Protocols and Video Articles Authored by Patricia McCracken (Translated to German)

Annual Ambient Black Carbon Associated with Shorter Telomeres in Elderly Men: Veterans Affairs Normative Aging Study Environmental Health Perspectives. Nov, 2010 | Pubmed ID: 21465749 Telomere length reflects biological age and is inversely associated with risk of cardiovascular disease (CVD). Ambient air pollution is associated with CVD, but its effect on telomere length is unknown.

A Balancing Act: Mechanisms by Which the Fetus Avoids Rejection by the Maternal Immune System Reproduction (Cambridge, England). Jun, 2011 | Pubmed ID: 21389077 Successful pregnancy requires strict temporal regulation of maternal immune function to accommodate the growing fetus. Early implantation is facilitated by inflammatory processes that ensure adequate vascular remodeling and placental invasion. To prevent rejection of the fetus, this inflammation must be curtailed; reproductive immunologists are discovering that this process is orchestrated by the fetal unit and, in particular, the extravillous trophoblast. Soluble and particulate factors produced by the trophoblast regulate maternal immune cells within the decidua, as well as in the periphery. The aim of this review is to discuss the action of recently discovered immunomodulatory factors and mechanisms, and the potential effects of dysregulation of such mechanisms on the maternal immune response that may result in pregnancy loss or preeclampsia.

Daily Functioning in Chronic Pain: Study of Structural Relations with Posttraumatic Stress Disorder Symptoms, Pain Intensity, and Pain Avoidance The Korean Journal of Pain. Mar, 2011 | Pubmed ID: 21390174 This study aimed to evaluate processes from the mutual maintenance model in relation to daily functioning in patients with both chronic pain and a history of a traumatic experience. The mechanism illustrated the structural relations for daily functioning among pain intensity, hyperarousal, re-experiencing, trauma avoidance, and pain avoidance.

Regulated Suppression of NF-ÎºB Throughout Pregnancy Maintains a Favourable Cytokine Environment Necessary for Pregnancy Success Journal of Reproductive Immunology. Apr, 2011 | Pubmed ID: 21411157 Th1 immune responses are suppressed in pregnancy, but the temporal regulation and the mechanism(s) underlying this immune alteration are unknown. We assessed the expression of Th1 cytokines IFNÎ³, IL-2 and TNFÎ± in response to stimulation in isolated T-cells from pregnant women throughout gestation. Using flow cytometry we demonstrated an early and sustained reduction in IFNÎ³ and IL-2 production in CD3+ T-cells, but TNFÎ± levels are not reduced until the third trimester. We assessed the expression of NF-ÎºB and T-bet, transcription factors that play a central role in Th1 immune responses, throughout pregnancy. In isolated T-cells levels of available p65 were suppressed early in pregnancy, but T-bet expression was suppressed only in the third trimester. In contrast to p65, T-bet expression was transcriptionally regulated, with diminished T-bet mRNA in third-trimester samples. Re-expression of p65 in T-cells from third-trimester pregnant women resulted in an induction of T-bet expression in response to PMA stimulation and a concomitant increase in the production of IL-2 and IFNÎ³. The suppressive effect of pregnancy was ameliorated as early as 72h post-partum when p65 levels returned to normal as did the level of inducible IFNÎ³ and IL-2. TNFÎ± levels in post-partum women were significantly increased relative to non-pregnant controls. The pregnancy-specific suppression of p65 and subsequent loss of cytokine production suggest that this transcription factor acts specifically to regulate the cytokine environment that is required for pregnancy success.

Attenuation of Hematoma Size and Neurological Injury with Curcumin Following Intracerebral Hemorrhage in Mice Journal of Neurosurgery. Jul, 2011 | Pubmed ID: 21417704 Intracerebral hemorrhage (ICH) is associated with significant morbidity and mortality. Acute hematoma enlargement is an important predictor of neurological injury and poor clinical prognosis; but neurosurgical clot evacuation may not be feasible in all patients and treatment options remain largely supportive. Thus, novel therapeutic approaches to promote hematoma resolution are needed. In the present study, the authors investigated whether the curry spice curcumin limited neurovascular injury following ICH in mice.

Psychological Advances in Chronic Pain: a Concise Selective Review of Research from 2010 Current Opinion in Supportive and Palliative Care. Jun, 2011 | Pubmed ID: 21430540 It is difficult to hold an organized view of psychological research related to chronic pain. There are many different theories and variables and the volume of literature is vast. The purpose of this review is to highlight some key trends in this research in 2010.

Comprehensive Family-based Association Study of the Glutamate Transporter Gene SLC1A1 in Obsessive-compulsive Disorder American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics. Jun, 2011 | Pubmed ID: 21445956 SLC1A1 encodes a neuronal glutamate transporter and is a promising candidate gene for obsessive-compulsive disorder (OCD). Several independent research groups have reported significant associations between OCD and single nucleotide polymorphisms (SNPs) in this gene. Previously, we evaluated 13 SNPs in, or near, SLC1A1 and reported a strong association signal with rs301443, a SNP 7.5 kb downstream of the gene [Shugart et al. (2009); Am J Med Genet Part B 150B:886â€“892]. The aims of the current study were first, to further investigate this finding by saturating the region around rs301443; and second, to explore the entire gene more thoroughly with a dense panel of SNP markers. We genotyped an additional 111 SNPs in or near SLC1A1, covering from 9 kb upstream to 84 kb downstream of the gene at average spacing of 1.7 kb per SNP, and conducted family-based association analyses in 1,576 participants in 377 families.We found that none of the surrounding markers were in linkage disequilibrium with rs301443, nor were any associated with OCD. We also found that SNP rs4740788, located about 8.8 kb upstream of the gene, was associated with OCD in all families (P = 0.003) and in families with male affecteds (P = 0.002). A three-SNP haplotype (rs4740788â€“rs10491734â€“rs10491733) was associated with OCD in the total sample (P = 0.00015) and in families with male affecteds (P = 0.0007). Although of nominal statistical significance considering the number of comparisons, these findings provide further support for the involvement of SLC1A1 in the pathogenesis of OCD.

Erhaltung. Die Wirtschaftliche Bedeutung Der Fledermäuse in Der Landwirtschaft Science (New York, N.Y.). Apr, 2011 | Pubmed ID: 21454775

Population Growth of Mexican Free-tailed Bats (Tadarida Brasiliensis Mexicana) Predates Human Agricultural Activity BMC Evolutionary Biology. 2011 | Pubmed ID: 21457563 Human activities, such as agriculture, hunting, and habitat modification, exert a significant effect on native species. Although many species have suffered population declines, increased population fragmentation, or even extinction in connection with these human impacts, others seem to have benefitted from human modification of their habitat. Here we examine whether population growth in an insectivorous bat (Tadarida brasiliensis mexicana) can be attributed to the widespread expansion of agriculture in North America following European settlement. Colonies of T. b. mexicana are extremely large (~10(6) individuals) and, in the modern era, major agricultural insect pests form an important component of their food resource. It is thus hypothesized that the growth of these insectivorous bat populations was coupled to the expansion of agricultural land use in North America over the last few centuries.

Pharmacokinetics of Oseltamivir in Breast Milk and Maternal Plasma American Journal of Obstetrics and Gynecology. Jun, 2011 | Pubmed ID: 21457910 Women in the postpartum period are at high risk for complications from influenza. Pharmacokinetic data of oseltamivir phosphate in postpartum women, however, are lacking.

Psychopharmacological Effects of Oxycodone in Volunteers with and Without Generalized Anxiety Disorder Experimental and Clinical Psychopharmacology. Apr, 2011 | Pubmed ID: 21463065 A number of studies have documented a relationship between anxiety disorders and opioid misuse and abuse, and there is some data to suggest that some people use opioids in an attempt to reduce their anxiety. We tested the hypothesis that volunteers with an anxiety disorder would report a more positive spectrum of subjective effects (i.e., greater ratings of drug liking and wanting to take the drug again) from oxycodone, a mu opioid agonist, than would volunteers without the disorder, and that oxycodone would have greater reinforcing efficacy in volunteers with the anxiety disorder. In addition to subjective and reinforcing effects, the psychomotor and physiological effects of oxycodone also were assessed. Individuals with generalized anxiety disorder (GAD, n = 8) and nonanxious controls (CTL, n = 8) were administered 0, 10, and 20 mg oxycodone (per os) in 3 separate sessions. Oxycodone produced a number of effects in a dose-related fashion in both groups. However, on several subjective effects measures, only CTL participants reported effects of oxycodone (e.g., high, lightheaded). Neither group had statistically significant increases in peak liking or "take drug again" ratings in the oxycodone conditions relative to the placebo condition, and in neither group did the drug function as a reinforcer, as measured by the Multiple-Choice Procedure (Griffiths, Troisi, Silverman, & Mumford, 1993). Anxiety ratings were low in the GAD group (in the absence of drug), and this may have lessened the possibility of detecting a more positive spectrum of oxycodone effects in this group than in the CTL group.

Pharmacokinetics of Oseltamivir According to Trimester of Pregnancy American Journal of Obstetrics and Gynecology. Jun, 2011 | Pubmed ID: 21492824 The purpose of this study was to determine pharmacokinetic parameters for oseltamivir in all trimesters of pregnancy. Thirty pregnant women, 10 per trimester, who were receiving oseltamivir phosphate (75 mg) were recruited to study first-dose pharmacokinetics. Plasma samples were obtained at 0, 0.5, 1, 2, 4, 8, and 12 hours after the first dose. Samples were analyzed for oseltamivir and oseltamivir carboxylate levels. With the use of a noncompartmental model, we estimated the area-under-the-curve, maximum concentration, time-to-maximum concentration, and half-life. There were no significant differences in the pharmacokinetics of oseltamivir by trimester, except for an increased half-life in the first trimester for oseltamivir phosphate and an increased maximum concentration in the third trimester for oseltamivir carboxylate. The levels of oseltamivir carboxylate that were observed were within the range that was needed to achieve inhibitory concentrations at 50% for pandemic H1N1. The pharmacokinetics of oseltamivir does not change significantly according to trimester of pregnancy.

Analyse Der Rechteckigen Resonant Hohlräume Im Terahertz Parallel-Platte Wellenleiter Optics Letters. Apr, 2011 | Pubmed ID: 21499387 Wir beschreiben eine experimentelle und theoretische Charakterisierung von rechteckigen resonant Hohlräume in Parallel-Platte Hohlleitern, integriert mit Terahertz-Impulse. Wenn die Waveguide mit der niedrigsten Ordnung quer-elektrischen Modus aufgeregt ist, weisen diese Hohlräume Resonanzen mit schmalen Linewidths. Breitbandübertragung Spektren werden mit den Ergebnissen der Modus übereinstimmende Berechnungen für die verschiedenen Dimensionen der Hohlraum verglichen.

Pain-related Anxiety in Children and Adolescents: Mind the Gap Pain. Sep, 2011 | Pubmed ID: 21514730

Acrolein Inhalation Prevents Vascular Endothelial Growth Factor-induced Mobilization of Flk-1+/Sca-1+ Cells in Mice Arteriosclerosis, Thrombosis, and Vascular Biology. Jul, 2011 | Pubmed ID: 21527748 Acrolein is a toxic chemical present in tobacco, wood, and coal smoke, as well as automobile exhaust. Because exposure to these pollutants is associated with an increase in cardiovascular disease risk, we studied the effects of acrolein on Flk-1(+)/Sca-1(+) cells that are involved in vascular repair.

Diminished Gray Matter Within the Hypothalamus in Autism Disorder: a Potential Link to Hormonal Effects? Biological Psychiatry. Aug, 2011 | Pubmed ID: 21531390 Subjects with autism suffer from impairments of social interaction, deviations in language usage, as well as restricted and stereotyped patterns of behavior. These characteristics are found irrespective of age, IQ, and gender of affected subjects. However, brain changes due to age, IQ, and gender might pose potential confounds in autism neuroimaging analyses.

A Rate-limiting Role for Dickkopf-1 in Bone Formation and the Remediation of Bone Loss in Mouse and Primate Models of Postmenopausal Osteoporosis by an Experimental Therapeutic Antibody The Journal of Pharmacology and Experimental Therapeutics. Aug, 2011 | Pubmed ID: 21531794 Genetic studies have linked both osteoporotic and high bone mass phenotypes to low-density lipoprotein receptor-related proteins (LRP4, LRP5, and LRP6). LRPs are receptors for inhibitory Dickkopf-1 (DKK1) protein, and treatment modalities that modulate LRP/DKK1 binding therefore may act as stimulators of bone mass accrual. Here, we report that RH2-18, a fully human monoclonal anti-DKK1 antibody elicits systemic pharmacologic bone efficacy and new bone formation at endosteal bone surfaces in vivo in a mouse model of estrogen-deficiency-induced osteopenia. This was paralleled by partial-to-complete resolution of osteopenia (bone mineral density) at all of the skeletal sites investigated in femur and lumbar-vertebral bodies and the restoration of trabecular bone microarchitecture. More importantly, testing of RH2-18 in adult, osteopenic rhesus macaques demonstrated a rate-limiting role of DKK1 at multiple skeletal sites and responsiveness to treatment. In conclusion, this study provides pharmacologic evidence for the modulation of DKK1 bioactivity in the adult osteopenic skeleton as a viable approach to resolve osteopenia in animal models. Thus, data described here suggest that targeting DKK1 through means such as a fully human anti-DKK1-antibody provides a potential bone-anabolic treatment for postmenopausal osteoporosis.

Psychological Flexibility May Reduce Insomnia in Persons with Chronic Pain: a Preliminary Retrospective Study Pain Medicine (Malden, Mass.). Jun, 2011 | Pubmed ID: 21539701 Sleep disturbance is a common complaint in people with chronic pain, and is associated with a range of adverse outcomes including reports of greater pain and disability. Research into insomnia with chronic pain sufferers has not yet examined the role of psychological flexibility, a process from acceptance and commitment therapy. We examined this role.

Lack of Pharmacokinetic and Pharmacodynamic Interactions of Roflumilast with (R, S)-warfarin in Healthy Adult Subjects International Journal of Clinical Pharmacology and Therapeutics. Jun, 2011 | Pubmed ID: 21612746 Roflumilast is a novel, orally active, selective phosphodiesterase 4 inhibitor recently approved for the treatment of severe COPD. The pharmacological effect is mediated mainly by its active metabolite roflumilast N-oxide.

The Role of Wildlife in Transboundary Animal Diseases Animal Health Research Reviews / Conference of Research Workers in Animal Diseases. Jun, 2011 | Pubmed ID: 21615975 This paper identifies some of the more important diseases at the wildlife-livestock interface and the role wildlife plays in disease transmission. Domestic livestock, wildlife and humans share many similar pathogens. Pathogens of wild or domestic animal origin that can cause infections in humans are known as zoonotic organisms and the converse are termed as anthroponotic organisms. Seventy-seven percent of livestock pathogens and 91% of domestic carnivore pathogens are known to infect multiple hosts, including wildlife. Understanding this group of pathogens is critical to public health safety, because they infect a wide range of hosts and are most likely to emerge as novel causes of infection in humans and domestic animals. Diseases at the wildlife-livestock interface, particularly those that are zoonotic, must be an area of focus for public health programs and surveillance for emerging infectious diseases. Additionally, understanding wildlife and their role is a vital part of understanding the epidemiology and ecology of diseases. To do this, a multi-faceted approach combining capacity building and training, wildlife disease surveillance, wildlife-livestock interface and disease ecology studies, data and information sharing and outbreak investigation are needed.

Intervention to Lower Household Wood Smoke Exposure in Guatemala Reduces ST-segment Depression on Electrocardiograms Environmental Health Perspectives. Nov, 2011 | Pubmed ID: 21669557 A large body of evidence suggests that fine particulate matter (PM) air pollution is a cause of cardiovascular disease, but little is known in particular about the cardiovascular effects of indoor air pollution from household use of solid fuels in developing countries. RESPIRE (Randomized Exposure Study of Pollution Indoors and Respiratory Effects) was a randomized trial of a chimney woodstove that reduces wood smoke exposure.

How to Give Difficult Feedback Physician Executive. May-Jun, 2011 | Pubmed ID: 21675320

Inhibition of MMPs by Alcohols Dental Materials : Official Publication of the Academy of Dental Materials. Sep, 2011 | Pubmed ID: 21676453 While screening the activity of potential inhibitors of matrix metalloproteinases (MMPs), due to the limited water solubility of some of the compounds, they had to be solubilized in ethanol. When ethanol solvent controls were run, they were found to partially inhibit MMPs. Thus, the purpose of this study was to compare the MMP-inhibitory activity of a series of alcohols.

Factorial Validity and Reliability of the Chinese Version of the Pain Vigilance and Awareness Questionnaire (ChPVAQ) in a Sample of Chinese Patients with Chronic Pain Pain Medicine (Malden, Mass.). Jul, 2011 | Pubmed ID: 21692975 The Pain Vigilance and Awareness Questionnaire (PVAQ) has been shown to be a reliable measure for assessing attention to pain. Different factor structures have been reported in Western populations; yet, whether the known factor models could be replicated in non-Western populations and the psychometric properties of the scale remain unclear. This study aimed to examine the factorial validity and psychometric properties of the Chinese version of the PVAQ (ChPVAQ).

The Role of Treatment Expectancy in Youth Receiving Exposure-based CBT for Obsessive Compulsive Disorder Behaviour Research and Therapy. Sep, 2011 | Pubmed ID: 21723534 The purpose of this investigation was to examine correlates of parent, child, and therapist treatment expectations and their role in the exposure-based treatment of childhood obsessive compulsive disorder (OCD). Treatment expectations were assessed among 49 youth with primary OCD, their parents, and therapists as part of the baseline evaluation and post-treatment clinical outcomes were determined by blind evaluators. Baseline depressive symptoms, child/parent-rated functional impairment, externalizing behavior problems, number of comorbid psychiatric disorders, and a lower perception of control were associated with lower pre-treatment expectations. Parent expectation was associated with parental OCD symptoms, child depressive symptoms and child-reported impairment. Therapist expectations inversely correlated with child depressive symptoms, externalizing problems, and child-rated impairment. Pre-treatment OCD severity and prior treatment history were not linked to expectancy. Finally, higher treatment expectations were linked to better treatment response, lower attrition, better homework compliance, and reduced impairment.

Suicide Attempts and Nonsuicidal Self-injury in the Treatment of Resistant Depression in Adolescents: Findings from the TORDIA Study Journal of the American Academy of Child and Adolescent Psychiatry. Aug, 2011 | Pubmed ID: 21784297 To evaluate the clinical and prognostic significance of suicide attempts (SAs) and nonsuicidal self-injury (NSSI) in adolescents with treatment-resistant depression.

Genome-wide Association Study of the Child Behavior Checklist Dysregulation Profile Journal of the American Academy of Child and Adolescent Psychiatry. Aug, 2011 | Pubmed ID: 21784300 A potentially useful tool for understanding the distribution and determinants of emotional dysregulation in children is a Child Behavior Checklist profile, comprising the Attention Problems, Anxious/Depressed, and Aggressive Behavior clinical subscales (CBCL-DP). The CBCL-DP indexes a heritable trait that increases susceptibility for later psychopathology, including severe mood problems and aggressive behavior. We have conducted a genome-wide association study of the CBCL-DP in children with attention-deficit/hyperactivity disorder (ADHD).

A Copy Number Variation Morbidity Map of Developmental Delay Nature Genetics. Sep, 2011 | Pubmed ID: 21841781 To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We estimate that âˆ¼14.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59 pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets. This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic basis of developmental delay, intellectual disability and autism spectrum disorders.

Helicobacter Felis--associated Gastric Disease in Microbiota-restricted Mice The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. Sep, 2011 | Pubmed ID: 21852692 Human Helicobacter pylori infection leads to multiple pathological consequences, including gastritis and adenocarcinoma. Although this association has led to the classification of H. pylori as a type 1 carcinogen, it is not clear if additional nonhelicobacter gastric microbiota play a role in these diseases. In this study, we utilized either specific pathogen-free C57BL/6 mice (B6.SPF) or mice colonized with altered Schaedler flora (B6.ASF) to evaluate the role of nonhelicobacter gastric microbiota in disease development after Helicobacter felis infection. Despite similar histological changes, H. felis persisted in B6.ASF stomachs, while H. felis could no longer be detected in the majority of B6.SPF mice. The B6.SPF mice also acquired multiple Lactobacillus spp. in their stomachs after H. felis infection. Our data indicate that potential mechanisms responsible for the ineffective H. felis clearance in the B6.ASF model include the absence of new gastric microbiota to compete for the gastric niche, the lack of expression of new gastric mucins, and a reduced ratio of H. felis-specific IgG2c:IgG1 serum antibodies. These data suggest that although H. felis is sufficient to initiate gastric inflammation and atrophy, bacterial eradication and the systemic immune response to infection are significantly influenced by pre-existing and acquired gastric microbiota.

The Management of Community-acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Oct, 2011 | Pubmed ID: 21880587 Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed. Areas that warrant future investigations are also highlighted.

Acceptance and Values-based Action in Chronic Pain: a Three-year Follow-up Analysis of Treatment Effectiveness and Process Behaviour Research and Therapy. Nov, 2011 | Pubmed ID: 21885034 Recent developments in CBT emphasize the promotion of psychological flexibility to improve daily functioning for people with a wide range of health conditions. In particular, one of these approaches, Acceptance and Commitment Therapy (ACT), has been studied for treatment of chronic pain. While trials have provided good support for treatment effectiveness through follow-ups of as long as seven months, the longer-term impact is not known. The present study of 108 participants with chronic pain examined outcomes three years after treatment completion and included analyses of two key treatment processes, acceptance of pain and values-based action. Overall, results indicated significant improvements in emotional and physical functioning relative to the start of treatment, as well as good maintenance of treatment gains relative to an earlier follow-up assessment. Effect size statistics were generally medium or large. At the three-year follow-up, 64.8% of patients had reliably improved in at least one key domain. Improvements in acceptance of pain and values-based action were associated with improvements in outcome measures. A "treatment responder" analysis, using variables collected at pre-treatment and shorter term follow-up, failed to identify any salient predictors of response. This study adds to the growing literature supporting the effectiveness of ACT for chronic pain and yields evidence for both statistical and clinical significance of improvements over a three-year period.

