Sperm Competition Dynamics: Ejaculate Fertilising Efficiency Changes Differentially with Time

BMC Evolutionary Biology. 2008  |  Pubmed ID: 19087292

A fundamental challenge in evolutionary biology is to resolve the mechanisms that maintain paternity a hypervariable fitness component. Because females are often sexually promiscuous, this challenge hinges on establishing the mechanisms through which the ejaculates of different males compete for fertilisation (sperm competition). The competitive quality of an ejaculate is mediated by the relative number of live sperm and their motile performance. The differential rate at which rival ejaculates lose their fertilising efficiency over time is therefore expected to influence the outcome of sperm competition.

Fetal Magnetic Resonance Imaging in Isolated Diaphragmatic Hernia: Volume of Herniated Liver and Neonatal Outcome

American Journal of Obstetrics and Gynecology. Mar, 2009  |  Pubmed ID: 19110232

We sought to use magnetic resonance (MR) imaging (MRI) to estimate percentage of fetal thorax occupied by lung, liver, and other abdominal organs in pregnancies with congenital diaphragmatic hernia (CDH).

Synaptic Activity-responsive Element in the Arc/Arg3.1 Promoter Essential for Synapse-to-nucleus Signaling in Activated Neurons

Proceedings of the National Academy of Sciences of the United States of America. Jan, 2009  |  Pubmed ID: 19116276

The neuronal immediate early gene Arc/Arg-3.1 is widely used as one of the most reliable molecular markers for intense synaptic activity in vivo. However, the cis-acting elements responsible for such stringent activity dependence have not been firmly identified. Here we combined luciferase reporter assays in cultured cortical neurons and comparative genome mapping to identify the critical synaptic activity-responsive elements (SARE) of the Arc/Arg-3.1 gene. A major SARE was found as a unique approximately 100-bp element located at >5 kb upstream of the Arc/Arg-3.1 transcription initiation site in the mouse genome. This single element, when positioned immediately upstream of a minimal promoter, was necessary and sufficient to replicate crucial properties of endogenous Arc/Arg-3.1's transcriptional regulation, including rapid onset of transcription triggered by synaptic activity and low basal expression during synaptic inactivity. We identified the major determinants of SARE as a unique cluster of neuronal activity-dependent cis-regulatory elements consisting of closely localized binding sites for CREB, MEF2, and SRF. Consistently, a SARE reporter could readily trace and mark an ensemble of cells that have experienced intense activity in the recent past in vivo. Taken together, our work uncovers a novel transcriptional mechanism by which a critical 100-bp element, SARE, mediates a predominant component of the synapse-to-nucleus signaling in ensembles of Arc/Arg-3.1-positive activated neurons.

Cryptic Preference for MHC-dissimilar Females in Male Red Junglefowl, Gallus Gallus

Proceedings. Biological Sciences / The Royal Society. Mar, 2009  |  Pubmed ID: 19129124

An increasing number of studies test the idea that females increase offspring fitness by biasing fertilization in favour of genetically compatible partners; however, few have investigated or controlled for corresponding preferences in males. Here, we experimentally test whether male red junglefowl, Gallus gallus, prefer genetically compatible females, measured by similarity at the major histocompatibility complex (MHC), a key gene complex in vertebrate immune function. Theory predicts that because some degree of MHC heterozygosity favours viability, individuals should prefer partners that carry MHC alleles different from their own. While male fowl showed no preference when simultaneously presented with an MHC-similar and an MHC-dissimilar female, they showed a 'cryptic' preference, by allocating more sperm to the most MHC-dissimilar of two sequentially presented females. These results provide the first experimental evidence that males might respond to the MHC similarity of a female through differential ejaculate expenditure. By revealing that cryptic male behaviours may bias fertilization success in favour of genetically compatible partners, this study demonstrates the need to experimentally disentangle male and female effects when studying preferences for genetically compatible partners.

SOAR and the Polybasic STIM1 Domains Gate and Regulate Orai Channels

Nature Cell Biology. Mar, 2009  |  Pubmed ID: 19182790

Influx of Ca(2+) through store-operated Ca(2+) channels (SOCs) is a central component of receptor-evoked Ca(2+) signals. Orai channels are SOCs that are gated by STIM1, a Ca(2+) sensor located in the ER but how it gates and regulates the Orai channels is unknown. Here, we report the molecular basis for gating of Orais by STIM1. All Orai channels are fully activated by the conserved STIM1 amino acid fragment 344-442, which we termed SOAR (the STIM1 Orai activating region). SOAR acts in combination with STIM1 (450-485) to regulate the strength of interaction with Orai1. Activation of Orai1 by SOAR recapitulates all the kinetic properties of Orai1 activation by STIM1. However, mutations of STIM1 within SOAR prevent activation of Orai1 but not co-clustering of STIM1 and Orai1 in response to Ca(2+) store depletion, indicating that STIM1-Orai1 co-clustering is not sufficient for Orai1 activation. An intact carboxy terminus alpha-helicial region of Orai is required for activation by SOAR. Deleting most of the Orai1 amino terminus impaired Orai1 activation by STIM1, but Orai1(Delta1-73) interacted with and was fully activated by SOAR. Accordingly, the characteristic inward rectification of Orai is mediated by an interaction between the polybasic STIM1 (672-685) and a Pro-rich region in the N terminus of Orai1. Hence, the essential properties of Orai1 function can be rationalized by interactions with discrete regions of STIM1.

Native Store-operated Ca2+ Influx Requires the Channel Function of Orai1 and TRPC1

The Journal of Biological Chemistry. Apr, 2009  |  Pubmed ID: 19228695

With the discovery of STIM1 and Orai1 and gating of both TRPC and Orai1 channels by STIM1, a central question is the role of each of the channels in the native store-operated Ca(2+) influx (SOCs). Here, we used a strategy of knockdown of Orai1 and of TRPC1 alone and in combination and rescue by small interfering RNA-protected mutants (sm) of smOrai1 and smTRPC1 to demonstrate that in human embryonic kidney (HEK) cells, rescue of SOCs required co-transfection of low levels of both smOrai1 and smTRPC1. The pore mutant Orai1(E106Q) failed to rescue the SOCs in the presence or absence of TRPC1 and, surprisingly, the pore mutant TRPC1(F562A) failed to rescue the SOCs in the presence or absence of Orai1. TRPC1 is gated by electrostatic interaction between TRPC1(D639D,D640D) with STIM1(K684K, K685K). Strikingly, the channel-dead TRPC1(D639K,D640K) that can be rescued only by the STIM1(K684E,K685E) mutant could restore SOCs only when expressed with Orai1 and STIM1(K684E,K685E). Accordingly, we found a mutual requirement of Orai1 and TRPC1 for their interaction with the native STIM1 in HEK cells. By contrast, SOC and the CRAC current in Jurkat cells were inhibited by knockdown of Orai1 but were not influenced by knockdown on TRPC1 or TRPC3. These findings define the molecular makeup of the native SOCs in HEK cells and the role of a STIM1-Orai1-TRPC1 complex in SOC activity.

Acute Uncomplicated Appendicitis: Case Time of Day Influences Hospital Length of Stay

Surgical Infections. Feb, 2009  |  Pubmed ID: 19250008

Acute appendicitis is the most common surgical infection requiring operative intervention, and length of stay (LOS) typically is short. The timing of emergency appendectomies for acute appendicitis depends on many factors, including anesthesia and operating room availability, staffing, convenience, acuity of illness, and surgeon preference. Efforts to decrease LOS in surgery patients have focused largely on elective operations. We hypothesized that operative time of day would determine when patients were discharged after appendectomy.

What Do General Practitioners Do Differently when Consulting with a Medical Student?

Medical Education. Mar, 2009  |  Pubmed ID: 19250354

The practice of having medical students see patients in a general practice setting, in their own consulting rooms, prior to the GP preceptor joining the consultation does not increase general practitioner (GP) consultation time. How do GPs meet the needs of both patient and student without extending consultation time? This study sought to quantify and compare GP consultation activities with and without students.

Enterobius Vermicularis Infestation of a Hysterectomy Specimen in a Patient with a Colonic Reservoir

American Journal of Obstetrics and Gynecology. Jun, 2009  |  Pubmed ID: 19268877

A 43-year-old woman (gravida 2, para 1011) with a history of uterine leiomyomata and a Barnett colonic reservoir underwent a supracervical hysterectomy. Final pathology revealed Enterobius vermicularis within the myometrium and adnexal vasculature. Infection may have occurred through a modified mode given the presence of a Barnett colonic reservoir and absence of an anus.

The Genome Sequence of Taurine Cattle: a Window to Ruminant Biology and Evolution

Science (New York, N.Y.). Apr, 2009  |  Pubmed ID: 19390049

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.

Genome-wide Survey of SNP Variation Uncovers the Genetic Structure of Cattle Breeds

Science (New York, N.Y.). Apr, 2009  |  Pubmed ID: 19390050

The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.

Bos Taurus Genome Assembly

BMC Genomics. 2009  |  Pubmed ID: 19393050

We present here the assembly of the bovine genome. The assembly method combines the BAC plus WGS local assembly used for the rat and sea urchin with the whole genome shotgun (WGS) only assembly used for many other animal genomes including the rhesus macaque.

Unlocking the Bovine Genome

BMC Genomics. 2009  |  Pubmed ID: 19393070

The draft genome sequence of cattle (Bos taurus) has now been analyzed by the Bovine Genome Sequencing and Analysis Consortium and the Bovine HapMap Consortium, which together represent an extensive collaboration involving more than 300 scientists from 25 different countries.

Depolarization-induced Slow Current in Cerebellar Purkinje Cells Does Not Require Metabotropic Glutamate Receptor 1

Neuroscience. Sep, 2009  |  Pubmed ID: 19409231

Activation of cerebellar Purkinje cells by either brief depolarizing steps or bursts of climbing fiber synaptic activation evokes a slow inward current, which we have previously called depolarization-induced slow current or DISC. DISC is triggered by Ca influx via voltage-sensitive Ca channels and is attenuated by inhibitors of vacuolar ATPase or vesicle fusion. This led us to suggest that DISC required vesicular release of glutamate from the somatodendritic region of Purkinje cells. Furthermore, we found that DISC was attenuated by the mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt), indicating that DISC required autocrine activation of metabotropic glutamate receptor 1 (mGluR1). Here, we have revisited the role of mGluR1 and found that it is, in fact, not required for DISC. CPCCOEt, but not three other specific mGluR1 antagonists (JNJ16259685, alpha-amino-5-carboxy-3-methyl-2-thiopheneacetic acid (3-MATIDA), Bay 36-7620), attenuated DISC, even though all four of these drugs produced near-complete blockade of current evoked by puffs of the exogenous mGluR1/5 agonist DHPG. Cerebellar slices derived from mGluR1 null mice showed substantial DISC that was still attenuated by CPCCOEt. mGluR5 is functionally similar to mGluR1, but is not expressed at high levels in cerebellar Purkinje cells. 2-Methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), an mGluR5 antagonist, did not attenuate DISC, and DISC was still present in Purkinje cells derived from mGluR1/mGluR5 double null mice. Thus, neither mGluR1 nor mGluR5 is required for DISC in cerebellar Purkinje cells.

Respiratory Viral Infections Within One Year After Pediatric Lung Transplant

Transplant Infectious Disease : an Official Journal of the Transplantation Society. Aug, 2009  |  Pubmed ID: 19422670

To characterize epidemiology and risk factors for respiratory viral infections (RVI) in pediatric lung transplant recipients within the first post-transplant year, a retrospective multicenter study of pediatric lung transplant recipients from 1988 to 2005 was conducted at 14 centers in the United States and Europe. Data were recorded for 1 year post transplant. Associations between RVI and continuous and categorical risk factors were assessed using Wilcoxon's rank-sum and chi(2) tests, respectively. Associations between time to RVI and risk factors or survival were assessed by multivariable Cox proportional hazards models. Of 576 subjects, 79 subjects (14%) had 101 RVI in the first year post transplant. Subjects with RVI were younger than those without RVI (median ages 9.7, 13; P<0.01). Viruses detected included adenovirus (n=25), influenza (n=9), respiratory syncytial virus (n=21), parainfluenza virus (n=19), enterovirus (n=4), and rhinovirus (n=22). In a multivariable model for time to first RVI, etiology other than cystic fibrosis (CF), younger age, and no induction therapy were independently associated with risk of RVI. Cytomegalovirus serostatus and acute rejection were not associated with RVI. RVI was independently associated with decreased 12-month survival (hazard ratio 2.6, 95% confidence interval 1.6-4.4). RVI commonly occurs after pediatric lung transplantation with risk factors including younger age and non-CF diagnosis. RVI is associated with decreased 1-year survival.

A 46-year-old Man with an Equestrian-related Head Injury

Journal of Emergency Nursing: JEN : Official Publication of the Emergency Department Nurses Association. Jun, 2009  |  Pubmed ID: 19446128

A Review of Sentinel Lymph Node Evaluation and the Need for Its Incorporation into Veterinary Oncology

Veterinary and Comparative Oncology. Jun, 2009  |  Pubmed ID: 19453362

Being the first lymph node or nodes to which many primary tumours reliably drain, the disease status of the sentinel lymph node/s (SLN) is important in the prediction of survival. SLN identification and biopsy are critical in the staging of human cancers. The status of the SLN helps determine prognosis and shape treatment plans. SLN evaluation is currently not routinely performed in veterinary oncology, not even at specialty oncology practices. Given the prognostic importance of lymph node involvement in tumours such as mammary gland carcinoma, osteosarcoma, synovial cell sarcoma and mast cell tumours, SLN evaluation should be incorporated into routine clinical practice so as to improve our clinical assessment of veterinary oncologic patients.

The Risk, Prevention, and Outcome of Cytomegalovirus After Pediatric Lung Transplantation

Transplantation. May, 2009  |  Pubmed ID: 19461492

A retrospective review of pediatric lung transplant recipients at 14 centers in North America and Europe was conducted to characterize the epidemiology and the risk factors for cytomegalovirus (CMV) and to explore the impact of preventative antiviral therapy.

Core Competencies for Fellowship Training in Psychosomatic Medicine: a Collaborative Effort by the APA Council on Psychosomatic Medicine, the ABPN Psychosomatic Committee, and the Academy of Psychosomatic Medicine

Psychosomatics. Nov-Dec, 2009  |  Pubmed ID: 19996225

Effectiveness of Point-of-care Testing for Therapeutic Control of Chronic Conditions: Results from the PoCT in General Practice Trial

The Medical Journal of Australia. Jun, 2009  |  Pubmed ID: 19485840

To compare the clinical effectiveness of point-of-care testing (PoCT) and that of pathology laboratory testing, as measured by therapeutic control in chronic conditions.

A Thematic Analysis for How Patients, Prescribers, Experts, and Patient Advocates View the Prescription Choice Process

Research in Social & Administrative Pharmacy : RSAP. Jun, 2009  |  Pubmed ID: 19524863

Typically, patients are unaware of the cost consequences regarding prescribing decisions during their clinical encounter and rarely talk with their physicians about costs of prescription drugs. Prescription medications that are deemed by patients to be too costly when the costs become known after purchase are discontinued or used at suboptimal doses compared to prescription medications that are deemed to be worth the cost.

Regenerative Growth in Drosophila Imaginal Discs is Regulated by Wingless and Myc

Developmental Cell. Jun, 2009  |  Pubmed ID: 19531351

The study of regeneration would be aided greatly by systems that support large-scale genetic screens. Here we describe a nonsurgical method for inducing tissue damage and regeneration in Drosophila larvae by inducing apoptosis in the wing imaginal disc in a spatially and temporally regulated manner. Tissue damage results in localized regenerative proliferation characterized by altered expression of patterning genes and growth regulators as well as a temporary loss of markers of cell fate commitment. Wingless and Myc are induced by tissue damage and are important for regenerative growth. Furthermore, ectopic Myc enhances regeneration when other growth drivers tested do not. As the animal matures, the ability to regenerate is lost and cannot be restored by activation of Wingless or Myc. This system is conducive to forward genetic screens, enabling an unbiased search for genes that regulate both the extent of and the capacity for regeneration.

The MTOR Kinase Differentially Regulates Effector and Regulatory T Cell Lineage Commitment

Immunity. Jun, 2009  |  Pubmed ID: 19538929

Effector T cell differentiation requires the simultaneous integration of multiple, and sometimes opposing, cytokine signals. We demonstrated mTOR's role in dictating the outcome of T cell fate. mTOR-deficient T cells displayed normal activation and IL-2 production upon initial stimulation. However, such cells failed to differentiate into T helper 1 (Th1), Th2, or Th17 effector cells. The inability to differentiate was associated with decreased STAT transcription factor activation and failure to upregulate lineage-specific transcription factors. Under normally activating conditions, T cells lacking mTOR differentiated into Foxp3(+) regulatory T cells. This was associated with hyperactive Smad3 activation in the absence of exogenous TGF-beta. Surprisingly, T cells selectively deficient in TORC1 do not divert to a regulatory T cell pathway, implicating both TORC1 and TORC2 in preventing the generation of regulatory T cells. Overall, our studies suggest that mTOR kinase signaling regulates decisions between effector and regulatory T cell lineage commitment.

Gold Laser Tonsillectomy--a Safe New Method

International Journal of Pediatric Otorhinolaryngology. Sep, 2009  |  Pubmed ID: 19556015

To determine if Gold laser tonsillectomy is an acceptably safe method of removing tonsils by comparing its complication rates to other established methods, namely Coblation tonsillectomy and cold steel dissection tonsillectomy.

TRPC Channels As STIM1-regulated SOCs

Channels (Austin, Tex.). Jul-Aug, 2009  |  Pubmed ID: 19574740

Store-operated Ca(2+) channels (SOCs) are Ca(2+) influx channels at the plasma membrane whose opening is determined by the level of Ca(2+) stored in the endoplasmic reticulum lumen. SOCs are activated in response to receptor-mediated or passive depletion of ER Ca(2+) to regulate many Ca(2+)-dependent cellular functions. Early work implicated the TRPC channels as SOCs. More recently, it was found that the Orai channels mediate the CRAC current and that the Ca(2+) binding protein STIM1 functions as the ER Ca(2+) sensor that mediates activation of the SOCs in response to depletion of ER Ca(2+). Key questions are whether both TRPC and Orai channels are opened by STIM1 and the molecular mechanism by which STIM1 opens the SOCs. Ample biochemical and functional evidence indicate interaction of the TRPC channels with STIM1. Furthermore, it was found that STIM1 gates TRPC channels by electrostatic interaction of STIM1(K684,K685) in the polybasic domain of STIM1 with two negative charges (aspartates or glutamates) that are conserved in all TRPC channels. Charge mutants of STIM1(K684,K685) and TRPC1(D639,D640) and TRPC3(D697,D698) were used to develop further direct evidence for the function of TRPC channels as SOCs. The evidence in favor of TRPC channels as SOCs are discussed.

