indicative of prolonged loneliness in childhood, also predicted depressive symptoms at age 13. Parent and peer-related loneliness at age 5 and 9, peer acceptance variables, and duration of parent loneliness did not predict depression. Our results suggest that enduring peer-related loneliness during childhood constitutes an interpersonal stressor that predisposes children to adolescent depressive symptoms. Possible mediators are discussed.

Percutaneous Management of a Fontan Fenestration: in Search for the Ideal Restriction-occlusion Device

Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. Jan, 2010  |  Pubmed ID: 19937791

Most devices devices available for percutaneous closure of Fontan fenestrations tend to be bulky. The aim of this study was to evaluate a low profile custom made device and assess its efficacy and safety.

Volume Load Paradox While Preparing for the Fontan: Not Too Much for the Ventricle, Not Too Little for the Lungs

Interactive Cardiovascular and Thoracic Surgery. Feb, 2010  |  Pubmed ID: 19945986

Ventricular dysfunction is frequently encountered in Fontan patients. Cardiologists and cardiac surgeons have, therefore, mainly focused on preservation of cardiac function, limiting the early volume overload as much as possible both in magnitude and duration. This resulted in improved cardiac function but, in some patients, also in poor pulmonary artery (PA) growth which in turn resulted in a poor final Fontan circuit. The volume requirements for optimal growth and development of the ventricle and the lungs are different and divergent. Avoiding overload of the ventricle is important, but excessive protection from volume overload may not be necessary and may result in PA hypoplasia, which in turn will severely affect the Fontan circuit.

The Fontan Circulation: Who Controls Cardiac Output?

Interactive Cardiovascular and Thoracic Surgery. Mar, 2010  |  Pubmed ID: 19995891

In a Fontan circuit the mechanisms involved in control of cardiac output at rest and during exercise differ significantly from normal. The classical model presumes an unlimited preload which is not available in the Fontan circuit. This review critically analyses the role of contractility, heart rate, and afterload and highlights the importance of pulmonary vascular resistance (PVR) in determining adequate preload and, therefore, cardiac output in these patients. A conceptual model of the determinants of cardiac output in Fontan patients is presented.

Reverse Glenoid Component Fixation: is a Posterior Screw Necessary?

Journal of Shoulder and Elbow Surgery / American Shoulder and Elbow Surgeons ... [et Al.]. Jun, 2010  |  Pubmed ID: 20056452

Reverse shoulder arthroplasty has become more prevalent for the treatment of complex shoulder issues. Prosthetic designs vary in both the number and orientation of screws recommended for securing the glenoid base plate. This study examined the contribution of the posterior glenoid screw for stabilizing the glenosphere by comparing constructs with no posterior screw, a standard posterior screw directed into the glenoid neck, and a long posterior screw (LPS) into the scapular spine.

The Influence of Pulmonary Regurgitation on Regional Right Ventricular Function in Children After Surgical Repair of Tetralogy of Fallot

European Journal of Echocardiography : the Journal of the Working Group on Echocardiography of the European Society of Cardiology. May, 2010  |  Pubmed ID: 20085920

Pulmonary regurgitation after repair of tetralogy of Fallot (TOF) results in right ventricular (RV) dysfunction with significant late morbidity and mortality. The aim was to assess the influence of pulmonary regurgitation on regional RV function.

Effects of Tesamorelin, a Growth Hormone-releasing Factor, in HIV-infected Patients with Abdominal Fat Accumulation: a Randomized Placebo-controlled Trial with a Safety Extension

Journal of Acquired Immune Deficiency Syndromes (1999). Mar, 2010  |  Pubmed ID: 20101189

HIV-infected patients receiving antiretroviral therapy often demonstrate excess visceral fat. A growth hormone-releasing factor, tesamorelin, may selectively reduce visceral fat in this population. We investigated the effects of tesamorelin (GHRH(1-44)) in HIV-infected patients with central fat accumulation.

Ramipril Mitigates Radiation-induced Impairment of Neurogenesis in the Rat Dentate Gyrus

Radiation Oncology (London, England). 2010  |  Pubmed ID: 20122169

Sublethal doses of whole brain irradiation (WBI) are commonly administered therapeutically and frequently result in late delayed radiation injuries, manifesting as severe and irreversible cognitive impairment. Neural progenitors within the subgranular zone (SGZ) of the dentate gyrus are among the most radiosensitive cell types in the adult brain and are known to participate in hippocampal plasticity and normal cognitive function. These progenitors and the specialized SZG microenvironment required for neuronal differentiation are the source of neurogenic potential in the adult dentate gyrus, and provide a continuous supply of immature neurons which may then migrate into the adjacent granule cell layer to become mature granule cell neurons. The extreme radiosensitivity of these progenitors and the SGZ microenvironment suggests the hippocampus as a prime target for radiation-induced cognitive impairment. The brain renin-angiotensin system (RAS) has previously been implicated as a potent modulator of neurogenesis within the SGZ and selective RAS inhibitors have been implicated as mitigators of radiation brain injury. Here we investigate the angiotensin converting enzyme (ACE) inhibitor, ramipril, as a mitigator of radiation injury in this context.

Stent Expansion of Stretch Gore-Tex Grafts in Children with Congenital Heart Lesions

Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. May, 2010  |  Pubmed ID: 20146322

To evaluate the efficacy and safety of expanding vascular shunt grafts beyond original nominal diameter using stents.

Exercise for Dysmenorrhoea

Cochrane Database of Systematic Reviews (Online). 2010  |  Pubmed ID: 20166071

Dysmenorrhoea is characterised by cramping lower abdominal pain that may radiate to the lower back and upper thighs and is commonly associated with nausea, headache, fatigue and diarrhoea. Physical exercise has been suggested as a non-medical approach to the management of these symptoms.

Differentiation of Glioma and Radiation Injury in Rats Using in Vitro Produce Magnetically Labeled Cytotoxic T-cells and MRI

PloS One. 2010  |  Pubmed ID: 20195476

A limitation with current imaging strategies of recurrent glioma undergoing radiotherapy is that tumor and radiation injury cannot be differentiated with post contrast CT or MRI, or with PET or other more complex parametric analyses of MRI data. We propose to address the imaging limitation building on emerging evidence indicating that effective therapy for recurrent glioma can be attained by sensitized T-cells following vaccination of primed dendritic cells (DCs). The purpose of this study was to determine whether cord blood T-cells can be sensitized against glioma cells (U-251) and if these sensitized cytotoxic T-cells (CTLs) can be used as cellular magnetic resonance imaging probes to identify and differentiate glioma from radiation necrosis in rodent models.

Psychological Adjustment to Gynaecological Cancer: Patients' Illness Representations, Coping Strategies and Mood Disturbance

Psychology & Health. Jun, 2010  |  Pubmed ID: 20204950

This study examined associations between illness representation dimensions specified by the self-regulation model, coping and mood in recently diagnosed gynaecological cancer patients. Participants were 61 patients recruited from a specialist outpatient gynaecology clinic. Patients completed a survey measuring their cognitive illness representations (IPQ-R), coping strategies (COPE) and mood (POMS-SF). Consistent with research into other illnesses, the study found theoretically congruent cross-sectional associations between illness representations and mood disturbance. Support was found for a possible path whereby higher denial and avoidant coping might mediate the relationships between cyclical timeline and illness coherence representations and more negative mood. There were no mediational relationships for other coping strategies. Mediation of the relationship between illness representations and mood by avoidant coping has important theoretical and practical implications. These are discussed, as are direct relationships between illness representations and mood.

Sutureless Rescue of a Severely Hypoplastic Pulmonary Artery

European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery. Mar, 2010  |  Pubmed ID: 19846316

The management of severely hypoplastic pulmonary arteries in the adolescent or adult with congenital heart disease is challenging. A patient with pulmonary atresia and ventricular septal defect (PA-VSD) presented with severe cyanosis due to a kinked and thrombosed right ventricle to pulmonary artery conduit. Retrograde wedge angiography showed a patent right and a diminutive left pulmonary artery deep in the lung hilus. Treatment options were limited and therefore a different strategy had to be considered to rescue the lung segments. This case report describes the novel use of a covered stent to successfully obtain a sutureless connection between a vascular graft and a diminutive pulmonary artery during a hybrid procedure.

A Comparison of Ultrasound and Electromyography Measures of Force and Activation to Examine the Mechanics of Abdominal Wall Contraction

Clinical Biomechanics (Bristol, Avon). Feb, 2010  |  Pubmed ID: 19879679

Ultrasound imaging is a valuable tool which, when applied appropriately, has the potential to provide information regarding the mechanics of abdominal muscle contraction. Typically, changes in muscle thickness are obtained and interpreted. However, the link between ultrasound measures of muscle thickening and EMG measures of activation is not clear.

Ever Heard of the Obturator Vein?

Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. Feb, 2010  |  Pubmed ID: 19882714

We report a complication related to advancement of a large diameter long sheath in the obturator vein. In an adult with a previously thrombosed femoral vein, the obturator vein was inadvertently cannulated. During percutaneous pulmonary valve implantation, the Ensemble(R) delivery system could not be advanced after repositioning attempt. The obturator vein had been perforated and sheath was coiled up in the pelvis leading to a retroperitoneal pelvic hematoma. Continuity of the vein was established using two self-expanding covered stents. The obturator vein runs dorsally and joins the inferior caval vein at a very acute angle posterior in the pelvis, creating a corner in which stiff catheters or sheaths may get entrapped.