Gene Flow and Hybridization Between Numerically Imbalanced Populations of Two Duck Species in the Falkland Islands PloS One. 2011 | Pubmed ID: 21887236 Interspecific hybridization is common in plants and animals, particularly in waterfowl (Anatidae). One factor shown to contribute to hybridization is restricted mate choice, which can occur when two species occur in sympatry but one is rare. The Hubbs principle, or "desperation hypothesis," states that under such circumstances the rarer species is more likely to mate with heterospecifics. Here we report interspecific hybridization between two waterfowl species that coexist in broad sympatry and mixed flocks throughout southern South America. Speckled teal (Anas flavirostris) and yellow-billed pintails (Anas georgica) are abundant in continental South America, but in the Falkland Islands speckled teal outnumber yellow-billed pintails approximately ten to one. Using eight genetic loci (mtDNA and 7 nuclear introns) coupled with Bayesian assignment tests and relatedness analysis, we identified a speckled teal x yellow-billed pintail F(1) hybrid female and her duckling sired by a male speckled teal. Although our sample in the Falkland Islands was small, we failed to identify unequivocal evidence of hybridization or introgression in a much larger sample from Argentina using a three-population "isolation with migration" coalescent analysis. While additional data are needed to determine if this event in the Falkland Islands was a rare singular occurrence, our results provide further support for the "desperation hypothesis," which states that scarcity in one population and abundance of another will often lead to hybridization.

Executive Summary: the Management of Community-acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Oct, 2011 | Pubmed ID: 21890766 Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed. Areas that warrant future investigations are also highlighted.

Coaching As a Leadership Style Physician Executive. Sep-Oct, 2011 | Pubmed ID: 21932730

Is T-wave Alternans Testing Feasible in Candidates for Prophylactic Implantable Defibrillators? Netherlands Heart Journal : Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. Jan, 2011 | Pubmed ID: 22020855 Previous studies have demonstrated that microvolt T-wave alternans (TWA) screening in patients with ischaemic and dilated cardiomyopathy is effective in identifying patients at high or low risk of sudden cardiac death. It remains unclear which percentage of potential recipients of an implantable cardioverter defibrillator (ICD) are able to perform TWA testing using an exercise protocol which is, at this moment, the golden standard. In this study, we evaluated the feasibility of TWA in the risk stratification of potential ICD recipients with ischaemic or dilated cardiomyopathy.

Controlled Comparison of Family Cognitive Behavioral Therapy and Psychoeducation/relaxation Training for Child Obsessive-compulsive Disorder Journal of the American Academy of Child and Adolescent Psychiatry. Nov, 2011 | Pubmed ID: 22024003 To examine the efficacy of exposure-based cognitive-behavioral therapy (CBT) plus a structured family intervention (FCBT) versus psychoeducation plus relaxation training (PRT) for reducing symptom severity, functional impairment, and family accommodation in youths with obsessive-compulsive disorder (OCD).

Risperidon-bezogenen Verbesserung Der Reizbarkeit Bei Kindern Mit Autismus Ist Keine Änderungen Im Serum Von Epidermalen Wachstumsfaktor Und Interleukin-13 Zugeordnet Journal of Child and Adolescent Psychopharmacology. Dec, 2011 | Pubmed ID: 22070180 Risperidon hat sich gezeigt, zur Verbesserung der schwerer Verhaltensstörungen bei Kindern mit Autismus. Hier fragten wir, ob Risperidon-assoziierte Verbesserung Änderungen in Konzentrationen von entzündlichen Moleküle im Serum dieser Fächer verbunden war. Sieben Moleküle wurden identifiziert als würdig weitere Beurteilung anhand einer pilot 31 entzündliche Marker in 21 Medikamente-freie Themen mit Autismus im Vergleich zu 15 gesunden Kontrollgruppen: epidermalen Wachstumsfaktor (EGF), Interferon-γ (IFN-γ), Interleukin (IL)-13, IL-17, Monozyt Chemoattractant Protein-1 (MCP-1), IL-1 und IL-1-Rezeptor-Antagonist. Serumkonzentration dieser Marker entstanden dann in einer anderen Reihe von Themen, die in einer doppelblinden, klinische Studie und eine erweiterte Gruppe von gesunden Probanden teilnahmen. In der ersten Analyse, Proben von Patienten mit Autismus bei geplanten Besuche wurden gegenüber Besuche nach achtwöchiger Behandlung mit Placebo (n = 37) oder Risperidon (n = 40). Die Zytokin-Konzentrationen im 8-Wochen-Zeitraum für Risperidon und Placebo-Gruppen stabil geblieben. In der zweiten Analyse, wir weiter die Unterschiede zwischen Medikamenten-freie Themen mit Autismus untersucht (n = 77) und gesunden Kontrollgruppen (rekrutiertes unabhängig; n = 19). Serumspiegel von EGF wurden bei Patienten mit Autismus erhoben (Median = 103 Pg/mL, n = 75) im Vergleich zu gesunden Kontrollen (75 Pg/mL, n = 19; p < 0,05), und Ebenen der IL-13 wurden gesenkt, bei Autismus (Median = 0,8 Pg/mL, n = 77) im Vergleich zu Kontrollen (9,8 Pg/mL, n = 19; p = 0.0003). Diese Veränderungen nicht korrelieren mit standardisierten Maßnahmen für eine Diagnose von Autismus verwendet. Zusammenfassend lässt sich sagen war Risperidon-induzierte klinische Verbesserung bei Patienten mit Autismus nicht Änderungen in die entzündliche Serum-Marker gemessen zugeordnet. Ob veränderte Ebenen der EGF und IL-13 spielen eine Rolle in der Pathogenese oder Phänotyp des Autismus erfordert weitere Untersuchungen.

Effect of Reduction in Household Air Pollution on Childhood Pneumonia in Guatemala (RESPIRE): a Randomised Controlled Trial Lancet. Nov, 2011 | Pubmed ID: 22078686 Pneumonia causes more child deaths than does any other disease. Observational studies have indicated that smoke from household solid fuel is a significant risk factor that affects about half the world's children. We investigated whether an intervention to lower indoor wood smoke emissions would reduce pneumonia in children.

Generating Human Intestinal Tissue from Pluripotent Stem Cells in Vitro Nature Protocols. Dec, 2011 | Pubmed ID: 22082986 Here we describe a protocol for generating 3D human intestinal tissues (called organoids) in vitro from human pluripotent stem cells (hPSCs). To generate intestinal organoids, pluripotent stem cells are first differentiated into FOXA2(+)SOX17(+) endoderm by treating the cells with activin A for 3 d. After endoderm induction, the pluripotent stem cells are patterned into CDX2(+) mid- and hindgut tissue using FGF4 and WNT3a. During this patterning step, 3D mid- or hindgut spheroids bud from the monolayer epithelium attached to the tissue culture dish. The 3D spheroids are further cultured in Matrigel along with prointestinal growth factors, and they proliferate and expand over 1-3 months to give rise to intestinal tissue, complete with intestinal mesenchyme and epithelium comprising all of the major intestinal cell types. To date, this is the only method for efficiently directing the differentiation of hPSCs into 3D human intestinal tissue in vitro.

Beyond Diagnosis: Evolving Prostate Biopsy in the Era of Focal Therapy Prostate Cancer. 2011 | Pubmed ID: 22110983 Despite decades of use as the "gold standard" in the detection of prostate cancer, the optimal biopsy regimen is still not universally agreed upon. While important aspects such as the need for laterally placed biopsies and the importance of apical cancer are known, repeated studies have shown significant patients with cancer on subsequent biopsy when the original biopsy was negative and an ongoing suspicion of cancer remained. Attempts to maximise the effectiveness of repeat biopsies have given rise to the alternate approaches of saturation biopsy and the transperineal approach. Recent interest in focal treatment of prostate cancer has further highlighted the need for accurate detection of prostate cancer, and in response, the introduction of transperineal template-guided biopsy. While the saturation biopsy approach and the transperineal template approach increase the detection rate of cancer in men with a previous negative biopsy and appear to have acceptable morbidity, there is a lack of clinical trials evaluating the different biopsy strategies. This paper reviews the evolution of prostatic biopsy and current controversies.

Vergebung Nach Der Akuten Behandlung Bei Kindern Und Jugendlichen Mit Angststörungen: Erkenntnisse Aus Den CAMS Journal of Consulting and Clinical Psychology. Dec, 2011 | Pubmed ID: 22122292 Über Remissionsraten in ängstlich Jugend Berichten, die in dem Kind/Jugendlichen Angst multimodale Studie (CAMS) teilgenommen haben. Die CAMS, einer multizentrischen klinischen Studie randomisiert 488 Kinder und Jugendliche (Alter von 7 bis 17 Jahre; 79 % europäischer Abstammung; 50 % weiblich) mit Trennung, sozialen und/oder generalisierte Angststörung eine 12-wöchige Behandlung von Sertralin (SRT), kognitive Verhaltenstherapie (CBT), deren Kombination (Kamm) oder klinische Behandlung mit Placebo Pille (PBO).

Cancer Cell Metabolism Cold Spring Harbor Symposia on Quantitative Biology. 2011 | Pubmed ID: 22156302 Although the generation of a distinctive metabolic profile is a well-known aspect of cancer, the significance of these adaptations and their potential for exploitation for anticancer therapy has not been fully appreciated until recently. Many oncogenic changes known to affect intracellular signaling pathways play an active role in mediating these metabolic changes, which, in turn, function to support cancer cell growth and replication. In this chapter, we discuss the most current findings in cancer cell metabolism in terms of their impact on tumor cell growth as well as their potential for identifying new targets for therapeutic intervention.

Effects of Particulate Air Pollution on Blood Pressure in a Highly Exposed Population in Beijing, China: a Repeated-measure Study Environmental Health : a Global Access Science Source. 2011 | Pubmed ID: 22188661 Particulate Matter (PM) exposure is critical in Beijing due to high population density and rapid increase in vehicular traffic. PM effects on blood pressure (BP) have been investigated as a mechanism mediating cardiovascular risks, but results are still inconsistent. The purpose of our study is to determine the effects of ambient and personal PM exposure on BP.

Testicular Choriocarcinoma: an Unusual Case of Paraneoplastic Thyrotoxicosis QJM : Monthly Journal of the Association of Physicians. Jul, 2012 | Pubmed ID: 21652536

Design and Subject Characteristics in the Federally-funded Citalopram Trial in Children with Pervasive Developmental Disorders Journal of Autism and Developmental Disorders. Mar, 2012 | Pubmed ID: 21667200 The Studies to Advance Autism Research and Treatment Network conducted a randomized trial with citalopram in children with Pervasive developmental disorders (PDDs). We present the rationale, design and sample characteristics of the citalopram trial. Subjects (128 boys, 21 girls) had a mean age of 9.3 (Â±3.12) years; 132 (88.6%) were diagnosed with autistic disorder (4.7% with Asperger's Disorder; 6.7% with PDD-not otherwise specified). Less than half of the subjects were intellectually disabled; 117 (78.5%) were rated Moderate or Marked on the Clinical Global Impression for Severity. Study measures were similar to previous Research Units on Pediatric Psychopharmacology trials. Subjects in this trial were slightly older and more likely to have complaints of repetitive behavior than participants in RUPP trials.

Is Obsessive-compulsive Disorder an Anxiety Disorder, and What, if Any, Are Spectrum Conditions? A Family Study Perspective Psychological Medicine. Jan, 2012 | Pubmed ID: 21733222 Experts have proposed removing obsessive-compulsive disorder (OCD) from the anxiety disorders section and grouping it with putatively related conditions in DSM-5. The current study uses co-morbidity and familiality data to inform these issues.

Evaluation of the Field Efficacy of an Avirulent Live Lawsonia Intracellularis Vaccine in Foals Veterinary Journal (London, England : 1997). Jun, 2012 | Pubmed ID: 21741284 Equine proliferative enteropathy caused by Lawsonia intracellularis is an emerging disease with as yet unaddressed preventative measures. The hypothesis of this study was that vaccination will prevent clinical and sub-clinical disease. Weanling Thoroughbreds (n=202) from Central Kentucky were randomly assigned into two groups (vaccinated and non-vaccinated). Vaccinated foals received 30 mL of an avirulent, live L. intracellularis vaccine intra-rectally twice, 30 days apart. Foals were monitored for clinical disease, total solids and average weight gain until yearling age. There was an overall decreased disease incidence on the farms involved in the study that did not differ significantly between the groups. This decreased disease prevalence in the study population may be associated with the ongoing vaccine trial on these farms, as disease prevalence in Central Kentucky did not change in 2009 compared to 2008.

Phase I Dose Escalation Study of KOS-1584, a Novel Epothilone, in Patients with Advanced Solid Tumors Cancer Chemotherapy and Pharmacology. Feb, 2012 | Pubmed ID: 21874318 First-in-man study of KOS-1584, a second generation epothilone.

Psychometric Properties of a Korean Version of the Chronic Pain Acceptance Questionnaire in Chronic Pain Patients Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. Aug, 2012 | Pubmed ID: 21927915 Accepting pain rather than trying to control it has been the focus of recent pain management research. Pain acceptance often has been assessed using the chronic pain acceptance questionnaire (CPAQ). This study aimed to evaluate the factor structure and other psychometric properties of a Korean language version of the CPAQ (KCPAQ).

MRSI Correlates of Cognitive-behavioral Therapy in Pediatric Obsessive-compulsive Disorder Progress in Neuro-psychopharmacology & Biological Psychiatry. Jan, 2012 | Pubmed ID: 21983143 The brain mechanisms of cognitive-behavioral therapy (CBT), a highly effective treatment for pediatric obsessive-compulsive disorder (OCD), are unknown. Neuroimaging in adult OCD indicates that CBT is associated with metabolic changes in striatum, thalamus, and anterior cingulate cortex. We therefore probed putative metabolic effects of CBT on these brain structures in pediatric OCD using proton magnetic resonance spectroscopic imaging (1H MRSI).

The Multifunctional Poly(A)-binding Protein (PABP) 1 is Subject to Extensive Dynamic Post-translational Modification, Which Molecular Modelling Suggests Plays an Important Role in Co-ordinating Its Activities The Biochemical Journal. Feb, 2012 | Pubmed ID: 22004688 PABP1 [poly(A)-binding protein 1] is a central regulator of mRNA translation and stability and is required for miRNA (microRNA)-mediated regulation and nonsense-mediated decay. Numerous protein, as well as RNA, interactions underlie its multi-functional nature; however, it is unclear how its different activities are co-ordinated, since many partners interact via overlapping binding sites. In the present study, we show that human PABP1 is subject to elaborate post-translational modification, identifying 14 modifications located throughout the functional domains, all but one of which are conserved in mouse. Intriguingly, PABP1 contains glutamate and aspartate methylations, modifications of unknown function in eukaryotes, as well as lysine and arginine methylations, and lysine acetylations. The latter dramatically alter the pI of PABP1, an effect also observed during the cell cycle, suggesting that different biological processes/stimuli can regulate its modification status, although PABP1 also probably exists in differentially modified subpopulations within cells. Two lysine residues were differentially acetylated or methylated, revealing that PABP1 may be the first example of a cytoplasmic protein utilizing a 'methylation/acetylation switch'. Modelling using available structures implicates these modifications in regulating interactions with individual PAM2 (PABP-interacting motif 2)-containing proteins, suggesting a direct link between PABP1 modification status and the formation of distinct mRNP (messenger ribonucleoprotein) complexes that regulate mRNA fate in the cytoplasm.

Solitary Rectal Ulcer Syndrome in Children and Adolescents Journal of Pediatric Gastroenterology and Nutrition. Feb, 2012 | Pubmed ID: 22094902 The aim of this study was to describe the presenting symptoms, endoscopic and histologic findings, and clinical courses of pediatric patients diagnosed with solitary rectal ulcer syndrome (SRUS).

Homeobox Genes in Obsessive-compulsive Disorder American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics. Jan, 2012 | Pubmed ID: 22095678 Despite evidence that obsessive-compulsive disorder (OCD) is a familial neuropsychiatric condition, progress aimed at identifying genetic determinants of the disorder has been slow. The OCD Collaborative Genetics Study (OCGS) has identified several OCD susceptibility loci through linkage analysis.

Zyklische Hydroxyamidines Als Amid Isoster: Entdeckung Des Oxadiazolines Und Oxadiazines Als Potenter Und Hoch Wirksame γ-Sekretase-Modulatoren In-vivo Journal of Medicinal Chemistry. Jan, 2012 | Pubmed ID: 22098494 Zyklische Hydroxyamidines wurden entwickelt und validiert als Isosteric Ersatz der Amid-Funktionen. Verbindungen mit diesen strukturellen Motiven fanden metabolisch stabil zu sein und sehr wünschenswert pharmakokinetischen Profile zu besitzen. Diese Entwürfe wurden zur Identifizierung der γ-Sekretase-Modulatoren führt zu höchst wirkungsvolle Agenten für die Reduktion des zentralen Nervensystems Aβ(42) in verschiedenen Tiermodellen angewendet.

Training for General Practitioners in Opioid Prescribing for Chronic Pain Based on Practice Guidelines: a Randomized Pilot and Feasibility Trial The Journal of Pain : Official Journal of the American Pain Society. Jan, 2012 | Pubmed ID: 22112421 This study is a pilot and feasibility study that compares 2 training experiences to improve appropriate opioid prescribing for chronic pain. Both training conditions included education in relation to opioid guidelines. Following education, 1 condition included training aimed at improving psychological flexibility and the other included training in practical knowledge and skills related to pain management. Eighty-one general practitioners (GPs) took part in the study, each having been randomly assigned to 1 of the training conditions. It proved easy to recruit GPs to the training. Overall, GPs demonstrated increased knowledge of opioid prescribing for chronic pain and decreases in concerns related to prescribing following training. However, there were no changes observed in reported prescribing practices or in secondary measures of well-being. There were also no significant differences between the training conditions, other than a greater increase in intention to use prescribing guidelines in the psychological flexibility condition. Feasibility and acceptability of the training methods were generally rated high. The psychological flexibility condition was rated higher than the comparison condition in terms of interest and satisfaction. Finally, processes of psychological flexibility before and after training significantly correlated with measures of GP well-being, providing partial support for the relevance of these processes as a focus in GP training.

The Epidemiology of Chemical Eye Exposures Reported to the Victorian Poisons Information Centre European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine. Dec, 2012 | Pubmed ID: 22113167 We aimed to determine the epidemiology of chemical eye exposures reported to the Victorian Poisons Information Centre, Australia.

Impact of Pap Test Compliance and Cervical Cancer Screening Intervals on Human Papillomavirus Vaccine Acceptance Journal of Lower Genital Tract Disease. Jan, 2012 | Pubmed ID: 22126831 The objective of this study was to determine the impact of Pap test compliance and cervical cancer screening intervals on human papillomavirus (HPV) vaccination acceptance.

Multilocus Coalescent Analysis of Haemoglobin Differentiation Between Low- and High-altitude Populations of Crested Ducks (Lophonetta Specularioides) Molecular Ecology. Jan, 2012 | Pubmed ID: 22151704 Hypoxia is a key factor determining survival, and haemoglobins are targets of selection in species native to high-altitude regions. We studied population genetic structure and evaluated evidence for local adaptation in the crested duck (Lophonetta specularioides). Differentiation, gene flow and time since divergence between highland and lowland populations were assessed for three haemoglobin genes (Î±(A) , Î±(D) , Î²(A) ) and compared to seven reference loci (six autosomal introns and mtDNA). Four derived amino acid replacements were found in the globin genes that had elevated Î¦(ST) values between the Andean highlands and Patagonian lowlands. A single Î²(A) -globin polymorphism at a site known to influence O(2) affinity was fixed for different alleles in the two populations, whereas three Î±(A) - and Î±(D) -globin polymorphisms exhibited high heterozygosity in the highlands but not in the lowlands. Coalescent analyses supported restricted gene flow for haemoglobin alleles and mitochondrial DNA but nonzero gene flow for the introns. Simulating genetic data under a drift-migration model of selective neutrality, the Î²(A) -globin fell outside the 95% confidence limit of simulated data, suggesting that directional selection is maintaining different variants in the contrasting elevational environments, thereby restricting migration of Î²(A) -globin alleles. The Î±(A) - and Î±(D) -globins, by contrast, did not differ from the simulated values, suggesting that variants in these genes are either selectively neutral, or that the effects of selection could not be differentiated from background levels of population structure and linkage disequilibrium. This study illustrates the combined effects of selection and population history on inferring levels of population divergence for a species distributed across an altitudinal gradient in which selection for hypoxia resistance has likely played an important role.

PKM2: a Gatekeeper Between Growth and Survival Cell Research. Mar, 2012 | Pubmed ID: 22184007

The E3 Ubiquitin Ligase Mule Acts Through the ATM-p53 Axis to Maintain B Lymphocyte Homeostasis The Journal of Experimental Medicine. Jan, 2012 | Pubmed ID: 22213803 Cellular homeostasis is controlled by pathways that balance cell death with survival. Mcl-1 ubiquitin ligase E3 (Mule) is an E3 ubiquitin ligase that targets the proapoptotic molecule p53 for polyubiquitination and degradation. To elucidate the role of Mule in B lymphocyte homeostasis, B cell-specific Mule knockout (BMKO) mice were generated using the Cre-LoxP recombination system. Analysis of BMKO mice showed that Mule was essential for B cell development, proliferation, homeostasis, and humoral immune responses. p53 transactivation was increased by two- to fourfold in Mule-deficient B cells at steady state. Genetic ablation of p53 in BMKO mice restored B cell development, proliferation, and homeostasis. p53 protein was increased in resting Mule-deficient mouse embryonic fibroblasts (MEFs) and embryonic stem (ES) cells. Loss of Mule in both MEFs and B cells at steady state resulted in increased levels of phospho-ataxia telangiectasia mutated (ATM) and the ATM substrate p53. Under genotoxic stress, BMKO B cells were resistant to apoptosis, and control MEFs exhibited evidence of a physical interaction between Mule and phospho-ATM. Phospho-ATM, phospho-p53, and Brca1 levels were reduced in Mule-deficient B cells and MEFs subjected to genotoxic stress. Thus, Mule regulates the ATM-p53 axis to maintain B cell homeostasis under both steady-state and stress conditions.

COMT Val158Met, BDNF Val66Met, and OPRM1 Asn40Asp and Methamphetamine Dependence Treatment Response: Preliminary Investigation Journal of Clinical Psychopharmacology. Feb, 2012 | Pubmed ID: 22217949

Lipid Peroxidation Product 4-hydroxy-trans-2-nonenal Causes Endothelial Activation by Inducing Endoplasmic Reticulum Stress The Journal of Biological Chemistry. Mar, 2012 | Pubmed ID: 22228760 Lipid peroxidation products, such as 4-hydroxy-trans-2-nonenal (HNE), cause endothelial activation, and they increase the adhesion of the endothelium to circulating leukocytes. Nevertheless, the mechanisms underlying these effects remain unclear. We observed that in HNE-treated human umbilical vein endothelial cells, some of the protein-HNE adducts colocalize with the endoplasmic reticulum (ER) and that HNE forms covalent adducts with several ER chaperones that assist in protein folding. We also found that at concentrations that did not induce apoptosis or necrosis, HNE activated the unfolded protein response, leading to an increase in XBP-1 splicing, phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2Î±, and the induction of ATF3 and ATF4. This increase in eukaryotic translation initiation factor 2Î± phosphorylation was prevented by transfection with protein kinase-like ER kinase siRNA. Treatment with HNE increased the expression of the ER chaperones, GRP78 and HERP. Exposure to HNE led to a depletion of reduced glutathione and an increase in the production of reactive oxygen species (ROS); however, glutathione depletion and ROS production by tert-butyl-hydroperoxide did not trigger the unfolded protein response. Pretreatment with a chemical chaperone, phenylbutyric acid, or adenoviral transfection with ATF6 attenuated HNE-induced monocyte adhesion and IL-8 induction. Moreover, phenylbutyric acid and taurine-conjugated ursodeoxycholic acid attenuated HNE-induced leukocyte rolling and their firm adhesion to the endothelium in rat cremaster muscle. These data suggest that endothelial activation by HNE is mediated in part by ER stress, induced by mechanisms independent of ROS production or glutathione depletion. The induction of ER stress may be a significant cause of vascular inflammation induced by products of oxidized lipids.