Binge Drinking Upregulates Accumbens MGluR5-Homer2-PI3K Signaling: Functional Implications for Alcoholism

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Jul, 2009  |  Pubmed ID: 19587272

The glutamate receptor-associated protein Homer2 regulates alcohol-induced neuroplasticity within the nucleus accumbens (NAC), but the precise intracellular signaling cascades involved are not known. This study examined the role for NAC metabotropic glutamate receptor (mGluR)-Homer2-phosphatidylinositol 3-kinase (PI3K) signaling in regulating excessive alcohol consumption within the context of the scheduled high alcohol consumption (SHAC) model of binge alcohol drinking. Repeated bouts of binge drinking ( approximately 1.5 g/kg per 30 min) elevated NAC Homer2a/b expression and increased PI3K activity in this region. Virus-mediated knockdown of NAC Homer2b expression attenuated alcohol intake, as did an intra-NAC infusion of the mGluR5 antagonist MPEP [2-methyl-6-(phenylethynyl)pyridine hydrochloride] (0.1-1 microg/side) and the PI3K antagonist wortmannin (50 ng/side), supporting necessary roles for mGluR5/Homer2/PI3K in binge alcohol drinking. Moreover, when compared with wild-type littermates, transgenic mice with an F1128R point mutation in mGluR5 that markedly reduces Homer binding exhibited a 50% reduction in binge alcohol drinking, which was related to reduced NAC basal PI3K activity. Consistent with the hypothesis that mGluR5-Homer-PI3K signaling may be a mechanism governing excessive alcohol intake, the "anti-binge" effects of MPEP and wortmannin were not additive, nor were they observed in the mGluR5(F1128R) transgenic mice. Finally, mice genetically selected for a high versus low SHAC phenotype differed in NAC mGluR, Homer2, and PI3K activity, consistent with the hypothesis that augmented NAC mGluR5-Homer2-PI3K signaling predisposes a high binge alcohol-drinking phenotype. Together, these data point to an important role for NAC mGluR5-Homer2-PI3K signaling in regulating binge-like alcohol consumption that has relevance for our understanding of the neurobiology of alcoholism and its pharmacotherapy.

Eosinophilic Granuloma of the Lung and Rib

Asian Cardiovascular & Thoracic Annals. Apr, 2009  |  Pubmed ID: 19592555

Langerhans-cell histiocytosis is characterized by abnormal proliferation of Langerhans cells, and frequently associated with cigarette smoking. A 24-year-old man who underwent excisional biopsy of a pulmonary nodule and segmental rib resection was found to have the eosinophilic granuloma variation of Langerhans-cell histiocytosis.

Do Clients with Acquired Brain Injury Use the Splints Prescribed by Occupational Therapists? A Descriptive Study

NeuroRehabilitation. 2009  |  Pubmed ID: 19597275

Clients with acquired brain injury often demonstrate hypertonicity and decreased function in their upper limbs, requiring appropriate intervention. Splinting is one of the intervention methods that is widely used to address these issues. Literature shows that some clients are not using splints following fabrication. However, there is a paucity of research about the factors that influence clients to use or not use splints. This study aims to investigate these influential factors for clients with upper limb hypertonicity. Two survey tools including therapist and client questionnaires were developed and completed by both therapists and clients. Six therapists and 14 clients participated in this study and completed the relevant questionnaires. The results illustrate that most clients (13 out of 14) were continuing to use their splints four weeks following discharge from hospital. The main goals of choosing splints for both therapists and clients were prevention of contracture and deformity. The most indicated client reasons for adhering to the splint wearing program were therapist-related factors including clients' trust and reliance on their therapists. Further reasons for clients implementing the recommended splint-wearing program and clinical implications are discussed.

How to Use Balloons As Anchors to Facilitate Cannulation of the Coronary Sinus Left Ventricular Lead Placement and to Regain Lost Coronary Sinus or Target Vein Access

Heart Rhythm : the Official Journal of the Heart Rhythm Society. Aug, 2009  |  Pubmed ID: 19632642

Coronary venous anatomy can make successful implantation of a cardiac resynchronization therapy device difficult or impossible. Venogram and coronary balloons can be used as anchors to facilitate initial coronary sinus (CS) cannulation and left ventricular lead placement and to recover lost CS and target vein access.

Design, Implementation and Results of the Quality Control Program for the Australian Government's Point of Care Testing in General Practice Trial

Annals of Clinical Biochemistry. Sep, 2009  |  Pubmed ID: 19641009

From 2005 to 2007 the Australian Government funded a multicentre, clustered randomized controlled trial to determine the clinical effectiveness, cost-effectiveness, satisfaction and safety of point of care testing (PoCT) in general practice (GP). PoC tests measured (and devices used) in the trial were haemoglobin A1c and urine albumin:creatinine ratio (DCA 2000), lipids (Cholestech LDX) and international normalized ratio (CoaguChek S).

Molecular Determinants of Fast Ca2+-dependent Inactivation and Gating of the Orai Channels

Proceedings of the National Academy of Sciences of the United States of America. Aug, 2009  |  Pubmed ID: 19706554

Ca(2+) influx by store-operated Ca(2+) influx channels (SOCs) mediates many cellular functions regulated by Ca(2+), and excessive SOC-mediated Ca(2+) influx is cytotoxic and associated with disease. One form of SOC is the CRAC current that is mediated by Orai channels activated by STIM1. A fundamental property of the native CRAC and of the Orais is fast Ca(2+)-dependent inactivation, which limits Ca(2+) influx to guard against cellular damage. The molecular mechanism of this essential regulatory mechanism is unknown. We report here the fast Ca(2+)-dependent inactivation is mediated by three conserved glutamates in the C termini (CT) of Orai2 and Orai3, which show prominent fast Ca(2+)-dependent inactivation compared with Orai1. Transfer of the CT between the Orais transfers both the extent of channel opening and the mode of fast Ca(2+)-dependent inactivation. Fast Ca(2+)-dependent inactivation of the Orais also requires a domain of STIM1; fragments of STIM1 that efficiently open Orai channels do not evoke fast inactivation unless they include an anionic sequence that is C-terminal to the STIM1-Orai activating region (SOAR). Our studies suggest that Orai CT are necessary and sufficient to control pore opening and uncover the molecular mechanism of fast Ca(2+)-dependent inactivation that has implications for Ca(2+) influx by SOC in physiological and pathological states.

CRT Delivery Systems Based on Guide Support for LV Lead Placement

Heart Rhythm : the Official Journal of the Heart Rhythm Society. Sep, 2009  |  Pubmed ID: 19716095

Intravenous Leiomyomatosis with Intracardiac Extension: a Single-institution Experience

American Journal of Obstetrics and Gynecology. Dec, 2009  |  Pubmed ID: 19729144

The aim of this study was to outline the surgical management and outcomes for patients diagnosed with intravenous leiomyomatosis with intracardiac extension at a single institution.

Modeling Source-filter Interaction in Belting and High-pitched Operatic Male Singing

The Journal of the Acoustical Society of America. Sep, 2009  |  Pubmed ID: 19739766

Nonlinear source-filter theory is applied to explain some acoustic differences between two contrasting male singing productions at high pitches: operatic style versus jazz belt or theater belt. Several stylized vocal tract shapes (caricatures) are discussed that form the bases of these styles. It is hypothesized that operatic singing uses vowels that are modified toward an inverted megaphone mouth shape for transitioning into the high-pitch range. This allows all the harmonics except the fundamental to be "lifted" over the first formant. Belting, on the other hand, uses vowels that are consistently modified toward the megaphone (trumpet-like) mouth shape. Both the fundamental and the second harmonic are then kept below the first formant. The vocal tract shapes provide collective reinforcement to multiple harmonics in the form of inertive supraglottal reactance and compliant subglottal reactance. Examples of lip openings from four well-known artists are used to infer vocal tract area functions and the corresponding reactances.

Prepublication Data Sharing

Nature. Sep, 2009  |  Pubmed ID: 19741685

Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.

Cystic Sarcoma of the Psoas Muscle Masquerading As Appendicitis

The American Surgeon. Sep, 2009  |  Pubmed ID: 19774964

Cytomegalovirus Immunoglobulin Decreases the Risk of Cytomegalovirus Infection but Not Disease After Pediatric Lung Transplantation

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. Oct, 2009  |  Pubmed ID: 19782286

Cytomegalovirus (CMV) has been associated with morbidity, including chronic allograft rejection, in transplant recipients. Data from adult centers suggests that CMV hyperimmune globulin (CMVIG) and ganciclovir together are superior in preventing CMV viremia than ganciclovir alone.

Fungal Infections in Pediatric Lung Transplant Recipients: Colonization and Invasive Disease

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. Nov, 2009  |  Pubmed ID: 19782585

The purpose of this study was to evaluate the epidemiology and investigate the impact of colonization and pulmonary fungal infections (PFIs).

Goose Neck Snare for LV Lead Placement in Difficult Venous Anatomy

Pacing and Clinical Electrophysiology : PACE. Dec, 2009  |  Pubmed ID: 19821941

Venous anatomy frequently impairs placement of the left ventricular (LV) lead. In some cases, the wire will not advance into the vein and in others wire position is lost as the lead is advanced. This article describes how a commonly available goose neck snare is used to gain access to the distal end of the wire as it re-enters the coronary sinus retrograde via collaterals through an adjacent vein. The snare is advanced into the coronary sinus through the same catheter as the wire. The snare opens perpendicular to the long axis of the coronary sinus due to which the wire must pass through the open loop, provided the diameter of the snare is approximately the same as the coronary sinus. Thus no time-consuming manipulation of the snare is required. With access to both ends of the wire the vein is approached either retrograde (over the distal end) or antegrade (over the proximal end) while the other end of the wire is secured by the operator. Gaining control of both ends of the wire with a snare is another example of adapting interventional techniques for the device implantation. Unlike venoplasty, the snare does not evoke credentialing concerns and can be easily implemented by most implanting physicians.

Complications of Laparoscopy in Benign and Oncologic Gynecological Surgery

Reviews in Obstetrics and Gynecology. 2009  |  Pubmed ID: 19826574

The evolution of laparoscopy from a diagnostic tool to a modality for major surgical procedures has been rapid and represents one of the most important surgical advancements in the past 30 years. Laparoscopy holds many advantages over laparotomy, including smaller surgical scars, faster recovery from surgery, and decreased time for return of bowel function. However, an appreciation of its potential complications is vital to patient care.

School-based Interventions on Childhood Obesity: a Meta-analysis

American Journal of Preventive Medicine. Nov, 2009  |  Pubmed ID: 19840696

Over the past decade, childhood obesity has been recognized as an increasing health problem worldwide. It is a predictor of obesity during adulthood, which is strongly linked to chronic lifestyle diseases.

Genomic and Epigenetic Evidence for Oxytocin Receptor Deficiency in Autism

BMC Medicine. 2009  |  Pubmed ID: 19845972

Autism comprises a spectrum of behavioral and cognitive disturbances of childhood development and is known to be highly heritable. Although numerous approaches have been used to identify genes implicated in the development of autism, less than 10% of autism cases have been attributed to single gene disorders.

Role of a Percutaneous Ventricular Assist Device in Decision Making for a Cardiac Transplant Program

The Annals of Thoracic Surgery. Nov, 2009  |  Pubmed ID: 19853093

The role of a percutaneous ventricular assist device (VAD) for left heart support in the management of patients in cardiogenic shock is not well defined.

Using Rural and Remote Settings in the Undergraduate Medical Curriculum: AMEE Guide No. 47

Medical Teacher. Nov, 2009  |  Pubmed ID: 19909036

The goal of global equity in health care requires that the training of health-care professionals be better tuned to meet the needs of the communities they serve. In fact medical education is being driven into isolated communities by factors including workforce undersupply, education pedagogy, medical practice and research needs. Rural and remote medical education (RRME) happens in rural hospitals and rural general practices, singly or in combination, generally for periods of 4 to 40 weeks. An effective RRME programme matches the context of the local health service and community. Its implementation reflects the local capacity for providing learning opportunities, facilitates collaboration of all participants and capitalises on local creativity in teaching. Implementation barriers stem from change management, professional culture and resource allocation. Blending learning approaches as much as technology and local culture allow is central to achieving student learning outcomes and professional development of local medical teachers. RRME harnesses the rich learning environment of communities such that students rapidly achieve competence and confidence in a primary care/generalist setting. Longer programmes with an integrated (generalist) approach based in the immersion learning paradigm appear successful in returning graduates to rural practice and a career track with a quality lifestyle.

A New Model to Understand the Career Choice and Practice Location Decisions of Medical Graduates

Rural and Remote Health. Oct-Dec, 2009  |  Pubmed ID: 19943714

Australian medical education is increasingly influenced by rural workforce policy. Therefore, understanding the influences on medical graduates' practice location and specialty choice is crucial for medical educators and medical workforce planners. The South Australian Flinders University Parallel Rural Community Curriculum (PRCC) was funded by the Australian Government to help address the rural doctor workforce shortage. The PRCC was the first community based medical education program in Australia to teach a full academic year of medicine in South Australian rural general practices. The aim of this research was to identify what factors influence the career choices of PRCC graduates.

An Anomalous Type IV Secretion System in Rickettsia is Evolutionarily Conserved

PloS One. 2009  |  Pubmed ID: 19279686

Bacterial type IV secretion systems (T4SSs) comprise a diverse transporter family functioning in conjugation, competence, and effector molecule (DNA and/or protein) translocation. Thirteen genome sequences from Rickettsia, obligate intracellular symbionts/pathogens of a wide range of eukaryotes, have revealed a reduced T4SS relative to the Agrobacterium tumefaciens archetype (vir). However, the Rickettsia T4SS has not been functionally characterized for its role in symbiosis/virulence, and none of its substrates are known.

Helicopter Air Medical Transport Safety: What is the Role of the Emergency Nurse?

Journal of Emergency Nursing: JEN : Official Publication of the Emergency Department Nurses Association. Apr, 2009  |  Pubmed ID: 19285186

Design and Evaluation of a Probe for Simultaneous EEG and Near-infrared Imaging of Cortical Activation

Physics in Medicine and Biology. Apr, 2009  |  Pubmed ID: 19287076

We present a novel probe design which enables simultaneous electroencephalography (EEG) and near-infrared (NIR) optical imaging to be performed in a manner which is easy to apply, allows for optimum co-registration of the two forms of data and maximizes the number of sensors which can be applied to a given area. Our probe design is evaluated using a dual-modality, tissue-mimicking phantom and by performing a simple functional activation study of the human motor cortex. We successfully acquired NIR optical and EEG data simultaneously for both our phantom and our human motor cortex experiments, clearly demonstrating the effectiveness and suitability of our 'opto-electrode'.

The Prognosis for Spontaneous Labor in Women with Uncomplicated Term Pregnancies: Implications for Cesarean Delivery on Maternal Request

Obstetrics and Gynecology. Apr, 2009  |  Pubmed ID: 19305324

To assess the prognosis for vaginal delivery in women with entirely normal pregnancies who began spontaneous labor at term.

Gold Laser Adenoidectomy: Long-term Safety and Efficacy Results

International Journal of Pediatric Otorhinolaryngology. Jun, 2009  |  Pubmed ID: 19324425

To report the long-term results of Gold laser adenoidectomy with pressure equalization tube (PET) placement by measuring the incidence of otorrhea and middle ear effusion after tube extrusion.

Wellness Programmes for Persons Living with HIV/AIDS: Experiences from Eastern Cape Province, South Africa

Global Public Health. 2009  |  Pubmed ID: 19343601

Columbia University's International Centre for AIDS Care and Treatment Programmes (ICAP) supports the establishment of HIV prevention, care and treatment programmes, in resource-limited countries, through the President's Emergency Plan for AIDS Relief. In South Africa (SA), ICAP has collaborated with the Eastern Cape Department of Health since 2004, to support HIV treatment and care programmes at public healthcare facilities in rural and urban areas. Adherence, psychosocial and other supportive services have been combined into Wellness Programmes that have been situated within hospital-based Wellness Centres in two rural regions, and integrated within primary healthcare facilities in a third. This paper reviews components of wellness services for people living with HIV/AIDS including: voluntary counselling and testing, disclosure and prevention, ongoing counselling, health literacy and peer education, community- and home-based care, adherence support, and associated comprehensive care continuums. It also describes local context in which the Wellness Programmes were established. Finally it describes processes, successes and challenges, with programme development, and useful indicators monitored, lessons learned and strategies to strengthen and expand such programmes. Insights provided may inform other efforts to create sustainable systems of interdisciplinary care and accessible psychosocial support for HIV-infected persons within public facilities in resource-constrained settings.

Preclosure Pressure Gradients Predict Patent Ductus Arteriosus Patients at Risk for Later Left Pulmonary Artery Stenosis

Pediatric Cardiology. Oct, 2009  |  Pubmed ID: 19365650

The objective of this study was to evaluate the incidence of pre-existing catheterization left pulmonary artery (LPA) gradients and correlation of these gradients with later LPA stenosis after successful patent ductus arteriosus (PDA) occlusion. We performed a single-center review of 130 patients with PDA closure from October 1993 to February 2005. We analyzed the pre-PDA closure LPA pressure gradients at catheterization to determine if these were predictive of late LPA stenosis. On follow-up, a V (max) >2 m/s by echocardiogram (transthoracic echocardiography; TTE) was considered indicative of possible LPA stenosis. Left lung perfusion of <35% was considered diagnostic of significant LPA stenosis. Post PDA closure, possible LPA stenosis by TTE was seen in 8 of 128 patients (6.25%). Seven of these eight had precatheter LPA gradients >7 mm Hg. Five of these had perfusion scans, three of the five had significant LPA stenosis, and two underwent LPA angioplasty. Patients with LPA catheter gradients >7 mm Hg were more likely to have possible LPA stenosis by TTE, significant LPA stenosis by lung scan, and intervention with LPA angioplasty. In conclusion, a preclosure main pulmonary artery-to-LPA pressure gradient >7 mm Hg was found in all patients who developed significant LPA stenosis on follow-up after transcatheter PDA closure. It appears likely that these patients have LPA abnormality rather than stenosis caused by the PDA occlusion device. Patients with preclosure LPA gradients >7 mm Hg should undergo follow-up evaluations for detection of significant stenosis and may require treatment if an important flow abnormality is documented.

Psychiatrists for Medically Complex Patients: Bringing Value at the Physical Health and Mental Health/substance-use Disorder Interface

Psychosomatics. Mar-Apr, 2009  |  Pubmed ID: 19377017

In their current configuration, traditional reactive consultation-liaison services see a small percentage of the general-hospital patients who could benefit from their care. These services are poorly reimbursed and bring limited value in terms of clinical improvement and reduction in health-service use.

Torticollis with Tonsillitis. Is Imaging Necessary?

BMJ Case Reports. 2009  |  Pubmed ID: 21687001

Peptidyl-prolyl Isomerase FKBP52 Controls Chemotropic Guidance of Neuronal Growth Cones Via Regulation of TRPC1 Channel Opening

Neuron. Nov, 2009  |  Pubmed ID: 19945390

Immunophilins, including FK506-binding proteins (FKBPs), are protein chaperones with peptidyl-prolyl isomerase (PPIase) activity. Initially identified as pharmacological receptors for immunosuppressants to regulate immune responses via isomerase-independent mechanisms, FKBPs are most highly expressed in the nervous system, where their physiological function as isomerases remains unknown. We demonstrate that FKBP12 and FKBP52 catalyze cis/trans isomerization of regions of TRPC1 implicated in controlling channel opening. FKBP52 mediates stimulus-dependent TRPC1 gating through isomerization, which is required for chemotropic turning of neuronal growth cones to netrin-1 and myelin-associated glycoprotein and for netrin-1/DCC-dependent midline axon guidance of commissural interneurons in the developing spinal cord. By contrast, FKBP12 mediates spontaneous opening of TRPC1 through isomerization and is not required for growth cone responses to netrin-1. Our study demonstrates a novel physiological function of proline isomerases in chemotropic nerve guidance through TRPC1 gating and may have significant implication in clinical applications of immunophilin-related therapeutic drugs.