Architectural Analysis of Human Abdominal Wall Muscles: Implications for Mechanical Function

Spine. Sep, 2010  |  Pubmed ID: 20890265

STUDY DESIGN.: Cadaveric analysis of human abdominal muscle architecture. OBJECTIVE.: To quantify the architectural properties of rectus abdominis (RA), external oblique (EO), internal oblique (IO), and transverse abdominis (TrA), and model mechanical function in light of these new data. SUMMARY OF BACKGROUND DATA.: Knowledge of muscle architecture provides the structural basis for predicting muscle function. Abdominal muscles greatly affect spine loading, stability, injury prevention, and rehabilitation; however, their architectural properties are unknown. METHODS.: Abdominal muscles from 11 elderly human cadavers were removed intact, separated into regions, and microdissected for quantification of physiologic cross-sectional area, fascicle length, and sarcomere length. From these data, sarcomere operating length ranges were calculated. RESULTS.: IO had the largest physiologic cross-sectional area and RA the smallest, and would thus generate the largest and smallest isometric forces, respectively. RA had the longest fascicle length, followed by EO, and would thus be capable of generating force over the widest range of lengths. Measured sarcomere lengths, in the postmortem neutral spine posture, were significantly longer in RA and EO (3.29 ± 0.07 and 3.18 ± 0.11 μm) compared to IO and TrA (2.61 ± 0.06 and 2.58 ± 0.05 μm) (P < 0.0001). Biomechanical modeling predicted that RA, EO and TrA act at optimal force-generating length in the midrange of lumbar spine flexion, where IO can generate approximately 90% of its maximum force. CONCLUSION.: These data provide clinically relevant insights into the ability of the abdominal wall muscles to generate force and change length throughout the lumbar spine range of motion. This will impact the understanding of potential postures in which the force-generating and spine stabilizing ability of these muscles become compromised, which can guide exercise/rehabilitation development and prescription. Future work should explore the mechanical interactions among these muscles and their relationship to spine health and function.

A Novel Method of Boron Delivery Using Sodium Iodide Symporter for Boron Neutron Capture Therapy

Journal of Radiation Research. 2010  |  Pubmed ID: 20921830

Boron Neutron Capture Therapy (BNCT) effectiveness depends on the preferential sequestration of boron in cancer cells relative to normal tissue cells. We present a novel strategy for sequestering boron using an adenovirus expressing the sodium iodide symporter (NIS). Human glioma grown subcutaneously in athymic mice and orthotopic rat brain tumors were transfected with NIS using a direct tumor injection of adenovirus. Boron bound as sodium tetrafluoroborate (NaBF(4)) was administered systemically several days after transfection. Tumors were excised hours later and assessed for boron concentration using inductively coupled plasma atomic emission spectroscopy. In the human glioma transfected with NIS, boron concentration was more than 10 fold higher with 100 mg/kg of NaBF(4), compared to tumor not transfected. In the orthotopic tumor model, the presence of NIS conferred almost 4 times the boron concentration in rat tumors transfected with human virus compared with contralateral normal brain not transfected. We conclude that adenovirus expressing NIS has the potential to be used as a novel boron delivery agent and should be explored for future clinical applications.

Divergent Roles of Reactive Oxygen Species in the Responses of Perinatal Adrenal Chromaffin Cells to Hypoxic Challenges

Respiratory Physiology & Neurobiology. Dec, 2010  |  Pubmed ID: 20804866

The fetus and neonate experience variable patterns of low P(O)₂(hypoxia) ranging from acute, sustained, and intermittent. Adaptation to hypoxia involves activation of key transcription factors, known as hypoxia-inducible factors (e.g. HIF-1α, HIF-2α), which regulate a number of genes in different cell types. This review focuses on the signaling pathways that mediate proper physiological responses of perinatal adrenomedullary chromaffin cells (AMC) to varying patterns of hypoxic challenges, and particularly on the controversial role of reactive oxygen species (ROS). At birth, acute hypoxia (seconds to minutes) directly stimulates catecholamine release from AMC via K+ channel inhibition, mediated by a decrease in mitochondrial-derived ROS. By contrast, exposure to chronic sustained hypoxia (CSH) induces HIF-2α in a fetal-derived chromaffin cell line independently of changes in ROS. Exposure to chronic intermittent hypoxia (CIH) activates antioxidant responses via the regulator Nrf-2, in association with an increase in ROS and the induction of HIF-1α. We propose that the physiological responses of perinatal AMC to hypoxia and the ensuing directional changes in ROS are dependent on the pattern and duration of the hypoxic exposure.

Overview of Modern Radiation Therapy

Texas Medicine. Aug, 2010  |  Pubmed ID: 20809439

Radiation therapy continues to evolve with modern computers and digital imaging. The term "adaptive" in this field addresses the desire to improve in the implementation of radiotherapy with the goal to achieve real-time imaging and planning of the target through a prescribed course of therapy. The frontier of adaptive therapy has arrived and will be applied to all aspects of radiation oncology.

A Comparison of Frequent and Infrequent Visitors to an Urban Emergency Department

The Journal of Emergency Medicine. Feb, 2010  |  Pubmed ID: 18462906

Frequent visitors account for a high proportion of Emergency Department (ED) visits and costs. Some of these visits could be handled effectively in less expensive primary care settings. Effective interventions to redirect these patients to primary care depend on an in-depth understanding of frequent visitors and the reasons they seek care in the ED. The objective of this study was to explore the differences between frequent visitors and infrequent visitors who seek medical care in one urban ED, as a first step toward developing effective interventions to direct patients to effective sources of care. In structured interviews, we asked 69 frequent visitors and 99 infrequent visitors to an inner-city, adult ED about medical diagnoses, general health, depression, alcohol abuse, physical functioning, self-perceived social support, primary care and ED service use, payment method, satisfaction with their primary care physician, and demographic characteristics. Differences in responses between groups were compared using t-tests for continuous variables and chi-square for categorical variables. Frequent visitors were more likely than infrequent visitors to be insured by Medicaid (53% vs. 39%, respectively) and less likely to be uninsured (13% vs. 24%, respectively) or have private insurance (6% vs. 15%, respectively). They reported higher levels of stress, lower levels of social support, and worse general health status. They were much more likely to screen positive for depression (47% vs. 27%, respectively, p = 0.017). Frequent visitors were more likely to have a primary care physician (75% vs. 66%, respectively), and 45% of the frequent visitors had a primary care physician at the ED hospital compared to 23% of the infrequent visitors. These findings suggest the need to improve access to frequent visitors' primary care physicians, screen them for depression, and offer psychological and social services more aggressively. These findings may apply to other inner city EDs.

Architectural and Morphological Assessment of Rat Abdominal Wall Muscles: Comparison for Use As a Human Model

Journal of Anatomy. Sep, 2010  |  Pubmed ID: 20646108

The abdominal wall is a composite of muscles that are important for the mechanical stability of the spine and pelvis. Tremendous clinical attention is given to these muscles, yet little is known about how they function in isolation or how they interact with one another. Given the morphological, vascular, and innervation complexities associated with these muscles and their proximity to the internal organs, an appropriate animal model is important for understanding their physiological and mechanical significance during function. To determine the extent to which the rat abdominal wall resembles that of human, 10 adult male Sprague-Dawley rats were killed and formalin-fixed for architectural and morphological analyses of the four abdominal wall muscles (rectus abdominis, external oblique, internal oblique, and transversus abdominis). Physiological cross-sectional areas and optimal fascicle lengths demonstrated a pattern that was similar to human abdominal wall muscles. In addition, sarcomere lengths measured in the neutral spine posture were similar to human in their relation to optimal sarcomere length. These data indicate that the force-generating and length change capabilities of these muscles, relative to one another, are similar in rat and human. Finally, the fiber lines of action of each abdominal muscle were similar to human over most of the abdominal wall. The main exception was in the lower abdominal region (inferior to the pelvic crest), where the external oblique becomes aponeurotic in human but continues as muscle fibers into its pelvic insertion in the rat. We conclude that, based on the morphology and architecture of the abdominal wall muscles, the adult male Sprague-Dawley rat is a good candidate for a model representation of human, particularly in the middle and upper abdominal wall regions.

Effects of Eccentric Exercise-induced Muscle Damage on Intramyocellular Lipid Concentration and High Energy Phosphates

European Journal of Applied Physiology. Dec, 2010  |  Pubmed ID: 20706732

Eccentric exercise is known to cause changes to the ultrastructure of skeletal muscle and, in turn, may alter the ability of the muscle to store and utilise intracellular substrates such as intramyocellular lipid (IMCL). The purpose of this study was to test the hypothesis that exercise-induced muscle damage (EIMD) results in IMCL accumulation. Six males (31 ± 6 years; mean ± SD, and 72.3 ± 9.7 kg body mass) performed 300 unilateral, maximal, isokinetic, eccentric contractions (Ecc) (30° s(-1)) of the quadriceps on an isokinetic dynamometer, followed immediately by an equal amount of work by the contralateral leg but with concentric action (Con). Phosphate compounds and IMCL content of the vastus lateralis of both legs were measured using (31)P and (1)H magnetic resonance spectroscopy. IMCL content was higher in Ecc than Con 24 h post but the reverse was evident 48 h post-exercise (P = 0.046). A significant time × trial interaction for resting [P(i)] (P = 0.045), showed increases in Ecc across time but no change in Con. A significant main effect of trial (P = 0.002) was apparent indicating the Ecc leg had marked metabolic dysfunction. The P(i)/PCr ratio showed a significant effect of trial (P = 0.001) with an increase evident in Ecc leg, primarily due to increases in [P(i)]. The present study highlights changes in IMCL content of skeletal muscle following EIMD.