Psychopharmacology of Autism Spectrum Disorders Pediatric Clinics of North America. Feb, 2012 | Pubmed ID: 22284801 At present, no evidence-based effective pharmacologic options are available for treating the core deficits of autism spectrum disorders (ASDs), which are best addressed by behavioral and educational interventions. However, such evidence exists for several of the frequently associated/comorbid symptoms such as aggression and severe irritability, hyperactivity, and repetitive behaviors, which can become a major source of additional distress and interference in functioning. This article offers information on the psychopharmacology of ASD that is current, relevant, and organized in a user-friendly manner, to form a concise but informative reference guide for primary pediatric clinicians.

Synthese Und Malariamedikament Und Antituberculosis Aktivitäten Einer Reihe Von Natürlichen Und Unnatürlichen 4-methoxy-6-styryl-pyran-2-ones, Dihydro-Analoga Und Foto-Dimer Bioorganic & Medicinal Chemistry. Feb, 2012 | Pubmed ID: 22285027 Frühere Studien haben die 3,6-dialkyl-4-hydroxy-pyran-2-one marine mikrobielle Stoffwechselprodukte Pseudopyronines A und B sein bescheidenes Wachstum-Inhibitoren von Mycobacterium Tuberculosis und eine Reihe von tropischen Krankheiten einschließlich Plasmodium Falciparum und Leishmania Donovani identifiziert. In dem Bemühen, erweitern die Struktur-Wirkungs wurden die Beziehung dieser Verbindungsklasse gegenüber Infektionskrankheiten, eine Bibliothek von Naturprodukten und natürlichen Produkt-wie 4-methoxy-6-styryl-pyran-2-ones und eine Teilmenge der katalytisch reduzierte Beispiele synthetisiert. Darüber hinaus wurden die photochemische Reaktivität einiger der 4-methoxy-6-styryl-pyran-2-ones untersucht woraus sich Kopf an Kopf und Kopf-Schwanz-Cyclobutan-Dimer sowie Beispiele für asymmetrische Aniba-Dimer Typ A Dimer. Alle Verbindungen wurden für die Zytotoxizität und Aktivitäten gegen M. Tuberkulose, p. Falciparum, L. Donovani, Trypanosoma Brucei gambiense und Trypanosoma Cruzi ausgewertet. Der Styryl-Pyranone, natürliches Produkt 3 und nicht-natürliche Styrol und Naphthalin ersetzt Beispiele 13, 18, 21, 22 und 23 ausgestellt gegen Malaria-Aktivität (IC (50) < 10μM) mit selektivität indizes (SI) > 10. Δ(7) Dihydro-Analoga wurden in der Regel weniger aktiv oder Selektivität fehlte. Kopf an Kopf und Kopf-Schwanz-Photodimers 5 und 34 ausgestellt moderate IC (50) s von 2,3 bis 17μM Richtung einige der parasitären Organismen, während die Aniba-Dimer-Typ-asymmetrischen Dimere 31 und 33 wurden als mäßig aktiv gegen p. Falciparum IC (50 () 1.5 und 1.7μM) mit guter Selektivität (SI ∼80) identifiziert. 4-Tert-Butyl Aniba-Dimer ein Analogon 33 stellte auch Aktivität in Richtung L. Donovani (IC (50) 4.5μM), vorschlagen Weiterentwicklung dieser letzteren Gerüst könnte zur Identifizierung der neue Leads für die doppelte Behandlung von Malaria und Leishmaniose.

A New in Vivo Model for Luteolysis Using Systemic Pulsatile Infusions of PGF(2Î±) Prostaglandins & Other Lipid Mediators. Mar, 2012 | Pubmed ID: 22300963 A new in vivo model for studying luteolysis was developed in sheep to provide a convenient method for collecting corpora lutea for molecular, biochemical, and histological analysis during a procedure that mimics natural luteolysis. It was found that the infusion of prostaglandin F(2Î±) (PGF(2Î±)) at 20 Î¼g/min/h into the systemic circulation during the mid luteal phase of the cycle allowed sufficient PGF(2Î±) to escape across the lungs and thus mimic the transient 40% decline in the concentration of progesterone in peripheral plasma seen at the onset of natural luteolysis in sheep. Additional 1h-long systemic infusions of PGF(2Î±), given at physiological intervals, indicated that two infusions were not sufficient to induce luteolysis. However, an early onset of luteolysis and estrus was induced in one out of three sheep with three infusions, two out of three sheep with four infusions, and three out of three sheep with five infusions. Reducing the duration of each systemic infusion of PGF(2Î±) from 1h to 30 min failed to induce luteolysis and estrus even after six systemic infusions indicating that, not only are the amplitude and frequency of PGF(2Î±) pulses essential for luteolysis, but the actual duration of each pulse is also critical. We conclude that a minimum of five systemic pulses of PGF(2Î±), given in an appropriate amount and at a physiological frequency and duration, are required to mimic luteolysis consistently in all sheep. The five pulse regimen thus provides a new accurate in vivo model for studying molecular mechanisms of luteolysis.

Francisella Tularensis Inhibits the Intrinsic and Extrinsic Pathways to Delay Constitutive Apoptosis and Prolong Human Neutrophil Lifespan Journal of Immunology (Baltimore, Md. : 1950). Apr, 2012 | Pubmed ID: 22357630 Francisella tularensis is a facultative intracellular bacterium that infects many cell types, including neutrophils. We demonstrated previously that F. tularensis inhibits NADPH oxidase assembly and activity and then escapes the phagosome to the cytosol, but effects on other aspects of neutrophil function are unknown. Neutrophils are short-lived cells that undergo constitutive apoptosis, and phagocytosis typically accelerates this process. We now demonstrate that F. tularensis significantly inhibited neutrophil apoptosis as indicated by morphologic analysis as well as annexin V and TUNEL staining. Thus, âˆ¼80% of infected neutrophils remained viable at 48 h compared with âˆ¼50% of control cells, and âˆ¼40% of neutrophils that ingested opsonized zymosan. In keeping with this finding, processing and activation of procaspases-8, -9, and -3 were markedly diminished and delayed. F. tularensis also significantly impaired apoptosis triggered by Fas crosslinking. Of note, these effects were dose dependent and could be conferred by either intracellular or extracellular live bacteria, but not by formalin-killed organisms or isolated LPS and capsule, and were not affected by disruption of wbtA2 or FTT1236/FTL0708-genes required for LPS O-antigen and capsule biosynthesis. In summary, we demonstrate that F. tularensis profoundly impairs constitutive neutrophil apoptosis via effects on the intrinsic and extrinsic pathways, and thereby define a new aspect of innate immune evasion by this organism. As defects in neutrophil turnover prevent resolution of inflammation, our findings also suggest a mechanism that may in part account for the neutrophil accumulation, granuloma formation, and severe tissue damage that characterizes lethal pneumonic tularemia.

Improving the Farmland Biodiversity Value of Riparian Buffer Strips: Conflicts and Compromises Journal of Environmental Quality. Mar-Apr, 2012 | Pubmed ID: 22370397 The intensity of management of lowland grassland fields in the United Kingdom, coupled with the fact that such grasslands dominate much of the lowland landscape, means that there are now few opportunities for many plants, invertebrates, birds, or mammals to survive. The Scottish Agricultural College (SAC) has investigated whether fencing off the margins of such fields next to watercourses to control diffuse pollution has any positive impacts on biodiversity, based on assessments of vegetation composition and condition and structure of assemblages of invertebrates of importance as foodstuffs to farmland birds. Fencing watercourses increased the abundance of key groups of invertebrates. However, the invertebrate species diversity was not increased unless the margins were â‰¥ 5.4 m in width. Margins established in the study area to prevent access by livestock to watercourses or to enhance biodiversity are generally â‰¤ 2.6 m wide and are therefore unlikely to provide conditions for additional invertebrate species to use. The dense, tall swards within such margins are also unlikely to provide foraging opportunities for farmland birds. Management (such as low-intensity grazing by livestock in the margins) is essential to provide the conditions required for these groups, but this could conflict with the diffuse pollution mitigation aims. A compromise is proposed whereby limited autumn/winter grazing by livestock could be used to open the vegetation structure in the margins. Grazing by livestock at that time may be acceptable since it is not occurring in the period of main diffuse pollution concern (i.e., the fecal contamination of watercourses and bathing waters in the spring and summer). It is also essential that a landscape-scale approach is taken, driven by knowledge of the full needs of the species concerned, when deciding where best to target agri-environmental actions aimed at farmland bird conservation.

A Residual Granuloma in Association with a Dental Implant Implant Dentistry. Apr, 2012 | Pubmed ID: 22382756 At times, dental implants are placed into sites with a history of periapical pathology. Sometimes the infection is active, and other times the tooth may have been extracted years before implant placement. In either case, the possibility exists for long-term residual cysts or infections that can negatively impact the prognosis of the implant. In this case report, an implant is placed into a healed mandibular ridge several months after extraction of the tooth. A radiolucency was noted on routine radiographic examination 2 years later. Surgical inspection and histology revealed a periapical granuloma with acute and chronic inflammatory cells. After surgical curettage of the site, the patient healed without complication. Implants may develop apical pathology as a result of a preexisting long-term residual infection.

Heterogeneity in Genetic Diversity Among Non-coding Loci Fails to Fit Neutral Coalescent Models of Population History PloS One. 2012 | Pubmed ID: 22384117 Inferring aspects of the population histories of species using coalescent analyses of non-coding nuclear DNA has grown in popularity. These inferences, such as divergence, gene flow, and changes in population size, assume that genetic data reflect simple population histories and neutral evolutionary processes. However, violating model assumptions can result in a poor fit between empirical data and the models. We sampled 22 nuclear intron sequences from at least 19 different chromosomes (a genomic transect) to test for deviations from selective neutrality in the gadwall (Anas strepera), a Holarctic duck. Nucleotide diversity among these loci varied by nearly two orders of magnitude (from 0.0004 to 0.029), and this heterogeneity could not be explained by differences in substitution rates alone. Using two different coalescent methods to infer models of population history and then simulating neutral genetic diversity under these models, we found that the observed among-locus heterogeneity in nucleotide diversity was significantly higher than expected for these simple models. Defining more complex models of population history demonstrated that a pre-divergence bottleneck was also unlikely to explain this heterogeneity. However, both selection and interspecific hybridization could account for the heterogeneity observed among loci. Regardless of the cause of the deviation, our results illustrate that violating key assumptions of coalescent models can mislead inferences of population history.

Arx is Required for Normal Enteroendocrine Cell Development in Mice and Humans Developmental Biology. May, 2012 | Pubmed ID: 22387004 Enteroendocrine cells of the gastrointestinal (GI) tract play a central role in metabolism, digestion, satiety and lipid absorption, yet their development remains poorly understood. Here we show that Arx, a homeodomain-containing transcription factor, is required for the normal development of mouse and human enteroendocrine cells. Arx expression is detected in a subset of Neurogenin3 (Ngn3)-positive endocrine progenitors and is also found in a subset of hormone-producing cells. In mice, removal of Arx from the developing endoderm results in a decrease of enteroendocrine cell types including gastrin-, glucagon/GLP-1-, CCK-, secretin-producing cell populations and an increase of somatostatin-expressing cells. This phenotype is also observed in mice with endocrine-progenitor-specific Arx ablation suggesting that Arx is required in the progenitor for enteroendocrine cell development. In addition, depletion of human ARX in developing human intestinal tissue results in a profound deficit in expression of the enteroendocrine cell markers CCK, secretin and glucagon while expression of a pan-intestinal epithelial marker, CDX2, and other non-endocrine markers remained unchanged. Taken together, our findings uncover a novel and conserved role of Arx in mammalian endocrine cell development and provide a potential cause for the chronic diarrhea seen in both humans and mice carrying Arx mutations.

Exposure to Ambient Air Fine Particulate Matter Prevents VEGF-induced Mobilization of Endothelial Progenitor Cells from the Bone Marrow Environmental Health Perspectives. Jun, 2012 | Pubmed ID: 22418586 Exposure to ambient fine particulate matter air pollution (PM(2.5); < 2.5 Âµm in aerodynamic diameter) induces endothelial dysfunction and increases the risk for cardiovascular disease. Endothelial progenitor cells (EPCs) contribute to postnatal endothelial repair and regeneration. In humans and mice, EPC levels are decreased upon exposure to elevated levels of PM(2.5).

CD8(+) T Cells Sabotage Their Own Memory Potential Through IFN-Î³-dependent Modification of the IL-12/IL-15 Receptor Î± Axis on Dendritic Cells Journal of Immunology (Baltimore, Md. : 1950). Apr, 2012 | Pubmed ID: 22430740 CD8(+) T cell responses have been shown to be regulated by dendritic cells (DCs) and CD4(+) T cells, leading to the tenet that CD8(+) T cells play a passive role in their own differentiation. In contrast, by using a DNA vaccination model, to separate the events of vaccination from those of CD8(+) T cell priming, we demonstrate that CD8(+) T cells, themselves, actively limit their own memory potential through CD8(+) T cell-derived IFN-Î³-dependent modification of the IL-12/IL-15RÎ± axis on DCs. Such CD8(+) T cell-driven cytokine alterations result in increased T-bet and decreased Bcl-2 expression, and thus decreased memory progenitor formation. These results identify an unrecognized role for CD8(+) T cells in the regulation of their own effector differentiation fate and a previously uncharacterized relationship between the balance of inflammation and memory formation.

Studies of Iron(II) and Iron(III) Complexes with Fac-N2O, Cis-N2O2 and N2O3 Donor Ligands: Models for the 2-His 1-carboxylate Motif of Non-heme Iron Monooxygenases Dalton Transactions (Cambridge, England : 2003). May, 2012 | Pubmed ID: 22434362 Enzymes in the oxygen-activating class of mononuclear non-heme iron oxygenases (MNOs) contain a highly conserved iron center facially ligated by two histidine nitrogen atoms and one carboxylate oxygen atom that leave one face of the metal center (three binding sites) open for coordination to cofactor, substrate, and/or dioxygen. A comparative family of [Fe(II/III)(N(2)O(n))(L)(4-n))](Â±x), n = 1-3, L = solvent or Cl(-), model complexes, based on a ligand series that supports a facially ligated N,N,O core that is then modified to contain either one or two additional carboxylate chelate arms, has been structurally and spectroscopically characterized. EPR studies demonstrate that the high-spin d(5) Fe(III)g = 4.3 signal becomes more symmetrical as the number of carboxylate ligands decreases across the series Fe(N(2)O(3)), Fe(N(2)O(2)), and Fe(N(2)O(1)), reflecting an increase in the E/D strain of these complexes as the number of exchangeable/solvent coordination sites increases, paralleling the enhanced distribution of electronic structures that contribute to the spectral line shape. The observed systematic variations in the Fe(II)-Fe(III) oxidation-reduction potentials illustrate the fundamental influence of differential carboxylate ligation. The trend towards lower reduction potential for the iron center across the [Fe(III)(N(2)O(1))Cl(3)](-), [Fe(III)(N(2)O(2))Cl(2)](-) and [Fe(III)(N(2)O(3))Cl](-) series is consistent with replacement of the chloride anions with the more strongly donating anionic O-donor carboxylate ligands that are expected to stabilize the oxidized ferric state. This electrochemical trend parallels the observed dioxygen sensitivity of the three ferrous complexes (Fe(II)(N(2)O(1)) < Fe(II)(N(2)O(2)) < Fe(II)(N(2)O(3))), which form Î¼-oxo bridged ferric species upon exposure to air or oxygen atom donor (OAD) molecules. The observed oxygen sensitivity is particularly interesting and discussed in the context of Î±-ketoglutarate-dependent MNO enzyme mechanisms.

Psychosocial Functioning in Children and Adolescents with Extreme Obesity Journal of Clinical Psychology in Medical Settings. Sep, 2012 | Pubmed ID: 22437944 The aim of this study was to investigate the psychosocial differences among obese pediatric patients, particularly those who are "extremely obese" as compared to "obese." Information was collected for 249 subjects at a multidisciplinary treatment clinic for obese youth. A battery of measures was administered and demographic data and height/weight was obtained. The results showed positive correlations between degree of obesity, psychosocial functioning, and quality of life. Specifically, the "extremely obese" were significantly more depressed, more socially anxious, and had poorer quality of life than the "obese" group. Girls and Caucasians were more socially anxious than boys and African Americans, respectively. There is mounting evidence that children and adolescents who are extremely obese are most at risk for psychiatric and medical disorders. Thus, targeting this group for assessment and/or designing treatment options specific for "extremely obese" youth is critical for the successful management of this population.

A Radar-enabled Collaborative Sensor Network Integrating COTS Technology for Surveillance and Tracking Sensors (Basel, Switzerland). 2012 | Pubmed ID: 22438713 The feasibility of using Commercial Off-The-Shelf (COTS) sensor nodes is studied in a distributed network, aiming at dynamic surveillance and tracking of ground targets. Data acquisition by low-cost (

EccA1, a Component of the Mycobacterium Marinum ESX-1 Protein Virulence Factor Secretion Pathway, Regulates Mycolic Acid Lipid Synthesis Chemistry & Biology. Mar, 2012 | Pubmed ID: 22444592 Pathogenic mycobacteria, which cause multiple diseases including tuberculosis, secrete factors essential for disease via the ESX-1 protein export system and are partially protected from host defenses by their lipid-rich cell envelopes. These pathogenic features of mycobacterial biology are believed to act independently of each other. Key ESX-1 components include three ATPases, and EccA1 (Mycobacterium marinum MMAR_5443; M.Â tuberculosis Rv3868) is the least characterized. Here we show that M.Â marinum EccA1's ATPase activity is required for ESX-1-mediated protein secretion, and surprisingly for the optimal synthesis of mycolic acids, integral cell-envelope lipids. Increased mycolic acid synthesis defects, observed when an EccA1-ATPase mutant is expressed in an eccA1-null strain, correlate with decreased inÂ vivo virulence and intracellular growth. These data suggest that two mycobacterial virulence hallmarks, ESX-1-dependent protein secretion and mycolic acid synthesis, are critically linked via EccA1.

Genome-wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes Journal of the American Academy of Child and Adolescent Psychiatry. Apr, 2012 | Pubmed ID: 22449649 The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability.

Evaluation of High-resolution Peripheral Quantitative Computed Tomography, Finite Element Analysis and Biomechanical Testing in a Pre-clinical Model of Osteoporosis: a Study with Odanacatib Treatment in the Ovariectomized Adult Rhesus Monkey Bone. Jun, 2012 | Pubmed ID: 22469953 This study aimed to validate finite element analysis (FEA) estimation of strength, identify high-resolution peripheral quantitative computed tomography (HR-pQCT) measures correlating with strength, and evaluate the precision of HR-pQCT measurements to longitudinally monitor effects of osteoporosis treatment in ovariectomized (OVX) non-human primates (NHPs). HR-pQCT images were acquired in three groups of NHPs: Intact (n=10), OVX-odanacatib treated (OVX-ODN 30 mg/kg, n=10) and OVX-vehicle treated (OVX-Veh, n=10) at the ultradistal (UD) and distal 1/3 radii and tibia at 12, 16 and 20 months. FEA estimates of bone strength using the Pistoia criterion were validated by ex-vivo mechanical compression (r(2)=0.95) of the UD radius. Single linear regressions of FEA-determined ultimate stress showed high correlation with HR-pQCT derived parameters: integral vBMD (r(2)=0.86), bone volume fraction (r(2)=0.84) and cortical thickness (r(2)=0.79). Precision of HR-pQCT measurements, obtained from an excised radius and tibia, showed low variation (CV=0.005%-5.6%) and helped identify possible sources of error. Comparison of OVX-Veh and Intact groups showed decreases in bone parameters demonstrating trends consistent with bone loss. Comparison of OVX-ODN and OVX-Veh groups showed a treatment effect with increases in bone parameters: integral vBMD (477Â±27 vs. 364Â±22 mgHA/cm(3)) and cortical thickness (Ct.Th) (0.90Â±0.07 vs. 0.64Â±0.04 mm) at the UD radius, Ct.Th (2.15Â±0.28 vs. 1.56Â±0.08 mm) at the distal 1/3 radius. Axial compression peak stress calculated and obtained experimentally showed the OVX-ODN group was 33% stronger than the OVX-Veh group. We conclude that HR-pQCT and FEA serve as robust techniques to longitudinally monitor bone parameters and strength in NHP's.

9,400 Years of Cosmic Radiation and Solar Activity from Ice Cores and Tree Rings Proceedings of the National Academy of Sciences of the United States of America. Apr, 2012 | Pubmed ID: 22474348 Understanding the temporal variation of cosmic radiation and solar activity during the Holocene is essential for studies of the solar-terrestrial relationship. Cosmic-ray produced radionuclides, such as (10)Be and (14)C which are stored in polar ice cores and tree rings, offer the unique opportunity to reconstruct the history of cosmic radiation and solar activity over many millennia. Although records from different archives basically agree, they also show some deviations during certain periods. So far most reconstructions were based on only one single radionuclide record, which makes detection and correction of these deviations impossible. Here we combine different (10)Be ice core records from Greenland and Antarctica with the global (14)C tree ring record using principal component analysis. This approach is only possible due to a new high-resolution (10)Be record from Dronning Maud Land obtained within the European Project for Ice Coring in Antarctica in Antarctica. The new cosmic radiation record enables us to derive total solar irradiance, which is then used as a proxy of solar activity to identify the solar imprint in an Asian climate record. Though generally the agreement between solar forcing and Asian climate is good, there are also periods without any coherence, pointing to other forcings like volcanoes and greenhouse gases and their corresponding feedbacks. The newly derived records have the potential to improve our understanding of the solar dynamics and to quantify the solar influence on climate.

Comparison of an Inertial Sensor System of Lameness Quantification with Subjective Lameness Evaluation Equine Veterinary Journal. Nov, 2012 | Pubmed ID: 22563674 Subjective evaluation of mild lameness has been shown to have poor interobserver reliability. Traditional methods of objective lameness evaluation require specialised conditions and equipment. Wireless inertial sensor systems have been developed to allow for simple, rapid, objective lameness detection in horses trotted over ground.