Assessing Agreement Between Point of Care and Laboratory Results for Lipid Testing from a Clinical Perspective

Clinical Biochemistry. Mar, 2010  |  Pubmed ID: 19961841

Investigate agreement between lipid pathology results from point-of-care testing (PoCT) devices and laboratories.

Association of the Small GTPase Rheb with the NMDA Receptor Subunit NR3A

Neuro-Signals. 2010  |  Pubmed ID: 21135540

The NMDAR subunit NR3A is most highly expressed during the second postnatal week, when synaptogenesis reaches peak levels. Genetic ablation or overexpression of the NR3A subunit negatively interferes with the maturation of cortical synapses and leads to changes in the shape and number of dendritic spines, the density of which is increased in NR3A knock-out mice and decreased in NR3A-overexpressing transgenic mice. Alterations in spine density have been linked to dysregulation of mTOR signaling and synaptic protein translation. Using a yeast two-hybrid system, we identified the mTOR-activating GTPase Rheb as an interacting protein of the NMDAR subunit NR3A. We confirmed the interaction in mammalian cells by expressing recombinant Rheb and NR3A and showed that Rheb and NR3A could be co-immunoprecipitated from synaptic plasma membranes from the developing rat brain. These data suggest that NR3A sequesters synaptic Rheb and might thus function as a break of the mTOR-dependent synaptic translation of protein.

Promoting Adherence to Psychotropic Medication for Youth-part 2

Journal of Psychosocial Nursing and Mental Health Services. Dec, 2010  |  Pubmed ID: 21117522

Although prescriptions for psychotropic medications for children are at an all-time high, medication adherence rates for children are often low. In Part 1 of this article set, literature regarding adherence to psychotropic medications for children was reviewed. Important issues related to adherence included parental and child attitudes, complex dosing schedules, and barriers to communication between parents and providers. In Part 2, the focus will be on strategies to improve medication adherence, including communication, education, and behavioral strategies.

Localized Disruption of Narp in Medial Prefrontal Cortex Blocks Reinforcer Devaluation Performance

Learning & Memory (Cold Spring Harbor, N.Y.). Dec, 2010  |  Pubmed ID: 21127001

Neuronal activity regulated pentraxin (Narp) is a secreted protein that regulates α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPAR) aggregation and synaptogenesis. Mapping of Narp-positive neurons in brain has revealed it is prominently expressed in several limbic system projection pathways. Consistent with this localization pattern, Narp knockout mice show deficits in using the current value of a reinforcer to guide behavior, a critical function of the limbic system. To help assess whether this behavioral deficit is due to impairment of synaptogenesis during development or in modulating synaptic signaling in the mature brain, we have used a dominant negative Narp viral construct which blocks trafficking of endogenous Narp to axons. Focal injection of this viral construct into the medial prefrontal cortex (mPFC) of adult mice, a region containing Narp-positive projection neurons, blocked reinforcer devaluation. Thus, these results indicate that Narp released from mPFC neurons plays a key role in mediating synaptic changes underlying instrumental reinforcer devaluation.

The Accuracy of Photoscreening at Detecting Treatable Ocular Conditions in Children with Down Syndrome

Journal of AAPOS : the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus. Dec, 2010  |  Pubmed ID: 21168069

Children with Down syndrome (DS) have an increased prevalence of ocular disorders, including amblyopia, strabismus, and refractive error. Health maintenance guidelines from the Down Syndrome Medical Interest Group recommend ophthalmologic examinations every 1 to 2 years for these children. Photoscreening may be a cost-effective option for subsequent screening evaluations after an initial complete examination, but no study has evaluated the accuracy of photoscreening in children with DS. The purpose of this study is to determine the sensitivity, specificity, and positive and negative predictive values of photoscreening in detecting treatable ocular conditions in children with DS.

Homeostatic Scaling Requires Group I MGluR Activation Mediated by Homer1a

Neuron. Dec, 2010  |  Pubmed ID: 21172614

Homeostatic scaling is a non-Hebbian form of neural plasticity that maintains neuronal excitability and informational content of synaptic arrays in the face of changes of network activity. Here, we demonstrate that homeostatic scaling is dependent on group I metabotropic glutamate receptor activation that is mediated by the immediate early gene Homer1a. Homer1a is transiently upregulated during increases in network activity and evokes agonist-independent signaling of group I mGluRs that scales down the expression of synaptic AMPA receptors. Homer1a effects are dynamic and play a role in the induction of scaling. Similar to mGluR-LTD, Homer1a-dependent scaling involves a reduction of tyrosine phosphorylation of GluA2 (GluR2), but is distinct in that it exploits a unique signaling property of group I mGluR to confer cell-wide, agonist-independent activation of the receptor. These studies reveal an elegant interplay of mechanisms that underlie Hebbian and non-Hebbian plasticity.

Past, Present, and Future: Critical Analysis of Use of Gastric Bands in Obese Patients

Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy. 2010  |  Pubmed ID: 21437077

Adjustable gastric banding (AGB) is quickly becoming the most popular bariatric operation performed in the United States and Canada. Patients are particularly fond of the simplicity of the tool, the relatively low morbidity of the surgery, the quick recovery, and overall results. The gastric band has evolved over its 35-year history into a very successful adjustable tool used to restrict food consumption and limit caloric intake. The percent of excessive weight loss after banding can range from 30%-60% and depends on the time out from surgery. Along with weight loss, there is good resolution of the co-morbid conditions that are associated with excess weight and improvements in quality of life demonstrated after banding. Nutrition and follow up are extremely important after banding to ensure good compliance and adequate weight loss. Failure to follow the postoperative diet, exercise regiment, or mechanical failure of the band can lead to failure to lose adequate weight. While there are particular early and late complications associated with this surgery, the safety profile of the AGB is very appealing when compared to other bariatric operations. As we continue to reduce the morbidity of the procedure, the simple adjustable band concept has a lot of potential to remain a primary technique of maintaining long term weight loss. In conclusion, AGB has and continues to play an important role in the treatment of morbid obesity. It offers reasonably good weight loss results with very little morbidity, and the future of the adjustable band is bright.

Total Pulmonary Vein Occlusion Complicating Pulmonary Vein Isolation: Diagnosis and Treatment

Heart Rhythm : the Official Journal of the Heart Rhythm Society. Sep, 2010  |  Pubmed ID: 20206715

Pulmonary vein stenosis (PVS) complicating pulmonary vein isolation (PVI) can progress to total pulmonary vein occlusion (PVO). Little is known about the accuracy of noninvasive diagnosis and treatment of PVO.

The Angelman Syndrome Protein Ube3A Regulates Synapse Development by Ubiquitinating Arc

Cell. Mar, 2010  |  Pubmed ID: 20211139

Angelman Syndrome is a debilitating neurological disorder caused by mutation of the E3 ubiquitin ligase Ube3A, a gene whose mutation has also recently been associated with autism spectrum disorders (ASDs). The function of Ube3A during nervous system development and how Ube3A mutations give rise to cognitive impairment in individuals with Angleman Syndrome and ASDs are not clear. We report here that experience-driven neuronal activity induces Ube3A transcription and that Ube3A then regulates excitatory synapse development by controlling the degradation of Arc, a synaptic protein that promotes the internalization of the AMPA subtype of glutamate receptors. We find that disruption of Ube3A function in neurons leads to an increase in Arc expression and a concomitant decrease in the number of AMPA receptors at excitatory synapses. We propose that this deregulation of AMPA receptor expression at synapses may contribute to the cognitive dysfunction that occurs in Angelman Syndrome and possibly other ASDs.

Long-term Impact of Respiratory Viral Infection After Pediatric Lung Transplantation

Pediatric Transplantation. May, 2010  |  Pubmed ID: 20214745

To evaluate the epidemiology and to investigate the impact of RVI on chronic allograft rejection after pediatric lung transplantation, a retrospective study of pediatric lung transplant recipients from 2002 to 2007 was conducted. Association between RVI and continuous and categorical risk factors was assessed using Wilcoxon rank-sum tests and Fisher's exact tests, respectively. Association between risk factors and outcomes were assessed using Cox proportional hazards models. Fifty-five subjects were followed for a mean of 674 days (range 14-1790). Twenty-eight (51%) developed 51 RVI at a median of 144 days post-transplant (mean 246; range 1-1276); 41% of infections were diagnosed within 90 days. Twenty-five subjects developed 39 LRI, and eight subjects had 11 URI. Organisms recovered included rhinovirus (n = 14), adenovirus (n = 10), parainfluenza (n = 10), influenza (n = 5), and RSV (n = 4). Three subjects expired secondary to their RVI (two adenovirus, one RSV). Younger age and prior CMV infection were risks for RVI (HR 2.4 95% CI 1.1-5.3 and 17.0; 3.0-96.2, respectively). RVI was not associated with the development of chronic allograft rejection (p = 0.25) or death during the study period. RVI occurs in the majority of pediatric lung transplant recipients, but was not associated with mortality or chronic allograft rejection.

Excimer Laser to Open Refractory Subclavian Occlusion in 12 Consecutive Patients

Heart Rhythm : the Official Journal of the Heart Rhythm Society. May, 2010  |  Pubmed ID: 20226892

Ideally, new leads are placed via the axillary/cephalic vein on the same side as the initial implant; however, 3.6% to 9% of patients have chronic total subclavian/innominate occlusion. In most cases, a wire can be manipulated across the occlusion and venoplasty safely performed. Occasionally, a wire will not cross, and additional tools are required.

Homer1a-dependent Crosstalk Between NMDA and Metabotropic Glutamate Receptors in Mouse Neurons

PloS One. 2010  |  Pubmed ID: 20305784

A large number of evidences suggest that group-I metabotropic glutamate receptors (mGluR1a, 1b, 1c, 5a, 5b) can modulate NMDA receptor activity. Interestingly, a physical link exists between these receptors through a Homer-Shank multi-protein scaffold that can be disrupted by the immediate early gene, Homer1a. Whether such a versatile link supports functional crosstalk between the receptors is unknown.

Circulating Blood Volumes: a Review of Measurement Techniques and a Meta-analysis in Children

ASAIO Journal (American Society for Artificial Internal Organs : 1992). May-Jun, 2010  |  Pubmed ID: 20335800

The accurate determination of circulating blood volume (CBV) in children has many clinical applications. The purposes of this article were to review currently available CBV measurement techniques and perform a meta-analysis using values from many small-scale studies that calculated CBV values for normal healthy children. A literature review demonstrated numerous methods by which to determine CBV. However, these methods necessitate repetitive blood sampling, require the introduction of foreign substances into the bloodstream, or address the uncertainty of substance distribution and clearance. Many small-scale studies have calculated CBV values for normal healthy children, and we performed a meta-analysis using these values. Age groups were defined, and within each group, means +/- 1 and 2 standard deviations were compared. A pooled estimate of mean blood volume and a 95% confidence interval was calculated after Q-statistics calculations indicated that the groups were homogeneous. Mean values showed agreement with typically accepted normal values. A large-scale study should be repeated when a gold standard for CBV measurements is developed.

Lead Exposure During Synaptogenesis Alters Vesicular Proteins and Impairs Vesicular Release: Potential Role of NMDA Receptor-dependent BDNF Signaling

Toxicological Sciences : an Official Journal of the Society of Toxicology. Jul, 2010  |  Pubmed ID: 20375082

Lead (Pb(2+)) exposure is known to affect presynaptic neurotransmitter release in both in vivo and cell culture models. However, the precise mechanism by which Pb(2+) impairs neurotransmitter release remains unknown. In the current study, we show that Pb(2+) exposure during synaptogenesis in cultured hippocampal neurons produces the loss of synaptophysin (Syn) and synaptobrevin (Syb), two proteins involved in vesicular release. Pb(2+) exposure also increased the number of presynaptic contact sites. However, many of these putative presynaptic contact sites lack Soluble NSF attachment protein receptor complex proteins involved in vesicular exocytosis. Analysis of vesicular release using FM 1-43 dye confirmed that Pb(2+) exposure impaired vesicular release and reduced the number of fast-releasing sites. Because Pb(2+) is a potent N-methyl-D-aspartate receptor (NMDAR) antagonist, we tested the hypothesis that NMDAR inhibition may be producing the presynaptic effects. We show that NMDAR inhibition by aminophosphonovaleric acid mimics the presynaptic effects of Pb(2+) exposure. NMDAR activity has been linked to the signaling of the transsynaptic neurotrophin brain-derived neurotrophic factor (BDNF), and we observed that both the cellular expression of proBDNF and release of BDNF were decreased during the same period of Pb(2+) exposure. Furthermore, exogenous addition of BDNF rescued the presynaptic effects of Pb(2+). We suggest that the presynaptic deficits resulting from Pb(2+) exposure during synaptogenesis are mediated by disruption of NMDAR-dependent BDNF signaling.

The Primary Care Osteoporosis Risk of Fracture Screening (POROS) Study: Design and Baseline Characteristics

Contemporary Clinical Trials. Jul, 2010  |  Pubmed ID: 20382273

POROS evaluates a 3-step fracture risk screening program in women 50-64 not previously diagnosed with osteoporosis. This report details the research design and baseline characteristics.

Widespread Transcription at Neuronal Activity-regulated Enhancers

Nature. May, 2010  |  Pubmed ID: 20393465

We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified approximately 12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis.

An Accurate, Clinically Feasible Multi-gene Expression Assay for Predicting Metastasis in Uveal Melanoma

The Journal of Molecular Diagnostics : JMD. Jul, 2010  |  Pubmed ID: 20413675

Uveal (ocular) melanoma is an aggressive cancer that often forms undetectable micrometastases before diagnosis of the primary tumor. These micrometastases later multiply to generate metastatic tumors that are resistant to therapy and are uniformly fatal. We have previously identified a gene expression profile derived from the primary tumor that is extremely accurate for identifying patients at high risk of metastatic disease. Development of a practical clinically feasible platform for analyzing this expression profile would benefit high-risk patients through intensified metastatic surveillance, earlier intervention for metastasis, and stratification for entry into clinical trials of adjuvant therapy. Here, we migrate the expression profile from a hybridization-based microarray platform to a robust, clinically practical, PCR-based 15-gene assay comprising 12 discriminating genes and three endogenous control genes. We analyze the technical performance of the assay in a prospective study of 609 tumor samples, including 421 samples sent from distant locations. We show that the assay can be performed accurately on fine needle aspirate biopsy samples, even when the quantity of RNA is below detectable limits. Preliminary outcome data from the prospective study affirm the prognostic accuracy of the assay. This prognostic assay provides an important addition to the armamentarium for managing patients with uveal melanoma, and it provides a proof of principle for the development of similar assays for other cancers.

Rural Clinicians As Research Collaborators: Keeping the "care" in Our Career

The Canadian Journal of Nursing Research = Revue Canadienne De Recherche En Sciences Infirmières. Mar, 2010  |  Pubmed ID: 20420089

A Novel Approach for Repair of an Efferent Limb Obstruction in a Gastrojejunostomy

The American Surgeon. Apr, 2010  |  Pubmed ID: 20420264

Treatment of Psychopathy: a Review and Brief Introduction to the Mental Model Approach for Psychopathy

Behavioral Sciences & the Law. Mar-Apr, 2010  |  Pubmed ID: 20422648

Psychopathy is thought by many to be an untreatable disorder. This article puts the treatment of psychopathy into historical context and reviews research on the treatment of the disorder with adults (K = 8) and youth (K = 5). Findings indicate that treatment for adults shows low to moderate success with three of eight studies demonstrating treatment gains. Treatment of youth appears to be more promising with six of eight studies showing treatment benefits. Although less than optimal success rates with adults, we suggest that bright line distinctions regarding the treatability of those with psychopathic characteristics from non-psychopathic individuals are inappropriate at this time. We conclude with directions for future research and briefly introduce the mental models approach for the treatment of psychopathy in youths.

Premature Infants Display Increased Noxious-evoked Neuronal Activity in the Brain Compared to Healthy Age-matched Term-born Infants

NeuroImage. Aug, 2010  |  Pubmed ID: 20438855

This study demonstrates that infants who are born prematurely and who have experienced at least 40days of intensive or special care have increased brain neuronal responses to noxious stimuli compared to healthy newborns at the same postmenstrual age. We have measured evoked potentials generated by noxious clinically-essential heel lances in infants born at term (8 infants; born 37-40weeks) and in infants born prematurely (7 infants; born 24-32weeks) who had reached the same postmenstrual age (mean age at time of heel lance 39.2+/-1.2weeks). These noxious-evoked potentials are clearly distinguishable from shorter latency potentials evoked by non-noxious tactile sensory stimulation. While the shorter latency touch potentials are not dependent on the age of the infant at birth, the noxious-evoked potentials are significantly larger in prematurely-born infants. This enhancement is not associated with specific brain lesions but reflects a functional change in pain processing in the brain that is likely to underlie previously reported changes in pain sensitivity in older ex-preterm children. Our ability to quantify and measure experience-dependent changes in infant cortical pain processing will allow us to develop a more rational approach to pain management in neonatal intensive care.

Promoting the Use of Equestrian Helmets: Another Opportunity for Injury Prevention

Journal of Emergency Nursing: JEN : Official Publication of the Emergency Department Nurses Association. May, 2010  |  Pubmed ID: 20457328

HnRNP C Promotes APP Translation by Competing with FMRP for APP MRNA Recruitment to P Bodies

Nature Structural & Molecular Biology. Jun, 2010  |  Pubmed ID: 20473314

Amyloid precursor protein (APP) regulates neuronal synapse function, and its cleavage product Abeta is linked to Alzheimer's disease. Here, we present evidence that the RNA-binding proteins (RBPs) heterogeneous nuclear ribonucleoprotein (hnRNP) C and fragile X mental retardation protein (FMRP) associate with the same APP mRNA coding region element, and they influence APP translation competitively and in opposite directions. Silencing hnRNP C increased FMRP binding to APP mRNA and repressed APP translation, whereas silencing FMRP enhanced hnRNP C binding and promoted translation. Repression of APP translation was linked to colocalization of FMRP and tagged APP RNA within processing bodies; this colocalization was abrogated by hnRNP C overexpression or FMRP silencing. Our findings indicate that FMRP represses translation by recruiting APP mRNA to processing bodies, whereas hnRNP C promotes APP translation by displacing FMRP, thereby relieving the translational block.