Incorporation of Fetal DNA Detection Assay in a Noninvasive RhD Diagnostic Test

Prenatal Diagnosis. Oct, 2010  |  Pubmed ID: 20721880

The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

Science (New York, N.Y.). Dec, 2010  |  Pubmed ID: 21051598

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

Resilience Training for Functioning Adults: Program Description and Preliminary Findings from a Pilot Investigation

International Journal of Emergency Mental Health. 2010  |  Pubmed ID: 21138155

It has previously been asserted that the construct of resilience holds great promise for diverse high-risk populations and that resilience may be an attribute that can be acquired through training. A rich body of literature suggests the strengths that comprise resilience. This paper describes a resilience training program based upon the identified strengths of resilience and provides additional preliminary data from a pilot investigation which lend support to the idea that resilience can be acquired through training. Suggestions for future research are provided.

Comparative Analysis of the Cardioprotective Properties of Opioid Receptor Agonists in a Rat Model of Myocardial Infarction

Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. Nov, 2010  |  Pubmed ID: 21175523

This study was conducted to test the hypothesis that opioid receptor (OR)-mediated cardioprotection is agonist specific when administered prior to coronary artery occlusion and reperfusion in a rat model.

Institutional Profile: The Sheffield RNAi Screening Facility: a Service for High-throughput, Genome-wide Drosophila RNAi Screens

Future Medicinal Chemistry. Dec, 2010  |  Pubmed ID: 21428803

The Sheffield RNAi Screening Facility (SRSF) was established in November 2008, as Britain's first Drosophila RNAi screening centre, funded by the University of Sheffield, Biomedical Sciences Department and the Wellcome Trust. The SRSF was formed to service the needs of research groups wanting to carry out high-throughput RNAi screens with Drosophila cells. The rationale for the SRSF is to provide RNAi libraries and the specialist equipment and expertise to do such screens. The facility supports both plate reader assays, high-content microscopy as well as the equipment needed to process these samples in a high-throughput fashion. The SRSF can either be used to identify genes involved in disease representing future drug targets, or to identify genes involved in drug resistance and efficacy.

The Manganese Superoxide Dismutase Mimetic, M40403, Protects Adult Mice from Lethal Total Body Irradiation

Free Radical Research. May, 2010  |  Pubmed ID: 20298121

Over-expression of manganese superoxide dismutase (MnSOD) protects tissues from radiation. M40403 is a stable non-peptidyl mimetic of MnSOD that crosses cell membranes and is effective in reducing experimental inflammation. Male BALB/c mice were injected intraperitoneally (i.p.) and subcutaneously (s.c.) with M40403, 30 min before 6.5, 7.5 and 8.5 Gy total body irradiation (TBI). Whereas all control injected mice died after receiving 8.5 Gy TBI by day 17, 30 day survival of mice pre-treated i.p. with 40, 30, 20 or 10 mg/kg was 100%, 90%, 81% and 25%, respectively. The Dose Reduction Factor 50/30 for animals treated with 30 mg M40403 s.c. 30 min prior to TBI was 1.41. Decreased apoptosis of the large and particularly the small bowel and marked recovery of both lymphoid and hematopoietic tissues occurred in the M40403 pre-treated animals. M40403 is effective in reducing TBI-induced tissue destruction and has potential as a new radioprotective agent.

Pyrrolidine Dithiocarbamate (PDTC) Blocks Apoptosis and Promotes Ionizing Radiation-induced Necrosis of Freshly-isolated Normal Mouse Spleen Cells

Apoptosis : an International Journal on Programmed Cell Death. Jun, 2010  |  Pubmed ID: 20333468

Ionizing radiation (IR) is a pro-oxidant that kills cells by both apoptotic and necrotic mechanisms. Pyrrolidine dithiocarbamate (PDTC) is a thiol-containing compound that may act either as a pro- or anti-oxidant depending on the experimental conditions. This study was designed to determine whether PDTC would reduce or enhance IR-induced cell death of freshly-isolated normal mouse B6/129 spleen cells (NMSC). We determined the effect of increasing doses of IR, PDTC alone and PDTC followed by IR on the viability of NMSC. Annexin V and propidium iodide (Annexin V/PI) staining demonstrated a dose and time-dependent relationship in which PDTC enhanced the percentage of IR-induced apoptotic/necrotic NMSC. Trypan blue dye inclusion confirmed that a loss of membrane integrity was occurring 1 h after incubation with PDTC plus IR. Reduction in the glutathione (GSH)/glutathione disulfide (GSSG) ratio and GSH demonstrated that both IR (8.5 Gy) and PDTC acted as pro-oxidants, but their mechanisms of action differed: In contrast to IR, which promoted p53 activation and caspase 3/7-mediated apoptosis, PDTC inhibited IR-induced p53 and caspase 3/7 activity. However, PDTC increased H(2)O(2) formation and necrosis, resulting in an overall increase in IR-induced cell death. Catalase prevented the PDTC-induced increase in IR cytotoxicity implicating the generation of H(2)O(2) as a major factor in this mechanism. These results demonstrate that in NMSC PDTC acts as pro-oxidant and enhances IR-induced cell cytotoxicity by increasing H(2)O(2)formation and thiol oxidation. As such, they strongly suggest that the use of PDTC as an adjunct to reduce radiation toxicity should be avoided.

Animal Models for Medical Countermeasures to Radiation Exposure

Radiation Research. Apr, 2010  |  Pubmed ID: 20334528

Since September 11, 2001, there has been the recognition of a plausible threat from acts of terrorism, including radiological or nuclear attacks. A network of Centers for Medical Countermeasures against Radiation (CMCRs) has been established across the U.S.; one of the missions of this network is to identify and develop mitigating agents that can be used to treat the civilian population after a radiological event. The development of such agents requires comparison of data from many sources and accumulation of information consistent with the "Animal Rule" from the Food and Drug Administration (FDA). Given the necessity for a consensus on appropriate animal model use across the network to allow for comparative studies to be performed across institutions, and to identify pivotal studies and facilitate FDA approval, in early 2008, investigators from each of the CMCRs organized and met for an Animal Models Workshop. Working groups deliberated and discussed the wide range of animal models available for assessing agent efficacy in a number of relevant tissues and organs, including the immune and hematopoietic systems, gastrointestinal tract, lung, kidney and skin. Discussions covered the most appropriate species and strains available as well as other factors that may affect differential findings between groups and institutions. This report provides the workshop findings.

Interactions Between Heart Rate Variability and Pulmonary Gas Exchange Efficiency in Humans

Experimental Physiology. Jul, 2010  |  Pubmed ID: 20382666

The respiratory component of heart rate variability (respiratory sinus arrhythmia, RSA) has been associated with improved pulmonary gas exchange efficiency in humans via the apparent clustering and scattering of heart beats in time with the inspiratory and expiratory phases of alveolar ventilation, respectively. However, since human RSA causes only marginal redistribution of heart beats to inspiration, we tested the hypothesis that any association between RSA amplitude and pulmonary gas exchange efficiency may be indirect. In 11 patients with fixed-rate cardiac pacemakers and 10 healthy control subjects, we recorded R-R intervals, respiratory flow, end-tidal gas tension and the ventilatory equivalents for carbon dioxide and oxygen during 'fast' (0.25 Hz) and 'slow' paced breathing (0.10 Hz). Mean heart rate, mean arterial blood pressure, mean arterial pressure fluctuations, tidal volume, end-tidal CO(2), and were similar between pacemaker and control groups in both the fast and slow breathing conditions. Although pacemaker patients had no RSA and slow breathing was associated with a 2.5-fold RSA amplitude increase in control subjects (39 +/- 21 versus 97 +/- 45 ms, P < 0.001), comparable (main effect for breathing frequency, F(1,19) = 76.54, P < 0.001) and reductions (main effect for breathing frequency, F(1,19) = 23.90, P < 0.001) were observed for both cohorts during slow breathing. In addition, the degree of (r = 0.36, P = 0.32) and reductions (r = 0.29, P = 0.43) from fast to slow breathing were not correlated to the degree of associated RSA amplitude enhancements in control subjects. These findings suggest that the association between RSA amplitude and pulmonary gas exchange efficiency during variable-frequency paced breathing observed in prior human work is not contingent on RSA being present. Therefore, whether RSA serves an intrinsic physiological function in optimizing pulmonary gas exchange efficiency in humans requires further experimental validation.