Targeted Exchange of an Expression Cassette Encoding Cyclooxygenase-2 at the Ptgs1 Locus Prostaglandins & Other Lipid Mediators. Oct, 2012 | Pubmed ID: 22579447 Defining the multi-faceted roles of prostaglandins has been facilitated by studying mice with manipulated expression of the two enzymes encoding cyclooxygenase (COX) via gene targeting, with either knocked down expression of COX-1 or COX-2, a knocked-in COX-2 active site mutation and exchange of COX isoforms by insertion of a cassette encoding COX-1 into the COX-2 (Ptgs2) gene to create COX-1>COX-2 mice. Here, we sought to extend these studies by creating a new induced mutant strain with manipulated COX expression. We carried out gene targeting at the Ptgs1 locus to knock-in an expression cassette encoding COX-2 under Ptgs1 regulatory elements in a manner analogous used in COX-1>COX-2 targeting. While successful gene targeting at the Ptgs1 locus was achieved, the strategy did not yield a "basal" increase of COX-2 under Ptgs1 gene regulatory control in various cells and tissues from COX-2>COX-1 mice but rather resulted in a Ptgs1 null allele. Possible explanations as to why this strategy was unsuccessful include non-functionality of the hybrid signal peptide and aberrant transcript processing. Since a similar strategy had previously worked (i.e. COX-1 cDNA knocked-in to the Ptgs2 locus; COX-1>COX-2 mice) interpretations of our findings on murine COX biology and gene targeting are discussed.

Effectiveness of Tai Chi As a Community-based Falls Prevention Intervention: a Randomized Controlled Trial Journal of the American Geriatrics Society. May, 2012 | Pubmed ID: 22587850 To compare the effectiveness of tai chi and low-level exercise in reducing falls in older adults; to determine whether mobility, balance, and lower limb strength improved and whether higher doses of tai chi resulted in greater effect.

SPRY2 Loss Enhances ErbB Trafficking and PI3K/AKT Signalling to Drive Human and Mouse Prostate Carcinogenesis EMBO Molecular Medicine. Aug, 2012 | Pubmed ID: 22649008 Loss of SPRY2 and activation of receptor tyrosine kinases are common events in prostate cancer (PC). However, the molecular basis of their interaction and clinical impact remains to be fully examined. SPRY2 loss may functionally synergize with aberrant cellular signalling to drive PC and to promote treatment-resistant disease. Here, we report evidence for a positive feedback regulation of the ErbB-PI3K/AKT cascade by SPRY2 loss in in vitro as well as pre-clinical in vivo models and clinical PC. Reduction in SPRY2 expression resulted in hyper-activation of PI3K/AKT signalling to drive proliferation and invasion by enhanced internalization of EGFR/HER2 and their sustained signalling at the early endosome in a PTEN-dependent manner. This involved p38 MAPK activation by PI3K to facilitate clathrin-mediated ErbB receptor endocytosis. Finally, in vitro and in vivo inhibition of PI3K suppressed proliferation and invasion, supporting PI3K/AKT as a target for therapy particularly in patients with PTEN-haploinsufficient-, low SPRY2- and ErbB-expressing tumours. In conclusion, SPRY2 is an important tumour suppressor in PC since its loss drives the PI3K/AKT pathway via functional interaction with the ErbB system.

Factor Structure and Psychometric Properties of the Chinese Version of the 20-item Pain Anxiety Symptoms Scale (ChPASS-20) Journal of Pain and Symptom Management. Jun, 2012 | Pubmed ID: 22651953 The Pain Anxiety Symptoms Scale (PASS) was designed to assess pain-related anxiety and fear. Although the scale is a reliable measure with good psychometric properties, its validity among ethnic Chinese has yet to be evaluated.

Treatment for Chronic Pain for Adults in the Seventh and Eighth Decades of Life: a Preliminary Study of Acceptance and Commitment Therapy (ACT) Pain Medicine (Malden, Mass.). Jul, 2012 | Pubmed ID: 22680627 The purpose of this study was to examine results for older adults attending treatment based on Acceptance and Commitment Therapy (ACT) for chronic pain. Both clinical outcome and treatment process variables were examined.

Molecular Pathways Controlling Pancreas Induction Seminars in Cell & Developmental Biology. Aug, 2012 | Pubmed ID: 22743233 Recent advances in generating pancreatic cell types from human pluripotent stem cells has depended on our knowledge of the developmental processes that regulate pancreas development in vivo. The developmental events between gastrulation and formation of the embryonic pancreatic primordia are both rapid and dynamic and studies in frog, fish, chick, and mouse have identified the molecular basis of how the pancreas develops from multipotent endoderm progenitors. Here, we review the current status of our understanding of molecular mechanisms that control endoderm formation, endoderm patterning, and pancreas specification and highlight how these discoveries have allowed for the development of robust methods to generate pancreatic cells from human pluripotent stem cells.

Intraluteal Prostaglandin Biosynthesis and Signaling Are Selectively Directed Towards PGF2alpha During Luteolysis but Towards PGE2 During the Establishment of Pregnancy in Sheep Biology of Reproduction. Oct, 2012 | Pubmed ID: 22743300 In ruminants, endometrial prostalgandin (PG) F(2alpha) causes functional luteolysis, whereas luteal synthesis of PGF(2alpha) is required for structural luteolysis. PGE(2) is considered to be a luteoprotective mediator. Molecular aspects of luteal PGF(2alpha) and PGE(2) biosynthesis and signaling during the estrous cycle and establishment of pregnancy are largely unknown. The objectives of the present study were 1) to determine the regulation of proteins involved in PGF(2alpha) and PGE(2) biosynthesis, catabolism, transport and signaling in the corpus luteum (CL); 2) to investigate the transport of interferon tau (IFNT), PGF(2alpha), and PGE(2) from the uterus to the ovary through the vascular utero-ovarian plexus (UOP); and 3) to compare the intraluteal production of PGF(2alpha) and PGE(2) on Days 12, 14, and 16 of the estrous cycle and pregnancy in sheep. Our results indicate that luteal PG biosynthesis is selectively directed towards PGF(2alpha) at the time of luteolysis and towards PGE(2) during the establishment of pregnancy. Moreover, the ability of the CL of early pregnancy to resist luteolysis is due to increased intraluteal biosynthesis of PGE(2) and PGE(2) receptor (PTGER) 2 (also known as EP2)- and PTGER4 (also known as EP4)-mediated signaling. We also found that IFNT protein is not transported through the UOP from the uterus to the ovary; in contrast, a large proportion of endometrial PGE(2) is transported from the uterus to the ovary through the UOP. These results indicate that endometrial PGE(2) stimulated by pregnancy is transported locally to the ovary, which increases luteal PGE(2) biosynthesis and hence activates luteal PTGER2 and PTGER4 signaling, thus protecting the CL during the establishment of pregnancy in sheep.

Rehospitalization Following Percutaneous Coronary Intervention for Commercially Insured Patients with Acute Coronary Syndrome: a Retrospective Analysis BMC Research Notes. 2012 | Pubmed ID: 22747631 While prior research has provided important information about readmission rates following percutaneous coronary intervention, reports regarding charges and length of stay for readmission beyond 30 days post-discharge for patients in a large cohort are limited. The objective of this study was to characterize the rehospitalization of patients with acute coronary syndrome receiving percutaneous coronary intervention in a U.S. health benefit plan.

Discrimination of Ethanol-nicotine Drug Mixtures in Mice: Dual Interactive Mechanisms of Overshadowing and Potentiation Psychopharmacology. Dec, 2012 | Pubmed ID: 22763667 One possible basis for the proclivity of ethanol and nicotine co-abuse is an interaction between the discriminative stimulus (S(D)) effects of each drug.

What Primary Health-care Services Are Australian Consumers Willing to Accept from Nurse Practitioners? A National Survey Health Expectations : an International Journal of Public Participation in Health Care and Health Policy. Jul, 2012 | Pubmed ID: 22784392 BACKGROUND: Nurses are becoming increasingly important as providers of primary health care in Australia. In November 2010, Medicare provider rights and Pharmaceutical Benefits Scheme rights for nurse practitioners, working in private practice and in collaboration with a medical practitioner, were introduced in Australia. Although international evidence suggests that nurse practitioners would be appropriate and acceptable providers of care at the first point of contact, such as primary health care, there is little Australian evidence about what care consumers are willing to accept from nurse practitioners. OBJECTIVES: To ascertain what care Australian health-care consumers would accept from nurse practitioners in this setting. PARTICIPANTS: Australian adults over 18Â years of age. METHODS: National Survey delivered online. Information about the survey was disseminated through a media campaign, stakeholder engagement and through the health-care consumer networks nationally. RESULTS: The total number of respondents that started the survey was nÂ =Â 1883. Ninety-five percentage (nÂ =Â 1784) of respondents completed the survey. The majority of respondents were women, aged 25-54Â years, had completed tertiary education and had an annual household income of more than A$80Â 000. The majority of the respondents (nÂ =Â 1562, 87%) said they would be prepared to see a nurse practitioner for some of their primary health-care needs. CONCLUSIONS: The findings of this study suggest consumers are accepting of a range of activities undertaken by nurse practitioners in primary health care and this has relevance for primary health-care workforce mix and organization, particularly for areas that are underserved by medical practitioners.

Genetics of Pediatric Anxiety Disorders Child and Adolescent Psychiatric Clinics of North America. Jul, 2012 | Pubmed ID: 22800990 This article reviews the familiality, linkage, candidate gene, and genomewide association studies of obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, and other anxiety disorders (ie, generalized anxiety disorder, separation anxiety disorder, social phobia, and specific phobia). Studies involving children and adolescents are highlighted. Clinical and research implications are discussed.

Effects of Methamphetamine Abuse and Serotonin Transporter Gene Variants on Aggression and Emotion-processing Neurocircuitry Translational Psychiatry. 2012 | Pubmed ID: 22832817 Individuals who abuse methamphetamine (MA) exhibit heightened aggression, but the neurobiological underpinnings are poorly understood. As variability in the serotonin transporter (SERT) gene can influence aggression, this study assessed possible contributions of this gene to MA-related aggression. In all, 53 MA-dependent and 47 control participants provided self-reports of aggression, and underwent functional magnetic resonance imaging while viewing pictures of faces. Participants were genotyped at two functional polymorphic loci in the SERT gene: the SERT-linked polymorphic region (SERT-LPR) and the intron 2 variable number tandem repeat polymorphism (STin2 VNTR); participants were then classified as having high or low risk for aggression according to individual SERT risk allele combinations. Comparison of SERT risk allele loads between groups showed no difference between MA-dependent and control participants. Comparison of self-report scores showed greater aggression in MA-dependent than control participants, and in high genetic risk than low-risk participants. Signal change in the amygdala was lower in high genetic risk than low-risk participants, but showed no main effect of MA abuse; however, signal change correlated negatively with MA use measures. Whole-brain differences in activation were observed between MA-dependent and control groups in the occipital and prefrontal cortex, and between genetic high- and low-risk groups in the occipital, fusiform, supramarginal and prefrontal cortex, with effects overlapping in a small region in the right ventrolateral prefrontal cortex. The findings suggest that the investigated SERT risk allele loads are comparable between MA-dependent and healthy individuals, and that MA and genetic risk influence aggression independently, with minimal overlap in associated neural substrates.

Genotype-phenotype Analysis of 4q Deletion Syndrome: Proposal of a Critical Region American Journal of Medical Genetics. Part A. Sep, 2012 | Pubmed ID: 22847869 Chromosome 4q deletion syndrome (4q- syndrome) is a rare condition, with an estimated incidence of 1 in 100,000. Although variable, the clinical spectrum commonly includes craniofacial, developmental, digital, skeletal, and cardiac involvement. Data on the genotype-phenotype correlation within the 4q arm are limited. We present detailed clinical and genetic information by array CGH on 20 patients with 4q deletions. We identified a patient who has a âˆ¼465â€‰kb deletion (186,770,069-187,234,800, hg18 coordinates) in 4q35.1 with all clinical features for 4q deletion syndrome except for developmental delay, suggesting that this is a critical region for this condition and a specific gene responsible for orofacial clefts and congenital heart defects resides in this region. Since the patients with terminal deletions all had cleft palate, our results provide further evidence that a gene associated with clefts is located on the terminal segment of 4q. By comparing and contrasting our patients' genetic information and clinical features, we found significant genotype-phenotype correlations at a single gene level linking specific phenotypes to individual genes. Based on these data, we constructed a hypothetical partial phenotype-genotype map for chromosome 4q which includes BMP3, SEC31A, MAPK10, SPARCL1, DMP1, IBSP, PKD2, GRID2, PITX2, NEUROG2, ANK2, FGF2, HAND2, and DUX4 genes.

Elevated Glutamatergic Compounds in Pregenual Anterior Cingulate in Pediatric Autism Spectrum Disorder Demonstrated by 1H MRS and 1H MRSI PloS One. 2012 | Pubmed ID: 22848344 Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy ((1)H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p

A Parapatric Propensity for Breeding Precludes the Completion of Speciation in Common Teal (Anas Crecca, Sensu Lato) Molecular Ecology. Sep, 2012 | Pubmed ID: 22849532 Speciation is a process in which genetic drift and selection cause divergence over time. However, there is no rule dictating the time required for speciation, and even low levels of gene flow hinder divergence, so that taxa may be poised at the threshold of speciation for long periods of evolutionary time. We sequenced mitochondrial DNA (mtDNA) and eight nuclear introns (nuDNA) to estimate genomic levels of differentiation and gene flow between the Eurasian common teal (Anas crecca crecca) and the North American green-winged teal (Anas crecca carolinensis). These ducks come into contact in Beringia (north-eastern Asia and north-western North America) and have probably done so, perhaps cyclically, since the Pliocene-Pleistocene transition, ~2.6 Ma, when they apparently began diverging. They have diagnosable differences in male plumage and are 6.9% divergent in the mtDNA control region, with only 1 of 58 crecca and 2 of 86 carolinensis having haplotypes grouping with the other. Two nuclear loci were likewise strongly structured between these teal (Î¦(st) â‰¥ 0.35), but six loci were undifferentiated or only weakly structured (Î¦(st) = 0.0-0.06). Gene flow between crecca and carolinensis was ~1 individual per generation in both directions in mtDNA, but was asymmetrical in nuDNA, with ~1 and ~20 individuals per generation immigrating into crecca and carolinensis, respectively. This study illustrates that species delimitation using a single marker oversimplifies the complexity of the speciation process, and it suggests that even with divergent selection, moderate levels of gene flow may stall the speciation process short of completion.

Ein Ausbruch Von Klebsiella Pneumoniae Spät Beginnende Sepsis in Einer Neugeborenen-Intensivstation in Guatemala American Journal of Infection Control. Aug, 2012 | Pubmed ID: 22854378 Gramnegative Blutbahn Infektionen sind eine wichtige Ursache für neonatale Mortalität. Im Oktober 2009 untersuchten wir einen Klebsiella Spp-Ausbruch in einer Neugeborenen-Intensivstation in Guatemala.

Pain Acceptance-based Coping in Complex Regional Pain Syndrome Type I: Daily Relations with Pain Intensity, Activity, and Mood Journal of Behavioral Medicine. Aug, 2012 | Pubmed ID: 22854886 This study aimed to examine the temporal patterning of pain acceptance-based coping, activity, and mood in patients with complex regional pain syndrome Type I (CRPS-I), by using a daily diary method. A total of 30 patients with CRPS-I seeking treatment in a tertiary pain management center located in Seoul, Korea participated in the study. Multilevel random effects analyses indicated that (a) engagement in pain acceptance-based coping was significantly associated with lower same-day pain and negative mood and greater same-day activity and positive mood; (b) pain acceptance-based coping predicted increases in activity on the following day; (c) greater pain intensity was significantly associated with lower same-day pain acceptance-based coping and activity and greater same-day negative mood; and (d) pain intensity did not predict pain acceptance-based coping, activity, or mood on the following day. These findings suggest that patients with CRPS-I may benefit from responding to pain with acceptance. Further study and eventual application of this process in CRPS-I may improve upon the success of current approaches to this problem.

Air Pollution Exposure and Telomere Length in Highly Exposed Subjects in Beijing, China: a Repeated-measure Study Environment International. Nov, 2012 | Pubmed ID: 22871507 Ambient particulate matter (PM) exposure has been associated with short- and long-term effects on cardiovascular disease (CVD). Telomere length (TL) is a biomarker of CVD risk that is modified by inflammation and oxidative stress, two key pathways for PM effects. Whether PM exposure modifies TL is largely unexplored.

Natural IgM Mediates Complement-dependent Uptake of Francisella Tularensis by Human Neutrophils Via Complement Receptors 1 and 3 in Nonimmune Serum Journal of Immunology (Baltimore, Md. : 1950). Sep, 2012 | Pubmed ID: 22888138 A fundamental step in the life cycle of Francisella tularensis is bacterial entry into host cells. F. tularensis activates complement, and recent data suggest that the classical pathway is required for complement factor C3 deposition on the bacterial surface. Nevertheless, C3 deposition is inefficient and neither the specific serum components necessary for classical pathway activation by F. tularensis in nonimmune human serum nor the receptors that mediate infection of neutrophils have been defined. In this study, human neutrophil uptake of GFP-expressing F. tularensis strains live vaccine strain and Schu S4 was quantified with high efficiency by flow cytometry. Using depleted sera and purified complement components, we demonstrated first that C1q and C3 were essential for F. tularensis phagocytosis, whereas C5 was not. Second, we used purification and immunodepletion approaches to identify a critical role for natural IgM in this process, and then used a wbtA2 mutant to identify LPS O-Ag and capsule as prominent targets of these Abs on the bacterial surface. Finally, we demonstrate using receptor-blocking Abs that CR1 (CD35) and CR3 (CD11b/CD18) acted in concert for phagocytosis of opsonized F. tularensis by human neutrophils, whereas CR3 and CR4 (CD11c/CD18) mediated infection of human monocyte-derived macrophages. Altogether, our data provide fundamental insight into mechanisms of F. tularensis phagocytosis and support a model whereby natural IgM binds to surface capsular and O-Ag polysaccharides of F. tularensis and initiates the classical complement cascade via C1q to promote C3 opsonization of the bacterium and phagocytosis via CR3 and either CR1 or CR4 in a phagocyte-specific manner.

High Dose Vitamin D Therapy for Chronic Pain in Children and Adolescents with Sickle Cell Disease: Results of a Randomized Double Blind Pilot Study British Journal of Haematology. Oct, 2012 | Pubmed ID: 22924607 We report results of a pilot study of high-dose vitamin D in sickle cell disease (SCD). Subjects were given a 6-week course of oral high-dose cholecalciferol (4000-100Â 000 IU per week) or placebo and monitored prospectively for a period of six months. Vitamin D insufficiency and deficiency was present at baseline in 82Â·5% and 52Â·5% of subjects, respectively. Subjects who received high-dose vitamin D achieved higher serum 25-hydroxyvitamin D, experienced fewer pain days per week, and had higher physical activity quality-of-life scores. These findings suggest a potential benefit of vitamin D in reducing the number of pain days in SCD. Larger prospective studies with longer duration are needed to confirm these effects.

D-2-hydroxyglutarate Produced by Mutant IDH1 Perturbs Collagen Maturation and Basement Membrane Function Genes & Development. Sep, 2012 | Pubmed ID: 22925884 Isocitrate dehydrogenase-1 (IDH1) R132 mutations occur in glioma, but their physiological significance is unknown. Here we describe the generation and characterization of brain-specific Idh1 R132H conditional knock-in (KI) mice. Idh1 mutation results in hemorrhage and perinatal lethality. Surprisingly, intracellular reactive oxygen species (ROS) are attenuated in Idh1-KI brain cells despite an apparent increase in the NADP(+)/NADPH ratio. Idh1-KI cells also show high levels of D-2-hydroxyglutarate (D2HG) that are associated with inhibited prolyl-hydroxylation of hypoxia-inducible transcription factor-1Î± (Hif1Î±) and up-regulated Hif1Î± target gene transcription. Intriguingly, D2HG also blocks prolyl-hydroxylation of collagen, causing a defect in collagen protein maturation. An endoplasmic reticulum (ER) stress response induced by the accumulation of immature collagens may account for the embryonic lethality of these mutants. Importantly, D2HG-mediated impairment of collagen maturation also led to basement membrane (BM) aberrations that could play a part in glioma progression. Our study presents strong in vivo evidence that the D2HG produced by the mutant Idh1 enzyme is responsible for the above effects.

Serological Evidence of West Nile Virus Infection in Wild Migratory and Resident Water Birds in Eastern and Northern India Comparative Immunology, Microbiology and Infectious Diseases. Dec, 2012 | Pubmed ID: 22925932 To assess West Nile virus (WNV) infection in wild resident and migratory birds, we tested 3887 samples from 1784 birds belonging to 119 identified species within 30 families collected during 2008-10 from 13 states in India. The serum samples were tested for WNV antibodies initially by a competition ELISA and subsequently by a micro-plaque reduction neutralization test (Micro-PRNT), whereas tracheal and cloacal swabs were subjected to real-time RT-PCR for the detection of the WNV RNA. Twenty six birds (2.46%) out of 1058 tested showed evidence of flavivirus antibodies by ELISA. End point neutralization antibody determinations for WNV and Japanese encephalitis virus (JEV) showed that of the 22 ELISA positive sera, WNV-specific neutralizing antibodies were detected in 17 samples representing nine species of wild birds (residents: Purple swamphen, Little cormorant, Little egret, Black ibis and Spot-billed duck; residents with winter influx: Common coot and Mallard; migratory birds: Ruff and Purple heron), and two samples were positive for both WNV and JEV antibodies. The WNV-specific antibodies were most commonly detected in Mallards and Common coots. WNV genomic RNA was not detected by real-time RT-PCR. The results in this study suggest that wild resident birds are infected occasionally and wild migratory birds rarely with WNV. Additionally, our study provides evidence of WNV infection in eastern and northern India for the first time.