Gastrointestinal Stromal Tumor with Hemoperitoneum Masquerading As Appendicitis

International Surgery. Jan-Mar, 2010  |  Pubmed ID: 20480834

Gastrointestinal stromal tumor (GIST) is a rare condition with an annual worldwide incidence of 11 to 15 cases per million, with nearly 5000 cases occurring in the United States yearly. This tumor is found often when patients present with intraluminal gastrointestinal hemorrhage. Other manifestations include early satiety and unintentional weight loss. Multislice computed tomography is an appropriate modality used to diagnosis a GIST after clinical suspicion warrants such imaging. Hemoperitoneum secondary to ruptured GIST is rare. Our patient presented with classic appendicitis, but the etiology of his right lower-quadrant pain with peritonitis was found to be hemoperitoneum secondary to ruptured GIST originating from the ileum.

A Catalog of Reference Genomes from the Human Microbiome

Science (New York, N.Y.). May, 2010  |  Pubmed ID: 20489017

The human microbiome refers to the community of microorganisms, including prokaryotes, viruses, and microbial eukaryotes, that populate the human body. The National Institutes of Health launched an initiative that focuses on describing the diversity of microbial species that are associated with health and disease. The first phase of this initiative includes the sequencing of hundreds of microbial reference genomes, coupled to metagenomic sequencing from multiple body sites. Here we present results from an initial reference genome sequencing of 178 microbial genomes. From 547,968 predicted polypeptides that correspond to the gene complement of these strains, previously unidentified ("novel") polypeptides that had both unmasked sequence length greater than 100 amino acids and no BLASTP match to any nonreference entry in the nonredundant subset were defined. This analysis resulted in a set of 30,867 polypeptides, of which 29,987 (approximately 97%) were unique. In addition, this set of microbial genomes allows for approximately 40% of random sequences from the microbiome of the gastrointestinal tract to be associated with organisms based on the match criteria used. Insights into pan-genome analysis suggest that we are still far from saturating microbial species genetic data sets. In addition, the associated metrics and standards used by our group for quality assurance are presented.

A Specific Requirement of Arc/Arg3.1 for Visual Experience-induced Homeostatic Synaptic Plasticity in Mouse Primary Visual Cortex

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. May, 2010  |  Pubmed ID: 20505084

Visual experience scales down excitatory synapses in the superficial layers of visual cortex in a process that provides an in vivo paradigm of homeostatic synaptic scaling. Experience-induced increases in neural activity rapidly upregulates mRNAs of immediate early genes involved in synaptic plasticity, one of which is Arc (activity-regulated cytoskeleton protein or Arg3.1). Cell biological studies indicate that Arc/Arg3.1 protein functions to recruit endocytic machinery for AMPA receptor internalization, and this action, together with its activity-dependent expression, rationalizes a role for Arc/Arg3.1 in homeostatic synaptic scaling. Here, we investigated the role of Arc/Arg3.1 in homeostatic scaling in vivo by examining experience-dependent development of layer 2/3 neurons in the visual cortex of Arc/Arg3.1 knock-out (KO) mice. Arc/Arg3.1 KOs show minimal changes in basal and developmental regulation of excitatory synaptic strengths but display a profound deficit in homeostatic regulation of excitatory synapses by visual experience. As additional evidence of specificity, we found that the visual experience-induced regulation of inhibitory synapses is normal, although the basal inhibitory synaptic strength is increased in the Arc/Arg3.1 KOs. Our results demonstrate that Arc/Arg3.1 plays a selective role in regulating visual experience-dependent homeostatic plasticity of excitatory synaptic transmission in vivo.

A Case Report of Hereditary Leiomyomatosis and Renal Cell Cancer

American Journal of Obstetrics and Gynecology. Jun, 2010  |  Pubmed ID: 20510956

A 27-year-old woman, gravida 0, presented with uterine and cutaneous leiomyomata. Genetic testing confirmed hereditary leiomyomatosis and renal cell cancer syndrome, an autosomal dominant disorder caused by germline mutations in the fumarate hydratase gene. Specific screening guidelines do not exist and are often individual and treatment center dependent.

PDP or MA-PD? Medicare Part D Enrollment Decisions in CMS Region 25

Research in Social & Administrative Pharmacy : RSAP. Jun, 2010  |  Pubmed ID: 20511112

The Medicare Prescription Drug Improvement and Modernization Act of 2003 provides outpatient prescription drug coverage for Medicare beneficiaries through private insurers. This coverage is available through 2 primary venues: stand-alone prescription drug plans (PDPs) and integrated managed care (or Medicare Advantage) plans that also provide prescription drug coverage (MA-PDs).

Falls Are a Fact of Life for Some Patients After Discharge from a Rehabilitation Programme

Disability and Rehabilitation. 2010  |  Pubmed ID: 20540625

This paper reports on a 3-month post-discharge falls profile of a cohort of patients discharged home from an acute rehabilitation setting.

Male Reproductive Senescence Causes Potential for Sexual Conflict over Mating

Current Biology : CB. Jul, 2010  |  Pubmed ID: 20579882

The realization that senescence, age-dependent declines in survival and reproductive performance, pervades natural populations has brought its evolutionary significance into sharper focus. However, reproductive senescence remains poorly understood because it is difficult to separate male and female mechanisms underpinning reproductive success. We experimentally investigated male reproductive senescence in feral fowl, Gallus gallus domesticus, where socially dominant males monopolize access to females and the ejaculates of multiple males compete for fertilization. We detected the signal of senescence on multiple determinants of male reproductive success. The effect of age on status was dependent upon the intensity of intrasexual competition: old males were less likely to dominate male-biased groups where competition is intense but were as likely as young males to dominate female-biased groups. Mating and fertilization success declined sharply with male age largely as a result of population-level patterns. These age-dependent declines translated into sexually antagonistic payoffs: old males fertilized more eggs when they were dominant, but this resulted in females suffering a drastic reduction in fertility. Thus, male senescence causes potential for sexual conflict over mating, and the intensity of this conflict is modulated socially, by the probability of old males dominating reproductive opportunities.

Service Utilization During and After Outpatient Treatment for Comorbid Substance Use Disorder and Depression

Journal of Substance Abuse Treatment. Sep, 2010  |  Pubmed ID: 20598832

Patients with comorbid substance use disorder (SUD) and depression incur greater treatment costs than those with either disorder alone. Integrated treatment targeting both issues concurrently has been shown to reduce substance use and depression in this population, but little is known about the effects of such treatment on the utilization of costly health services. This study compared 18-month patterns of service utilization for 236 veterans with comorbid SUD depression randomly assigned to 6 months of either Integrated Cognitive Behavioral Therapy (ICBT) or Twelve-Step Facilitation Therapy. Treatment group differences were found for the utilization of psychotropic medication services and inpatient hospitalization. Higher rates of therapy attendance, lower baseline depression, and receiving ICBT all predicted shorter admissions for those hospitalized during treatment. Ethnicity and gender predicted medication service use both during and following treatment. The findings provide evidence supporting the long-term cost-effectiveness of integrated treatment for this high-risk population.

Meeting the Challenges of Training More Medical Students: Lessons from Flinders University's Distributed Medical Education Program

The Medical Journal of Australia. Jul, 2010  |  Pubmed ID: 20618112

To use data from an evaluation of the Flinders University Parallel Rural Community Curriculum (PRCC) to inform four immediate challenges facing medical education in Australia as medical student numbers increase.

MHC Heterozygosity and Survival in Red Junglefowl

Molecular Ecology. Aug, 2010  |  Pubmed ID: 20618904

Genes of the major histocompatibility complex (MHC) form a vital part of the vertebrate immune system and play a major role in pathogen resistance. The extremely high levels of polymorphism observed at the MHC are hypothesised to be driven by pathogen-mediated selection. Although the exact nature of selection remains unclear, three main hypotheses have been put forward; heterozygote advantage, negative frequency-dependence and fluctuating selection. Here, we report the effects of MHC genotype on survival in a cohort of semi-natural red junglefowl (Gallus gallus) that suffered severe mortality as a result of an outbreak of the disease coccidiosis. The cohort was followed from hatching until 250 days of age, approximately the age of sexual maturity in this species, during which time over 80% of the birds died. We show that on average birds with MHC heterozygote genotypes survived infection longer than homozygotes and that this effect was independent of genome-wide heterozygosity, estimated across microsatellite loci. This MHC effect appeared to be caused by a single susceptible haplotype (CD_c) the effect of which was masked in all heterozygote genotypes by other dominant haplotypes. The CD_c homozygous genotype had lower survival than all other genotypes, but CD_c heterozygous genotypes had survival probabilities equal to the most resistant homozygote genotype. Importantly, no heterozygotes conferred greater resistance than the most resistant homozygote genotype, indicating that the observed survival advantage of MHC heterozygotes was the product of dominant, rather than overdominant processes. This pattern and effect of MHC diversity in our population could reflect the processes ongoing in similarly small, fragmented natural populations.

Prevalence of Iron Deficiency in Children with Down Syndrome

The Journal of Pediatrics. Dec, 2010  |  Pubmed ID: 20650467

To determine the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in a sample of children with Down syndrome (DS) and to evaluate the effect of macrocytosis on the diagnosis of ID/IDA in these children.

Expression of the Retinoblastoma-related Gene Rb2/p130 in the Pathogenesis of Serous Carcinoma of the Ovary

Applied Immunohistochemistry & Molecular Morphology : AIMM / Official Publication of the Society for Applied Immunohistochemistry. Dec, 2010  |  Pubmed ID: 20661130

The purpose of this study was to evaluate the immunohistochemical Rb2/p130 expression in a series of benign, borderline, and malignant ovarian tumors.

Identification and Removal of Colanic Acid from Plasmid DNA Preparations: Implications for Gene Therapy

Gene Therapy. Dec, 2010  |  Pubmed ID: 20664542

Polysaccharide contaminants in plasmid DNA, including current good manufacturing practices (cGMP) clinical preparations, must be removed to provide the greatest safety and efficacy for use in gene therapy and other clinical applications. We developed assays and methods for the detection and removal of these polysaccharides, our Super Clean DNA (SC-DNA) process, and have shown that these contaminants in plasmid DNA preparations are responsible for toxicity observed post-injection in animals. Furthermore, these contaminants limit the efficacy of low and high doses of plasmid DNA administered by numerous delivery routes. In particular, colanic acid (CA) that is mainly long-chained, branched and has high molecular weight (MW) is most refractory when complexed to cationic delivery vehicles and injected intravenously (IV). Because CA is often extremely large and tightly intertwined with DNA, it must be degraded, in order, to be effectively removed. We have produced a recombinant, truncated colanic acid degrading enzyme (CAE) that successfully accomplishes this task. Initially, we isolated a newly identified CAE from a bacteriophage that required truncation for proper folding while retaining its full enzymatic activity during production. Any plasmid DNA preparation can be digested with CAE and further purified, providing a critical advance to non-viral gene therapy.

Mechanism of Photolytic Decomposition of N-halamine Antimicrobial Siloxane Coatings

ACS Applied Materials & Interfaces. Aug, 2010  |  Pubmed ID: 20669910

Generally, antimicrobial N-halamine siloxane coatings can be rehalogenated repetitively upon loss of their biocidal efficacies, a marked advantage over coatings containing other antimicrobial materials. However, the N-halamine materials tend to slowly decompose upon exposure to ultraviolet irradiation as in direct sunlight. In this work the mechanism of photolytic decomposition for the N-halamine siloxanes has been studied using spectroscopic and theoretical methods. It was found that the N-chlorinated coatings slowly decomposed upon UVA irradiation, whereas the unhalogenated coatings did not. Model compound evidence in this work suggests that upon UVA irradiation, the N-Cl bond dissociates homolytically, followed by a Cl radical migration to the alkyl side chain connected to the siloxane tethering group. An alpha and/or beta scission then occurs causing partial loss of the biocidal moiety from the surface of the coated material, thus precluding complete rechlorination. NMR, FTIR, GCMS, and computations at the DFT (U)B3LYP/6-311++G(2d,p) level of theory have been employed in reaching this conclusion.

Effect of Fractionation and Pyrolysis on Fuel Properties of Poultry Litter

Journal of the Air & Waste Management Association (1995). Jul, 2010  |  Pubmed ID: 20681435

Raw poultry litter has certain drawbacks for energy production such as high ash and moisture content, a corrosive nature, and low heating values. A combined solution to utilization of raw poultry litter may involve fractionation and pyrolysis. Fractionation divides poultry litter into a fine, nutrient-rich fraction and a coarse, carbon-dense fraction. Pyrolysis of the coarse fraction would remove the corrosive volatiles as bio-oil, leaving clean char. This paper presents the effect of fractionation and pyrolysis process parameters on the calorific value of char and on the characterization of bio-oil. Poultry litter samples collected from three commercial poultry farms were divided into 10 treatments that included 2 controls (raw poultry litter and its coarse fraction having particle size greater than 0.85 mm) and 8 other treatments that were combinations of three factors: type (raw poultry litter or its coarse fraction), heating rate (30 or 10 degrees C/min), and pyrolysis temperature (300 or 500 degrees C). After the screening process, the poultry litter samples were dried and pyrolyzed in a batch reactor under nitrogen atmosphere and char and condensate yields were recorded. The condensate was separated into three fractions on the basis of their density: heavy, medium, and light phase. Calorific value and proximate and nutrient analysis were performed for char, condensate, and feedstock. Results show that the char with the highest calorific value (17.39 +/- 1.37 MJ/kg) was made from the coarse fraction at 300 degrees C, which captured 68.71 +/- 9.37% of the feedstock energy. The char produced at 300 degrees C had 42 +/- 11 mg/kg arsenic content but no mercury. Almost all of the Al, Ca, Fe, K, Mg, Na, and P remained in the char. The pyrolysis process reduced ammoniacal-nitrogen (NH4-N) in char by 99.14 +/- 0.47% and nitrate-nitrogen (NO3-N) by 95.79 +/- 5.45% at 500 degrees C.

Urban Indian Voices: a Community-based Participatory Research Health and Needs Assessment

American Indian and Alaska Native Mental Health Research (Online). 2010  |  Pubmed ID: 20683823

This community-based participatory research (CBPR) project utilized a mixed-methods survey design to identify urban (Tulsa, OK) American Indian (AI) strengths and needs. Six hundred fifty AIs (550 adults and 100 youth) were surveyed regarding their attitudes and beliefs about their community. These results were used in conjunction with other community research efforts to inform program development, support proposals for external funding, and develop a comprehensive service system model to be implemented in the community.

Cutting Edge: Association with I Kappa B Kinase Beta Regulates the Subcellular Localization of Homer3

Journal of Immunology (Baltimore, Md. : 1950). Sep, 2010  |  Pubmed ID: 20693425

The signaling and adaptor protein Homer3 plays a role in controlling immune homeostasis and self-reactivity. Homer3 is recruited to the immune synapse (IS) following TCR ligation, although the mechanisms regulating this subcellular localization are unknown. We show that Homer3 specifically associates with a novel ubiquitin-like domain in the IkappaB kinase (IKK) beta subunit of the IKK complex. Homer3 associates with IKKbeta in T cells and colocalizes with the IKK complex at the IS. However, Homer3 is not required for IKK activation, as NF-kappaB signaling is intact in Homer3-deficient T cells. Instead, the IKK complex recruits Homer3 to the IS following TCR engagement, and we present evidence that this association regulates actin dynamics in T cells. These findings identify a novel interaction between two major signaling proteins and reveal an unexpected NF-kappaB-independent function for the IKK complex in regulating the subcellular localization of Homer3.

SRF Binding to SRE 6.9 in the Arc Promoter is Essential for LTD in Cultured Purkinje Cells

Nature Neuroscience. Sep, 2010  |  Pubmed ID: 20694003

It has been suggested that gene expression and protein synthesis are required for both long-term memory consolidation and late phases of long-term potentiation and long-term depression (LTD). The necessary genes and the specific transcription factor binding sites in their promoters remain unknown. We found that inhibition of the transcription factor SRF or its cofactor MAL blocked the late phase of LTD in mouse cultured cerebellar Purkinje cells, as did deletion of the immediate early gene Arc. Using neuronal bacterial artificial chromosome (BAC) transfection, we found that, in Arc-/- cells transfected with a wild-type Arc BAC, late-phase LTD was rescued. However, mutation of one SRF-binding site in the Arc promoter (SRE 6.9) blocked this rescue. Co-transfection of wild-type Arc and SRF engineered to bind mutated SRE 6.9 restored late-phase LTD in Arc-/-, SRE 6.9 mutant BAC cells. Thus, SRF binding to SRE 6.9 in the Arc promoter is required for the late phase of cerebellar LTD.

Functional Integration of New Neurons into Hippocampal Networks and Poststroke Comorbidities Following Neonatal Stroke in Mice

Epilepsy & Behavior : E&B. Aug, 2010  |  Pubmed ID: 20708575

Stroke in the developing brain is an important cause of chronic neurological morbidities including neurobehavioral dysfunction and epilepsy. Here, we describe a mouse model of neonatal stroke resulting from unilateral carotid ligation that results in acute seizures, long-term hyperactivity, spontaneous lateralized circling behavior, impaired cognitive function, and epilepsy. Exploration-dependent induction of the immediate early gene Arc (activity-regulated cytoskeleton associated protein) in hippocampal neurons was examined in the general population of neurons versus neurons that were generated approximately 1 week after the ischemic insult and labeled with bromodeoxyuridine. Although Arc was inducible in a network-specific manner after severe neonatal stroke, it was impaired, not only in the ipsilateral injured but also in the contralateral uninjured hippocampi when examined 6 months after the neonatal stroke. Severity of both the stroke injury and the acquired poststroke epilepsy negatively correlated with Arc induction and new neuron integration into functional circuits in the injured hippocampi.

An Endoplasmic Reticulum/plasma Membrane Junction: STIM1/Orai1/TRPCs

FEBS Letters. May, 2010  |  Pubmed ID: 19944100

Ca(2+) entering cells through store-operated channels (SOCs) affects most cell functions, and excess SOC is associated with pathologies. The molecular makeup of SOCs and their mechanisms of gating were clarified with the discovery of the Orais and STIM1. Another form of SOCs are the TRPCs. STIM1 gates both Orai and TRPC channels but does so by different mechanisms. Although the STIM1 SOAR domain mediates the binding of STIM1 to both channel types, SOAR is sufficient to open the Orais but the STIM1 polylysine domain mediates opening of the TRPC channels. This short review discusses recent findings on how STIM1 gates and regulates the Orais and TRPCs, and how the STIM1/Orai1/TRPCs complexes may function in vivo to mediate SOC activity.

Comparison of Clinical Evaluation of Genitourinary Symptoms in Female Adolescents Among Primary Care Versus Emergency Department Physicians

Journal of Pediatric and Adolescent Gynecology. Apr, 2010  |  Pubmed ID: 19643640

To compare clinical approaches to assessment and treatment of female adolescents with genitourinary symptoms among primary care and emergency department (ED) physicians.