Changes in Risk Perceptions Prospectively Predict Changes in Self-reported Speeding

Risk Analysis : an Official Publication of the Society for Risk Analysis. Jul, 2010  |  Pubmed ID: 20409047

Risk perception theories posit that changes in risk perception prompt subsequent changes in risk behavior. Prospective studies using observations made at three time-points offer the capacity to test this hypothesis by observing sequential changes in both risk perceptions and behavior. A telephone survey was administered by random-digit dialing to 255 adult Australian drivers at baseline (T1), 6 weeks (T2), and 14 weeks (T3). During weeks 2-5, a risk-perception-based anti-speeding mass media campaign was conducted. The survey assessed risk perception, operationalized as the proportion of time that driving at 70 km/h (43 mph) was perceived to be dangerous, and self-reported speeding behavior, defined as the frequency of respondents driving 5 km (3 mph) faster than the legal speed limit in built up areas. Higher T2 risk perception predicted lower T3 self-reports of speeding after controlling T1 risk perception and T1 and T2 self-reported speeding. This can be interpreted as changes in risk perceptions between T1 and T2 predicting changes in speeding between T2 and T3. Further analyses showed that increases in risk perception predicted lower subsequent self-reported speeding changes, but decreases in risk perception were unrelated to those changes. Risk perception changes were unrelated to recall of exposure to the media campaign. These findings support a dynamic view of the relationship between risk perception and self-reported behavior, and that risk perception theories can be applied to speeding.

Alcohol-related Image Priming and Aggression in Adolescents Aged 11-14

Addictive Behaviors. Aug, 2010  |  Pubmed ID: 20409646

In adults, alcohol-related stimuli prime aggressive responding without ingestion or belief of ingestion. This represents either experiential or socially-and culturally-mediated learning. Using a laboratory-based competitive aggression paradigm, we replicated adult findings in 103 11-14 year old adolescents below the legal UK drinking age. Using a two-independent group design, priming with alcohol-related imagery led participants to deliver louder noise punishments in a competition task than priming with beverage-related images. This effect was stronger in participants scoring low on an internalization measure. Priming effects in relatively alcohol-naïve participants could constitute evidence of socio-cultural transmission of scripts linking alcohol use and aggression. The enhanced effect in lower internalization scorers suggests that alcohol priming might undermine behavioral inhibition processes in otherwise stable adolescents.

Long-term Safety of NGX-4010, a High-concentration Capsaicin Patch, in Patients with Peripheral Neuropathic Pain

Journal of Pain and Symptom Management. Jun, 2010  |  Pubmed ID: 20538187

Postherpetic neuralgia (PHN) and painful human immunodeficiency virus-associated distal sensory polyneuropathy (HIV-DSP) are peripheral neuropathic pain syndromes that are difficult to treat. Current treatment options are often limited by poor tolerability.

The Relationship Between Trunk Muscle Activation and Trunk Stiffness: Examining a Non-constant Stiffness Gain

Computer Methods in Biomechanics and Biomedical Engineering. Dec, 2010  |  Pubmed ID: 20603728

The relationship between muscle activation, force and stiffness needs to be known to interpret the stability state of the spine. To test the relationship between these variables, a quick release approach was used to match quantified torso stiffness with an EMG activation-based estimate of individual muscle stiffnesses. The relationship between activation, force and stiffness was modelled as k = q x F/l, where k, F and l are muscle stiffness, force and length, respectively, and q is the dimensionless stiffness gain relating these variables. Under the tested experimental scenario, the 'stiffness gain', q, which linked activation with stiffness, demonstrated a decreasing trend with increasing levels of torso muscle activation. This highlights the likelihood that the choice of a single q value may be over simplistic to relate force to stiffness in muscles that control the spine. This has implications for understanding the potential for spine instability in situations requiring high muscular demand.

Mechanical Strength of the Side-to-side Versus Pulvertaft Weave Tendon Repair

The Journal of Hand Surgery. Apr, 2010  |  Pubmed ID: 20223604

The side-to-side (SS) tendon suture technique was designed to function as a repair that permits immediate postoperative activation and mobilization of a transferred muscle. This study was designed to test the strength and stiffness of the SS technique against a variation of the Pulvertaft (PT) repair technique.

Aneuploidy Detection in Mixed DNA Samples by Methylation-sensitive Amplification and Microarray Analysis

Clinical Chemistry. May, 2010  |  Pubmed ID: 20224049

Cell-free fetal nucleic acid, believed to be derived from the placenta/trophoblast, is present in the plasma of pregnant women; however, its use for predictive genetic testing has been severely limited because the circulating fetal DNA is present in a small quantity and mixed with a much larger quantity of maternal DNA. Methods for detecting fetal aneuploidy from the cell-free fetal DNA in plasma are highly sought after, but proposed methods must take into account the small quantity and highly contaminated nature of the available fetal DNA.

The Intersection of Ethics and Communication in Prenatal Imaging: Challenges for the Pediatric Radiologist

Pediatric Radiology. Apr, 2010  |  Pubmed ID: 20225115

Pediatric radiologists who practice prenatal imaging are often at the front lines of communication with pregnant patients and their partners. The communication process is particularly complex when a fetal abnormality is diagnosed. Regardless of whether the information is completely new and unexpected, or the patient is referred for tertiary imaging and counseling, few pediatric radiologists are trained specifically in the communication skills necessary to provide optimal care to the prospective parents. This paper reviews current literature regarding communication with patients about unexpected or difficult information, and illustrates key clinical and ethical features that make conversations with pregnant patients particularly challenging in the setting of fetal abnormalities.

Antioxidant Diet Supplementation Starting 24 Hours After Exposure Reduces Radiation Lethality

Radiation Research. Apr, 2010  |  Pubmed ID: 20334518

Antioxidants mitigate radiation-induced lethality when started soon after radiation exposure, a delivery time that may not be practical due to difficulties in distribution and because the oral administration of such agents may require a delay beyond the prodromal stage of the radiation syndrome. We report the unexpected finding that antioxidant supplementation starting 24 h after total-body irradiation resulted in better survival than antioxidant supplementation started soon after the irradiation. The antioxidant dietary supplement was l-selenomethionine, sodium ascorbate, N-acetyl cysteine, alpha-lipoic acid, alpha-tocopherol succinate, and co-enzyme Q10. Total-body irradiation with 8 Gy in the absence of antioxidant supplementation was lethal by day 16. When antioxidant supplementation was started soon after irradiation, four of 14 mice survived. In contrast, 14 of 18 mice receiving antioxidant supplementation starting 24 h after irradiation were alive and well 30 days later. The numbers of spleen colonies and blood cells were higher in mice receiving antioxidant supplementation starting 24 h after irradiation than in mice receiving radiation alone. A diet supplemented with antioxidants administered starting 24 h after total-body irradiation improved bone marrow cell survival and mitigated lethality, with a radiation protection factor of approximately 1.18.

Adolescent Smoking: Effect of School and Community Characteristics

American Journal of Preventive Medicine. Dec, 2010  |  Pubmed ID: 21084070

A substantial challenge in addressing adolescent tobacco use is that smoking behaviors occur in complex environments that involve the school setting and larger community context.

The Avian EB66(R) Cell Line, Application to Vaccines, and Therapeutic Protein Production

PDA Journal of Pharmaceutical Science and Technology / PDA. Sep-Oct, 2010  |  Pubmed ID: 21502045

Embryonated chicken eggs and primary chicken embryo fibroblasts (CEFs) have been used for decades as a means of manufacturing human and veterinary vaccines. However, these egg and CEF-based production systems are associated with many serious limitations in terms of their regulatory acceptability, production capacity, and supply chain risks. The development of a safer, cheaper, and more efficient cell substrate for vaccine production would represent a significant business advantage for vaccine manufacturers. Building on the exceptional properties of avian embryonic stem cells, Vivalis has created a new cell substrate, the Duck EB66® cell line. This article describes how this cell substrate was derived, the manufacture and qualification of a master cell bank, and the evaluation of the cell substrate for the manufacture of vaccines and human therapeutic proteins.

A Retrospective Case Series of Adaptive Servoventilation for Complex Sleep Apnea

Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine. Apr, 2011  |  Pubmed ID: 21509335

Central sleep apnea can be refractory to traditional positive airway pressure (PAP) therapy (CPAP or bilevel PAP), whether appearing first as a feature of baseline polysomnography or only later once PAP is applied in what is termed "complex sleep apnea" (CompSA). This retrospective study examined the efficacy of adaptive servoventilation (ASV) in 25 consecutive patients with PAP-refractory central sleep apnea, most exhibiting predominantly obstructive apnea during baseline polysomnography.

Planned Quit Attempts Among Ontario Smokers: Impact on Abstinence

Addiction (Abingdon, England). Nov, 2011  |  Pubmed ID: 21592249

To examine the use and role of planned quit attempts by smokers and their impact on abstinence.

Nurse Case-managed Tobacco Cessation Interventions for General Hospital Patients: Results of a Randomized Clinical Trial

The Canadian Journal of Nursing Research = Revue Canadienne De Recherche En Sciences Infirmières. Mar, 2011  |  Pubmed ID: 21661618

This randomized clinical trial was designed to test the efficacy of intensive versus brief smoking cessation interventions for hospital patients. The interventions included advice and pamphlets for Brief and bedside counselling, take-home materials, and 7 post-discharge telephone counselling calls over 2 months for Intensive. Confirmed 1-year abstinence was 28% for Intensive (85/301) and 24% for Brief (76/315). Abstinence was significantly higher for patients who did not use pharmacotherapy (36%) versus those who did (16%) and for patients with CVD (40%) versus other diagnoses (20%). Because this was a replication trial, benchmarks for planning can be suggested: 12% to 15% recruitment of identified smokers, 90% plus completion for Intensive, 15% drop-out, and 75% abstinence corroboration. The results consolidate findings for general inpatients, including expected absolute abstinence and treatment outcomes, the effect of CVD patients on outcomes, the reproducibility of high abstinence in a universal health-care system, and the need for more research to inform practice.