#ClinMed: What Have Social Media Got to Do with Medicine? Clinical Medicine (London, England). Aug, 2012 | Pubmed ID: 22930871

Fledermäuse Verfolgen Und Änderungen in Den Insekt-Schädling-Bevölkerungen Zu Nutzen PloS One. 2012 | Pubmed ID: 22952782 Die Rolle der Fledermäuse oder jede Generalist Raubtier bei der Unterdrückung der Beute Populationen ist abhängig von der Räuber Fähigkeit zu verfolgen und zu verfügbaren Beute zu nutzen. Verwenden eine qPCR fäkale DNA-Probe, dokumentieren wir signifikanten Zusammenhang zwischen den Zahlen des brasilianischen frei-tailed Fledermäuse (Tadarida Brasiliensis) verbrauchen Mais Ohrwurm (CEW) Falter (anderen Zea) und saisonale Schwankungen in CEW Populationen. Dieses Ergebnis steht im Einklang mit früheren Untersuchungen verknüpfen die Fledermäuse Diät mit Mustern von Migration, Fülle und Ernte Befall durch Schädlinge wichtig. Hier bestätigen wir opportunistische Fütterung auf eine der weltweit am meisten zerstörende Insekten und Unterstützung Modell Schätzungen über die Fledermäuse Ökosystem-Dienstleistungen. Regressionsanalyse CEW Verbrauch gegenüber der Nachtfalter Fülle an vier Insekt Trapping-Standorten weiter zeigt, dass Fledermäuse lokale Fülle von CEW innerhalb der regionalen Landschaft verfolgen. Schätzungen CEW-gen-Kopien in den Kot der Fledermäuse sind nicht verbunden mit saisonalen oder lokalen Mustern der CEW Fülle und Ergebnisse Gefangenschaft Fütterung Experimente zeigen, dass unsere qPCR-Assay kein direktes Maß von Zahlen oder Biomasse Beute verzehrt bereitstellt. Unsere Ergebnisse immer deutlicher für die Rolle der Generalist Raubtiere und Fledermäuse konkret zu unterstützen, als Agenten für die biologische Schädlingsbekämpfung und sprechen auf den Wert der Erhaltung der einheimischen-Generalist Raubtiere.

Initial In Vivo Quantification of Tc-99m Sestamibi Uptake As a Function of Tissue Type in Healthy Breasts Using Dedicated Breast SPECT-CT Journal of Oncology. 2012 | Pubmed ID: 22956950 A pilot study is underway to quantify in vivo the uptake and distribution of Tc-99m Sestamibi in subjects without previous history of breast cancer using a dedicated SPECT-CT breast imaging system. Subjects undergoing diagnostic parathyroid imaging studies were consented and imaged as part of this IRB-approved breast imaging study. For each of the seven subjects, one randomly selected breast was imaged prone-pendant using the dedicated, compact breast SPECT-CT system underneath the shielded patient support. Iteratively reconstructed and attenuation and/or scatter corrected images were coregistered; CT images were segmented into glandular and fatty tissue by three different methods; the average concentration of Sestamibi was determined from the SPECT data using the CT-based segmentation and previously established quantification techniques. Very minor differences between the segmentation methods were observed, and the results indicate an average image-based in vivo Sestamibi concentration of 0.10 Â± 0.16â€‰Î¼Ci/mL with no preferential uptake by glandular or fatty tissues.

Agreement Between Therapists, Parents, Patients, and Independent Evaluators on Clinical Improvement in Pediatric Obsessive-compulsive Disorder Journal of Consulting and Clinical Psychology. Dec, 2012 | Pubmed ID: 22963592 Independent evaluators (IE) are used widely in clinical trials to make unbiased determinations of treatment response. By virtue of being kept blind to treatment condition, however, IEs are also kept unaware of many pertinent clinical details that are relevant for decisions about clinical improvement. In this study, agreement among raters (children, parents, therapists, and IEs) about treatment response over the course of a 14-week clinical trial for pediatric obsessive-compulsive disorder (OCD) was examined in order to determine the utility of nonblind clinician and patient ratings of treatment response.

Metastatic Clear-cell Renal Carcinoma to the Parotid ANZ Journal of Surgery. Oct, 2012 | Pubmed ID: 23025682

Targeted MicroRNA Expression in Dairy Cattle Directs Production of Î²-lactoglobulin-free, High-casein Milk Proceedings of the National Academy of Sciences of the United States of America. Oct, 2012 | Pubmed ID: 23027958 Milk from dairy cows contains the protein Î²-lactoglobulin (BLG), which is not present in human milk. As it is a major milk allergen, we wished to decrease BLG levels in milk by RNAi. In vitro screening of 10 microRNAs (miRNAs), either individually or in tandem combinations, identified several that achieved as much as a 98% knockdown of BLG. One tandem construct was expressed in the mammary gland of an ovine BLG-expressing mouse model, resulting in 96% knockdown of ovine BLG in milk. Following this in vivo validation, we produced a transgenic calf, engineered to express these tandem miRNAs. Analysis of hormonally induced milk from this calf demonstrated absence of BLG and a concurrent increase of all casein milk proteins. The findings demonstrate miRNA-mediated depletion of an allergenic milk protein in cattle and validate targeted miRNA expression as an effective strategy to alter milk composition and other livestock traits.

Preoperative Assessment in the Elderly: Evaluation of a New Clinical Service Scottish Medical Journal. Nov, 2012 | Pubmed ID: 23028174 Older people represent the fastest growing sector of society and a growing proportion of those undergoing elective surgery. Older people are at the highest risk of increased length of stay and postoperative complications. We evaluated the development of a nurse-led multidimensional preoperative assessment for older people. An older people's preassessment nurse reviewed consecutive patients undergoing elective surgery who met the inclusion criteria. In the first five months control phase, assessment was not acted on. Following the intervention, patients were referred to appropriate specialties for input. A total of 141 patients were reviewed before and 172 patients reviewed after the introduction of the pilot. Length of stay was reduced from 8.9 to 4.9 days after the introduction of the pilot (P < 0.001). Delays were reduced from 9.9% to 2.3% (P = 0.004) and fewer procedures were cancelled at pre-assessment (17.7% before, 5.2% after; P < 0.001). Serious postoperative complications were reduced from 8.5% to 2.3% (P = 0.01). Coordinated multidisciplinary preoperative assessment in the elderly may reduce complications and length of stay.

Utility of the New Rheumatoid Arthritis 2010 ACR/EULAR Classification Criteria in Routine Clinical Care BMJ Open. 2012 | Pubmed ID: 23035013 The new 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for rheumatoid arthritis (RA) have been designed to classify early onset RA, but has not been studied to identify RA in patients with arthritis seen in routine clinical care where correct 'classification' of patients, when they are not selected for having RA would be important.

Immediate Effects of a Brief Mindfulness-based Body Scan on Patients with Chronic Pain Journal of Behavioral Medicine. Nov, 2012 | Pubmed ID: 23129105 Mindfulness-based stress reduction (MBSR) has benefits for those with chronic pain. MBSR typically entails an intensive 8-week intervention. The effects of very brief mindfulness interventions are unknown. Among those with chronic pain, the immediate effects of a 10Â min mindfulness-based body scan were compared with a control intervention. Fifty-five adult outpatients were randomly assigned to either: (1) mindfulness-based body scan (nÂ =Â 27) or (2) a reading about natural history (control group, nÂ =Â 28), provided via a 10Â min audio-recording. Interventions were delivered twice across 24Â h; once in the clinic and once in participants' 'normal' environment. Immediately before and after listening to the recording, participants rated pain severity, pain related distress, perceived ability for daily activities, perceived likelihood of pain interfering with social relations, and mindfulness. In the clinic, there was a significant reduction in ratings for pain related distress and for pain interfering with social relations for the body scan group compared with the control group (pÂ =Â 0.005; pÂ =Â 0.036, respectively). In the normal environment none of the ratings were significantly different between the groups. These data suggest that, in a clinic setting, a brief body scan has immediate benefits for those experiencing chronic pain. These benefits need to be confirmed in the field.

Discovery of a Fourth Evolutionary Lineage of Phytophthora Ramorum: EU2 Fungal Biology. Nov, 2012 | Pubmed ID: 23153808 Phytophthora ramorum is a recently introduced, aggressive Phytophthora species that has caused extensive mortality of oak and tanoak trees in the western USA and Japanese larch trees in the UK. P. ramorum is also present on Rhododendron, Camellia, and Viburnum in the nursery industry, which is thought to have been the pathway for its spread into new geographic regions including forests and natural ecosystems. Three lineages of P. ramorum have been described, informally designated EU1, NA1, and NA2, and each lineage is believed to originate from an as yet unknown exotic centre of origin. Preliminary SSR and sequence analysis of isolates from a UK P. ramorum survey revealed seven isolates with profiles that did not match the previously known lineages. Detailed SSR and multilocus sequence analysis of these isolates are presented, allowing us to assign these isolates to a new P. ramorum lineage, designated EU2. Although the known geographical origin of these isolates is currently limited to Northern Ireland and western Scotland, the EU2 lineage isolates have been obtained from four different host plants, including Japanese larch. All isolates are of A1 compatibility type, which implies that this finding does not increase the risk of outcrossing with the EU1 lineage isolates already present in the UK. The oldest EU2 strain was isolated in 2007 but no SSR-based intraEU2 lineage genotypic diversity was detected. The combination of these elements points to a recent introduction, despite emergency phytosanitary measures to control introduction and spread. A PCR-RFLP method for the rapid identification of EU2 lineage isolates is presented.

Social Accountability for Long-term Care Organizations: a Leadership and Mission Imperative Health Progress (Saint Louis, Mo.). Nov-Dec, 2012 | Pubmed ID: 23173543

Implementation of Portfolio Assessment of Student Competence in Two Dental School Populations Journal of Dental Education. Dec, 2012 | Pubmed ID: 23225675 The purpose of this article is to describe the process and procedures involved in the implementation of portfolio assessment at two dental schools. Portfolios can be defined as a purposeful collection of student work that involves reflection in which students identify gaps in their knowledge and abilities and develop strategies for correcting those gaps. Framed within the current context of dental education and the calls for change in the ways dental students are taught and assessed, these two dental schools embarked upon an assessment strategy aimed at engaging students in self-directed learning and self-assessment. Where one school chose the implementation of programmatic portfolios based on all program competencies, the other school implemented portfolio assessment around specific program competencies not typically captured easily with traditional assessment measures such as ethics and ethical decision making. In a competency-based dental curriculum in which competence has been defined as the ability to accurately self-assess, it makes sense that strategies aimed at developing the skill of self-assessment should be the goal of every dental education program.

"Decentering" Reflects Psychological Flexibility in People with Chronic Pain and Correlates with Their Quality of Functioning Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. Jul, 2013 | Pubmed ID: 22545976 Objective: Acceptance and mindfulness-based treatments for chronic pain attempts to alter the impact of pain-related thoughts and feelings on behavior without necessarily changing the thoughts and feelings themselves. A process called "decentering" appears relevant to these treatments because it includes the capacity to observe thoughts and feelings from a detached perspective, as transient events in the mind, that do not necessarily reflect reality or the self. This study examines relations of decentering with other processes related to "psychological flexibility" and the daily functioning of people with chronic pain. Method: Consecutive adults seeking treatment for chronic pain (N = 150) provided data for the study by completing a set of measures, including a measure of decentering, the Experiences Questionnaire (EQ). Results: The EQ demonstrated adequate internal consistency reliability, and correlation results supported its validity. Decentering significantly correlated with anxiety, depression, and psychosocial disability. In multiple regression analyses it added a significant increment to explained variance in the prediction of depression and psychosocial disability. Across all measures of functioning, pain acceptance and decentering combined accounted for an average of 23.6% of variance while pain accounted for 2.5%. Conclusions: People with chronic pain may benefit from the capacity to contact their thoughts and feelings from a perspective as a "separate observer," to see them as transient, and to experience them as cognitively "defused." (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Testosterone-related Cortical Maturation Across Childhood and Adolescence Cerebral Cortex (New York, N.Y. : 1991). Jun, 2013 | Pubmed ID: 22617851 Neuroendocrine theories of brain development hold testosterone as the predominant factor mediating sex-specific cortical growth and the ensuing lateralization of hemispheric function. However, studies to date have focussed on prenatal testosterone rather than pubertal changes in testosterone. Yet, animal studies have shown a high density of androgen-sensitive receptors in multiple key cortical areas, and puberty is known to coincide with both a significant rise in testosterone and the emergence of behavioral sex differences, suggesting peripubertal influences of testosterone on brain development. Here, we used linear mixed models to examine sex-specific cortical maturation associated with changes in testosterone levels in a longitudinal sample of developmentally healthy children and adolescents. A significant "sex by age by testosterone" interaction on cortical thickness (CTh) involving widespread areas of the developing brain was found. Testosterone levels were associated with CTh changes in regions of the left hemisphere in males and of the right hemisphere in females. In both sexes, the relationship between testosterone and CTh varied across the age span. These findings show the association between testosterone and CTh to be complex, highly dynamic, and to vary, depending on sex and age; they also suggest sex-related hemispheric lateralization effects of testosterone in humans.

Genome-wide Association Study of Obsessive-compulsive Disorder Molecular Psychiatry. Jul, 2013 | Pubmed ID: 22889921 Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469â€‰410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 Ã— 10(-6) and P=3.44 Ã— 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 Ã— 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 Ã— 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P

Ecology of Zoonotic Infectious Diseases in Bats: Current Knowledge and Future Directions Zoonoses and Public Health. Feb, 2013 | Pubmed ID: 22958281 Bats are hosts to a range of zoonotic and potentially zoonotic pathogens. Human activities that increase exposure to bats will likely increase the opportunity for infections to spill over in the future. Ecological drivers of pathogen spillover and emergence in novel hosts, including humans, involve a complex mixture of processes, and understanding these complexities may aid in predicting spillover. In particular, only once the pathogen and host ecologies are known can the impacts of anthropogenic changes be fully appreciated. Cross-disciplinary approaches are required to understand how host and pathogen ecology interact. Bats differ from other sylvatic disease reservoirs because of their unique and diverse lifestyles, including their ability to fly, often highly gregarious social structures, long lifespans and low fecundity rates. We highlight how these traits may affect infection dynamics and how both host and pathogen traits may interact to affect infection dynamics. We identify key questions relating to the ecology of infectious diseases in bats and propose that a combination of field and laboratory studies are needed to create data-driven mechanistic models to elucidate those aspects of bat ecology that are most critical to the dynamics of emerging bat viruses. If commonalities can be found, then predicting the dynamics of newly emerging diseases may be possible. This modelling approach will be particularly important in scenarios when population surveillance data are unavailable and when it is unclear which aspects of host ecology are driving infection dynamics.

Francisella Tularensis Alters Human Neutrophil Gene Expression: Insights into the Molecular Basis of Delayed Neutrophil Apoptosis Journal of Innate Immunity. 2013 | Pubmed ID: 22986450 We demonstrated recently that Francisella tularensis profoundly impairs human neutrophil apoptosis, but how this is achieved is largely unknown. Herein we used human oligonucleotide microarrays to test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, and now demonstrate that F. tularensis live vaccine strain (LVS) caused significant changes in neutrophil gene expression over a 24-hour time period relative to the uninfected controls. Of approximately 47,000 genes analyzed, 3,435 were significantly up- or downregulated by LVS, including 365 unique genes associated with apoptosis and cell survival. Specific targets in this category included genes asso-ciated with the intrinsic and extrinsic apoptotic pathways (CFLAR, TNFAIP3, TNFRSF10D, SOD2, BCL2A1, BIRC4, PIM2, TNFSF10, TNFRSF10C, CASP2 and CASP8) and genes that act via the NFÄ¸B pathway and other mechanisms to prolong cell viability (NFKB1, NFKB2 and RELA, IL1B, CAST, CDK2,GADD45B, BCL3, BIRC3, CDK2, IL1A, PBEF1, IL6, CXCL1, CCL4 and VEGF). The microarray data were confirmed by qPCR and pathway analysis. Moreover, we demonstrate that the X-linked inhibitor of apoptosis protein remained abundant in polymorphonuclear leukocytes over 48 h of LVS infection, whereas BAX mRNA and protein were progressively downregulated. These data strongly suggest that antiapoptotic and prosurvival mechanisms collaborate to sustain the viability of F. tularensis--infected neutrophils.

Application of a Rapid, Simple, and Accurate Adenovirus-based Method to Compare PET Reporter Gene/PET Reporter Probe Systems Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging. Jun, 2013 | Pubmed ID: 23054556 This study aims to use a simple, quantitative method to compare the HSV1sr39TK/(18)â€‰F-FHBG PET reporter gene/PET reporter probe (PRG/PRP) system with PRGs derived from human nucleoside kinases.

Acceptance and Values-based Treatment of Adolescents with Chronic Pain: Outcomes and Their Relationship to Acceptance Journal of Pediatric Psychology. Jan-Feb, 2013 | Pubmed ID: 23071352 Psychological treatments for pediatric chronic pain are moderately effective. However, there have been few studies of the psychological processes associated with treatment response. This study examines the effects of Acceptance and Commitment Therapy (ACT) treatment on a severely disabled group of adolescents with chronic pain, examining relationships between outcome and acceptance.

Brief Report: Social Disability in Autism Spectrum Disorder: Results from Research Units on Pediatric Psychopharmacology (RUPP) Autism Network Trials Journal of Autism and Developmental Disorders. Mar, 2013 | Pubmed ID: 23104617 There is growing interest in measuring social disability as a core element of autism spectrum disorders in medication trials. We conducted a secondary analysis on the Aberrant Behavior Checklist Social Withdrawal subscale using data from two federally-funded, multi-site, randomized trials with risperidone. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. Study 2 included 49 subjects assigned to risperidone only and 75 subjects assigned to risperidone plus parent training. After 8 weeks of treatment, all active treatments were superior to placebo (effect sizes ranging from 0.42 to 0.65). The findings suggest that the Social Withdrawal subscale may be a useful measure of social disability in acute treatment trials.

Science, Technology, Engineering, and Mathematics (STEM) Participation Among College Students with an Autism Spectrum Disorder Journal of Autism and Developmental Disorders. Jul, 2013 | Pubmed ID: 23114569 Little research has examined the popular belief that individuals with an autism spectrum disorder (ASD) are more likely than the general population to gravitate toward science, technology, engineering, and mathematics (STEM) fields. This study analyzed data from the National Longitudinal Transition Study-2, a nationally representative sample of students with an ASD in special education. Findings suggest that students with an ASD had the highest STEM participation rates although their college enrollment rate was the third lowest among 11 disability categories and students in the general population. Disproportionate postsecondary enrollment and STEM participation by gender, family income, and mental functioning skills were found for young adults with an ASD. Educational policy implications are discussed.

The Occurrence of Semicarbazide in the Meat and Shell of Bangladeshi Fresh-water Shrimp Food Chemistry. Feb, 2013 | Pubmed ID: 23194563 There is evidence that semicarbazide (SEM), a marker for the banned nitrofuran nitrofurazone, can arise from other, unrelated sources. Recently, Belgium rejected 54 consignments of Bangladeshi freshwater shrimp (Macrobrachium rosenbergii), following a laboratory decision to test meat and exoskeleton combined. To study the possible natural occurrence of SEM in wild shrimp, samples were collected and analysed from 29 sites across Bangladesh. SEM (

Nanowell-trapped Charged Ligand-bearing Nanoparticle Surfaces: a Novel Method of Enhancing Flow-resistant Cell Adhesion Advanced Healthcare Materials. Jul, 2013 | Pubmed ID: 23225491 Assuring cell adhesion to an underlying biomaterial surface is vital in implant device design and tissue engineering, particularly under circumstances where cells are subjected to potential detachment from overriding fluid flow. Cell-substrate adhesion is a highly regulated process involving the interplay of mechanical properties, surface topographic features, electrostatic charge, and biochemical mechanisms. At the nanoscale level, the physical properties of the underlying substrate are of particular importance in cell adhesion. Conventionally, natural, pro-adhesive, and often thrombogenic, protein biomaterials are frequently utilized to facilitate adhesion. In the present study, nanofabrication techniques are utilized to enhance the biological functionality of a synthetic polymer surface, polymethymethacrylate, with respect to cell adhesion. Specifically we examine the effect on cell adhesion of combining: 1. optimized surface texturing, 2. electrostatic charge and 3. cell adhesive ligands, uniquely assembled on the substrata surface, as an ensemble of nanoparticles trapped in nanowells. Our results reveal that the ensemble strategy leads to enhanced, more than simply additive, endothelial cell adhesion under both static and flow conditions. This strategy may be of particular utility for enhancing flow-resistant endothelialization of blood-contacting surfaces of cardiovascular devices subjected to flow-mediated shear.

Mutation of a Zinc-binding Residue in the Glycine Receptor Î±1 Subunit Changes Ethanol Sensitivity in Vitro and Alcohol Consumption in Vivo The Journal of Pharmacology and Experimental Therapeutics. Feb, 2013 | Pubmed ID: 23230213 Ethanol is a widely used drug, yet an understanding of its sites and mechanisms of action remains incomplete. Among the protein targets of ethanol are glycine receptors (GlyRs), which are potentiated by millimolar concentrations of ethanol. In addition, zinc ions also modulate GlyR function, and recent evidence suggests that physiologic concentrations of zinc enhance ethanol potentiation of GlyRs. Here, we first built a homology model of a zinc-bound GlyR using the D80 position as a coordination site for a zinc ion. Next, we investigated in vitro the effects of zinc on ethanol action at recombinant wild-type (WT) and mutant Î±1 GlyRs containing the D80A substitution, which eliminates zinc potentiation. At D80A GlyRs, the effects of 50 and 200 mM ethanol were reduced as compared with WT receptors. Also, in contrast to what was seen with WT GlyRs, neither adding nor chelating zinc changed the magnitude of ethanol enhancement of mutant D80A receptors. Next, we evaluated the in vivo effects of the D80A substitution by using heterozygous Glra1(D80A) knock-in (KI) mice. The KI mice showed decreased ethanol consumption and preference, and they displayed increased startle responses compared with their WT littermates. Other behavioral tests, including ethanol-induced motor incoordination and strychnine-induced convulsions, revealed no differences between the KI and WT mice. Together, our findings indicate that zinc is critical in determining the effects of ethanol at GlyRs and suggest that zinc binding at the D80 position may be important for mediating some of the behavioral effects of ethanol action at GlyRs.

Characterization of the Theta to Beta Ratio in ADHD: Identifying Potential Sources of Heterogeneity Journal of Attention Disorders. Jul, 2013 | Pubmed ID: 23264365 The goal of this study is to characterize the theta to beta ratio (THBR) obtained from electroencephalogram (EEG) measures, in a large sample of community and clinical participants with regard to (a) ADHD diagnosis and subtypes, (b) common psychiatric comorbidities, and (c) cognitive correlates.

Defining Treatment Response and Remission in Child Anxiety: Signal Detection Analysis Using the Pediatric Anxiety Rating Scale Journal of the American Academy of Child and Adolescent Psychiatry. Jan, 2013 | Pubmed ID: 23265634 To determine optimal Pediatric Anxiety Rating Scale (PARS) percent reduction and raw score cut-offs for predicting treatment response and remission among children and adolescents with anxiety disorders.