A Comparative Analysis of Recruitment Methods Used in a Randomized Trial of Diabetes Education Interventions

Contemporary Clinical Trials. Nov, 2010  |  Pubmed ID: 20713181

Recruitment methods heavily impact budget and outcomes in clinical trials. We conducted a post-hoc examination of the efficiency and cost of three different recruitment methods used in Journey for Control of Diabetes: the IDEA Study, a randomized controlled trial evaluating outcomes of group and individual diabetes education in New Mexico and Minnesota. Electronic databases were used to identify health plan members with diabetes and then one of the following three methods was used to recruit study participants: 1. Minnesota Method 1--Mail only (first half of recruitment period). Mailed invitations with return-response forms. 2. Minnesota Method 2--Mail and selective phone calls (second half of recruitment period). Mailed invitations with return-response forms and subsequent phone calls to nonresponders. 3. New Mexico Method 3--Mail and non-selective phone calls (full recruitment period): Mailed invitations with subsequent phone calls to all. The combined methods succeeded in meeting the recruitment goal of 623 subjects. There were 147 subjects recruited using Minnesota's Method 1, 190 using Minnesota's Method 2, and 286 using New Mexico's Method 3. Efficiency rates (percentage of invited patients who enrolled) were 4.2% for Method 1, 8.4% for Method 2, and 7.9% for Method 3. Calculated costs per enrolled subject were $71.58 (Method 1), $85.47 (Method 2), and $92.09 (Method 3). A mail-only method to assess study interest was relatively inexpensive but not efficient enough to sustain recruitment targets. Phone call follow-up after mailed invitations added to recruitment efficiency. Use of return-response forms with selective phone follow-up to non-responders was cost effective.

Narp Regulates Homeostatic Scaling of Excitatory Synapses on Parvalbumin-expressing Interneurons

Nature Neuroscience. Sep, 2010  |  Pubmed ID: 20729843

Homeostatic synaptic scaling alters the strength of synapses to compensate for prolonged changes in network activity and involves both excitatory and inhibitory neurons. The immediate-early gene Narp (neuronal activity-regulated pentraxin) encodes a secreted synaptic protein that can bind to and induce clustering of AMPA receptors (AMPARs). We found that Narp prominently accumulated at excitatory synapses on parvalbumin-expressing interneurons (PV-INs). Increasing network activity resulted in a homeostatic increase of excitatory synaptic strength onto PV-INs that increased inhibitory drive and this response was absent in neurons cultured from Narp-/- mice. Activity-dependent changes in the strength of excitatory inputs on PV-INs in acute hippocampal slices were also dependent on Narp and Narp-/- mice had increased sensitivity to kindling-induced seizures. We propose that Narp recruits AMPARs at excitatory synapses onto PV-INs to rebalance network excitation/inhibition dynamics following episodes of increased circuit activity.

Gene Expression Analysis Identifies Potential Biomarkers of Neurofibromatosis Type 1 Including Adrenomedullin

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Oct, 2010  |  Pubmed ID: 20739432

Plexiform neurofibromas (pNF) are Schwann cell tumors found in a third of individuals with neurofibromatosis type 1 (NF1). pNF can undergo transformation to malignant peripheral nerve sheath tumors (MPNST). There are no identified serum biomarkers of pNF tumor burden or transformation to MPNST. Serum biomarkers would be useful to verify NF1 diagnosis, monitor tumor burden, and/or detect transformation.

Association Between Gene Expression Profile, Proliferation and Metastasis in Uveal Melanoma

Current Eye Research. Sep, 2010  |  Pubmed ID: 20795869

Uveal melanomas cluster into two molecular groups based on their gene expression profile. Tumors with the class 1 signature rarely metastasize, whereas those with the class 2 signature have a very high rate of metastasis. However, the biological basis for this metastatic propensity of class 2 tumors remains unclear. Towards such an explanation, this study was conducted to determine whether class 2 tumors have a higher proliferative rate than class 1 tumors.

Oral Sucrose As an Analgesic Drug for Procedural Pain in Newborn Infants: a Randomised Controlled Trial

Lancet. Oct, 2010  |  Pubmed ID: 20817247

Many infants admitted to hospital undergo repeated invasive procedures. Oral sucrose is frequently given to relieve procedural pain in neonates on the basis of its effect on behavioural and physiological pain scores. We assessed whether sucrose administration reduces pain-specific brain and spinal cord activity after an acute noxious procedure in newborn infants.

A Clinical Picture of Guillain-Barré Syndrome in Children in the United States

Journal of Child Neurology. Dec, 2010  |  Pubmed ID: 20823034

The authors describe the demographics, clinical presentation, investigation, treatment, and outcomes of pediatric patients with Guillain-Barré syndrome. They identified 35 pediatric patients with Guillain-Barré syndrome presenting to a tertiary academic center over a 20-year period. The most common presenting symptoms were paresthesias (54%), weakness (49%), and myalgias (49%). Sensation was affected in 54% of patients, and hyporeflexia or areflexia was present in 94% of patients. Cranial nerve dysfunction (46%) and autonomic involvement (eg, changes in blood pressure, pulse, bowel/bladder control, or priapism; 46%) were also common. Autonomic dysfunction, cranial nerve involvement, and albuminocytological dissociation were significantly associated with a decreased time to nadir, the point when symptoms peaked (P = .015, .007, and .005, respectively). Although not statistically significant, treatment with plasmapheresis had a better success rate than intravenous immunoglobulin. The authors' results will help to further delineate the clinical picture of Guillain-Barré syndrome in children and refine treatment strategies.

Attenuated Long-term Arc Expression in the Aged Fascia Dentata

Neurobiology of Aging. Sep, 2010  |  Pubmed ID: 20850902

One prominent component of aging is a defect in memory stabilization. To understand how the formation of enduring memories is altered in the aged brain, long-term markers of the biological events that may mediate memory consolidation were used to examine the activity dynamics of hippocampal circuits over extended intervals. The immediate early gene Arc, which is implicated in both durable memory and synaptic plasticity, is expressed in the fascia dentata (FD) for long periods following behavioral experience. To test the hypothesis that aging alters long-term Arc transcription in the FD, a region critical for spatial memory and impaired with progressive age, young and aged rats explored a novel environment twice, separated by an 8-hour interval, and FD Arc transcription was assessed. Relative to young rats, (a) fewer granule cells in the aged FD transcribe arc 8 hours after spatial exploration, and (b) this decrease is correlated with impaired spatial memory. These findings are consistent with behavioral evidence of age-related decline in hippocampal-dependent memory processing long after an event is to be remembered, and reaffirm the integral role of the FD in the neural circuits supporting durable memory.

Promoting Adherence to Psychotropic Medication for Youth-part 1

Journal of Psychosocial Nursing and Mental Health Services. Oct, 2010  |  Pubmed ID: 20873702

Failure to adhere to medication regimens can lead to unnecessary disease progression, disease complications, reduced functional abilities, lower quality of life, and even death. Medication adherence for children taking psychotropic agents poses many special challenges for health care professionals, as there is a little empirical basis for improving adherence. In Part 1 of this two-part series, the limited literature on the topic of psychotropic medication adherence for youth is reviewed.

STIM1-dependent and STIM1-independent Function of Transient Receptor Potential Canonical (TRPC) Channels Tunes Their Store-operated Mode

The Journal of Biological Chemistry. Dec, 2010  |  Pubmed ID: 20926378

Ca(2+) influx by store-operated Ca(2+) channels is a key component of the receptor-evoked Ca(2+) signal. In all cells examined, transient receptor potential canonical (TRPC) channels mediate a significant portion of the receptor-stimulated Ca(2+) influx. Recent studies have revealed how STIM1 activates TRPC1 in response to store depletion; however, the role of STIM1 in TRPC channel activation by receptor stimulation is not fully understood. Here, we established mutants of TRPC channels that could not be activated by STIM1 but were activated by the "charge-swap" mutant STIM1(K684E,K685E). Significantly, WT but not mutant TRPC channels were inhibited by scavenging STIM1 with Orai1(R91W), indicating the STIM1 dependence and independence of WT and mutant TRPC channels, respectively. Importantly, mutant TRPC channels were robustly activated by receptor stimulation. Moreover, STIM1 and STIM1(K684E,K685E) reciprocally affected receptor-activated WT and mutant TRPC channels. Together, these findings indicate that TRPC channels can function as STIM1-dependent and STIM1-independent channels, which increases the versatility of TRPC channel function and their role in receptor-stimulated Ca(2+) influx.

Development of the Rural Immersion Programme for 5th-year Medical Students at the University Of Otago

The New Zealand Medical Journal. Sep, 2010  |  Pubmed ID: 20930906

To report the development of the first Rural Medical Immersion Programme (RMIP) of the University of Otago in New Zealand.

Peak Circulatory Power As an Indicator of Clinical Status in Children After Fontan Procedure

Pediatric Cardiology. Nov, 2010  |  Pubmed ID: 20957479

Peak circulatory power (CircP), a product of peak exercise oxygen uptake (VO(2)) and peak mean or systolic arterial blood pressure, has proved to be a strong predictor of poor outcome in adults with congenital heart disease. This study sought to compare CircP with other cardiopulmonary exercise (CPX) test variables and to assess whether CircP is superior in categorizing patients into well-functioning vs. poorly functioning at-risk groups in the pediatric population after a Fontan procedure. The CPX test reports of 50 patients were retrospectively reviewed after the Fontan procedure. The patients were divided into two groups. The well-functioning group included patients in New York Heart Association (NYHA) classes 1 and 2 (n = 36). The poorly functioning at-risk group included patients in NYHA classes 3 and 4 and those with significant indicators or outcomes of a poor prognosis (n = 14). The patients in the well-functioning group had significantly higher CircP values based on mean blood pressure (MBP) (P < 0.001), higher CircP values based on systolic blood pressure (SBP) (P < 0.001), and higher peak VO(2) (P = 0.004) than those in the poorly functioning at-risk group. At a cutoff value less than 2100.4 mmHg/mlO(2)/kg/min, CircP MBP had a sensitivity of 85% in categorizing children to the poorly functioning at-risk group. CircP correlated well with the clinical status of our patients. CircP and peak VO(2) did not differ significantly in ability to identify poorly functioning patients. Further prospective analysis is needed to assess whether CircP can serve as a prognostic marker for the pediatric population after Fontan procedure.

Development of Diagnostic Criteria for Serious Non-AIDS Events in HIV Clinical Trials

HIV Clinical Trials. Jul-Aug, 2010  |  Pubmed ID: 20974576

Serious non-AIDS (SNA) diseases are important causes of morbidity and mortality in the HAART era. We describe development of standard criteria for 12 SNA events for Endpoint Review Committee (ERC) use in START, a multicenter international HIV clinical trial.

The Effects of Inattention/impulsivity and ASD Symptom Severity on Social Skills in Toddlers

Developmental Neurorehabilitation. 2010  |  Pubmed ID: 21034283

The aim of the current study was to examine the effects of symptom severity of ASD and symptom severity of inattention and impulsivity in toddlers to determine the potential impact on social skills.

Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas

Science (New York, N.Y.). Dec, 2010  |  Pubmed ID: 21051595

Metastasis is a defining feature of malignant tumors and is the most common cause of cancer-related death, yet the genetics of metastasis are poorly understood. We used exome capture coupled with massively parallel sequencing to search for metastasis-related mutations in highly metastatic uveal melanomas of the eye. Inactivating somatic mutations were identified in the gene encoding BRCA1-associated protein 1 (BAP1) on chromosome 3p21.1 in 26 of 31 (84%) metastasizing tumors, including 15 mutations causing premature protein termination and 5 affecting its ubiquitin carboxyl-terminal hydrolase domain. One tumor harbored a frameshift mutation that was germline in origin, thus representing a susceptibility allele. These findings implicate loss of BAP1 in uveal melanoma metastasis and suggest that the BAP1 pathway may be a valuable therapeutic target.

Pediatric Specialists' Beliefs About Gastroesophageal Reflux Disease in Premature Infants

Pediatrics. Jan, 2010  |  Pubmed ID: 20008431

Wide variation exists in the treatment of suspected gastroesophageal reflux disease (GERD) in premature infants; it is unknown to what degree diagnosis and treatment are affected by the treating physician's medical specialty or interpretation of the medical literature.

Minimal Acute Rejection in Pediatric Lung Transplantation--does It Matter?

Pediatric Transplantation. Jun, 2010  |  Pubmed ID: 20059725

In adult lung transplantation, a single minimal AR episode is a significant predictor of BOS independent of other factors. However, the significance of single minimal AR episodes in children is unknown. A retrospective, multi-center analysis was performed to determine whether isolated single AR episodes are associated with an increased BOS risk in children. Risk factors for BOS, death, or re-transplantation, and a combined outcome of BOS, death, or re-transplantation were assessed. Original data included 577 patients (<21 yr of age). A total of 383 subjects were eligible for the study. Fifteen percent of patients developed BOS, and 13% of patients either died or underwent re-transplant within one-yr post-transplant. In the multivariable survival model for time to BOS, there was no significant risk to developing BOS after a single minimal AR (A1) episode (HR 1.7, 95% CI 0.64-4.8; p=0.28). Even after a second minimal AR episode, no significant risk for BOS was appreciated. However, a single episode of mild AR (A2) was associated with twice the risk of BOS within one-yr post-transplant. In this select cohort, a single minimal AR episode was not associated with an increased risk for BOS within one yr following lung transplantation, in contrast to previous reports in adults.

Safety and Early Outcomes Using a Corticosteroid-avoidance Immunosuppression Protocol in Pediatric Heart Transplant Recipients

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. May, 2010  |  Pubmed ID: 20061164

Long-term oral corticosteroids have been a mainstay of maintenance immunosuppression in pediatric heart transplantation. In this study, we report early clinical outcomes in a cohort of pediatric heart transplant recipients managed using a steroid-avoidance protocol.

Functional and Evolutionary Insights from the Genomes of Three Parasitoid Nasonia Species

Science (New York, N.Y.). Jan, 2010  |  Pubmed ID: 20075255

We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.

Genetics: Decoding a National Treasure

Nature. Jan, 2010  |  Pubmed ID: 20090741

Mortality Outcomes in Pediatric Rheumatology in the US

Arthritis and Rheumatism. Feb, 2010  |  Pubmed ID: 20112378

To describe mortality rates, causes of death, and potential mortality risk factors in pediatric rheumatic diseases in the US.

Revealing a Signaling Role of Phytosphingosine-1-phosphate in Yeast

Molecular Systems Biology. 2010  |  Pubmed ID: 20160710

Sphingolipids including sphingosine-1-phosphate and ceramide participate in numerous cell programs through signaling mechanisms. This class of lipids has important functions in stress responses; however, determining which sphingolipid mediates specific events has remained encumbered by the numerous metabolic interconnections of sphingolipids, such that modulating a specific lipid of interest through manipulating metabolic enzymes causes 'ripple effects', which change levels of many other lipids. Here, we develop a method of integrative analysis for genomic, transcriptomic, and lipidomic data to address this previously intractable problem. This method revealed a specific signaling role for phytosphingosine-1-phosphate, a lipid with no previously defined specific function in yeast, in regulating genes required for mitochondrial respiration through the HAP complex transcription factor. This approach could be applied to extract meaningful biological information from a similar experimental design that produces multiple sets of high-throughput data.

Autoimmune Hepatitis in Children--impact of Cirrhosis at Presentation on Natural History and Long-term Outcome

Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. Oct, 2010  |  Pubmed ID: 20163994

Little is known regarding the natural history of autoimmune hepatitis in children. The aims of this longitudinal cohort study were to determine the long-term prognosis of children with autoimmune hepatitis and to determine the effect of cirrhosis at presentation on survival.

Evoked Potentials Generated by Noxious Stimulation in the Human Infant Brain

European Journal of Pain (London, England). Mar, 2010  |  Pubmed ID: 19481484

While human infants can display distinctive behavioural and physiological spinal cord and brainstem responses to noxious stimulation, it is not known whether cortical neurons are specifically activated by noxious stimuli in newborns. Here, using a novel approach to time-lock an EEG recording to a clinically required heel lance, we show the presence of a distinct nociceptive-specific potential in newborn infants (35-39 weeks postmenstrual age). The potential can be observed in single trials in the central electrodes (Cz and CPz) and using principal component analysis is characterised by a positivity that occurs at approximately 560 ms post-stimulus (N420-P560; P, positive; N, negative). The magnitude of the nociceptive-specific potential is not dependent on sleep state, whereas an earlier potential (N150-P260-N430), which is sleep-state dependent, is evoked by both noxious and non-noxious stimulation. These results provide the first direct evidence of specific noxious-evoked neural activity in the infant brain and suggest that newborn infants are capable of the sensory-discriminative aspects of pain experience.

Age-related Changes in Arc Transcription and DNA Methylation Within the Hippocampus

Neurobiology of Aging. Dec, 2011  |  Pubmed ID: 20189687

The transcription of genes that support memory processes are likely to be impacted by the normal aging process. Because Arc is necessary for memory consolidation and enduring synaptic plasticity, we examined Arc transcription within the aged hippocampus. Here, we report that Arc transcription is reduced within the aged hippocampus compared to the adult hippocampus during both "off line" periods of rest, and following spatial behavior. This reduction is observed within ensembles of CA1 "place cells", which make less mRNA per cell, and in the dentate gyrus (DG) where fewer granule cells are activated by behavior. In addition, we present data suggesting that aberrant changes in methylation of the Arc gene may be responsible for age-related decreases in Arc transcription within CA1 and the DG. Given that Arc is necessary for normal memory function, these subregion-specific epigenetic and transcriptional changes may result in less efficient memory storage and retrieval during aging.

A High-resolution Map of Human Evolutionary Constraint Using 29 Mammals

Nature. Oct, 2011  |  Pubmed ID: 21993624

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

Prolapsed Double-canted Bipolar Left Ventricular Lead for Pacing the Left Atrium Via the Coronary Sinus: Experience in 11 Patients

Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. Oct, 2011  |  Pubmed ID: 22016306

AimsHigh thresholds and frequent lead dislodgement limit pacing the left atrium (LA) from the mid to distal coronary sinus (CS). The aim of this report is to describe a method for and the results of prolapsing a double-canted bipolar lead into the mid-to-distal CS to eliminate lead dislodgement and improve pacing thresholds.Methods and resultsAfter CS access the 9 Fr. anatomic sheath is withdrawn to the right atrium (RA) over an extra support wire. A double-canted bipolar lead is advanced into the RA until the proximal bend is outside the tip of the sheath. With the stylet withdrawn to the proximal bend, the sheath and lead are advanced over the wire back into the CS. The lead distal to the proximal bend is prolapsed beside the sheath as the tip of the sheath enters the CS. The lead was successfully prolapsed in 11 consecutive patients. In one patient, capture was >5 V in all locations. Of the 10 successful implants, the acute thresholds were: mean 1.53 V, median 1.35 V, range 0.4-4.0 V. Chronic thresholds were: mean 2 V, median 2 V range 0.4-4.0 V. There were no displaced leads or lead fractures through 6-10 months of follow-up.ConclusionsProlapse of a commercially available double-canted bipolar passive fixation lead eliminates lead dislodgment and improves thresholds providing a means for permanent pacing of the LA from the mid to distal CS and provides the design principles for a dedicated lead.