Implicit Alcohol-aggression Scripts and Alcohol-related Aggression on a Laboratory Task in 11- to 14-year-old Adolescents

Aggressive Behavior. Sep-Oct, 2011  |  Pubmed ID: 21678430

Social scripts are commonly shared representations of behavior in social contexts, which are seen to be partly transmitted through social and cultural media. Research suggests that people hold scripts associated with alcohol-related aggression, but, unlike general aggression scripts, there is little evidence of social transmission. To demonstrate social transmission of alcohol-related aggression scripts, learning mechanisms based on personal experience should be minimized. We used a lexical decision task to examine implicit links between alcohol and aggression in alcohol-naïve adolescents who have limited personal or vicarious experience of alcohol-related aggression. One hundred and four 11-14 year old adolescents made lexical decisions on aggressive or nonaggressive words preceded by 40-ms alcohol or nonalcohol word primes. Repeated measures analyses of group data showed that alcohol word primes did not lead to faster responses to aggressive words than to nonaggressive words, nor were responses to aggressive words faster when they were preceded by alcohol word primes than by nonalcohol word primes. However, at an individual level, faster recognition times to the alcohol prime/aggression target word combination predicted aggression on a competitive laboratory task in 14 year olds only. This occurred only when the competitive aggression task was preceded by a visual presentation of alcoholic, but not nonalcoholic beverage, images. We concluded that alcohol-related aggression scripts are not strongly developed in this age group, but individual differences in script strength are linked to alcohol-related laboratory aggression.

Human Cardiac Autonomic Responses to Head-up Tilting During 72-h Starvation

European Journal of Applied Physiology. Oct, 2011  |  Pubmed ID: 22038145

Starvation may change autonomic nervous system activity and sensitivity such that a greater vagal withdrawal may occur during a sympathetic challenge. Six healthy humans endured a 3-day, water-only fast, during which participants were subjected to passive 80° head-up tilt testing twice on each day (a.m. and p.m.). Heart rate, heart rate variability (HRV), ventilation [Formula: see text], and respiration ([Formula: see text] and [Formula: see text]) were recorded during supine rest and head-up tilting. On Day 1 (a.m.), supine heart rate was 46.0 ± 3.3 beats min(-1), increasing to 51.6 ± 7.4 beats min(-1) on Day 3 (p.m.). On Day 1 (a.m.), supine high frequency HRV was 57.9 ± 31.6(NU), increasing to 69.5 ± 21.3(NU) on Day 3 (p.m.). Tilt-induced increases in heart rate were greater following starvation (10.5 ± 7.8 vs. 16.1 ± 8.6 beats min(-1)), and tilt-induced decreases in high frequency HRV were greater following starvation (-4.1 ± 27.7 vs. -28.0 ± 20.8(NU)). Supine V'CO(2) remained unchanged, whereas V'O(2) increased and respiratory exchange ratio decreased (0.91 ± 0.10 vs. 0.80 ± 0.05). Greater vagal withdrawal and elevated heart rate induced by head-up tilting during starvation may indicate increased autonomic sensitivity.

Can Seizure-Alert Dogs Predict Seizures?

Epilepsy Research. Dec, 2011  |  Pubmed ID: 22050976

An index observation where a dog was trained to alert to, as well as respond to, human tonic-clonic seizures led to further research and refinement of training techniques. This was followed by anecdotal reports of pet dogs spontaneously anticipating human epileptic seizures. An industry has since developed training Seizure-Alert Dogs (SADs) to give humans warnings of their seizures. In some cases this has been accompanied by a reduction in seizure frequency. SADs may be trained along with the person with epilepsy, responding specifically to that person's seizures, or may be trained separately. Recent sceptical reports of non-epileptic seizures in some people with SADs have cast doubt on dogs' ability to anticipate true epileptic seizures. This may reflect selection criteria for training programmes as well as training methods used, but does not necessarily indicate that SADs might not be able to predict epileptic seizures. Whether the seizures are epileptic or non-epileptic, it is speculated that SADs probably alert to subtle pre-ictal human behaviour changes, but may also be sensitive to heart rate or olfactory cues. As yet, however, no rigorous data exist as to whether seizure prediction by SADS is better than chance, and what false positive and negative prediction rates might be.

ISSLS Prize Winner: Adaptations to the Multifidus Muscle in Response to Experimentally Induced Intervertebral Disc Degeneration

Spine. Oct, 2011  |  Pubmed ID: 21301396

Basic science study of the rabbit multifidus muscle response to intervertebral disc degeneration.

Architectural Analysis of Human Abdominal Wall Muscles: Implications for Mechanical Function

Spine. Mar, 2011  |  Pubmed ID: 21325932

Using FISH to Increase the Yield and Accuracy of Karyotypes from Spontaneous Abortion Specimens

Prenatal Diagnosis. Aug, 2011  |  Pubmed ID: 21484844

Cytogenetic analysis of spontaneous abortions is frequently complicated by culture failure and maternal cell contamination (MCC). The objective of the study is to demonstrate that multiplex fluorescence in situ hybridization (FISH) can increase the yield and accuracy of karyotypes from spontaneous abortion specimens.

Early Prostate Cancer--which Treatment Do Men Prefer and Why?

BJU International. Jun, 2011  |  Pubmed ID: 21083643

Preference (prospective cohort).

Discipline of Provider and Model of Care Influence Impact of an Arthritis Educational Intervention in Primary Care

Arthritis Care & Research. Nov, 2011  |  Pubmed ID: 22076836

OBJECTIVE: To identify both provider and organizational characteristics that predicted outcomes following an educational intervention (nine hour workshop and follow-up reinforcement activities) developed to improve the management of arthritis in primary care. METHODS: Providers completed a survey at baseline and at six months post workshop, including a case scenario for early RA. Providers' were asked how they would manage the case and their responses were coded to calculate a best practice score, ranging from 0 to 7. Two-level hierarchical linear modeling was used to determine which of the measured provider and organizational factors predicted best practice scores at follow-up. RESULTS: 275 multidisciplinary providers from 131 organizations completed both baseline and follow-up surveys. Best practice scores increased by 17% (P < 0.01); however, the mean score at 6-month follow-up remained relatively low (2.68). Significant predictors of best practice scores at follow-up were discipline of providers and model of primary care in which they worked (P<0.05), adjusting for baseline practice scores and clustering of providers within organizations. Physicians, nurse practitioners and rehabilitation therapists scored higher than nurses, students and other health care providers (P<0.01). Physician networks scored significantly lower than providers from multi-disciplinary oriented models of care (P=0.02). CONCLUSIONS: These results have implications for the education of health professionals and the design of models of care to enhance arthritis care delivery. © 2011 by the American College of Rheumatology.

Duplication of the ZIC2 Gene is Not Associated with Holoprosencephaly

American Journal of Medical Genetics. Part A. Nov, 2011  |  Pubmed ID: 22105922

Cytogenetic testing using genomic microarrays presents a clinical challenge when data regarding the phenotypic consequences of the genomic alteration are not available. We describe a chromosome 13q32.3 duplication discovered by microarray testing in a fetus with a prenatally detected apparently balanced de novo translocation 46,XY,t(2;13)(q37;q32). Microarray analysis on the fetal DNA showed duplications of 384 and 564 kb at the breakpoint regions on chromosomes 2q37.3 and 13q32.3, respectively. There were no disease-associated genes in the duplicated region on chromosome 2q37. The duplicated region on chromosome 13q contains the ZIC2 gene. Haploinsufficiency of ZIC2 is known to cause holoprosencephaly and other brain malformations. Studies in the mouse models have suggested that over expression of ZIC2 may also lead to brain malformations. Fetal MRI of the brain was normal and the family elected to continue the pregnancy. An apparently normal baby was born at term. At 3 months of age a physical exam showed no abnormalities and no developmental delay. This report shows that duplication of ZIC2 is not necessarily associated with brain malformations. We also describe the phenotype from four additional patients with duplications of the region of chromosome 13 containing ZIC2 and three previously described patients with supernumerary marker chromosomes derived from distal chromosome 13. None of the eight patients had holoprosencephaly or brain malformations, indicating that duplication of ZIC2 is not associated with brain anomalies. This information will be useful for counseling in other occurrences of this duplication identified by microarray. © 2011 Wiley Periodicals, Inc.

Mechanically Relevant Consequences of the Composite Laminate-like Design of the Abdominal Wall Muscles and Connective Tissues

Medical Engineering & Physics. Dec, 2011  |  Pubmed ID: 22137674

Together, three abdominal wall muscles (external oblique, internal oblique and transversus abdominis) form a tightly bound muscular sheet that has been likened to a composite-laminate structure. Previous work has demonstrated the ability of force generated by these three muscles to be passed between one another through connective tissue linkages. Muscle fibres in each muscle are obliquely oriented with respect to its neighbouring muscles. It is proposed here is that this unique morphology of the abdominal wall muscles functions, through the application of constraining forces amongst the muscles, to increase force- and stiffness-generating capabilities. This paper presents a mathematical formulation of the stress-strain relationship for a transversely isotropic fibrous composite, and establishes a strengthening and stiffening effect when stress can be transferred between the fibrous layers. Application of empirical mechanical properties to this formulation demonstrates this effect for the abdominal wall muscles and, in greater proportion, for the anterior aponeurosis of the abdominal wall. This has implications for increasing the stiffness and passive load bearing ability of the abdominal wall muscles, and has the potential to modulate the whole muscle force-length and force-velocity relationships during contraction.