1H MRSI of Middle Frontal Gyrus in Pediatric ADHD Journal of Psychiatric Research. Apr, 2013 | Pubmed ID: 23273650 Neuroimaging studies in multiple modalities have implicated the left or right dorsolateral prefrontal cortex (here, middle frontal gyrus) in attentional functions, in ADHD, and in dopamine agonist treatment of ADHD. The far lateral location of this cortex in the brain, however, has made it difficult to study with magnetic resonance spectroscopy (MRS). We used the smaller voxel sizes of the magnetic resonance spectroscopic imaging (MRSI) variant of MRS, acquired at a steep coronal-oblique angle to sample bilateral middle frontal gyrus in 13 children and adolescents with ADHD and 13 age- and sex-matched healthy controls. Within a subsample of the ADHD patients, aspects of attention were also assessed with the Trail Making Task. In right middle frontal gyrus only, mean levels of N-acetyl-aspartateÂ +Â N-acetyl-aspartyl-glutamate (tNAA), creatineÂ +Â phosphocreatine (Cr), choline-compounds (Cho), and myo-inositol (mI) were significantly lower in the ADHD than in the control sample. In the ADHD patients, lower right middle frontal Cr was associated with worse performance on Trails A and B (focused attention, concentration, set-shifting), while the opposite relationship held true for the control group on Trails B. These findings add to evidence implicating right middle frontal cortex in ADHD. Lower levels of these multiple species may reflect osmotic adjustment to elevated prefrontal cortical perfusion in ADHD and/or a previously hypothesized defect in astrocytic production of lactate in ADHD resulting in decelerated energetic metabolism (Cr), membrane synthesis (Cho, mI), and acetyl-CoA substrate for NAA synthesis. Lower Cr levels may indicate attentional or executive impairments.

Ascaris Co-infection Does Not Alter Malaria-induced Anaemia in a Cohort of Nigerian Preschool Children Malaria Journal. 2013 | Pubmed ID: 23282136 Co-infection with malaria and intestinal parasites such as Ascaris lumbricoides is common. Malaria parasites induce a pro-inflammatory immune response that contributes to the pathogenic sequelae, such as malarial anaemia, that occur in malaria infection. Ascaris is known to create an anti-inflammatory immune environment which could, in theory, counteract the anti-malarial inflammatory immune response, minimizing the severity of malarial anaemia. This study examined whether Ascaris co-infection can minimize the severity of malarial anaemia.

Genetic and Phenotypic Divergence Between Low- and High-altitude Populations of Two Recently Diverged Cinnamon Teal Subspecies Evolution; International Journal of Organic Evolution. Jan, 2013 | Pubmed ID: 23289570 Spatial variation in the environment can lead to divergent selection between populations occupying different parts of a species' range, and ultimately lead to population divergence. The colonization of new areas can thus facilitate divergence in beneficial traits, yet with little differentiation at neutral genetic markers. We investigated genetic and phenotypic patterns of divergence between low- and high-altitude populations of cinnamon teal inhabiting normoxic and hypoxic regions in the Andes and adjacent lowlands of South America. Cinnamon teal showed strong divergence in body size (PC1; P(ST) = 0.56) and exhibited significant frequency differences in a single nonsynonymous Î±-hemoglobin amino acid polymorphism (Asn/Ser-Î±9; F(ST) = 0.60) between environmental extremes, despite considerable admixture of mtDNA and intron loci (F(ST) = 0.004-0.168). Inferences of strong population segregation were further supported by the observation of few mismatched individuals in either environmental extreme. Coalescent analyses indicated that the highlands were most likely colonized from lowland regions but following divergence, gene flow has been asymmetric from the highlands into the lowlands. Multiple selection pressures associated with high-altitude habitats, including cold and hypoxia, have likely shaped morphological and genetic divergence within South American cinnamon teal populations.

Treatment and Prognostic Factors for Long-term Outcome in Patients with Anti-NMDA Receptor Encephalitis: an Observational Cohort Study Lancet Neurology. Feb, 2013 | Pubmed ID: 23290630 Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disorder in which the use of immunotherapy and the long-term outcome have not been defined. We aimed to assess the presentation of the disease, the spectrum of symptoms, immunotherapies used, timing of improvement, and long-term outcome.

Using the Nominal Group Technique to Engage People with Chronic Pain in Health Service Development The International Journal of Health Planning and Management. Jan, 2013 | Pubmed ID: 23319399 In this methodological paper, we discuss the use of the nominal group technique to facilitate the involvement of people with chronic pain and other stakeholder groups in the design of a community-based pain management programme. On the basis of our experiences of using the technique in a study conducted in the south-west region of the UK, we explore conceptual and logistical issues relating to patient involvement in health service development, discuss political issues relating to the articulation and synthesis of different stakeholder perspectives, and provide a description of how the technique can be applied in the aforementioned context. We conclude that although the nominal group technique is not a panacea for the difficulties encountered in patient involvement, it does offer advantages over other approaches. Copyright Â© 2013 John Wiley & Sons, Ltd.

Long-term in Vivo Monitoring of Mouse and Human Hematopoietic Stem Cell Engraftment with a Human Positron Emission Tomography Reporter Gene Proceedings of the National Academy of Sciences of the United States of America. Jan, 2013 | Pubmed ID: 23319634 Positron emission tomography (PET) reporter genes allow noninvasive whole-body imaging of transplanted cells by detection with radiolabeled probes. We used a human deoxycytidine kinase containing three amino acid substitutions within the active site (hdCK3mut) as a reporter gene in combination with the PET probe [(18)F]-L-FMAU (1-(2-deoxy-2-(18)fluoro-Î²-L-arabinofuranosyl)-5-methyluracil) to monitor models of mouse and human hematopoietic stem cell (HSC) transplantation. These mutations in hdCK3mut expanded the substrate capacity allowing for reporter-specific detection with a thymidine analog probe. Measurements of long-term engrafted cells (up to 32 wk) demonstrated that hdCK3mut expression is maintained in vivo with no counter selection against reporter-labeled cells. Reporter cells retained equivalent engraftment and differentiation capacity being detected in all major hematopoietic lineages and tissues. This reporter gene and probe should be applicable to noninvasively monitor therapeutic cell transplants in multiple tissues.

Pilot Randomized Trial of Bupropion for Adolescent Methamphetamine Abuse/dependence The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine. Apr, 2013 | Pubmed ID: 23333007 To perform a pilot clinical trial of bupropion for methamphetamine abuse/dependence among adolescents.

Restless Legs Syndrome in Children with Chronic Kidney Disease Pediatric Nephrology (Berlin, Germany). May, 2013 | Pubmed ID: 23334386 Restless legs syndrome (RLS) is considerably more common among adults with chronic kidney disease (CKD) than in the general population and is associated with increased morbidity and mortality. There is limited information on RLS in children with CKD. Failure to account for conditions that might mimic RLS can lead to overdiagnosis of this syndrome.

Protein O-GlcNAcylation is a Novel Cytoprotective Signal in Cardiac Stem Cells Stem Cells (Dayton, Ohio). Apr, 2013 | Pubmed ID: 23335157 Clinical trials demonstrate the regenerative potential of cardiac stem cell (CSC) therapy in the postinfarcted heart. Despite these encouraging preliminary clinical findings, the basic biology of these cells remains largely unexplored. The principal requirement for cell transplantation is to effectively prime them for survival within the unfavorable environment of the infarcted myocardium. In the adult mammalian heart, the Î²-O-linkage of N-acetylglucosamine (i.e., O-GlcNAc) to proteins is a unique post-translational modification that confers cardioprotection from various otherwise lethal stressors. It is not known whether this signaling system exists in CSCs. In this study, we demonstrate that protein O-GlcNAcylation is an inducible stress response in adult murine Sca-1(+) /lin(-) CSCs and exerts an essential prosurvival role. Posthypoxic CSCs responded by time-dependently increasing protein O-GlcNAcylation upon reoxygenation. We used pharmacological interventions for loss- and gain-of-function, that is, enzymatic inhibition of O-GlcNAc transferase (OGT) (adds the O-GlcNAc modification to proteins) by TT04, or inhibition of OGA (removes O-GlcNAc) by thiamet-G (ThG). Reduction in the O-GlcNAc signal (via TT04, or OGT gene deletion using Cre-mediated recombination) significantly sensitized CSCs to posthypoxic injury, whereas augmenting O-GlcNAc levels (via ThG) enhanced cell survival. Diminished O-GlcNAc levels render CSCs more susceptible to the onset of posthypoxic apoptotic processes via elevated poly(ADP-ribose) polymerase cleavage due to enhanced caspase-3/7 activation, whereas promoting O-GlcNAcylation can serve as a pre-emptive antiapoptotic signal regulating the survival of CSCs. Thus, we report the primary demonstration of protein O-GlcNAcylation as an important prosurvival signal in CSCs, which could enhance CSC survival prior to in vivo autologous transfer.

Stepwise Colonization of the Andes by Ruddy Ducks and the Evolution of Novel Î²-globin Variants Molecular Ecology. Mar, 2013 | Pubmed ID: 23346994 Andean uplift played a key role in Neotropical bird diversification, yet past dispersal and genetic adaptation to high-altitude environments remain little understood. Here we use multilocus population genetics to study population history and historical demographic processes in the ruddy duck (Oxyura jamaicensis), a stiff-tailed diving duck comprising three subspecies distributed from Canada to Tierra del Fuego and inhabiting wetlands from sea level to 4500 m in the Andes. We sequenced the mitochondrial DNA, four autosomal introns and three haemoglobin genes (Î±(A), Î±(D), Î²(A)) and used isolation-with-migration (IM) models to study gene flow between North America and South America, and between the tropical and southern Andes. Our analyses indicated that ruddy ducks dispersed first from North America to the tropical Andes, then from the tropical Andes to the southern Andes. While no nonsynonymous substitutions were found in either Î± globin gene, three amino acid substitutions were observed in the Î²(A) globin. Based on phylogenetic reconstruction and power analysis, the first Î²(A) substitution, found in all Andean individuals, was acquired when ruddy ducks dispersed from low altitude in North America to high altitude in the tropical Andes, whereas the two additional substitutions occurred more recently, when ruddy ducks dispersed from high altitude in the tropical Andes to low altitude in the southern Andes. This stepwise colonization pattern accompanied by polarized Î²(A) globin amino acid replacements suggest that ruddy ducks first acclimatized or adapted to the Andean highlands and then again to the lowlands. In addition, ruddy ducks colonized the Andean highlands via a less common route as compared to other waterbird species that colonized the Andes northwards from the southern cone of South America.

Impact of Periodontitis on Oral Health-related Quality of Life Journal of Dentistry. Apr, 2013 | Pubmed ID: 23357646 To investigate the impact of chronic periodontitis on oral health-related quality of life (OHRQoL) using the full version of the Oral Health Impact Profile (OHIP-49) and the Oral Health Quality of Life-UK (OHQoL-UK) questionnaires.

Global and Regional Burden of Hospital Admissions for Severe Acute Lower Respiratory Infections in Young Children in 2010: a Systematic Analysis Lancet. Apr, 2013 | Pubmed ID: 23369797 The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010.

Feeding Problems and Nutrient Intake in Children with Autism Spectrum Disorders: A Meta-analysis and Comprehensive Review of the Literature Journal of Autism and Developmental Disorders. Feb, 2013 | Pubmed ID: 23371510 We conducted a comprehensive review and meta-analysis of research regarding feeding problems and nutrient status among children with autism spectrum disorders (ASD). The systematic search yielded 17 prospective studies involving a comparison group. Using rigorous meta-analysis techniques, we calculated the standardized mean difference (SMD) with standard error and corresponding odds ratio (OR) with 95Â % confidence intervals (CI). Results indicated children with ASD experienced significantly more feeding problems versus peers, with an overall SMD of 0.89 (0.08) and a corresponding OR of 5.11, 95Â % CI 3.74-6.97. Nutrient analyses indicated significantly lower intake of calcium (SMD: -0.65 [0.29]; OR: 0.31, 95Â % CI 0.11-0.85) and protein (SMD: -0.58 [0.25]; OR: 0.35, 95Â % CI: 0.14-0.56) in ASD. Future research must address critical questions regarding the cause, long-term impact, and remediation of atypical feeding in this population.

The Epidemiology and Clinical Characteristics of Young Children Hospitalized with Respiratory Syncytial Virus Infections in Guatemala (2007-2010) The Pediatric Infectious Disease Journal. Feb, 2013 | Pubmed ID: 23380666 BACKGROUND:: There have been few population-based studies from Central America on respiratory syncytial virus (RSV) infections in young children. We report population-based incidence rates and describe epidemiological and clinical characteristics of children < 5 years old hospitalized with RSV infections in Guatemala. METHODS:: Prospective, active hospital-based surveillance for acute respiratory infections in children

Tamm-Horsfall Protein Zeigten Zu Basolateraler Der Dicke Aufsteigende Gliedmaßen, Interstitium Und Kreislauf Während Der Wiederherstellung Nach Akute Kidney Injury American Journal of Physiology. Renal Physiology. Feb, 2013 | Pubmed ID: 23389456 Tamm-Horsfall-Protein (THP) ist ein Glykoprotein, das normalerweise auf die apikale Membran-Domäne der Niere dicken aufsteigenden Gliedmaßen (TAL) ausgerichtet. Wir haben zuvor gezeigt, dass THP Tal Schutz zu proximalen Tubuli gegen akute Nieren Schädigung (AKI) über eine mögliche Nebensprechen zwischen den zwei funktionell unterschiedlichen röhrenförmigen Segmenten verleiht. Umfang, Zeitpunkt, Spezifität und funktionelle Auswirkungen der Basolateraler Translokation von THP während AKI bleiben jedoch unklar. Anhand einer Ischämie-Reperfusion (IRI) Modell murine aki zeigen wir hier, dass THP Ausdruck im TAL unten-geregelt auf dem Höhepunkt der Verletzung ist es deutlich herraufreguliert 48 Stunden nach IRI zwar. Konfokale Immunofluoreszenz und Immunoelectron Mikroskopie zeigen eine große Umleitung von THP während der Wiederherstellung der apikale Membran-Domäne Tal in Richtung Basolateraler Domäne, Interstitium und basalen Fach S3-Segmente. Dies entspricht mit erhöhter THP im Serum, aber nicht im Urin. Die insgesamt epitheliale Polarität der TAL-Zellen ändert sich nicht, wie Sie durch richtige apikale gezielte NKCC2 und Basolateraler Ausrichtung der Na +-K +-ATPase. Im Vergleich zu den Wildtyp, zeigen THP-/-Mäuse eine deutlich verzögerte renale Erholung nach IRI, wegen möglicherweise reduzierten Funkentstörung von THP Pro-inflammatorische Zytokine und Chemokine wie MCP-1 während der Wiederherstellung. Zusammengenommen, unsere Daten deuten darauf hin, dass THP Umverteilung in das TAL nachdem AKI ein Protein-spezifisches Event ist und erhöhte interstitielle Präsenz negativ die sich entwickelnden entzündliche Signalisierung im benachbarten proximalen Tubuli reguliert, dadurch Nieren Wiederherstellung. Die Erhöhung der Serum THP kann als prognostische Biomarker für die Wiederherstellung von AKI verwendet werden.

Interobserver Variability Using a Commercially Available System of Archived Digital Radiography with Integrated Computer-assisted Measurements for Scoliosis Cobb Angles Journal of Pediatric Orthopedics. Mar, 2013 | Pubmed ID: 23389571 The purpose of this study was to determine if digital enhancements could improve upon published and interobserver variability for Cobb angle measurements of idiopathic scoliosis using a commercially available PACS system. The study also sought to determine if experience of the observer affected overall variability and to evaluate the time required to measure Cobb angles using 3 different techniques. As the decision for scoliosis treatment requires serial radiographic measurements by 1 or more observers at different times, precise landmark identification and curve measurement should decrease variability and improve accuracy.

Ovarian Hormones and the Heterogeneous Receptor Mechanisms Mediating the Discriminative Stimulus Effects of Ethanol in Female Rats Behavioural Pharmacology. Apr, 2013 | Pubmed ID: 23399883 Past studies have suggested that progesterone-derived ovarian hormones contribute to the discriminative stimulus effects of ethanol, particularly via progesterone metabolites that act at Î³-aminobutyric acid type A (GABA(A)) receptors. It is unknown whether loss of ovarian hormones in women, for example, after menopause, may be associated with altered receptor mediation of the effects of ethanol. The current study measured the substitution of allopregnanolone, pregnanolone, pentobarbital, midazolam, dizocilpine, TFMPP, and RU 24969 in female sham and ovariectomized rats trained to discriminate 1.0 g/kg ethanol from water. The groups did not differ in the substitution of GABA(A)-positive modulators (barbiturates, benzodiazepines, neuroactive steroids) or the N-methyl-D-aspartate receptor antagonist dizocilpine. Similarly, blood-ethanol concentration did not differ between the groups, and plasma adrenocorticotropic hormone, progesterone, pregnenolone, and deoxycorticosterone were unchanged 30 min after administration of 1.0 g/kg ethanol or water. However, substitution of neuroactive steroids and RU 24969, a 5-hydroxytryptamine (5-HT)(1A/1B) receptor agonist, was lower than observed in previous studies of male rats, and TFMPP substitution was decreased in ovariectomized rats. Ovarian hormones appear to contribute to 5-HT receptor mediation of the discriminative stimulus effects of ethanol in rats.

Genome-wide Association Study of Obsessive-compulsive Disorder Molecular Psychiatry. Jul, 2013 | Pubmed ID: 23399913

Exploring the Manifestations of Anxiety in Children with Autism Spectrum Disorders Journal of Autism and Developmental Disorders. Feb, 2013 | Pubmed ID: 23400347 This study explores the manifestation and measurement of anxiety symptoms in 415 children with ASDs on a 20-item, parent-rated, DSM-IV referenced anxiety scale. In both high and low-functioning children (IQ above vs. below 70), commonly endorsed items assessed restlessness, tension and sleep difficulties. Items requiring verbal expression of worry by the child were rarely endorsed. Higher anxiety was associated with functional language, IQ above 70 and higher scores on several other behavioral measures. Four underlying factors emerged: Generalized Anxiety, Separation Anxiety, Social Anxiety and Over-arousal. Our findings extend our understanding of anxiety across IQ in ASD and provide guidance for improving anxiety outcome measurement.

Nutrient Transporters: the Achilles' Heel of Anabolism Trends in Endocrinology and Metabolism: TEM. Apr, 2013 | Pubmed ID: 23402769 Highly proliferative cells, including cancer cells, require a constant supply of molecular building blocks to support their growth. To acquire substrates such as glucose and amino acids from the extracellular space, dividing cells rely on transporter proteins in the plasma membrane. Numerous studies link transcriptional and post-translational control of nutrient transporter expression with proliferation, highlighting the importance of nutrient transporters in both physiologic and pathologic growth. Here we review recent work that spotlights the crucial role of nutrient transporters in cell growth and proliferation, discuss post-translational mechanisms for coordinating expression of different transporters, and consider the therapeutic potential of targeting these proteins in cancer and other diseases characterized by inappropriate cell division.

Flexion and Extension Radiographic Evaluation for the Clearance of Potential Cervical Spine Injures in Trauma Patients European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. Jul, 2013 | Pubmed ID: 23404352 Flexion and extension radiographs are often used in the setting of trauma to clear a cervical spine injury. The utility of such tests, however, remains to be determined. We hypothesized that in patients who underwent a negative computed tomography (CT) cervical spine scan, flexion and extension radiographs did not yield useful additional information.

Methicillin-resistant Staphylococcus Aureus Colonization Among Pediatric Health Care Workers from Different Outpatient Settings American Journal of Infection Control. Feb, 2013 | Pubmed ID: 23433983 Staphylococcus aureus colonization rates in pediatric health care workers from different types of outpatient settings were determined from December 2008 through May 2010. Colonization rates for Staphylococcus aureus and, specifically, methicillin-resistant Staphylococcus aureus (MRSA) rates were similar to the rates that have been reported for the general population. The predominant MRSA pulsed-field gel electrophoresis type associated with colonization in these health care workers is not MRSA USA300.

Popcorn Coaching Physician Executive. Jan-Feb, 2013 | Pubmed ID: 23437760

The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-year Follow-up Journal of the American Academy of Child and Adolescent Psychiatry. Mar, 2013 | Pubmed ID: 23452683 To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3 to 5 up to 9 to 12 years during a 6-year follow-up after the original Preschool ADHD Treatment Study (PATS).

Longitudinal Relationship Between Personal CO and Personal PM2.5 Among Women Cooking with Woodfired Cookstoves in Guatemala PloS One. 2013 | Pubmed ID: 23468847 Household air pollution (HAP) due to solid fuel use is a major public health threat in low-income countries. Most health effects are thought to be related to exposure to the fine particulate matter (PM) component of HAP, but it is currently impractical to measure personal exposure to PM in large studies. Carbon monoxide (CO) has been shown in cross-sectional analyses to be a reliable surrogate for particles

Molecular and Cellular Pathology of Very-long-chain Acyl-CoA Dehydrogenase Deficiency Molecular Genetics and Metabolism. May, 2013 | Pubmed ID: 23480858 Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is diagnosed in the US through newborn screening (NBS). NBS often unequivocally identifies affected individuals, but a growing number of variant patterns can represent mild disease or heterozygous carriers.

Molecular Epidemiology of Vancomycin-resistant Enterococcal Bacteraemia: Results from the Canadian Nosocomial Infection Surveillance Program, 1999-2009 The Journal of Antimicrobial Chemotherapy. Jul, 2013 | Pubmed ID: 23524466 Vancomycin-resistant enterococci (VRE) can be associated with serious bacteraemia. The focus of this study was to characterize the molecular epidemiology of VRE from bacteraemia cases that were isolated from 1999 to 2009 as part of Canadian Nosocomial Infection Surveillance Program (CNISP) surveillance activities.

Estimation of the National Disease Burden of Influenza-associated Severe Acute Respiratory Illness in Kenya and Guatemala: a Novel Methodology PloS One. 2013 | Pubmed ID: 23573177 Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden.

Loss of TSC2 Confers Resistance to Ceramide and Nutrient Deprivation Oncogene. Apr, 2013 | Pubmed ID: 23604129 Nutrient stress that produces quiescence and catabolism in normal cells is lethal to cancer cells, because oncogenic mutations constitutively drive anabolism. One driver of biosynthesis in cancer cells is the mammalian target of rapamycin complex 1 (mTORC1) signaling complex. Activating mTORC1 by deleting its negative regulator tuberous sclerosis complex 2 (TSC2) leads to hypersensitivity to glucose deprivation. We have previously shown that ceramide kills cells in part by triggering nutrient transporter loss and restricting access to extracellular amino acids and glucose, suggesting that TSC2-deficient cells would be hypersensitive to ceramide. However, murine embryonic fibroblasts (MEFs) lacking TSC2 were highly resistant to ceramide-induced death. Consistent with the observation that ceramide limits access to both amino acids and glucose, TSC2(-/-) MEFs also had a survival advantage when extracellular amino acids and glucose were both reduced. As TSC2(-/-) MEFs were resistant to nutrient stress despite sustained mTORC1 activity, we assessed whether mTORC1 signaling might be beneficial under these conditions. In low amino acid and glucose medium, and following ceramide-induced nutrient transporter loss, elevated mTORC1 activity significantly enhanced the adaptive upregulation of new transporter proteins for amino acids and glucose. Strikingly, the introduction of oncogenic Ras abrogated the survival advantage of TSC2(-/-) MEFs upon ceramide treatment most likely by increasing nutrient demand. These results suggest that, in the absence of oncogene-driven biosynthetic demand, mTORC1-dependent translation facilitates the adaptive cellular response to nutrient stress.Oncogene advance online publication, 22 April 2013; doi:10.1038/onc.2013.139.