Arc/Arg3.1 Regulates an Endosomal Pathway Essential for Activity-dependent β-amyloid Generation

Cell. Oct, 2011  |  Pubmed ID: 22036569

Assemblies of β-amyloid (Aβ) peptides are pathological mediators of Alzheimer's Disease (AD) and are produced by the sequential cleavages of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase. The generation of Aβ is coupled to neuronal activity, but the molecular basis is unknown. Here, we report that the immediate early gene Arc is required for activity-dependent generation of Aβ. Arc is a postsynaptic protein that recruits endophilin2/3 and dynamin to early/recycling endosomes that traffic AMPA receptors to reduce synaptic strength in both hebbian and non-hebbian forms of plasticity. The Arc-endosome also traffics APP and BACE1, and Arc physically associates with presenilin1 (PS1) to regulate γ-secretase trafficking and confer activity dependence. Genetic deletion of Arc reduces Aβ load in a transgenic mouse model of AD. In concert with the finding that patients with AD can express anomalously high levels of Arc, we hypothesize that Arc participates in the pathogenesis of AD.

Lymphatic Ascites Following Pelvic and Paraaortic Lymphadenectomy Procedures for Gynecologic Malignancies

Gynecologic Oncology. Nov, 2011  |  Pubmed ID: 22101154

OBJECTIVE: Lymphatic ascites is an unusual complication in patients with cancer. In the gynecologic oncology patient population, the most common etiology is operative lymph node dissection. The purpose of this study was to explore the incidence, presenting symptoms, methods of diagnosis and treatment modalities utilized for lymphatic ascites in patients undergoing lymph node dissection for gynecologic cancers. METHODS: This observational study retrospectively reviewed the charts of patients who underwent lymphadenectomy as part of the surgical management for a gynecologic cancer. Patients that developed postoperative lymphatic ascites between January 2000 and December 2010 were included for analysis. Data extracted from the medical records included tumor pathology, number of harvested lymph nodes, postoperative course, method of diagnosis and treatment. RESULTS: From a total of 300 surgical staging procedures, 12 patients with lymphatic ascites were identified (4%). The most common reported symptom was leakage of clear fluid per vagina (7, 58%), followed by abdominal distension (4, 33%). The median interval from surgery to development of symptoms was 12.5days (range 0-22days). 5 patients had complete resolution of symptoms with dietary modifications alone while 7 patients required paracentesis. The median time from surgery to resolution of symptoms was 44days (range 9-99). CONCLUSION: Lymphatic ascites is an under recognized and infrequently reported postoperative complication. Although it usually resolves spontaneously or with conservative management without sequelae, this condition can significantly prolong postoperative recovery and cause patient discomfort. To our knowledge this is the largest group of patients undergoing gynecologic surgical staging procedures to be reviewed for the occurrence of lymphatic ascites.

Gel Formulation Containing Mixed Surfactant and Lipids Associating with Carboplatin

Chemistry & Biodiversity. Dec, 2011  |  Pubmed ID: 22162158

The interaction of amphiphilic molecules such as lipids and surfactants with the hydrophilic drug carboplatin was investigated to identify suitable self-assembling components for a potential gel-based delivery formulation. (1) H-NMR Studies in sodium bis(2-ethylhexyl) sulfosuccinate (aerosol-OT, AOT)-based reverse micelles show that carboplatin associates and at least partially penetrates the surfactant interface. Langmuir monolayers formed by dipalmitoyl(phosphatidyl)choline are penetrated by carboplatin. Carboplatin was found to also penetrate the more rigid monolayers containing cholesterol. A combined mixed surfactant gel formulation containing carboplatin and cholesterol for lymphatic tissue targeting was investigated for the intracavitary treatment of cancer. This formulation consists of a blend of the surfactants lecithin and AOT (1 : 3 ratio), an oil phase of isopropyl myristate, and an aqueous component. The phases of the system were defined within a pseudo-ternary phase diagram. At low oil content, this formulation produces a gel-like system over a wide range of H(2) O content. The carboplatin release from the formulation displays a prolonged discharge with a rate three to five times slower than that of the control. Rheological properties of the formulation exhibit pseudoplastic behavior. Microemulsion and Langmuir monolayer studies support the interactions between carboplatin and amphiphilic components used in this formulation. To target delivery of carboplatin, two formulations containing cholesterol were characterized. These two formulations with cholesterol showed that, although cholesterol does little to alter the phases in the pseudo-ternary system or to increase the initial release of the drug, it contributes significantly to the structure of the formulation under physiological temperature, as well as increases the rate of steady-state discharge of carboplatin.

Genome Sequence of an Australian Kangaroo, Macropus Eugenii, Provides Insight into the Evolution of Mammalian Reproduction and Development

Genome Biology. Dec, 2011  |  Pubmed ID: 22212627

The Significance of a Thickened Endometrial Echo in Asymptomatic Postmenopausal Patients

Maturitas. Feb, 2011  |  Pubmed ID: 21075567

The purpose of this study was to evaluate the significance of a thickened endometrial echo in an asymptomatic, postmenopausal patient.Study design: A retrospective review was conducted of all women who underwent transvaginal ultrasonography between January 2003 and August 2008, were found to have an endometrial thickness of at least 5mm and were subjected to endometrial sampling.

The Acceptability of Human Papillomavirus Vaccine Among Parents and Guardians of Newborn to 10-year-old Children

Journal of Pediatric and Adolescent Gynecology. Apr, 2011  |  Pubmed ID: 20709581

The purpose of our study was to evaluate HPV vaccine acceptance among parents and guardians of children aged 0-10 years.

Enhanced Polyubiquitination of Shank3 and NMDA Receptor in a Mouse Model of Autism

Cell. May, 2011  |  Pubmed ID: 21565394

We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This "gain-of-function" phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/ΔC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/ΔC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder.

Survival Rates of Children with Acute Lymphoblastic Leukemia Presenting to a Pediatric Rheumatologist in the United States

Journal of Pediatric Hematology/oncology. Aug, 2011  |  Pubmed ID: 21572344

Approximately 30% of pediatric acute lymphoblastic leukemia patients present with musculoskeletal symptoms and are often referred first to a pediatric rheumatologist. We examined the survival and causes of death of these patients presenting to a pediatric rheumatologist and compared the rates with that reported in the hematology-oncology literature.

Polymorphic Microsatellite Loci in Polemonium Brandegei and P. Viscosum (section Melliosoma, Polemoniaceae)

American Journal of Botany. Jan, 2011  |  Pubmed ID: 21613077

PREMISE OF THE STUDY: Microsatellite markers were isolated in Polemonium brandegei and P. viscosum to be used in future studies of mating system evolution, population structure, and hybridization. METHODS AND RESULTS: Six loci were used in a preliminary genetic diversity study in two populations each of the closely related Polemonium brandegei and P. viscosum. We found 39 alleles across the six loci (average 7 per locus), with overall levels of observed heterozygosities ranging from 0.067 to 0.867 in P. brandegei and 0.000 to 0.666 in P. viscosum. Additional primers are reported, but require further design and optimization. CONCLUSIONS: The reported markers will aid in further studies of mating system evolution, population structure, and hybridization in P. brandegei and P. viscosum.

Polymeric Antimicrobial N-halamine Epoxides

ACS Applied Materials & Interfaces. Aug, 2011  |  Pubmed ID: 21657263

A new N-halamine copolymer has been prepared, characterized, and evaluated for antimicrobial efficacy, stability toward hydrolyses, and stability toward UVA degradation when covalently bound to cellulose fibers. A copolymer of 3-chloro-2-hydroxypropylmethacrylate and glycidyl methacrylate was coated onto cotton, and, after curing, was treated with an aqueous solution containing the potassium salt of 5,5-dimethylhydantoin to form a coating which became antimicrobial upon exposure to househod bleach (sodium hypochlorite). The coating inactivated S. aureus and E. coli O157:H7 within minutes of contact time and was quite stable toward washing and UVA photodegradation.

N-halamine Copolymers for Use in Antimicrobial Paints

ACS Applied Materials & Interfaces. Aug, 2011  |  Pubmed ID: 21786779

A series of copolymers containing units of a novel hydantoinylacrylamide and the sodium salt of 2-(acrylamido)-2-methylpropanesulfonic acid have been synthesized. The homopolymer of the hydantoinylacrylamide compound was insoluble in water, while the copolymers with the sulfonic acid sodium salt were water-dispersible/soluble, with the solution becoming completely transparent when the feed ratio for the copolymer contained 7 parts of the hydantoin moiety to 3 parts of the sodium sulfonate moiety. The polymers were added into a commercial water-based latex paint, and upon drying, the painted surfaces treated with the water-miscible copolymers were rendered antimicrobial following chlorination with dilute household bleach. The chlorinated homopolymer failed to provide an antimicrobial property for the paint because of its tendency to isolate into aggregates in the paint, while the completely miscible copolymers were capable of 6-log inactivation of Staphylococcus aureus and Escherichia coli O157:H7 within 5 min of contact time.

Predictors of Suicide-related Hospitalization Among U.S. Veterans Receiving Treatment for Comorbid Depression and Substance Dependence: Who is the Riskiest of the Risky?

Suicide & Life-threatening Behavior. Oct, 2011  |  Pubmed ID: 21815915

This study examined whether widely accepted suicide risk factors are useful in predicting suicide-related hospitalization, beyond history of a suicide attempt, in high-risk treatment-seeking veterans with depression and substance dependence. Negative mood regulation expectancies were the only significant predictor of hospitalization during 6-months of outpatient treatment. History of a suicide attempt was the only significant predictor of hospitalization during the one-year follow-up period. Results suggest that within high-risk populations, standard suicide risk factors may not identify individuals who will engage in suicidal behaviors resulting in hospitalization. Assessing negative mood regulation expectations may assist in identifying those most at risk.

Robotic Radical Parametrectomy for Unstaged Invasive Endometrial Carcinoma

International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. Nov, 2011  |  Pubmed ID: 21840521

A 51-year-old woman underwent total laparoscopic hysterectomy for complex hyperplasia; however, final postoperative pathology revealed a deeply invasive high-grade adenocarcinoma. The patient was, therefore, unstaged. Forty-five days later, she underwent robot-assisted radical parametrectomy, upper vaginectomy, and bilateral salpingo-oophorectomy with pelvic and para-aortic lymph node dissection.

A Shift in Sensory Processing That Enables the Developing Human Brain to Discriminate Touch from Pain

Current Biology : CB. Sep, 2011  |  Pubmed ID: 21906948

When and how infants begin to discriminate noxious from innocuous stimuli is a fundamental question in neuroscience [1]. However, little is known about the development of the necessary cortical somatosensory functional prerequisites in the intact human brain. Recent studies of developing brain networks have emphasized the importance of transient spontaneous and evoked neuronal bursting activity in the formation of functional circuits [2, 3]. These neuronal bursts are present during development and precede the onset of sensory functions [4, 5]. Their disappearance and the emergence of more adult-like activity are therefore thought to signal the maturation of functional brain circuitry [2, 4]. Here we show the changing patterns of neuronal activity that underlie the onset of nociception and touch discrimination in the preterm infant. We have conducted noninvasive electroencephalogram (EEG) recording of the brain neuronal activity in response to time-locked touches and clinically essential noxious lances of the heel in infants aged 28-45 weeks gestation. We show a transition in brain response following tactile and noxious stimulation from nonspecific, evenly dispersed neuronal bursts to modality-specific, localized, evoked potentials. The results suggest that specific neural circuits necessary for discrimination between touch and nociception emerge from 35-37 weeks gestation in the human brain.

Personal Survival Kits

Air Medical Journal. Sep-Oct, 2011  |  Pubmed ID: 21930081

The Contribution of Recess to Children's School-Day Physical Activity

Journal of Physical Activity & Health. May, 2011  |  Pubmed ID: 21934153

BACKGROUND: Recess is an important component of a Comprehensive School Physical Activity Program, providing approximately 1268 and 914 steps for boys and girls, respectively, within a 15-minute time period. The purpose of this study was to determine the contribution of unstructured recess on children's school-day physical activity levels and to examine if recess and school-day physical activity levels varied by BMI, gender, and grade level. METHODS: One-hundred sixty 3rd-5th grade students from two elementary schools wore pedometers during four recess periods. Results: Recess accounted for 17-44% of school-day step counts. There was a significant main effect for grade level, but not for BMI or gender, on the percentage of school day steps accumulated during recess. CONCLUSIONS: A 15-minute recess makes a valuable contribution to children's school day physical activity, especially for the least active children. More research is warranted to determine environmental influences on children's recess physical activity.

Arc-dependent Synapse-specific Homeostatic Plasticity

Proceedings of the National Academy of Sciences of the United States of America. Jan, 2011  |  Pubmed ID: 21187403

Both theoretical and experimental research has indicated that the synaptic strength between neurons in a network needs to be properly fine-tuned and controlled by homeostatic mechanisms to ensure proper network function. One such mechanism that has been extensively characterized is synaptic homeostatic plasticity or global synaptic scaling. This mechanism refers to the bidirectional ability of all synapses impinging on a neuron to actively compensate for changes in the neuron's overall excitability. Here, using a combination of electrophysiological, two-photon glutamate uncaging and imaging methods, we show that mature individual synapses, independent of neighboring synapses, have the ability to autonomously sense their level of activity and actively compensate for it in a homeostatic-like fashion. This synapse-specific homeostatic plasticity, similar to global synaptic plasticity, requires the immediate early gene Arc. Together, our results document an extra level of regulation of synaptic function that bears important computational consequences on information storage in the brain.

Lead Exposure During Synaptogenesis Alters NMDA Receptor Targeting Via NMDA Receptor Inhibition

Neurotoxicology. Mar, 2011  |  Pubmed ID: 21192972

N-methyl-D-aspartate receptor (NMDAR) ontogeny and subunit expression are altered during developmental lead (Pb²+) exposure. However, it is unknown whether these changes occur at the synaptic or cellular level. Synaptic and extra-synaptic NMDARs have distinct cellular roles, thus, the effects of Pb²+ on NMDAR synaptic targeting may affect neuronal function. In this communication, we show that Pb²+ exposure during synaptogenesis in hippocampal neurons altered synaptic NMDAR composition, resulting in a decrease in NR2A-containing NMDARs at established synapses. Conversely, we observed increased targeting of the obligatory NR1 subunit of the NMDAR to the postsynaptic density (PSD) based on the increased colocalization with the postsynaptic protein PSD-95. This finding together with increased binding of the NR2B-subunit specific ligand [³H]-ifenprodil, suggests increased targeting of NR2B-NMDARs to dendritic spines as a result of Pb²+ exposure. During brain development, there is a shift of NR2B- to NR2A-containing NMDARs. Our findings suggest that Pb²+ exposure impairs or delays this developmental switch at the level of the synapse. Finally, we show that alter expression of NMDAR complexes in the dendritic spine is most likely due to NMDAR inhibition, as exposure to the NMDAR antagonist aminophosphonovaleric acid (APV) had similar effects as Pb²+ exposure. These data suggest that NMDAR inhibition by Pb²+ during synaptogensis alters NMDAR synapse development, which may have lasting consequences on downstream signaling.

Development of a Risk-stratification Tool for Medical Child Abuse in Failure to Thrive

Pediatrics. Dec, 2011  |  Pubmed ID: 22123876

To develop a risk-stratification tool to help identify medical child abuse (MCA) in children evaluated for failure to thrive (FTT).

Role for MTOR Signaling and Neuronal Activity in Morphine-induced Adaptations in Ventral Tegmental Area Dopamine Neurons

Neuron. Dec, 2011  |  Pubmed ID: 22196333

While the abuse of opiate drugs continues to rise, the neuroadaptations that occur with long-term drug exposure remain poorly understood. We describe here a series of chronic morphine-induced adaptations in ventral tegmental area (VTA) dopamine neurons, which are mediated via downregulation of AKT-mTORC2 (mammalian target of rapamycin complex-2). Chronic opiates decrease the size of VTA dopamine neurons in rodents, an effect seen in humans as well, and concomitantly increase the excitability of the cells but decrease dopamine output to target regions. Chronic morphine decreases mTORC2 activity, and overexpression of Rictor, a component of mTORC2, prevents morphine-induced changes in cell morphology and activity. Further, local knockout of Rictor in VTA decreases DA soma size and reduces rewarding responses to morphine, consistent with the hypothesis that these adaptations represent a mechanism of reward tolerance. Together, these findings demonstrate a novel role for AKT-mTORC2 signaling in mediating neuroadaptations to opiate drugs of abuse.

Subclavian Venoplasty by the Implanting Physicians in 373 Patients over 11 Years

Heart Rhythm : the Official Journal of the Heart Rhythm Society. Apr, 2011  |  Pubmed ID: 21147260

The need to add a lead(s) despite subclavian/innominate obstruction is increasing. Subclavian venoplasty may be a good alternative to the commonly employed options; however, there are few reports in the literature, and all are by interventional radiologists.

Physician Knowledge of and Adherence to the Revised Breast Cancer Screening Guidelines by the United States Preventive Services Task Force

American Journal of Obstetrics and Gynecology. Sep, 2011  |  Pubmed ID: 21689807

We sought to assess knowledge and adherence to the revised US Preventive Services Task Force breast cancer screening guidelines among gynecologic care providers.

Population Based Age Stratified Morbidities of Premature Infants in Switzerland

Swiss Medical Weekly. 2011  |  Pubmed ID: 21706450

To provide population-based, gestational age (GA) stratified incidence of mortality and morbidities.

Vulnerability of Older Latino and Asian Immigrants with Limited English Proficiency

Journal of the American Geriatrics Society. Jul, 2011  |  Pubmed ID: 21718269

To explore the implications of limited English proficiency (LEP) for disparities in health status and healthcare service use of older Latino and Asian immigrants.

Wilderness Communications

Wilderness & Environmental Medicine. Sep, 2011  |  Pubmed ID: 21723163

When an emergency situation arises in a remote location, the ability to communicate with outside sources of assistance can prove very valuable. This article reviews the different types of communications technologies available to individuals in remote locations, including satellite telephones, personal locator beacons, satellite messengers, cellular telephones, and the different licensed and non-licensed 2-way radio services available for personal use. It also discusses basic radio communications techniques, emergency communication, requesting ground or air casualty evacuation, and selecting communications devices for different applications.

Social Accountability in Medical Education--an Australian Rural and Remote Perspective

Medical Teacher. 2011  |  Pubmed ID: 21774653

Australia's medical education system is undergoing a socially motivated transformation focused on improving access to medical care for rural and remote communities. A rural and remote backbone of Rural Clinical Schools (RCS), University Departments of Rural Health, regional medical schools, and the postgraduate college, ACRRM, have enabled community responsive innovation and partnerships with rural health services that once would have been difficult to imagine. This article argues that this transformation is succeeding because of the passionate leadership of rural medical and community leaders, government seed funding to encourage rural medicine as an academic discipline, rigorous research and consultation that underpinned each step of the innovation pathway, and a political campaign to invest in rural medical education as a form of rural social capital.