Cigarette Type 'switchers': a Descriptive Analysis

Canadian Journal of Public Health. Revue Canadienne De Santé Publique. Nov-Dec, 2011  |  Pubmed ID: 22164564

Combined Atorvastatin and Ramipril Mitigate Radiation-induced Impairment of Dentate Gyrus Neurogenesis

Journal of Neuro-oncology. Feb, 2011  |  Pubmed ID: 20617366

Whole brain irradiation (WBI) is commonly administered therapeutically and is routinely associated with late delayed radiation injuries, manifesting as severe and irreversible cognitive impairment. Neural progenitors within the subgranular zone (SGZ) of the dentate gyrus are among the most radiosensitive cell types in the adult brain and are known to participate in hippocampal plasticity and normal cognitive function. These progenitors and the specialized SGZ microenvironment required for neuronal differentiation are the source of neurogenic potential in the adult dentate gyrus, and provide a continuous supply of immature neurons which may then migrate into the adjacent granule cell layer to become mature granule cell neurons. The extreme radiosensitivity of these progenitors and the SGZ microenvironment implicate them as potentially significant contributors to radiation-induced cognitive impairment. Previous reports suggest that statin drugs may be neuroprotective and may promote neurogenesis within the SGZ following both traumatic and ischemic brain injury. Here we investigate whether atorvastatin might similarly protect progenitors and/or preserve neurogenic potential within the SGZ when administered following radiation injury. We also investigate whether such mitigating effects might be enhanced by administering atorvastatin in combination with the angiotensin converting enzyme (ACE) inhibitor, ramipril, which has previously been shown to produce subtle mitigating effects in this context. Atorvastatin was administered to adult male Fisher 344 rats beginning 24 h post-WBI at doses of 10 and 15 Gy, and maintained daily until sacrifice at 12 weeks post-WBI. Combined atorvastatin and ramipril (atorvastatin + ramipril) were administered according to the same protocol following WBI doses of 10 Gy. Progenitor proliferation, neuronal differentiation, and microglial activation were assayed immunohistochemically. Our results indicate that chronic administration of atorvastatin is relatively ineffective as a mitigator of radiation injury in this context, whereas atorvastatin + ramipril appear to interact synergistically to potently and selectively mitigate radiation-induced disruption of neurogenic signaling within SGZ microenvironment.

Incidence of False Positive Rotator Cuff Pathology in MRIs of Patients with Adhesive Capsulitis

Orthopedics. May, 2011  |  Pubmed ID: 21598899

The purpose of this study was to compare the incidence of presumed rotator cuff pathology based on radiologist and surgeon interpretation of preoperative magnetic resonance images (MRIs) with actual rotator cuff pathology found intraoperatively in patients undergoing arthroscopic capsular release for adhesive capsulitis.The medical records of 38 consecutive patients who underwent arthroscopic glenohumeral capsular release for adhesive capsulitis between September 2001 and May 2007 were retrospectively reviewed. Radiologist and surgeon predicted status of the rotator cuff by prospective MRI interpretation was compared to the actual status of the rotator cuff intraoperatively. Radiologists' preoperative MRI interpretations predicted a 57.9% incidence of rotator cuff pathology, while operative findings revealed a true incidence of only 13.2% (P<.0001). Radiologists accurately predicted the absence or presence of a rotator cuff tear in 19 of 38 cases (50%), compared to the surgeon, who correctly interpreted 29 of 38 MRIs (76.3%).Interpretations of shoulder MRIs in patients with adhesive capsulitis may provide misleading information regarding rotator cuff pathology. The actual findings of shoulder MRI scans may lead to the appearance of false rotator cuff pathology in this population, and a high percentage of false positive MRI reports of rotator cuff tears was observed in these patients. If MRI is chosen as a diagnostic adjunct in this patient population, careful consideration should be given to its interpretation to avoid unnecessary or possibly aggravating surgical intervention.

A Targeted, Conventional Assay, Emergency Department HIV Testing Program Integrated with Existing Clinical Procedures

Annals of Emergency Medicine. Jul, 2011  |  Pubmed ID: 21684415

Various HIV testing models have been described, but widespread implementation has lagged. We describe a clinical HIV testing program notable for its use of conventional (nonrapid) assays, native hospital personnel, and an electronic system to aid targeted patient selection.

Microarray Assessment of Methylation in Individual Mouse Blastocyst Stage Embryos Shows That in Vitro Culture May Have Widespread Genomic Effects

Human Reproduction (Oxford, England). Sep, 2011  |  Pubmed ID: 21685140

Although assisted reproductive technology (ART) is reported to result in abnormal genomic imprinting and/or altered genomic methylation, few if any studies have used high-throughput methods to analyze genomic methylation in ART embryos. We hypothesized that a microarray-based assessment of genomic methylation could be used to reveal differences between ART and normal preimplantation embryos.

Are Kids Too Busy?: Early Adolescents' Perceptions of Discretionary Activities, Overscheduling, and Stress

The Journal of School Health. Sep, 2011  |  Pubmed ID: 21831071

The activity patterns of children, especially after-school patterns, are receiving more professional attention. However, evidence regarding the value of various activities in children's lives is contradictory. The purpose of this study was to assess perceptions of discretionary activities, overscheduling, and levels of stress from adolescents' perspective.

Chronic Hypoxia Upregulates Adenosine 2a Receptor Expression in Chromaffin Cells Via Hypoxia Inducible Factor-2α: Role in Modulating Secretion

Biochemical and Biophysical Research Communications. Sep, 2011  |  Pubmed ID: 21840298

Catecholamine (CAT) release from chromaffin tissue plays an essential role in the fetus which develops in a low O₂ environment (hypoxia). To address molecular mechanisms regulating CAT secretion in low O₂, we exposed a fetal chromaffin-derived cell line (MAH cells) to chronic hypoxia (CHox; 2% O₂, 24h) and assessed gene expression using microarrays, quantitative RT-PCR, and western blot. CHox caused a dramatic ∼12× upregulation of adenosine A2a receptor (A2aR) mRNA, an effect critically dependent upon hypoxia-inducible factor (HIF)-2α which bound the promoter of the A2aR gene. In amperometric studies, acute hypoxia and high K⁺ (30 mM) evoked quantal CAT secretion that was enhanced after CHox, and further potentiated during simultaneous A2aR activation by adenosine. A2aR activation also enhanced stimulus-induced rise in intracellular Ca²⁺ in control, but not HIF-2α-deficient, MAH cells. Thus, A2aR, adenosine, and HIF-2α are key contributors to the potentiation of CAT secretion in developing chromaffin cells during chronic hypoxia.

Identification of Phase II in Vivo Metabolites of Alkyl-anthracenes in Rainbow Trout (Oncorhynchus Mykiss)

Chemosphere. Nov, 2011  |  Pubmed ID: 21907385

Metabolism of xenobiotics is a two-step process that increases the polarity of compounds to facilitate their excretion. In previous work, the major in vitro phase I metabolites of alkyl-anthracenes by rainbow trout (Oncorhynchus mykiss) CYP enzymes were shown to be predominantly ring hydroxylated metabolites. Here, we present the first report on the identification of in vivo phase II metabolites of alkyl-anthracenes in juvenile rainbow trout. Bile was collected from trout injected with individual alkyl-anthracenes with, in some cases, a co-injection of β-naphthoflavone (BNF). Some samples were digested with the β-glucuronidase enzyme to confirm the presence of glucuronide conjugates. The metabolites were separated using a water-acetonitrile gradient on a HPLC system equipped with a C(18) column and a UV-diode array detector. Trout with endogenous and BNF-induced enzymes produced the same metabolites, but higher concentrations of metabolites were detected after enzyme induction. Alkyl-anthracenes were metabolized predominantly on the rings as evidenced by the UV spectral analysis. Likewise, mass spectrometry and UV spectral analysis confirmed a predominance of glucuronide conjugates for all systems investigated.

COAMFTE Accreditation and California MFT Licensing Exam Success

Journal of Marital and Family Therapy. Oct, 2011  |  Pubmed ID: 22007780

Professional accreditation of graduate programs in marital and family therapy (MFT) is intended to ensure the strength of the education students receive. However, there is great difficulty in assessing the real-world impact of accreditation on students. Only one measure is applied consistently to graduates of all MFT programs, regardless of accreditation status: licensure examinations. Within California, COAMFTE-accredited, regionally (WASC) accredited, and state-approved programs all may offer degrees qualifying for licensure. Exam data from 2004, 2005, and 2006 (n = 5,646 examinees on the Written Clinical Vignette exam and n = 3,408 first-time examinees on the Standard Written Exam) were reviewed to determine the differences in exam success among graduates of programs at varying levels of accreditation. Students from COAMFTE-accredited programs were more successful on both California exams than were students from other WASC-accredited or state-approved universities. There were no significant differences between (non-COAMFTE) WASC-accredited universities and state-approved programs. Differences could be related to selection effects, if COAMFTE programs initially accept students of higher quality. Implications for therapist education and training are discussed.