Meta-analysis of Association Between Obsessive-compulsive Disorder and the 3' Region of Neuronal Glutamate Transporter Gene SLC1A1 American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics. Jun, 2013 | Pubmed ID: 23606572 The neuronal glutamate transporter gene SLC1A1 is a candidate gene for obsessive-compulsive disorder (OCD) based on linkage studies and convergent evidence implicating glutamate in OCD etiology. The 3' end of SLC1A1 is the only genomic region with consistently demonstrated OCD association, especially when analyzing male-only probands. However, specific allele associations have not been consistently replicated, and recent OCD genome-wide association and meta-analysis studies have not incorporated all previously associated SLC1A1 SNPs. To clarify the nature of association between SLC1A1 and OCD, pooled analysis was performed on all available relevant raw study data, comprising a final sample of 815 trios, 306 cases and 634 controls. This revealed weak association between OCD and one of nine tested SLC1A1 polymorphisms (rs301443; uncorrected Pâ€‰=â€‰0.046; non-significant corrected P). Secondary analyses of male-affecteds only (Nâ€‰=â€‰358 trios and 133 cases) demonstrated modest association between OCD and a different SNP (rs12682807; uncorrected Pâ€‰=â€‰0.012; non-significant corrected P). Findings of this meta-analysis are consistent with the trend of previous candidate gene studies in psychiatry and do not clarify the putative role of SLC1A1 in OCD pathophysiology. Nonetheless, it may be important to further examine the potential associations demonstrated in this amalgamated sample, especially since the SNPs with modest associations were not included in the more highly powered recent GWAS or in a past meta-analysis including five SLC1A1 polymorphisms. This study underscores the need for much larger sample sizes in future genetic association studies and suggests that next-generation sequencing may be beneficial in examining the potential role of rare variants in OCD.

Shear- Vs. Nanotopography-guided Control of Growth of Endothelial Cells on RGD-nanoparticle-nanowell Arrays Journal of Biological Engineering. 2013 | Pubmed ID: 23607894 Endothelialization of therapeutic cardiovascular implants is essential for their intravascular hemocompatibility. We previously described a novel nanowell-RGD-nanoparticle ensemble, which when applied to surfaces led to enhanced endothelialization and retention under static conditions and low flow rates. In the present study we extend our work to determine the interrelated effects of flow rate and the orientation of ensemble-decorated surface arrays on the growth, adhesion and morphology of endothelial cells. Human umbilical vascular endothelial cells (HUVECs) were grown on array surfaces with either 1 Î¼m Ã— 5 Î¼m spacing ("parallel to flow") and 5 Î¼m Ã— 1 Î¼m spacing ("perpendicular to flow") and were exposed to a range of shear stress of (0 to 4.7 Â± 0.2 dynÂ·cm-2 ), utilizing a pulsatile flow chamber. Under physiological flow (4.7 Â± 0.2 dynÂ·cm-2), RGD-nanoparticle-nanowell array patterning significantly enhanced cell adhesion and spreading compared with control surfaces and with static conditions. Furthermore, improved adhesion coincided with higher alignment to surface patterning, intimating the importance of interaction and response to the array surface as a means of resisting flow detachment. Under sub-physiological condition (1.7 Â± 0.3 dynÂ·cm-2; corresponding to early angiogenesis), nanowell-nanoparticle patterning did not provide enhanced cell growth and adhesion compared with control surfaces. However, it revealed increased alignment along the direction of flow, rather than the direction of the pattern, thus potentially indicating a threshold for cell guidance and related retention. These results could provide a cue for controlling cell growth and alignment under varying physiological conditions.

The Time of Our Lives: Reflections on the Art of Geriatric Nursing Journal of Gerontological Nursing. Jun, 2013 | Pubmed ID: 23614385

Development of a Transmission Model for Dengue Virus Virology Journal. 2013 | Pubmed ID: 23617898 Dengue virus (DENV) research has historically been hampered by the lack of a susceptible vertebrate transmission model. Recently, there has been progress towards such models using several varieties of knockout mice, particularly those deficient in type I and II interferon receptors. Based on the critical nature of the type I interferon response in limiting DENV infection establishment, we assessed the permissiveness of a mouse strain with a blunted type I interferon response via gene deficiencies in interferon regulatory factors 3 and 7 (IRF3/7 -/- -/-) with regards to DENV transmission success. We investigated the possibility of transmission to the mouse by needle and infectious mosquito, and subsequent transmission back to mosquito from an infected animal during its viremic period.

Findings from the Community Health Intervention Program in South Carolina: Implications for Reducing Cancer-Related Health Disparities Journal of Cancer Education : the Official Journal of the American Association for Cancer Education. May, 2013 | Pubmed ID: 23645547 The South Carolina Cancer Prevention and Control Research Network (SC-CPCRN) implemented the Community Health Intervention Program (CHIP) mini-grants initiative to address cancer-related health disparities and reduce the cancer burden among high-risk populations across the state. The mini-grants project implemented evidence-based health interventions tailored to the specific needs of each community. This study aims to support the SC-CPCRN's goals of moving toward greater dissemination and implementation of evidence-based programs in the community to improve public health, prevent disease, and reduce the cancer burden. Three community-based organizations were awarded $10,000 each to implement one of the National Cancer Institute's evidence-based interventions. Each group had 12Â months to complete their project. SC-CPCRN investigators and staff provided guidance, oversight, and technical assistance for each project. Grantees provided regular updates and reports to their SC-CPCRN liaisons to capture vital evaluation information. The intended CHIP mini-grant target population reach was projected to be up to 880 participants combined. Actual combined reach of the three projects reported upon completion totaled 1,072 individuals. The majority of CHIP participants were African-American females. Participants ranged in age from 19 to 81Â years. Evaluation results showed an increase in physical activity, dietary improvements, and screening participation. The success of the initiative was the result of a strong community-university partnership built on trust. Active two-way communication and an honest open dialogue created an atmosphere for collaboration. Communities were highly motivated. All team members shared a common goal of reducing cancer-related health disparities and building greater public health capacity across the state.

Is Procedural Sedation with Propofol Acceptable for Complex Imaging? A Comparison of Short Vs. Prolonged Sedations in Children Pediatric Radiology. May, 2013 | Pubmed ID: 23649207 BACKGROUND: Concerns exist in the community of non-anesthesiologist sedation providers regarding the appropriateness of prolonged sedations using propofol for outpatient procedures. OBJECTIVE: To investigate interventions required, completion rate and resource use in prolonged vs. short sedations using propofol in outpatients. MATERIALS AND METHODS: We reviewed retrospectively 213 children sedated with propofol by a non-anesthesiologist sedation service. Cohorts were composed a priori of children sedated for â‰¥1Â h and

Committed Action: An Application of the Psychological Flexibility Model to Activity Patterns in Chronic Pain The Journal of Pain : Official Journal of the American Pain Society. May, 2013 | Pubmed ID: 23651881 Whether a person with chronic pain avoids activity, persists with activity, or overexerts himself or herself is considered important to the quality of his or her daily functioning. However, results from studies of these activity patterns have not always yielded clear and consistent findings. It is suggested that applying the psychological flexibility model to activity patterns may clarify and integrate research in this area. Psychological flexibility is defined as the ability to persist or to change behavior in a setting of competing psychological influences, guided by goals, and dependent on what the situation at hand affords. One aspect of psychological flexibility that appears pertinent to chronic pain is called committed action. Committed action is essentially goal-directed, flexible persistence. The purpose of the current study was to develop a measure of committed action, the committed action questionnaire (CAQ), in people seeking treatment for chronic pain (NÂ =Â 216), to examine preliminary reliability and validity, and to test how well a summary score from the measure is able to predict patient health and functioning. Results generally support the internal consistency of the CAQ and show that it is correlated with another established component of psychological flexibility. In regression analyses the CAQ was able to account for significant variance in depression, social functioning, mental health, vitality, and general health, beyond the contributions of pain and acceptance of pain. PERSPECTIVE: The psychological flexibility model may be useful for understanding patterns of behavior in relation to chronic pain. It appears possible to assess a process in this model called committed action, and this process appears related to important aspects of functioning.

Genome Sequences of 65 Helicobacter Pylori Strains Isolated from Asymptomatic Individuals and Patients with Gastric Cancer, Peptic Ulcer Disease, or Gastritis Pathogens and Disease. Jul, 2013 | Pubmed ID: 23661595 Helicobacter pylori, inhabitant of the gastric mucosa of over half of the world population, with decreasing prevalence in the U.S., has been associated with a variety of gastric pathologies. However, the majority of H.Â pylori-infected individuals remain asymptomatic, and negative correlations between H.Â pylori and allergic diseases have been reported. Comprehensive genome characterization of H.Â pylori populations from different human host backgrounds including healthy individuals provides the exciting potential to generate new insights into the open question whether human health outcome is associated with specific H.Â pylori genotypes or dependent on other environmental factors. We report the genome sequences of 65 H.Â pylori isolates from individuals with gastric cancer, preneoplastic lesions, peptic ulcer disease, gastritis, and from asymptomatic adults. Isolates were collected from multiple locations in North America (USA and Canada) as well as from Columbia and Japan. The availability of these H.Â pylori genome sequences from individuals with distinct clinical presentations provides the research community with a resource for detailed investigations into genetic elements that correlate either positively or negatively with the epidemiology, human host adaptation, and gastric pathogenesis and will aid in the characterization of strains that may favor the development of specific pathology, including gastric cancer.

New Antibacterial Germacrene from Verbesina Negrensis Planta Medica. May, 2013 | Pubmed ID: 23670623 Several health benefits have been attributed to members of the Verbesina genus, including promotion of urinary and gastrointestinal health. Verbesina species are also reported to exhibit antibacterial, antiparasitic, and antioxidant activities. Although members of the Verbesina genus produce various pharmacologically relevant chemicals as secondary metabolites, including eudesmanes, flavonoids, guanidine alkaloids, acetylenic compounds, and germacrenes, the active compounds required for these benefits remain unknown. To investigate potential antimicrobial activities of Verbesina negrensis, crude extracts from plant aerial structures were evaluated. Following chemical fractionation, the chloroformic extract from Verbesina negrensis was subjected to bioassay-guided isolation using disk diffusion assays to determine antimicrobial activity. The active compound was characterized as 6Î²-cinnamoyloxy-1Î²-hydroxy-10Î±-metoxy-3-oxo-germacra-4,5Z-ene (1). Fractions containing 1 inhibited both Enterococcus faecalis (ATCC 29 212) and Staphylococcus aureus (ATCC 29213). The MIC for 1 was determined by microbroth dilution assay to be 64 Âµg/mL for both E. faecalis and S. aureus.

How Acceptable Are Primary Health Care Nurse Practitioners to Australian Consumers? Collegian (Royal College of Nursing, Australia). 2013 | Pubmed ID: 23678782 International evidence indicates that nurses working in primary care can provide effective care and achieve positive health outcomes for patients similar to that provided by doctors. Nurse practitioners employed in primary health care perform some tasks previously exclusive to the GP role due to their advanced skills, knowledge and training. In November 2010 Medicare provider rights and Pharmaceutical Benefits Scheme rights were provided for nurse practitioners working in private practice, and in collaboration with a medical practitioner. However, there is limited evidence about how acceptable nurse practitioners are to Australian consumers and what knowledge consumers have of the nurse practitioner role in the delivery of primary health care. The aim of this study was to examine Australian health care consumers' perceptions of nurse practitioners working in primary health care. This paper reports on the results of seven focus groups (n = 77 participants) conducted around Australia. Focus groups participants were asked how acceptable nurse practitioners are as provides of primary health care. Although there was some confusion about the role of nurse practitioners and how this role differed from other primary health care nurses, participants in the focus groups were very positive about nurse practitioners and would find them acceptable in providing primary health care.

Genome-wide Sequencing of Phytophthora Lateralis Reveals Genetic Variation Among Isolates from Lawson Cypress (Chamaecyparis Lawsoniana) in Northern Ireland FEMS Microbiology Letters. Jul, 2013 | Pubmed ID: 23678994 Phytophthora lateralis is a fungus-like (oomycete) pathogen of trees in the family Cupressaceae, including Chamaecyparis lawsoniana (Lawson cypress or Port Orford cedar). Known in North America since the 1920s, presumably having been accidentally introduced from its assumed East Asian centre of origin, until recently, this pathogen has not been identified causing disease in Europe except for a few isolated outbreaks. However, since 2010, there have been several reports of infection of C.Â lawsoniana by P.Â lateralis in the United Kingdom, including Northern Ireland. We sequenced the genomes of four isolates of P.Â lateralis from two sites in Northern Ireland in 2011. Comparison with the closely related tree and shrub pathogen P.Â ramorum (cause of ramorum disease of larch and other species in the UK) shows that P.Â lateralis shares 91.47% nucleotide sequence identity over the core conserved compartments of the genome. The genomes of the four Northern Ireland isolates are almost identical, but we identified several single-nucleotide polymorphisms (SNPs) that distinguish between isolates, thereby presenting potential molecular markers of use for tracking routes of spread and in epidemiological studies. Our data reveal very low rates of heterozygosity (compared with P.Â ramorum), consistent with inbreeding within this P.Â lateralis population.

Demonstration of Quantum Entanglement Between a Single Electron Spin Confined to an InAs Quantum Dot and a Photon Physical Review Letters. Apr, 2013 | Pubmed ID: 23679636 The electron spin state of a singly charged semiconductor quantum dot has been shown to form a suitable single qubit for quantum computing architectures with fast gate times. A key challenge in realizing a useful quantum dot quantum computing architecture lies in demonstrating the ability to scale the system to many qubits. In this Letter, we report an all optical experimental demonstration of quantum entanglement between a single electron spin confined to a single charged semiconductor quantum dot and the polarization state of a photon spontaneously emitted from the quantum dot's excited state. We obtain a lower bound on the fidelity of entanglement of 0.59Â±0.04, which is 84% of the maximum achievable given the timing resolution of available single photon detectors. In future applications, such as measurement-based spin-spin entanglement which does not require sub-nanosecond timing resolution, we estimate that this system would enable near ideal performance. The inferred (usable) entanglement generation rate is 3Ã—10(3) s(-1). This spin-photon entanglement is the first step to a scalable quantum dot quantum computing architecture relying on photon (flying) qubits to mediate entanglement between distant nodes of a quantum dot network.

Structure-dependent Complexation of Fe(3+) by Anthracyclines. 1. The Importance of Pendent Hydroxyl Functionality The Journal of Physical Chemistry. B. Jun, 2013 | Pubmed ID: 23692060 We have investigated the stability of doxorubicin and daunorubicin complexes with Fe(3+) in aqueous solution. Doxorubicin and daunorubicin are anthracycline chemotherapeutic agents that differ structurally by the presence of a hydroxymethylketone functionality in doxorubicin versus a methyl ketone moiety in daunorubicin. We demonstrate that the presence of the hydroxyl group in doxorubicin enhances its 1:1 complexation with Fe(3+) relative to that seen for daunorubicin. We utilize UV-visible absorbance, circular dichroism, fluorescence and EPR spectroscopies, molecular dynamics, and semiempirical calculations to understand how the presence of an additional hydroxyl group affects the interactions of anthracyclines with Fe(3+). Our data indicate that the binding mode of iron in the complex is different for doxorubicin and daunorubicin.

Mule/Huwe1/Arf-BP1 Suppresses Ras-driven Tumorigenesis by Preventing C-Myc/Miz1-mediated Down-regulation of P21 and P15 Genes & Development. May, 2013 | Pubmed ID: 23699408 Tumorigenesis results from dysregulation of oncogenes and tumor suppressors that influence cellular proliferation, differentiation, apoptosis, and/or senescence. Many gene products involved in these processes are substrates of the E3 ubiquitin ligase Mule/Huwe1/Arf-BP1 (Mule), but whether Mule acts as an oncogene or tumor suppressor in vivo remains controversial. We generated K14Cre;Mule(flox/flox(y)) (Mule kKO) mice and subjected them to DMBA/PMA-induced skin carcinogenesis, which depends on oncogenic Ras signaling. Mule deficiency resulted in increased penetrance, number, and severity of skin tumors, which could be reversed by concomitant genetic knockout of c-Myc but not by knockout of p53 or p19Arf. Notably, in the absence of Mule, c-Myc/Miz1 transcriptional complexes accumulated, and levels of p21CDKN1A (p21) and p15INK4B (p15) were down-regulated. In vitro, Mule-deficient primary keratinocytes exhibited increased proliferation that could be reversed by Miz1 knockdown. Transfer of Mule-deficient transformed cells to nude mice resulted in enhanced tumor growth that again could be abrogated by Miz1 knockdown. Our data demonstrate in vivo that Mule suppresses Ras-mediated tumorigenesis by preventing an accumulation of c-Myc/Miz1 complexes that mediates p21 and p15 down-regulation.

Integration and Progress in Pain Research: a Comment on Esteve and Ramirez-Maestre Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. May, 2013 | Pubmed ID: 23702829

Emergence of Multidrug-resistant Salmonella Enterica Serotype 4,[5],12:i:- Involving Human Cases in Canada: Results from the Canadian Integrated Program on Antimicrobial Resistance Surveillance (CIPARS), 2003-10 The Journal of Antimicrobial Chemotherapy. May, 2013 | Pubmed ID: 23710071 OBJECTIVES: Over the last decade, a marked increase in Salmonella enterica serotype 4,[5],12:i:- with a core resistance to ampicillin, streptomycin, sulphonamides and tetracycline (ASSuT) has been observed in Europe. This study describes the emergence and characterization of isolates of multidrug-resistant Salmonella 4,[5],12:i:- in Canada. METHODS: Human clinical isolates of Salmonella 4,[5],12:i:- were identified by provincial laboratories from 2003 to 2010. Serotyping and phage typing were performed by standardized methodologies. MIC values were determined using broth microdilution. PCR was used to determine the presence of resistance genes. Multilocus sequence typing was performed on a selected number of isolates. RESULTS: A total of 26â€Š251 Salmonella were submitted as part of the Canadian Integrated Program on Antibiotic Resistance Surveillance (CIPARS). Of these, Salmonella 4,[5],12:i:- accounted for a total of 766 isolates (2.9%), and the number increased significantly from 42 (1.4%) in 2003 to 164 (4.8%) in 2010. The ASSuT+ phenotype was observed in 11.9% (nâ€Š=â€Š91) of Salmonella 4,[5],12:i:- isolates and increased from two isolates in 2003 to 35 isolates in 2010. Two sequence types (STs) were observed. ST34 was mainly associated with the ASSuT isolates (nâ€Š=â€Š24; 38%), which contained blaTEM, strA-strB, tet(B) and sul2. ST19 was more likely to be associated with the ACSSuT phenotype and contained blaTEM, floR, strA-strB, sul2 and tet(A) or blaPSE-1, floR, aadA2, sul1 and tet(G). CONCLUSIONS: The prevalence of Salmonella 4,[5],12:i:- has significantly increased from 2003 to 2010 and it is now the fifth most common serotype reported in Canada causing human disease. Similar antimicrobial resistance patterns, phage types and STs have been observed in Europe.

A 24-month Evaluation of Amalgam and Resin-based Composite Restorations: Findings from The National Dental Practice-Based Research Network Journal of the American Dental Association (1939). Jun, 2013 | Pubmed ID: 23729455 Knowing which factors influence restoration longevity can help clinicians make sound treatment decisions. The authors analyzed data from The National Dental Practice-Based Research Network to identify predictors of early failures of amalgam and resin-based composite (RBC) restorations.

Anger, Injustice, and the Continuing Search for Psychological Mechanisms of Pain, Suffering, and Disability Pain. May, 2013 | Pubmed ID: 23732188

Binge Eating in Obese Adolescents: Emotional and Behavioral Characteristics and Impact on Health-related Quality of Life Clinical Child Psychology and Psychiatry. Jun, 2013 | Pubmed ID: 23749140 Purpose: This study explored binge eating among an adolescent obese population to ascertain the prevalence of bingeing, the relationship between binge eating and body mass index (BMI), and to evaluate significant relationships between binge eating, emotional/behavioral functioning, and health-related quality of life.Methods: Participants included 102 overweight adolescents aged 12-17 years presenting to a multidisciplinary outpatient obesity clinic. Data obtained included height, weight, and self-report questionnaire data on emotional and behavioral functioning.Results: Binge eating prevalence included 33% moderate to severe binge eating. Binge eating was significantly positively related to BMI and depression, negative mood, feelings of ineffectiveness, negative self-esteem and significantly negatively related to somatic complaints and all aspects of health-related quality of life. Important demographic differences emerged with regard to the impact of binge eating on health-related quality of life with Caucasians, females, and older groups experiencing more pervasive impact.Conclusions: This research suggests that bingeing behaviors have pervasive and important implications for health-related quality of life for obese adolescents.

The Therapeutic Relationship in Cognitive-Behavioral Therapy and Pharmacotherapy for Anxious Youth Journal of Consulting and Clinical Psychology. Jun, 2013 | Pubmed ID: 23750468 Objective: We examined the therapeutic relationship with cognitive-behavioral therapists and with pharmacotherapists for youth from the Child/Adolescent Anxiety Multimodal Study (Walkup et al., 2008). The therapeutic relationship was examined in relation to treatment outcomes. Method: Participants were 488 youth (ages 7-17 years; 50% male) randomized to cognitive-behavioral therapy (CBT; Coping Cat), pharmacotherapy (sertraline), their combination, or placebo pill. Participants met criteria for generalized anxiety disorder, social phobia, and/or separation anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994). The therapeutic relationship was assessed by youth report at Weeks 6 and 12 of treatment using the Child's Perception of Therapeutic Relationship scale (Kendall et al., 1997). Outcome measures (Pediatric Anxiety Rating Scale; Research Units on Pediatric Psychopharmacology Anxiety Study Group, 2002; and Clinical Global Impressions Scales; Guy, 1976) were completed by independent evaluators blind to condition. Results: For youth who received CBT only, a stronger therapeutic relationship predicted positive treatment outcome. In contrast, the therapeutic relationship did not predict outcome for youth receiving sertraline, combined treatment, or placebo. Conclusion: A therapeutic relationship may be important for anxious youth who receive CBT alone. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Intrauterine Inhibition of Prostaglandin Transporter Protein Blocks Release of Luteolytic PGF2alpha Pulses Without Suppressing Endometrial Expression of Estradiol or Oxytocin Receptor in Ruminants Biology of Reproduction. Jun, 2013 | Pubmed ID: 23759308 In ruminants, prostaglandin F2 alpha (PGF2Î±) is synthesized and released in a pulsatile pattern from the endometria luminal epithelial (LE) cells during the process of luteolysis. Prostaglandin transporter (PGT) is a 12-transmembrane solute carrier organic anion transporter protein which facilitates transport of PGF2Î±. The present study determined the effects of inhibition of PGT protein on pulsatile release of luteolytic PGF2Î± and the underlined cell signaling mechanisms. Results indicate that intrauterine inhibition of the PGT protein inhibits the pulsatile release of PGF2Î± from the endometrium and maintains functional corpus luteum. Surprisingly, inhibition of PGT-mediated luteolytic pulses is not associated with spatial regulation of estrogen and oxytocin receptors in the LE of the endometrium and is also not accompanied by decreased biosynthesis of PGF2Î± or increased catabolism of PGF2Î± by the endometrium. Importantly, PGT inhibitor increases expression of pERK1/2 proteins in the LE of the endometrium. Knock-down of ERK1/2 genes in LE cells reverses the inhibitory effects of PGT inhibitor on release of PGF2Î±. In conclusion, intrauterine inhibition of PGT inhibits the pulsatile release of PGF2Î± from the endometrium without modulating spatial expressions of estrogen and oxytocin receptor proteins and metabolism of PGF2Î± at the time of luteolysis. Activation of ERK1/2 pathways and interactions between ERK1/2 and PGT protein appear to be important cell signaling mechanisms that control PGT-mediated efflux transport function. PGT emerges as an important final component in the luteolytic machinery which controls the release of luteolytic pulses of PGF2Î± from the endometrium in sheep.