Systemic Administration of Guanosine Promotes Functional and Histological Improvement Following an Ischemic Stroke in Rats

Brain Research. Aug, 2011  |  Pubmed ID: 21774919

Previously we have found that extracellular guanosine (Guo) has neuroprotective properties in in vitro and in vivo. Moreover, extracellular Guo significantly increased in the ipsilateral hemisphere within 2h following focal stroke in rats, and remained elevated for one week. Therefore, we hypothesized that Guo could be a potential candidate for a non-toxic neuroprotective agent. In the present study, we examined the effects of Guo on rats following permanent middle cerebral artery occlusion (MCAO). We also determined whether Guo can precondition neurons by modulating endoplasmic reticulum (ER) stress proteins. As most therapies employ a combination treatment regimen, we optimized the neuroprotection by combining pre- and post-MCAO treatments with Guo, attempting to reduce both ischemic cell death and improve functional recovery. A combination of 4mg/kg Guo given 30min pre-stroke and 8mg/kg Guo given 3, 24 and 48h post-stroke exerted the most significant decrease in infarct volume and sustainable improvement in neurological function. Moreover, these effects are not attributable to Guo metabolites. Measurements taken 6h post-MCAO from animals pre-treated with Guo did not reveal any significant changes in ER stress proteins (GRP 78 and 94) or HSP 70, but did reveal significantly increased levels of m-calpain. Thus, our data indicate that there is a treatment regimen for Guo as a neuroprotectant following ischemic stroke. The mechanism by which Guo confers neuroprotection may involve an increase in m-calpain, possibly resulting from a mild increase in intracellular calcium. M-calpain may be involved in the preconditioning response to ischemia by upregulating endogenous pro-survival mechanisms in neurons.

Parents of Adolescents Who Have Committed Sexual Offenses: Characteristics, Challenges, and Interventions

Clinical Child Psychology and Psychiatry. Aug, 2011  |  Pubmed ID: 21852316

This article discusses the importance of a systems approach to working with adolescents who have offended sexually. Literature concerning family backgrounds of these youths is reviewed, highlighting histories of family violence, parental depression and child maltreatment, problematic communication patterns, parental psychological inaccessibility, inconsistent discipline, and failure of the family to acknowledge the youth's offending behavior. Such issues and other special challenges presented by parents of these adolescents, particularly as the issues impact caregiver support and supervision, can be significant barriers to a youth's successful treatment. However, when these barriers are addressed through a systems approach that actively involves parents in assessment and therapeutic phases of intervention, treatment of an adolescent who sexually offended is likely to be enhanced. The importance of offering parents multiple intervention strategies at various stages in the therapeutic process is emphasized; interventions might include individual, family, and multi-family group therapy, and psychoeducation and support groups.

Genome Sequence of an Australian Kangaroo, Macropus Eugenii, Provides Insight into the Evolution of Mammalian Reproduction and Development

Genome Biology. 2011  |  Pubmed ID: 21854559

We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development.

Risk Factors for Glaucoma: What Do They Really Mean?

Australian Journal of Primary Health. 2011  |  Pubmed ID: 21896259

Glaucoma is an insidious eye disease, potentially putting 4% of older Australians at risk of blindness, unless detected sufficiently early for initiation of effective treatment. This paper reports on the strengths of evidence and glaucoma risk factors that can be identified by primary health care providers from a patient's history. A comprehensive search of peer-reviewed databases identified relevant secondary evidence published between 2002 and 2007. Risk factors that could be determined from a patient's history were identified. A novel glaucoma risk factor reference guide was constructed according to evidence strength and level of concern regarding risk of developing glaucoma. The evidence is strong and consistent regarding the risk of developing glaucoma, and elevated intraocular pressure, advancing age, non-Caucasian ethnicity and family history of glaucoma. There is moderate evidence of association with glaucoma, and migraine, eye injury, myopia and long-term use of corticosteroids. There is conflicting evidence for living in a rural location, high blood pressure, diabetes and smoking. Early detection of people at risk of developing glaucoma can be initiated using our risk factor guide coupled with a comprehensive patient history. Timely future assessment and subsequent management strategies for at-risk individuals can then be effectively and efficiently actioned.

Pre-adolescent Alcohol Expectancies: Critical Shifts and Associated Maturational Processes

Experimental and Clinical Psychopharmacology. Dec, 2011  |  Pubmed ID: 21942260

Children's alcohol expectancies shift in late childhood/early adolescence in ways thought to lead to increased risk for adolescent alcohol use. The precise nature of this shift and the maturational processes that may influence it remain to be clarified. To these ends, we compared expectancy endorsement by grade across four expectancy domains: positive, negative, arousal, and sedation, in a cross-sectional sample of 3rd-6th grade children attending afterschool programs (n = 299). Structural equation modeling (SEM) was then used to describe the relationships between expectancies and differences in (a) cognitive ability and concept formation, (b) risk-taking personality traits, and (c) social exposure or values regarding alcohol-related information. Results showed those children in higher grades endorsed significantly more positive, negative, and sedating expectancies for alcohol than their younger peers. Concept formation partially and fully mediated the relationships between grade and both positive and sedating expectancies, respectively, but not the relationship between grade and negative expectancies. Sensation seeking did not increase across grades in this sample, and the relationship between sensation seeking and positive expectancies was fully mediated by reported alcohol exposure and values. This study provides a basis for future exploration of developmental influences on alcohol expectancies, an understanding of which may be helpful in the design of prevention efforts targeting high-risk youth before adolescence.

Comparative and Demographic Analysis of Orang-utan Genomes

Nature. Jan, 2011  |  Pubmed ID: 21270892

'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.

Correlates of Depression Among Older Kurdish Refugees

Social Work. Apr, 2011  |  Pubmed ID: 21553579

Little is known about the psychological status of older refugees who have immigrated from war-torn areas in the Middle East. This study examined the nature and predictors of depression among older Kurds living in one city in the United States. Older Kurds (N = 70) were recruited and surveyed by trained Kurdish interviewers in their native dialect. The majority of participants had very low incomes; had no education; were illiterate in their own language; and had little to no ability to speak, read, or write English. Elevated levels of depression were found, with 67.1 percent scoring above the clinical cutoff for depression and 25.7 percent scoring in the severe depression range. Depression was associated with demographic (age), stressor (migratory grief, death of spouse, number of medical conditions, functional disability, and income), and coping (English proficiency and social support) variables. Health conditions exerted the greatest effect. Migratory grief and social support were also significant predictors of depression. Results suggest substantial psychological distress among this understudied population of older refugees. Implications for research and practice with older members of newly established refugee populations are discussed.

Willingness of Pregnant Women to Vaccinate Themselves and Their Newborns with the HPV Vaccine

Vaccine. Jun, 2011  |  Pubmed ID: 21557976

To evaluate the willingness of pregnant women to accept the HPV vaccine for their newborns as well as themselves.

Professional Technical Standards in Colleges and Schools of Pharmacy

American Journal of Pharmaceutical Education. Apr, 2011  |  Pubmed ID: 21655404

To determine the prevalence, characteristics, and use of professional technical standards among colleges and schools of pharmacy accredited by the Accreditation Council for Pharmacy Education (ACPE).

Roundtable: Revisiting Innovative Leaders in Medical Education

MEDICC Review. Jul, 2011  |  Pubmed ID: 21778952

Sexual Behaviors of Children: What is Normal and What is Concerning?

The Journal of the Arkansas Medical Society. Sep, 2011  |  Pubmed ID: 21916383

Characterization of Single-nucleotide Variation in Indian-origin Rhesus Macaques (Macaca Mulatta)

BMC Genomics. 2011  |  Pubmed ID: 21668978

Rhesus macaques are the most widely utilized nonhuman primate model in biomedical research. Previous efforts have validated fewer than 900 single nucleotide polymorphisms (SNPs) in this species, which limits opportunities for genetic studies related to health and disease. Extensive information about SNPs and other genetic variation in rhesus macaques would facilitate valuable genetic analyses, as well as provide markers for genome-wide linkage analysis and the genetic management of captive breeding colonies.

Replacement Behaviors for Identified Functions of Challenging Behaviors

Research in Developmental Disabilities. Mar-Apr, 2011  |  Pubmed ID: 21144703

Functional assessment has become a major feature of learning-based research. A critical element of the majority of these studies includes not only methods and procedures to identify the cause of the challenging behavior, but to establish replacement treatment methods. By far the most common intervention in the 176 studies we reviewed was reinforcement. Noncontingent reinforcement (NCR) was the most common reinforcement method, followed by differential reinforcement of other behavior (DRO). Reinforcement plus extinction was the second most commonly employed treatment followed by functional communication training with or without reinforcement. Researchers proved to be very creative. Forty different treatment methods were employed. The implications of these data are discussed.

Histology, Not Lymph Node Involvement, Predicts Long-Term Survival in Bronchopulmonary Carcinoids

The American Surgeon. Dec, 2011  |  Pubmed ID: 22273228

Recently, the incidence of bronchopulmonary carcinoid has increased substantially, whereas survival associated with both subtypes has declined. We reviewed our experience with bronchopulmonary carcinoid to identify factors associated with long-term survival. We reviewed our cancer registry from 1985 to 2009 for all patients undergoing surgical resection for bronchopulmonary carcinoid. Cox regression analysis was used to evaluate prognostic factors. Fifty-two patients met criteria for inclusion. Forty-three patients (82%) presented with typical histology. The likelihood of lymph node metastasis was similar for patients with typical histology and patients with atypical histology. For patients with typical histology, the 5-year survival rates with and without lymph node metastases were 100 per cent and 97 per cent, respectively (P = 0.420). The overall survival rate for patients with typical histology (97% at 5 years; 72% at 10 years) was significantly better than for patients with atypical histology (35% at 5 years, 0% at 10 years) (P < 0.001). Univariate and multivariate analyses demonstrated that long-term survival was associated with histology but not lymph node involvement (hazards ratio = 14.6, 95% confidence interval: 1.7, 125.2). Our data suggests that long-term survival is associated with histology, not lymph node involvement. We found tumor histology to be the strongest predictor of long-term survival in patients with pulmonary carcinoid tumors.

What is the Evidence for Environmental Causes of Challenging Behaviors in Persons with Intellectual Disabilities and Autism Spectrum Disorders?

Research in Developmental Disabilities. Mar-Apr, 2011  |  Pubmed ID: 21144702

An extensive literature on the causes of challenging behaviors has been developed, primarily in the applied behavior analysis literature. One hundred and seventy-three empirical studies were reviewed where functional assessment serves as the primary method of identifying these causes. Most of the studies were able to identify a clear function or functions. Most commonly established causes were attention, the efforts to acquire tangibles, negative reinforcement in the form of escape from tasks or environments, and sensory stimulation, also described as an alone condition. Examples are provided regarding how these conditions are investigated across studies. Biological and cognitive causes have also been demonstrated. However, to date the empirical literature is limited with the bulk of studies being correlational. Considerably more research is needed, but some causes and methods to identify them are beginning to emerge.

Teen with a Diffuse Erythematous, Pruritic Eruption

The Journal of Family Practice. Jan, 2011  |  Pubmed ID: 21209978

Person Characteristics of Individuals in Functional Assessment Research

Research in Developmental Disabilities. Mar-Apr, 2011  |  Pubmed ID: 21211941

This paper is a review of person characteristics that were present in 173 studies that were reviewed on functional assessment. The purpose was to give the reader an idea about the types of individuals for which functional assessment is appropriate and to outline persons and their characteristics which have the best research support. The majority of participants were diagnosed with intellectual disability and/or autism. Additionally more males that females were included and children were frequently studied versus adolescents and older adults. Finally, while the majority of studies employed experimental functional analysis, the number of participants per study was small. Conversely, functional analysis scales were used in far fewer studies, but with much larger sample sizes. Thus, relatively equal numbers of individuals have been studied with both methods.

Behaviors and Corresponding Functions Addressed Via Functional Assessment

Research in Developmental Disabilities. Mar-Apr, 2011  |  Pubmed ID: 21215596

One-hundred seventy-three studies that employed functional assessment were evaluated with respect to types of challenging behaviors studied and the functions identified that maintained those behaviors. For most studies, two to three behaviors were targeted. Of the 38 different challenging behaviors identified, self-injurious behavior (SIB) and aggression were by far the most studied. Other commonly studied behaviors were tantrums, stereotypies, property destruction, bizarre/inappropriate speech/vocalizations, and disruptive behaviors. The most commonly identified functions for both SIB and aggressions were attention and escape/demands. The implications of these and other data complied on target behaviors and maintaining variables are discussed.

Absorbance-based Assay for Membrane Disruption by Antimicrobial Peptides and Synthetic Copolymers Using Pyrroloquinoline Quinone-loaded Liposomes

Analytical Biochemistry. Apr, 2011  |  Pubmed ID: 21237129

A simple homogeneous assay for the detection of membrane permeabilization by antimicrobial peptides and synthetic copolymers is described. Liposomes encapsulating pyrroloquinoline quinone (PQQ), the prosthetic group of the apoenzyme glucose dehydrogenase (GDH), are used to detect membrane permeabilization by the antimicrobial peptides MSI-594 and MSI-78 as well as various synthetic antimicrobial copolymers in an optical microwell assay. PQQ-loaded liposomes and the peptide or copolymer are added to wells of a 96-well microtiter plate. If the integrity of the liposome is compromised, the PQQ encapsulated in the liposomes is released and available for activating the apoenzyme. The release of PQQ catalyzes a color change in the presence of apo-GDH, glucose, and the redox dye 1,6-dichlorophenol indophenol (DCPIP) that can be evaluated through a visual color change. For more quantitative measurements, the absorbance change over a 30min period was measured. The absorbance change is related to the activity and concentration for a given antimicrobial agent. Furthermore, by varying liposome compositions to include cholesterol, the potential toxicity of the peptide or polymer toward mammalian cells can be readily evaluated. The assay is simple and sensitive and will be useful for analyzing the membrane permeation/disruption properties of a host of antimicrobial peptides and synthetic polymers.

Rheb1 is Required for MTORC1 and Myelination in Postnatal Brain Development

Developmental Cell. Jan, 2011  |  Pubmed ID: 21238928

mTor kinase is involved in cell growth, proliferation, and differentiation. The roles of mTor activators, Rheb1 and Rheb2, have not been established in vivo. Here, we report that Rheb1, but not Rheb2, is critical for embryonic survival and mTORC1 signaling. Embryonic deletion of Rheb1 in neural progenitor cells abolishes mTORC1 signaling in developing brain and increases mTORC2 signaling. Remarkably, embryonic and early postnatal brain development appears grossly normal in these Rheb1f/f,Nes-cre mice with the notable exception of deficits of myelination. Conditional expression of Rheb1 transgene in neural progenitors increases mTORC1 activity and promotes myelination in the brain. In addition the Rheb1 transgene rescues mTORC1 signaling and hypomyelination in the Rheb1f/f,Nes-cre mice. Our study demonstrates that Rheb1 is essential for mTORC1 signaling and myelination in the brain, and suggests that mTORC1 signaling plays a role in selective cellular adaptations, rather than general cellular viability.

Stability of Symptoms of Autism Spectrum Disorders in Toddlers: an Examination Using the Baby and Infant Screen for Children with AUtIsm Traits-Part 1 (BISCUIT)

Developmental Neurorehabilitation. 2011  |  Pubmed ID: 21241177

The diagnostic stability of Autism Spectrum Disorders (ASD) at very young ages continues to be debated, despite empirical evidence that ASDs can be reliably diagnosed in children under the age of 3 years. This topic is of the upmost importance given that early intervention increases long-term outcomes in this population.

Extensive Thrombosis and First-trimester Pregnancy Loss Caused by Sticky Platelet Syndrome

Obstetrics and Gynecology. Feb, 2011  |  Pubmed ID: 21252804

Sticky platelet syndrome is an autosomal-dominant thrombophilia characterized by platelet hyperaggregability in the presence of adenosine diphosphate or epinephrine. The result clinically can be widespread thromboses, often arterial, in patients without apparent risk factors for thrombotic disease. Limited data exist regarding its role in adverse pregnancy outcomes.

Metabolic Responses to Wii Fit™ Video Games at Different Game Levels

Journal of Strength and Conditioning Research / National Strength & Conditioning Association. Mar, 2011  |  Pubmed ID: 21311348

The Wii Fit™ is a form of interactive gaming designed to elicit health and fitness benefits to replace sedentary gaming. This study was designed to determine the effectiveness of Wii Fit™ fitness games. The purpose of the study was to determine the %VO2max and energy expenditure from different Wii Fit™ games at different levels including the step and hula games. Eight healthy young women completed a preliminary trial to determine VO2max and later played the Wii Fit™ during 2 separate counterbalanced trials. During each session, subjects played levels of Wii Fit™ games for 10 minutes each level. One session involved beginning and intermediate hula, and the other session involved beginning and intermediate steps. The VO2 was measured continuously via metabolic cart, and rating of perceived exertion (RPE) was assessed at the end of each game level. The lowest %VO2max, kcal·min, and RPE occurred during the beginning step game and the highest values occurred during the intermediate hula game. Respiratory exchange ratio was significantly higher in the intermediate hula than beginning hula game but was not significantly different between step game levels. The intermediate hula and step games produced the greatest energy expenditure with an equivalent effect of a walking speed of >5.63 km·h (>3.5 miles·h). This is the first study to determine the percentage of VO2max and caloric expenditure elicited by different Wii Fit™ video games at different game levels in adults. Findings suggest that the Wii Fit™ can be used as an effective activity for promoting physical health in this population.

Activity-induced Notch Signaling in Neurons Requires Arc/Arg3.1 and is Essential for Synaptic Plasticity in Hippocampal Networks

Neuron. Feb, 2011  |  Pubmed ID: 21315255

Notch signaling in the nervous system has been most studied in the context of cell fate specification. However, numerous studies have suggested that Notch also regulates neuronal morphology, synaptic plasticity, learning, and memory. Here we show that Notch1 and its ligand Jagged1 are present at the synapse, and that Notch signaling in neurons occurs in response to synaptic activity. In addition, neuronal Notch signaling is positively regulated by Arc/Arg3.1, an activity-induced gene required for synaptic plasticity. In Arc/Arg3.1 mutant neurons, the proteolytic activation of Notch1 is disrupted both in vivo and in vitro. Conditional deletion of Notch1 in the postnatal hippocampus disrupted both long-term potentiation (LTP) and long-term depression (LTD), and led to deficits in learning and short-term memory. Thus, Notch signaling is dynamically regulated in response to neuronal activity, Arc/Arg3.1 is a context-dependent Notch regulator, and Notch1 is required for the synaptic plasticity that contributes to memory formation.

N-halamine Biocidal Coatings Via a Layer-by-layer Assembly Technique

Langmuir : the ACS Journal of Surfaces and Colloids. Apr, 2011  |  Pubmed ID: 21348478

Two N-halamine copolymer precursors, poly(2,2,6,6-tetramethyl-4-piperidyl methacrylate-co-acrylic acid potassium salt) and poly(2,2,6,6-tetramethyl-4-piperidyl methacrylate-co-trimethyl-2-methacryloxyethylammonium chloride) have been synthesized and successfully coated onto cotton fabric via a layer-by-layer (LbL) assembly technique. A multilayer thin film was deposited onto the fiber surfaces by alternative exposure to polyelectrolyte solutions. The coating was rendered biocidal by a dilute household bleach treatment. The biocidal efficacies of tested swatches composed of treated fibers were evaluated against Staphylococcus aureus and Escherichia coli. It was determined that chlorinated samples inactivated both S. aureus and E. coli O157:H7 within 15 min of contact time, whereas the unchlorinated control samples did not exhibit significant biocidal activities. Stabilities of the coatings toward washing and ultraviolet light exposure have also been studied. It was found that the stability toward washing was superior, whereas the UVA light stability was moderate compared to previously studied N-halamine moieties. The layer-by-layer assembly technique can be used to attach N-halamine precursor polymers onto cellulose surfaces without using covalently bonding tethering groups which limit the structure designs. In addition, ionic precursors are very soluble in water, thus promising for biocidal coatings without the use of organic solvents.