Correlation of Prostate-specific Antigen Nadir and Biochemical Failure After High-intensity Focused Ultrasound of Localized Prostate Cancer Based on the Stuttgart Failure Criteria - Analysis from the @-Registry

BJU International. Oct, 2011  |  Pubmed ID: 21332907

•To determine if the prostate-specific antigen (PSA) nadir after high-intensity focused ultrasound (HIFU) can be used as a predictor of the biochemical disease-free survival rate (DFSR).

Mutations in the Pre-replication Complex Cause Meier-Gorlin Syndrome

Nature Genetics. Apr, 2011  |  Pubmed ID: 21358632

Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears¹⁻³. Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evident, intellect is usually normal in this syndrome. We report here that individuals with this disorder show marked locus heterogeneity, and we identify mutations in five separate genes: ORC1, ORC4, ORC6, CDT1 and CDC6. All of these genes encode components of the pre-replication complex, implicating defects in replication licensing as the cause of a genetic syndrome with distinct developmental abnormalities.

Correlating Allostery with Rigidity

Molecular BioSystems. Feb, 2011  |  Pubmed ID: 21060909

Allosteric proteins demonstrate the phenomenon of a ligand binding to a protein at a regulatory or effector site and thereby changing the chemical affinity of the catalytic site. As such, allostery is extremely important biologically as a regulatory mechanism for molecular concentrations in many cellular processes. One particularly interesting feature of allostery is that often the catalytic and effector sites are separated by a large distance. Structural comparisons of allosteric proteins resolved in both inactive and active states indicate that a variety of structural rearrangement and changes in motions may contribute to general allosteric behavior. In general it is expected that the coupling of catalytic and regulatory sites is responsible for allosteric behavior. We utilize a novel examination of allostery using rigidity analysis of the underlying graph of the protein structures. Our results indicate a general global change in rigidity associated with allosteric transitions where the R state is more rigid than the T state. A set of allosteric proteins with heterotropic interactions is used to test the hypothesis that catalytic and effector sites are structurally coupled. Observation of a rigid path connecting the effector and catalytic sites in 68.75% of the structures points to rigidity as a means by which the distal sites communicate with each other and so contribute to allosteric regulation. Thus structural rigidity is shown to be a fundamental underlying property that promotes cooperativity and non-locality seen in allostery.

Measuring the Toxicity of Alkyl-phenanthrenes to Early Life Stages of Medaka (Oryzias Latipes) Using Partition-controlled Delivery

Environmental Toxicology and Chemistry / SETAC. Feb, 2011  |  Pubmed ID: 21072839

Alkyl-phenanthrenes are a class of compounds present in crude oil and toxic to developing fish. Most research on alkyl-phenanthrenes has focused on retene (7-isopropyl-1-methyl-phenanthrene), but little is known about the chronic toxicity of related congeners to the early life stages of fish. This project is the first to describe the chronic toxicity of a series of alkyl-phenanthrenes to the embryos of Japanese medaka (Oryzias latipes) using the partition-controlled delivery (PCD) method of exposure and is the first to establish a relationship between toxicity of alkyl-phenanthrenes and log P. With PCD, test concentrations were maintained by equilibrium partitioning of test chemicals from polydimethylsiloxane (PDMS) films containing various concentrations of C1 to C4 phenanthrenes. Log film:solution partition constants (log K(fs)) and aqueous solubility limits were determined for each alkyl-phenanthrene. The prevalence of abnormalities in fish embryos increased in an exposure-dependent manner, with median effective concentration (EC50) values lower than experimental solubility limits of the compounds, and typical of environmental concentrations. Alkyl-phenanthrenes were more toxic to medaka embryos than unsubstituted phenanthrene, with effects resembling those of dioxin and indicating a specific receptor-based mechanism of toxicity. These results extend conclusions for the Exxon Valdez oil spill, suggest a specific mechanism of toxicity for alkyl-phenanthrenes, and provide a model for assessing the risks of mixture toxicity.

Changes in Human Skeletal Muscle Length During Stimulated Eccentric Muscle Actions

The Journal of Physiological Sciences : JPS. Jan, 2011  |  Pubmed ID: 21080138

Following eccentric exercise, increases in muscle length alter the length-tension relation of skeletal muscle. However, its unclear if this change occurs during eccentric exercise. Therefore, 70 eccentric actions of the knee extensors of one leg (with superimposed electrical stimulation) were performed at 100°/s, from full extension to full flexion. Angle-specific eccentric force was recorded throughout. Force decreased at all angles although this was non-uniform. At 70°, force decreased by 25%, whereas at 130°, force decreased by 41%. Initial peak force was recorded at 100° (590 ± 232 N); the exercise bout induced a 21% decrease in peak force and a 10° shift in the position of peak force production to 90°. The rightward shift in the muscle length-tension relation thus occurred during eccentric exercise, where greater force loss at short muscle lengths suggested an eccentric-induced over-stretching of sarcomeres.

Anxiolytic and Anxiogenic Drug Effects on Male and Female Gerbils in the Black-white Box

Behavioural Brain Research. Jan, 2011  |  Pubmed ID: 20723567

Neurokinin-1, (NK1) receptor antagonists offer strong potential as anxiolytic drugs with few side effects. The use of the Mongolian gerbil for anxiety research offers advantages because gerbil NK1 receptors share a greater homology with human NK1 receptors than those of other rodents. Studies are needed to validate existing tests of anxiety for use with this species. This study examined the effects of two anxiolytics (buspirone and diazepam) and two anxiogenics (caffeine and FG142) on male and female gerbil behaviour in the black-white box (BWB). Diazepam was anxiolytic in males but not females. The anxiolytic effects of buspirone were apparent at the lower doses in both males and females. Higher doses resulted in sedative effects in both sexes. Caffeine produced mild anxiogenesis in females at the lowest dose, and in males at the highest dose. FG7142 was mildly anxiogenic in males and not at all in females. Findings are discussed in light of previous research. The gerbil BWB should not be used as a valid test of anxiety in its current form.

Oto-endoscopy: a Reliable and Validated Technique for Phenotyping Otitis Media in the Mouse

Hearing Research. Feb, 2011  |  Pubmed ID: 20870016

The mouse is a widely used model for investigating the pathophysiological and genetic bases of otitis media (OM). It has proven a valuable tool for investigating the multifactorial bases of OM including the role of pathogens, anatomical factors, inflammatory mediators and susceptibility loci. However, straightforward and robust phenotyping tools for identifying murine otitis media are lacking, which has precluded for example the identification of mice with OM in genetic screens without resorting to time-consuming histopathology. We have set out to develop a phenotyping platform for the detection of OM in mice utilizing oto-endoscopy. We have applied the technique to a cohort of mice genetically susceptible to chronic otitis media. We show that oto-endoscopy is a safe, reliable and valid method for detecting otitis media in the mouse and discuss its utility in screens to identify novel genes involved with susceptibility to OM.

The Effect of Dental Care on Cardiovascular Disease Outcomes: an Application of Instrumental Variables in the Presence of Heterogeneity and Self-selection

Health Economics. Oct, 2011  |  Pubmed ID: 20882577

Studies show a relationship between oral inflammatory processes and cardiovascular risk factors, suggesting that dental care may reduce the risk of cardiovascular disease (CVD) events. However, due to the differences between men and women in the development and presentation of CVD, such effects may vary by sex. We use a valid set of instrumental variables to evaluate these issues and include a test of essential heterogeneity. CVD events include new occurrences of heart attack (including death from heart attack), stroke (including death from stroke), angina, and congestive heart failure. Controls include age, race, education, marital status, foreign birthplace, and cardiovascular risk factors (health status, body mass index, alcohol use, smoking status, diabetes status, high-blood-pressure status, physical activity, and depression). Our analysis finds no evidence of essential heterogeneity. We find the minimum average treatment effect for women to be -0.01, but find no treatment effect for men. This suggests that women who receive dental care may reduce their risk of future CVD events by at least one-third. The findings may only apply to married middle-aged and older individuals as the data set is only representative for this group.

Decreasing the Adverse Effects of Cancer Therapy: National Cancer Institute Guidance for the Clinical Development of Radiation Injury Mitigators

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Jan, 2011  |  Pubmed ID: 21047979

Recently, many agents have been identified that target molecular pathways that can mitigate radiation toxicity. To date, no drugs have been approved as radiation injury mitigators, which are defined as agents administered after irradiation but before toxicity is manifest. In order to accelerate the application of potential mitigators for cancer patients, a meeting sponsored by the National Cancer Institute (NCI) and National Institute of Allergy and Infectious Diseases (NIAID) was held in January 2010. This article presents an algorithm to guide clinical trials for such agents in patients receiving radiotherapy or radiochemotherapy. It reviews the mechanisms of radiation injury, the clinical problem, the preclinical and clinical development of candidate agents, and the design and conduct of clinical trials. The central role of patient reported outcomes is outlined, as well as key lessons learned from prior clinical trials. Ultimately, the goal is to be able to apply such promising agents to improve the quality of life for patients receiving radiotherapy or chemoradiotherapy for cancer.