Testing the Credibility, Feasibility and Acceptability of an Optimised Behavioural Intervention (OBI) for Avoidant Chronic Low Back Pain Patients: Protocol for a Randomised Feasibility Study Trials. 2013 | Pubmed ID: 23764140 Chronic back pain continues to be a costly and prevalent condition. The latest NICE guidelines issued in 2009 state that for patients with persistent back pain (of between six weeks and twelve months duration), who are highly distressed and/or disabled and for whom exercise, manual therapy and acupuncture has not been beneficial, the evidence supports a combination of around 100 hours of combined physical and psychological treatment. This is costly, and may prove unacceptable to many patients. A key recommendation of these guidelines was for further randomised controlled trials (RCTs) of psychological treatment and to target treatment to specific sub-groups of patients. Recent trials that have included psychological interventions have shown only moderate improvement at best, and results are not maintained long term. There is therefore a need to test theoretically driven interventions that focus on specific high-risk sub-groups, in which the intervention is delivered at full integrity against a credible control.

Pathways of Introduction of the Invasive Aquatic Plant Cabomba Caroliniana Ecology and Evolution. Jun, 2013 | Pubmed ID: 23789056 The pathway and frequency of species' introductions can affect the extent, impact, and management of biological invasions. Here, we examine the pathway of introduction of the aquatic plant Cabomba caroliniana (fanwort) into Canada and the northern United States using plastid DNA sequence (intergenic spacers atpF-atpH, trnH-psbA, and trnL-trnF) and DNA content analyses. We test the hypothesis that the spread of fanwort is a result of commercial trade by comparing a Canadian population (Kasshabog Lake, ON) to native populations from southern U.S., introduced populations in northern U.S., and plants from commercial retailers. Thirteen plastid haplotypes were identified throughout North America, including one dominant haplotype, which was present in all C. caroliniana populations. Several rare haplotypes were used to infer shared colonization history. In particular, the Canadian population shared two rare alleles with a population from Massachusetts, suggesting range expansion of C. caroliniana from the northern U.S. However, the possibility of a commercial introduction cannot be excluded, as common alleles were shared between the Canadian population and both commercial and southern U.S. sources. Variation in C. caroliniana genome size was bimodal and populations were classified into "high" and "low" categories. The Canadian population had DNA contents similar to several northern U.S. populations (low DNA content). This may provide additional support for range expansion from these introduced populations rather than from commercial sources or populations in the southern U.S., which had high DNA content.

High-resolution Peripheral Quantitative Computed Tomography and Finite Element Analysis of Bone Strength at the Distal Radius in Ovariectomized Adult Rhesus Monkey Demonstrate Efficacy of Odanacatib and Differentiation from Alendronate Bone. Jun, 2013 | Pubmed ID: 23791777 Translational evaluation of disease progression and treatment response is critical to the development of therapies for osteoporosis. In this study, longitudinal in-vivo monitoring of odanacatib (ODN) treatment efficacy was compared to alendronate (ALN) in ovariectomized (OVX) non-human primates (NHPs) using high-resolution peripheral computed tomography (HR-pQCT). Treatment effects were evaluated using several determinants of bone strength, density and quality, including volumetric bone mineral density (vBMD), three-dimensional structure, finite element analysis (FEA) estimated peak force and biomechanical properties at the ultradistal (UD) radius at baseline, 3, 6, 9, 12, and 18months of dosing in three treatment groups: vehicle (VEH), low ODN (2mg/kg/day, L-ODN), and ALN (30Î¼g/kg/week). Biomechanical axial compression tests were performed at the end of the study. Bone strength estimates using FEA were validated by ex-vivo mechanical compression testing experiments. After 18months of dosing, L-ODN demonstrated significant increases from baseline in integral vBMD (13.5%), cortical thickness (24.4%), total bone volume fraction BV/TV (13.5%), FEA-estimated peak force (26.6%) and peak stress (17.1%), respectively. Increases from baseline for L-ODN at 18months were significantly higher than that for ALN in DXA-based aBMD (7.6%), cortical thickness (22.9%), integral vBMD (12.2%), total BV/TV (10.1%), FEA peak force (17.7%) and FEA peak stress (11.5%), respectively. These results demonstrate a superior efficacy of ODN treatment compared to ALN at the UD radii in ovariectomized NHPs.

Response to Rhinovirus Infection by Human Airway Epithelial Cells and Peripheral Blood Mononuclear Cells in an in Vitro Two-chamber Tissue Culture System PloS One. 2013 | Pubmed ID: 23799120 Human rhinovirus (HRV) infections are associated with the common cold, occasionally with more serious lower respiratory tract illnesses, and frequently with asthma exacerbations. The clinical features of HRV infection and its association with asthma exacerbation suggest that some HRV disease results from virus-induced host immune responses to infection. To study the HRV-infection-induced host responses and the contribution of these responses to disease, we have developed an in vitro model of HRV infection of human airway epithelial cells (Calu-3 cells) and subsequent exposure of human peripheral blood mononuclear cells (PBMCs) to these infected cells in a two-chamber trans-well tissue culture system. Using this model, we studied HRV 14 (species B) and HRV 16 (species A) induced cytokine and chemokine responses with PBMCs from four healthy adults. Infection of Calu-3 cells with either virus induced HRV-associated increases in FGF-Basic, IL-15, IL-6, IL-28A, ENA-78 and IP-10. The addition of PBMCs to HRV 14-infected cells gave significant increases in MIP-1Î², IL-28A, MCP-2, and IFN-Î± as compared with mock-infected cells. Interestingly, ENA-78 levels were reduced in HRV 14 infected cells that were exposed to PBMCs. Addition of PBMCs to HRV 16-infected cells did not induce MIP-1Î², IL-28A and IFN-Î± efficiently nor did it decrease ENA-78 levels. Our results demonstrate a clear difference between HRV 14 and HRV 16 and the source of PBMCs, in up or down regulation of several cytokines including those that are linked to airway inflammation. Such differences might be one of the reasons for variation in disease associated with different HRV species including variation in their link to asthma exacerbations as suggested by other studies. Further study of immune responses associated with different HRVs and PBMCs from different patient groups, and the mechanisms leading to these differences, should help characterize pathogenesis of HRV disease and generate novel approaches to its treatment.

Moderation of Antipsychotic-induced Weight Gain by Energy Balance Gene Variants in the RUPP Autism Network Risperidone Studies Translational Psychiatry. 2013 | Pubmed ID: 23799528 Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 Ã— 10(-6)), CNR1 (P=9.6 Ã— 10(-5)) and the leptin (LEP) promoter (P=1.4 Ã— 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 Ã— 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event.

Cost-effectiveness of Personalized Plaque Control for Managing the Gingival Manifestations of Oral Lichen Planus: a Randomized Controlled Study Journal of Clinical Periodontology. May, 2013 | Pubmed ID: 23800196 To undertake cost-effectiveness and cost-benefit analyses of an intervention to improve oral health in patients presenting with the gingival manifestations of oral lichen planus (OLP).

Seven Habits of Unproductive Thinking Physician Executive. May-Jun, 2013 | Pubmed ID: 23802392

Interactive Effects of Dehydroepiandrosterone and Testosterone on Cortical Thickness During Early Brain Development The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Jun, 2013 | Pubmed ID: 23804104 Humans and the great apes are the only species demonstrated to exhibit adrenarche, a key endocrine event associated with prepubertal increases in the adrenal production of androgens, most significantly dehydroepiandrosterone (DHEA) and to a certain degree testosterone. Adrenarche also coincides with the emergence of the prosocial and neurobehavioral skills of middle childhood and may therefore represent a human-specific stage of development. Both DHEA and testosterone have been reported in animal and in vitro studies to enhance neuronal survival and programmed cell death depending on the timing, dose, and hormonal context involved, and to potentially compete for the same signaling pathways. Yet no extant brain-hormone studies have examined the interaction between DHEA- and testosterone-related cortical maturation in humans. Here, we used linear mixed models to examine changes in cortical thickness associated with salivary DHEA and testosterone levels in a longitudinal sample of developmentally healthy children and adolescents 4-22 years old. DHEA levels were associated with increases in cortical thickness of the left dorsolateral prefrontal cortex, right temporoparietal junction, right premotor and right entorhinal cortex between the ages of 4-13 years, a period marked by the androgenic changes of adrenarche. There was also an interaction between DHEA and testosterone on cortical thickness of the right cingulate cortex and occipital pole that was most significant in prepubertal subjects. DHEA and testosterone appear to interact and modulate the complex process of cortical maturation during middle childhood, consistent with evidence at the molecular level of fast/nongenomic and slow/genomic or conversion-based mechanisms underlying androgen-related brain development.

Effect of Odanacatib on Bone Turnover Markers, Bone Density and Geometry of the Spine and Hip of Ovariectomized Monkeys: A Head-to-head Comparison with Alendronate Bone. Jun, 2013 | Pubmed ID: 23806798 Odanacatib (ODN) is a selective and reversible Cathepsin K (CatK) inhibitor currently being developed as a once weekly treatment for osteoporosis. Here, effects of ODN compared to alendronate (ALN) on bone turnover, DXA-based areal bone mineral density (aBMD), QCT-based volumetric BMD (vBMD) and geometric parameters were studied in ovariectomized (OVX) rhesus monkeys. Treatment was initiated 10days after ovariectomy and continued for 20months. The study consisted of four groups: L-ODN (2mg/kg, daily p.o.), H-ODN (8/4mg/kg daily p.o.), ALN (15Î¼g/kg, twice weekly, s.c.), and VEH (vehicle, daily, p.o.). L-ODN and ALN doses were selected to approximate the clinical exposures of the ODN 50-mg and ALN 70-mg once-weekly, respectively. L-ODN and ALN effectively reduced bone resorption markers uNTx and sCTx compared to VEH. There was no additional efficacy with these markers achieved with H-ODN. Conversely, ODN displayed inversely dose-dependent reduction of bone formation markers, sP1NP and sBSAP, and L-ODN reduced formation to a lesser degree than ALN. At month 18 post-OVX, L-ODN showed robust increases in lumbar spine aBMD (11.4%, p

Circumferential or Sectored Beam Arrangements for Stereotactic Body Radiation Therapy (SBRT) of Primary Lung Tumors: Effect on Target and Normal-structure Dose-volume Metrics Medical Dosimetry : Official Journal of the American Association of Medical Dosimetrists. Jun, 2013 | Pubmed ID: 23810414 To compare 2 beam arrangements, sectored (beam entry over ipsilateral hemithorax) vs circumferential (beam entry over both ipsilateral and contralateral lungs), for static-gantry intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) delivery techniques with respect to target and organs-at-risk (OAR) dose-volume metrics, as well as treatment delivery efficiency. Data from 60 consecutive patients treated using stereotactic body radiation therapy (SBRT) for primary non-small-cell lung cancer (NSCLC) formed the basis of this study. Four treatment plans were generated per data set: IMRT/VMAT plans using sectored (-s) and circumferential (-c) configurations. The prescribed dose (PD) was 60Gy in 5 fractions to 95% of the planning target volume (PTV) (maximum PTV dose ~ 150% PD) for a 6-MV photon beam. Plan conformality, R50 (ratio of volume circumscribed by the 50% isodose line and the PTV), and D2cm (Dmax at a distance â‰¥2cm beyond the PTV) were evaluated. For lungs, mean doses (mean lung dose [MLD]) and percent V30/V20/V10/V5Gy were assessed. Spinal cord and esophagus Dmax and D5/D50 were computed. Chest wall (CW) Dmax and absolute V30/V20/V10/V5Gy were reported. Sectored SBRT planning resulted in significant decrease in contralateral MLD and V10/V5Gy, as well as contralateral CW Dmax and V10/V5Gy (all p < 0.001). Nominal reductions of Dmax and D5/D50 for the spinal cord with sectored planning did not reach statistical significance for static-gantry IMRT, although VMAT metrics did show a statistically significant decrease (all p < 0.001). The respective measures for esophageal doses were significantly lower with sectored planning (p < 0.001). Despite comparable dose conformality, irrespective of planning configuration, R50 significantly improved with IMRT-s/VMAT-c (p < 0.001/p = 0.008), whereas D2cm significantly improved with VMAT-c (p < 0.001). Plan delivery efficiency improved with sectored technique (p < 0.001); mean monitor unit (MU)/cGy of PD decreased from 5.8 Â± 1.9 vs 5.3 Â± 1.7 (IMRT) and 2.7 Â± 0.4 vs 2.4 Â± 0.3 (VMAT). The sectored configuration achieves unambiguous dosimetric advantages over circumferential arrangement in terms of esophageal, contralateral CW, and contralateral lung sparing, in addition to being more efficient at delivery.

Up in Smoke? A Preliminary Open-Label Trial of Nicotine Replacement Therapy and Cognitive Behavioral Motivational Enhancement for Smoking Cessation Among Youth in Los Angeles Substance Use & Misuse. Jul, 2013 | Pubmed ID: 23822739 In 2008-2009, we conducted a 6-week, open-label trial of transdermal nicotine replacement therapy and practical counseling for 34 adolescents seeking smoking cessation in Los Angeles. Dependent outcomes were study retention, use of the patch, and 7-day quit status at the end-of-study and at follow-up visits. Predictors of outcomes included cigarette dependence, withdrawal symptoms, demographic and psychiatric measures, and other substance use. Variables significant in bivariate analysis (p < .10) were retained in a multivariate model. Subjects had significant pre-to-post reductions in quit rates, dependence, and withdrawal symptoms. Subjects also reported a high number of comorbidities. Implications for clinicians are discussed.

The Relationship Between Adjunctive Drinking, Blood Ethanol Concentration and Plasma Corticosterone Across Fixed-time Intervals of Food Delivery in Two Inbred Mouse Strains Psychoneuroendocrinology. Jul, 2013 | Pubmed ID: 23827168 Schedules of intermittent food delivery induce excessive fluid intake, termed schedule-induced polydipsia (SIP), and hypothalamic-pituitary-adrenal (HPA) axis activation is important for the expression and maintenance of this adjunctive behavior. Previous work has focused on examining the relationship between water intake and plasma corticosterone (CORT) in rats at a single or a limited range of fixed time (FT) intervals. However, little remains known regarding SIP and the corresponding stress response (1) across the bitonic function that epitomizes adjunctive behavior, (2) when ethanol is the available fluid, and (3) when a species other than rat or multiple strains are studied. Here we report the findings from ethanol-preferring C57BL/6J (B6) and non-preferring DBA/2J (D2) mice serially exposed to progressively larger FT intervals (0â†’60min) and given access to either water or a 5% (v/v) ethanol solution. Following 2 weeks of experience with each schedule, blood samples were collected at the conclusion of the last 60-min session to evaluate CORT and the blood ethanol concentration (BEC) achieved. While both strains exhibited a bitonic function of ethanol intake and BEC that peaked at or near a 5-min interval, only D2 mice showed a similar response with water. In contrast, CORT levels rose monotonically with incremental increases in the FT interval regardless of the strain examined or fluid type offered, indicating that glucocorticoid release likely reflects the aversive aspects of increasing intervals between reinforcement rather than engagement in adjunctive behavior. These findings also caution against the use of a single intensity stressor to evaluate the relationship between stress and ethanol intake, as the magnitude of stress appears to affect ethanol consumption in a non-linear fashion.

Type VII Collagen Associated with the Basement Membrane of Amniotic Epithelium Forms Giant Anchoring Rivets Which Penetrate AÂ massive Lamina Reticularis Placenta. Jul, 2013 | Pubmed ID: 23834951 In human amnion a simple cuboidal epithelium and underlying fibroblast layer are separated by an almost acellular compact layer rich in collagen types I and III. This (>10Â Î¼m) layer, which may be a thick lamina reticularis, apparently presents an unusual set of conditions. Integration of the multilaminous tissue across it is apparently achieved by waisted structures which we have observed with the light microscope in frozen, paraffin-wax and semi-thin resin sections. We have also captured transmission and scanning electron micrographs of the structures. These structures which cross the compact layer we call "rivets". The composition of these "rivets" has been examined immunocytochemically and in three dimensions using the confocal laser scanning epi-fluorescence microscope. The rivets contain type VII collagen and an Î±6 integrin. They associate with type IV collagen containing structures (basement membrane lamina densa and spongy coils) and a special population of fibroblasts which may generate, maintain or anchor rivets to the underlying mesenchymal layer. Although type VII collagen is well known to anchor basal lamina to underlying mesodermal collagen fibres these "rivets" are an order of magnitude larger than any previously described type VII collagen containing anchoring structures. Intriguing possible functions of these features include nodes for growth of fibrous collagen sheets and sites of possible enzymatic degradation during regulated amnion weakening approaching term. If these sites are confirmed to be involved in amnion degradation and growth they may represent important targets for therapeutic agents that are designed to delay preterm premature rupture of the membranes a major cause of fetal morbidity and mortality.

The Pediatric Infectious Disease JournalÂ® Newsletter The Pediatric Infectious Disease Journal. May, 2013 | Pubmed ID: 23838668

The Pediatric Infectious Disease JournalÂ® Newsletter The Pediatric Infectious Disease Journal. Jun, 2013 | Pubmed ID: 23838739

The Pediatric Infectious Disease JournalÂ® Newsletter The Pediatric Infectious Disease Journal. Jul, 2013 | Pubmed ID: 23838787

Assessing Anxiety in Youth with the Multidimensional Anxiety Scale for Children Journal of Clinical Child and Adolescent Psychology : the Official Journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53. Jul, 2013 | Pubmed ID: 23845036 The present study examined the psychometric properties, including discriminant validity and clinical utility, of the youth self-report and parent-report forms of the Multidimensional Anxiety Scale for Children (MASC) among youth with anxiety disorders. The sample included parents and youth (NÂ =Â 488, 49.6% male) ages 7 to 17 who participated in the Child/Adolescent Anxiety Multimodal Study. Although the typical low agreement between parent and youth self-reports was found, the MASC evidenced good internal reliability across MASC subscales and informants. The main MASC subscales (i.e., Physical Symptoms, Harm Avoidance, Social Anxiety, and Separation/Panic) were examined. The Social Anxiety and Separation/Panic subscales were found to be significantly predictive of the presence and severity of social phobia and separation anxiety disorder, respectively. Using multiple informants improved the accuracy of prediction. The MASC subscales demonstrated good psychometric properties and clinical utilities in identifying youth with anxiety disorders.

Strength Comparison of Four Techniques to Secure Implant Attachment Housings to Complete Dentures The Journal of Prosthetic Dentistry. Jul, 2013 | Pubmed ID: 23849608 Implant overdentures become thinner and weaker after direct transfer of implant attachment housings. While much has been published on denture repair, these data do not directly apply to implant overdentures because the introduction of a metal housing changes the character of the repair. It is desirable to make a strong repair to avoid prosthesis fracture.

Open-loop Phase Shifting for Fast Acquisition of Interferograms in Low Light Levels Applied Optics. Jul, 2013 | Pubmed ID: 23852208 Phase shifting interferometry relies on sets of interferograms taken at multiple known phase offsets to deduce the instantaneous phase of a quasi-static fringe pattern. The traditional method for introducing these phase shifts has been either to step a mirror, and measure the fringe pattern at each step, or to scan a mirror, integrating the fringe pattern for discrete time intervals while the fringes "move" on the detector. A stepping mirror eliminates this fringe smear but has typically required a closed-loop controller to ensure that the optical path introduced is accurately known. Furthermore, implementing rapid stepping of a moderately sized optic can prove difficult if the fringe phase needs to be measured on a short time scale. We report results demonstrating very fast (>100â€‰â€‰Hz) and precise phase shifting using a piezomodulated mirror operated in open-loop without any position feedback. Our method exploits the use of a synthetic driving waveform that is optimized to match the complex frequency response of the modulator and its supported optic. For phase measurements in the near-infrared at 2.15Â Î¼m, and with a time between steps as small as 0.2Â ms, we report errors below Î»/100 in the desired position of our optic, i.e., an effective optical path difference error of âˆ¼Î»/55. For applications in near-infrared stellar interferometry, this implies an enhancement in the fringe-tracking sensitivity of roughly 20% (in the photon-limited regime) over that which is conventionally realized using a swept mirror.

The Pediatric Infectious Disease JournalÂ® Newsletter The Pediatric Infectious Disease Journal. Aug, 2013 | Pubmed ID: 23856719

Positive Effects of Methylphenidate on Hyperactivity Are Moderated by Monoaminergic Gene Variants in Children with Autism Spectrum Disorders The Pharmacogenomics Journal. Jul, 2013 | Pubmed ID: 23856854 Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P

A Feasibility Study of Brief Group-based Acceptance and Commitment Therapy for Chronic Pain in General Practice: Recruitment, Attendance, and Patient Views Primary Health Care Research & Development. Jul, 2013 | Pubmed ID: 23866920 Acceptance and commitment therapy (ACT), a form of cognitive-behavioral therapy, may help meet a need for accessible and cost-effective treatments for chronic pain. ACT has a growing evidence base, but has not yet been tested within general practice settings. Aim The purpose of the present study was to examine the feasibility of conducting a full-scale randomized controlled trial of ACT in general practice.

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Articles by Patricia McCracken in JoVE

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Other articles by Patricia McCracken on PubMed

In JoVE (1)

Other Publications (200)

Articles by Patricia McCracken in JoVE

Medicine

Other articles by Patricia McCracken on PubMed

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