Aurora A is Differentially Expressed in Gliomas, is Associated with Patient Survival in Glioblastoma and is a Potential Chemotherapeutic Target in Gliomas

Cell Cycle (Georgetown, Tex.). Feb, 2012  |  Pubmed ID: 22274399

Aurora A is critical for mitosis and is overexpressed in several neoplasms. Its overexpression transforms cultured cells, and both its overexpression and knockdown cause genomic instability. In transgenic mice, Aurora A haploinsufficiency, not overexpression, leads to increased malignant tumor formation. Aurora A thus appears to have both tumor-promoting and tumor-suppressor functions. Here, we report that Aurora A protein, measured by quantitative protein gel blotting, is differentially expressed in major glioma types in lineage-specific patterns. Aurora A protein levels in WHO grade II oligodendrogliomas (n = 16) and grade III anaplastic oligodendrogliomas (n = 16) are generally low, similar to control epilepsy cerebral tissue (n = 11). In contrast, pilocytic astrocytomas (n = 6) and ependymomas (n = 12) express high Aurora A levels. Among grade II to grade III astrocytomas (n = 7, n = 14, respectively) and grade IV glioblastomas (n = 31), Aurora A protein increases with increasing tumor grade. We also found that Aurora A expression is induced by hypoxia in cultured glioblastoma cells and is overexpressed in hypoxic regions of glioblastoma tumors. Retrospective Kaplan-Meier analysis revealed that both lower Aurora A protein measured by quantitative protein gel blot (n = 31) and Aurora A mRNA levels measured by real-time quantitative RT-PCR (n = 58) are significantly associated with poorer patient survival in glioblastoma. Furthermore, we report that the selective Aurora A inhibitor MLN8237 is potently cytotoxic to glioblastoma cells, and that MLN8237 cytotoxicty is potentiated by ionizing radiation. MLN8237 also appeared to induce senescence and differentiation of glioblastoma cells. Thus, in addition to being significantly associated with survival in glioblastoma, Aurora A is a potential new drug target for the treatment of glioblastoma and possibly other glial neoplasms.

Stepping out Further from the Shadows: Disclosure of Harmful Radiologic Errors to Patients

Radiology. Feb, 2012  |  Pubmed ID: 22282177

A Prospective Study of Relationships Between Propositions About Risk and Driver Speeding

Accident; Analysis and Prevention. May, 2012  |  Pubmed ID: 22310037

Risk propositions are specific and modifiable hypotheses that people hold about the outcomes of risk-taking behavior. According to fuzzy trace theory (FTT), risk propositions arise from the subjective and idiosyncratic interpretations that people make about the meaning of risk information, and form the primary basis of decision-making. A community sample of 255 drivers was interviewed at baseline (T1), 6 weeks after baseline (T2) and 14 weeks after baseline (T3). We tested whether propositions about speeding-related risk at time 1 (T1) would predict speeding at time 3 (T3), controlling perceptions of speeding-related danger and other speeding-related variables (the perceived possibility of being caught and the enjoyment and excitement to be gained from speeding) measured at time 2 (T2). We also tested whether relationships between T1 propositions and T3 speeding would be mediated by T2 perceptions of danger. T1 propositions predicted T3 speeding independently of the control variables, and we also found evidence consistent with mediation by T2 danger. In line with FTT, risk propositions were not scaleable as a single dimension, but generally predicted speeding as independent entities. Taken together these findings support the view that drivers perceive speeding risk as a series of potentially modifiable propositions which may have item-specific influences on speeding behavior.

Beta Receptor-mediated Modulation of the Late Positive Potential in Humans

Psychopharmacology. Feb, 2012  |  Pubmed ID: 21847570

Electrophysiological studies have identified a scalp potential, the late positive potential (LPP), which is modulated by the emotional intensity of observed stimuli. Previous work has shown that the LPP reflects the modulation of activity in extrastriate visual cortical structures, but little is known about the source of that modulation.

The Slippery Slope: Lubricant Use and Rectal Sexually Transmitted Infections: a Newly Identified Risk

Sexually Transmitted Diseases. Jan, 2012  |  Pubmed ID: 22183849

Use of lubricant products is extremely common during receptive anal intercourse (RAI) yet has not been assessed as a risk for acquisition of sexually transmitted infections (STIs).

Using an Established Telehealth Model to Train Urban Primary Care Providers on Hypertension Management

Journal of Clinical Hypertension (Greenwich, Conn.). Jan, 2012  |  Pubmed ID: 22235823

The objective of this study was to determine whether a videoconference-based telehealth network can increase hypertension management knowledge and self-assessed competency among primary care providers (PCPs) working in urban Federally Qualified Health Centers (FQHCs). We created a telehealth network among 6 urban FQHCs and our institution to support a 12-session educational program designed to teach state-of-the-art hypertension management. Each 1-hour session included a brief lecture by a university-based hypertension specialist, case presentations by PCPs, and interactive discussions among the specialist and PCPs. Twelve PCPs (9 intervention and 3 controls) were surveyed at baseline and immediately following the curriculum. The mean number of correct answers on the 26-item hypertension knowledge questionnaire increased in the intervention group (13.11 [standard deviation (SD)]=3.06) to 17.44 [SD=1.59], P<.01) but not among controls (14.33 [SD=3.21] to 13.00 [SD=3.46], P=.06). Similarly, the mean score on a 7-item hypertension management self-assessed competency scale increased in the intervention group (4.68 [SD=0.94] to 5.41 [SD=0.89], P<.01) but not among controls (5.28 [SD=0.43] to 5.62 [SD=0.67], P=.64). This model holds promise for enhancing hypertension care provided by urban FQHC providers.

Passive Mechanical Properties of Rat Abdominal Wall Muscles Suggest an Important Role of the Extracellular Connective Tissue Matrix

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. Jan, 2012  |  Pubmed ID: 22267257

Abdominal wall muscles have a unique morphology suggesting a complex role in generating and transferring force to the spinal column. Studying passive mechanical properties of these muscles may provide insights into their ability to transfer force among structures. Biopsies from rectus abdominis (RA), external oblique (EO), internal oblique (IO), and transverse abdominis (TrA) were harvested from male Sprague-Dawley rats, and single muscle fibers and fiber bundles (4-8 fibers ensheathed in their connective tissue matrix) were isolated and mechanically stretched in a passive state. Slack sarcomere lengths were measured and elastic moduli were calculated from stress-strain data. Titin molecular mass was also measured from single muscle fibers. No significant differences were found among the four abdominal wall muscles in terms of slack sarcomere length or elastic modulus. Interestingly, across all four muscles, slack sarcomere lengths were quite long in individual muscle fibers (>2.4 µm), and demonstrated a significantly longer slack length in comparison to fiber bundles (p < 0.0001). Also, the extracellular connective tissue matrix provided a stiffening effect and enhanced the resistance to lengthening at long muscle lengths. Titin molecular mass was significantly less in TrA compared to each of the other three muscles (p < 0.0009), but this difference did not correspond to hypothesized differences in stiffness. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

A Randomized, Double-blind, Controlled Study of NGX-4010, a Capsaicin 8% Dermal Patch, for the Treatment of Painful HIV-associated Distal Sensory Polyneuropathy

Journal of Acquired Immune Deficiency Syndromes (1999). Feb, 2012  |  Pubmed ID: 22067661

Effective treatment of HIV-associated distal sensory polyneuropathy remains a significant unmet therapeutic need.

Toxicity of Hydroxylated Alkyl-phenanthrenes to the Early Life Stages of Japanese Medaka (Oryzias Latipes)

Aquatic Toxicology (Amsterdam, Netherlands). Jan, 2012  |  Pubmed ID: 22071127

Polycyclic aromatic hydrocarbons (PAH) are hydrophobic environmental contaminants with petrogenic, biogenic, and pyrogenic sources. Alkylated PAH predominate in crude oils, are found in sediment downstream of pulp and paper mills, and can be more toxic than their non-alkylated homologues. The enzymatic metabolism of alkyl phenanthrenes generates ring and chain hydroxylated derivatives. The main objective of this research was to estimate the potential role of hydroxylation in PAH toxicity and secondly to better understand the relative risk of different PAH in complex mixtures. This project assessed the toxicity of ring and chain hydroxylated 1-methylphenanthrenes to the early life stages of Japanese medaka (Oryzias latipes). Phenols were more toxic than benzylic alcohols, and some phenols were more than four times more toxic than their non-hydroxylated counterpart. Ring hydroxylation can increase PAH toxicity, and metabolism may enhance alkyl-PAH toxicity through the generation of such metabolites. This paper is the first to describe the relative toxicity of a suite of hydroxylated alkyl-PAH to the early life stages of fish, proposing an association between the preferential formation of para-quinones and enhanced toxicity.

The Effect of Distressing Imagery on Attention to and Persuasiveness of an Antialcohol Message: a Gaze-tracking Approach

Health Education & Behavior : the Official Publication of the Society for Public Health Education. Feb, 2012  |  Pubmed ID: 21632438

Background. Distressing imagery may inhibit health communications by inducing audiences to reduce distress by avoiding attention to persuasive messages. Method. This study used eye-tracking methods to compare gaze time allocated to a persuasive textual message, accompanied by either distressing high-resolution color images or less distressing two-color images with degraded outline and detail. Results. Participants in the distressing images condition showed lower intentions to reduce drinking in the following 3 months, which may have been mediated by lower gaze time to textual elements of the message. The effect was stronger in participants who both scored lower on dispositional mental disengagement and were more vulnerable to alcohol-related problems. Conclusions. These findings suggest that distressing imagery may inhibit persuasion by reducing audience attention to message components. Implications for message design are discussed.