Emerging Therapeutics for Primary Peritoneal Cancer

Expert Opinion on Emerging Drugs. Mar, 2011  |  Pubmed ID: 21352070

INTRODUCTION: Primary peritoneal cancer describes a malignancy that originates from the peritoneal lining of the abdomen. The diagnosis is clearest when the ovaries are uninvolved; however, this is rarely the case and, as such, the declaration is often made pathologically by extrinsic or secondary involvement of the ovaries. The disease shares nearly all of the clinicopathologic features of primary ovarian cancer, most importantly, a molecular homology, which has made it unfruitful for considering it a different entity. Because of this, both standard of care treatment algorithms and contemporary drug development protocols nearly uniformly consider these cancers as primary ovarian cancers. AREAS COVERED: A Medline search was performed as well as a review of trials presented in the National Cancer Institute clinical trials website (http://www.Clinicaltrials.gov). We also reviewed abstracts presented at recent oncology congresses, such as the 2010 Annual meetings of the Society of Gynecologic Oncologists and the American Society of Clinical Oncology. The purpose of this review is to highlight areas of current drug development for patients with primary peritoneal carcinoma. While there are numerous investigational agents being evaluated which follow patients with this disease, our review focuses on the most promising agents that are in mature clinical development. In addition, given the recent positive Phase III data of bevacizumab in the first-line setting for patients with this disease, we consider changes that we can anticipate in this field. EXPERT OPINION: Numerous novel agents are being explored in this disease with the majority focusing on direct and indirect perturbations of tumor angiogenesis. Based on ongoing and recently completed investigations, targeted therapies are likely to become part of the armamentarium of first-line and recurrent treatment for patients with peritoneal cancers. Future studies of pathway-specific targeting will probably include pretreatment biomarker selection or eligibility criteria as well as combinatorial strategies.

Minimally Invasive Staging of Endometrial Cancer is Feasible and Safe in Elderly Women

Journal of Minimally Invasive Gynecology. Mar-Apr, 2011  |  Pubmed ID: 21354065

To compare the surgical outcome of elderly and younger patients undergoing laparoscopic or robotic surgical staging of endometrial cancer.

The Kinase MTOR Regulates the Differentiation of Helper T Cells Through the Selective Activation of Signaling by MTORC1 and MTORC2

Nature Immunology. Apr, 2011  |  Pubmed ID: 21358638

The kinase mTOR has emerged as an important regulator of the differentiation of helper T cells. Here we demonstrate that differentiation into the T(H)1 and T(H)17 subsets of helper T cells was selectively regulated by signaling from mTOR complex 1 (mTORC1) that was dependent on the small GTPase Rheb. Rheb-deficient T cells failed to generate T(H)1 and T(H)17 responses in vitro and in vivo and did not induce classical experimental autoimmune encephalomyelitis (EAE). However, they retained their ability to become T(H)2 cells. Alternatively, when mTORC2 signaling was deleted from T cells, they failed to generate T(H)2 cells in vitro and in vivo but preserved their ability to become T(H)1 and T(H)17 cells. Our data identify mechanisms by which two distinct signaling pathways downstream of mTOR regulate helper cell fate in different ways. These findings define a previously unknown paradigm that links T cell differentiation with selective metabolic signaling pathways.

Parents' First Concerns of Their Child's Development in Toddlers with Autism Spectrum Disorders

Developmental Neurorehabilitation. 2011  |  Pubmed ID: 21410398

Investigations about first concerns among parents of toddlers with ASD and comparisons of the same with children diagnosed with other developmental disorders are scarce.

Mediating Influences of Negative Affect and Risk Perception on the Relationship Between Sensation Seeking and Adolescent Cigarette Smoking

Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Jun, 2011  |  Pubmed ID: 21436297

A substantial number of adolescents are current and regular cigarette smokers, and there is a need to better understand factors that contribute to smoking behavior during these years. Sensation seeking (SS) is one factor that has consistently been associated with smoking, but less is known about mechanisms that may explain this relationship.

Rural Longitudinal Integrated Clerkships: Lessons from Two Programs on Different Continents

Rural and Remote Health. Apr-Jun, 2011  |  Pubmed ID: 21449620

Flinders University in Australia has had a rural longitudinal integrated clerkship for selected medical students, the Parallel Rural Community Curriculum, since 1997. The Northern Ontario School of Medicine (NOSM) in Canada introduced a similar clerkship for all NOSM students in 2007. An external evaluation of both programs was conducted in 2006 and 2008, respectively. The aim of this article was to analyse the similarities in and differences between these two rural programs and determine key factors that could inform others interested in creating similar programs.

Transforming Health Professionals' Education

Lancet. Apr, 2011  |  Pubmed ID: 21481696

Demonstrating the Value of Longitudinal Integrated Placements to General Practice Preceptors

Medical Education. May, 2011  |  Pubmed ID: 21486321

This paper aims to consider why general practitioners (GPs) teach, in particular by defining the longitudinal supervisory relationships between rural clinician-preceptors and students.

Pericardial Free Patch Grafting As a Rescue Technique in Surgical Management of Right Atrial HSA

Journal of the American Animal Hospital Association. May-Jun, 2011  |  Pubmed ID: 21498592

A 7 yr old, neutered female vizsla underwent an exploratory thoracotomy after diagnosis of recurrent hemorrhagic pericardial effusion and a right auricular mass. Staging tests were negative for metastasis. The patient underwent a right, fourth intercostal thoracotomy, subtotal pericardectomy, right auricular mass excision, and pericardial free patch graft. The patient experienced blood loss during surgery, which required a packed red blood cell transfusion. The patient experienced transient arrhythmias postoperatively, but was discharged from the hospital 48 hr later. Histopathologic diagnosis of the mass was hemangiosarcoma. The patient was treated with carboplatin single-agent chemotherapy and palliative radiation therapy. The patient died at home, presumably from metastatic disease 260 days postoperatively. Surgical mass removal or debulking along with pericardial free patch grafting may be considered as palliative treatment options for dogs diagnosed with right auricular masses. In this case report, other techniques failed to repair the defect in the heart and a free patch graft offered a good rescue procedure with a favorable outcome without the need for inflow and outflow occlusion when used in conjunction with adjunctive therapies.

Effects of Symptoms of Co-morbid Psychopathology on Challenging Behaviours Among Infants and Toddlers with Autistic Disorder and PDD-NOS As Assessed with the Baby and Infant Screen for Children with AUtIsm Traits (BISCUIT)

Developmental Neurorehabilitation. 2011  |  Pubmed ID: 21548853

To examine whether level of symptoms of co-morbid psychopathology exacerbated challenging behaviours in young children with autism spectrum disorders (ASD).

The Effects of Hearing Impairment on Symptoms of Autism in Toddlers

Developmental Neurorehabilitation. 2011  |  Pubmed ID: 21548858

Individuals diagnosed with certain medical conditions, such as those with hearing loss or impairment, may present with symptoms that mimic those of Autism Spectrum Disorders (ASD). Therefore, the aim of this study was to investigate how hearing-compromised toddlers would score relative to toddlers diagnosed with an ASD on a measure of autism symptomatology.

Multi-modal Pain Measurements in Infants

Journal of Neuroscience Methods. Jan, 2012  |  Pubmed ID: 22285660

A non-invasive integrated method was developed to measure neural and behavioural responses to peripheral sensory and noxious stimulation in human infants. The introduction of a novel event-detection interface allows synchronous recording of: (i) muscle and central nervous system activity with surface electromyography (EMG), scalp electroencephalography (EEG) and near-infrared spectroscopy (NIRS); (ii) behavioural responses with video-recording and (iii) autonomic responses (heart rate, oxygen saturation, respiratory rate and cardiovascular activity) with electrocardiography (ECG) and pulse oximetry. The system can detect noxious heel lance and touch stimuli with precision (33μs and 624μs respectively) and accuracy (523μs and 256μs) and has 100% sensitivity and specificity for both types of stimulation. Its ability to detect response latencies accurately was demonstrated by a shift in latency of the vertex potential of 20.7±15.7ms (n=6 infants), following touch of the heel and of the shoulder, reflecting the distance between the two sites. This integrated system has provided reliable and reproducible measurements of responses to sensory and noxious stimulation in human infants on more than 100 test occasions.

Ivacaftor Potentiation of Multiple CFTR Channels with Gating Mutations

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society. Jan, 2012  |  Pubmed ID: 22293084

BACKGROUND: The investigational CFTR potentiator ivacaftor (VX-770) increased CFTR channel activity and improved lung function in subjects with CF who have the G551D CFTR gating mutation. The aim of this in vitro study was to determine whether ivacaftor potentiates mutant CFTR with gating defects caused by other CFTR gating mutations. METHODS: The effects of ivacaftor on CFTR channel open probability and chloride transport were tested in electrophysiological studies using Fischer rat thyroid (FRT) cells expressing different CFTR gating mutations. RESULTS: Ivacaftor potentiated multiple mutant CFTR forms with defects in CFTR channel gating. These included the G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P and G1349D CFTR gating mutations. CONCLUSION: These in vitro data suggest that ivacaftor has a similar effect on all CFTR forms with gating defects and support investigation of the potential clinical benefit of ivacaftor in CF patients who have CFTR gating mutations beyond G551D.

The Drosophila Melanogaster Genetic Reference Panel

Nature. Feb, 2012  |  Pubmed ID: 22318601

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics.

Long-Term (5- to 20-Year) Outcomes After Transcatheter or Surgical Treatment of Hemodynamically Significant Isolated Secundum Atrial Septal Defect

The American Journal of Cardiology. Feb, 2012  |  Pubmed ID: 22335856

Truly long-term follow-up data after transcatheter closure (TC) of atrial septal defects (ASDs) are scarce. We report the 5- to 20-year outcomes of TC and surgical closure (SC) for typical secundum ASD. We reviewed the records of patients with isolated secundum ASD and right ventricular volume overload who underwent TC or SC (January 1, 1986 to September 30, 2005). Follow-up was obtained through a combination of chart review, physician records, and telephone survey. We identified 375 patients (207 SC and 168 TC) and obtained follow-up data >5 years (median follow-up 10 years) for 300 (152 SC, 148 TC). Nine patients have died (3%). The New York Heart Association functional class was unchanged in 227 patients, improved in 25, and was worse in 15. Clinically significant arrhythmia was found in 28 patients (9.3%); 21% aged >40 years developed arrhythmia. On multivariate analysis, the odds of significant arrhythmia tended to be greater in the SC group, but this was statistically insignificant (95% confidence interval 0.68 to 3.9, p = 0.27). Age and preprocedure arrhythmia, but not TC or SC, were independent risk factors for late arrhythmia (p <0.001). No difference was found in the incidence of late, probably embolic, stroke in the TC (3%) versus SC (2%) groups. In conclusion, long-term outcomes after secundum ASD closure using modern methods are excellent. No significant differences were found between TC versus SC with regard to survival, functional capacity, atrial arrhythmias, or embolic neurologic events. Arrhythmia and neurologic events remain long-term risks after ASD closure, especially if the patient had pre-existing arrhythmia.

Disobedience and Driving in Patients with Epilepsy

Epilepsy & Behavior : E&B. Jan, 2012  |  Pubmed ID: 22112305

Motor vehicle accidents direct legislators to ensure pubic safety. We attempted to characterize and quantify driving risk in patients with seizures (PWS).

Adolescent Understanding and Acceptance of the HPV Vaccination in an Underserved Population in New York City

Journal of Oncology. 2012  |  Pubmed ID: 22187557

Background. HPV vaccination may prevent thousands of cases of cervical cancer. We aimed to evaluate the understanding and acceptance of the HPV vaccine among adolescents. Methods. A questionnaire was distributed to adolescents at health clinics affiliated with a large urban hospital system to determine knowledge pertaining to sexually transmitted diseases and acceptance of the HPV vaccine. Results. 223 adolescents completed the survey. 28% were male, and 70% were female. The mean age for respondents was 16 years old. Adolescents who had received the HPV vaccine were more likely to be female and to have heard of cervical cancer and Pap testing. Of the 143 adolescents who had not yet been vaccinated, only 4% believed that they were at risk of HPV infection and 52% were willing to be vaccinated. Conclusions. Surveyed adolescents demonstrated a marginal willingness to receive the HPV vaccine and a lack of awareness of personal risk for acquiring HPV.

Alzheimer's Therapeutics: Translation of Preclinical Science to Clinical Drug Development

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. Jan, 2012  |  Pubmed ID: 21937983

Over the past three decades, significant progress has been made in understanding the neurobiology of Alzheimer's disease. In recent years, the first attempts to implement novel mechanism-based treatments brought rather disappointing results, with low, if any, drug efficacy and significant side effects. A discrepancy between our expectations based on preclinical models and the results of clinical trials calls for a revision of our theoretical views and questions every stage of translation-from how we model the disease to how we run clinical trials. In the following sections, we will use some specific examples of the therapeutics from acetylcholinesterase inhibitors to recent anti-Aβ immunization and γ-secretase inhibition to discuss whether preclinical studies could predict the limitations in efficacy and side effects that we were so disappointed to observe in recent clinical trials. We discuss ways to improve both the predictive validity of mouse models and the translation of knowledge between preclinical and clinical stages of drug development.

Impact of Surgeon Volume on Patient Safety in Laparoscopic Gynecologic Surgery

Gynecologic Oncology. Jan, 2012  |  Pubmed ID: 22240566

OBJECTIVE: To determine the impact of surgeon volume on patient outcomes in gynecologic laparoscopic surgery. METHODS: We reviewed all patients who underwent a laparoscopic procedure between January 2000 and December 2008. Surgeons were divided into 3 groups based on surgical volume. The mean number of surgeries per year was calculated for each surgeon. Means were categorized into 3 groups. The low-, medium-, and high-volume surgeon groups were compared with respect to level of surgical complexity and intraoperative and postoperative complications. RESULTS: The study included 829 surgeries. Low-volume surgeons (n=5) performed 5 (31.3%) low-complexity, 10 (62.5%) intermediate-complexity, and 1 (6.3%) high-complexity procedures. Medium-volume surgeons (n=6) performed 26 (11.1%) low-complexity, 203 (86.8%) intermediate-complexity, and 5 (2.1%) high-complexity procedures. High-volume surgeons (n=5) performed 47 (8.1%) low-complexity, 439 (75.8%) intermediate-complexity, and 93 (16.1%) high-complexity procedures. The distribution of surgical complexity was significantly different between the 3 groups of surgeons defined by volume (P<0.001). Conversion rates were higher for low-volume surgeons when compared to high-volume surgeons (18.8% vs. 5.2%; P=0.04). Similarly, overall complication rates (<30days) were higher for low-volume surgeons compared to high-volume surgeons (31.3% vs. 17%, P=0.003). Mean length of hospital stay was longer for low-volume (2.4days) than for medium-volume (1.3days) and high-volume surgeons (1.6days) (P=0.003). CONCLUSION: High- and medium-volume gynecologic laparoscopists performed a greater proportion of intermediate- and high-complexity procedures than did low-volume surgeons. High-volume surgeons have a lower rate of conversions, overall postoperative complications, and shorter mean length of hospital stay when compared to low volume surgeons.

Disrupted Homer Scaffolds Mediate Abnormal MGluR5 Function in a Mouse Model of Fragile X Syndrome

Nature Neuroscience. Jan, 2012  |  Pubmed ID: 22267161

Enhanced metabotropic glutamate receptor subunit 5 (mGluR5) function is causally associated with the pathophysiology of fragile X syndrome, a leading inherited cause of intellectual disability and autism. Here we provide evidence that altered mGluR5-Homer scaffolds contribute to mGluR5 dysfunction and phenotypes in the fragile X syndrome mouse model, Fmr1 knockout (Fmr1(-/y)). In Fmr1(-/y) mice, mGluR5 was less associated with long Homer isoforms but more associated with the short Homer1a. Genetic deletion of Homer1a restored mGluR5-long Homer scaffolds and corrected several phenotypes in Fmr1(-/y) mice, including altered mGluR5 signaling, neocortical circuit dysfunction and behavior. Acute, peptide-mediated disruption of mGluR5-Homer scaffolds in wild-type mice mimicked many Fmr1(-/y) phenotypes. In contrast, Homer1a deletion did not rescue altered mGluR-dependent long-term synaptic depression or translational control of target mRNAs of fragile X mental retardation protein, the gene product of Fmr1. Our findings reveal new functions for mGluR5-Homer interactions in the brain and delineate distinct mechanisms of mGluR5 dysfunction in a mouse model of cognitive dysfunction and autism.

The Effectiveness of Screening and Brief Intervention on Reducing Driving While Intoxicated Citations

Population Health Management. Feb, 2012  |  Pubmed ID: 22204312

Abstract The purpose of this study was to use retrospective data, including citations for driving while intoxicated (DWI), to assess the long-term effectiveness of a program consisting of Screening and Brief Intervention (SBI) for at-risk alcohol users and its impact on traffic safety. A second objective was to study ethnic differences in response to SBI. During the time period of 1998-1999, LCF Research, together with the Lovelace Health System, participated in the Cutting Back SBI study for at-risk drinkers. A total of 426 subjects exhibiting at-risk drinking behaviors from the New Mexico cohort were examined for the study, including 211 subjects who received a brief counseling intervention and 215 in the no intervention control group. This study examined DWI citations for all 426 subjects during the 5 years following the Cutting Back study. The brief interventions were shown to have had a significant impact on reducing DWI citations for at-risk drinkers, with the added benefit lasting for the 5-year duration of the study. The SBI was found to be most effective at reducing DWI citations for Hispanic at-risk drinkers. Evidence is presented to show that screening to identify at-risk drinkers followed by a brief intervention has a statistically significant lasting impact on improving traffic safety. (Population Health Management 2012;15:52-57).

Neuronal Activity Regulates Glutamate Transporter Dynamics in Developing Astrocytes

Glia. Feb, 2012  |  Pubmed ID: 22052455

Glutamate transporters (GluTs) maintain a low ambient level of glutamate in the central nervous system (CNS) and shape the activation of glutamate receptors at synapses. Nevertheless, the mechanisms that regulate the trafficking and localization of transporters near sites of glutamate release are poorly understood. Here, we examined the subcellular distribution and dynamic remodeling of the predominant GluT GLT-1 (excitatory amino acid transporter 2, EAAT2) in developing hippocampal astrocytes. Immunolabeling revealed that endogenous GLT-1 is concentrated into discrete clusters along branches of developing astrocytes that were apposed preferentially to synapsin-1 positive synapses. Green fluorescent protein (GFP)-GLT-1 fusion proteins expressed in astrocytes also formed distinct clusters that lined the edges of astrocyte processes, as well as the tips of filopodia and spine-like structures. Time-lapse three-dimensional confocal imaging in tissue slices revealed that GFP-GLT-1 clusters were dynamically remodeled on a timescale of minutes. Some transporter clusters moved within developing astrocyte branches as filopodia extended and retracted, while others maintained stable positions at the tips of spine-like structures. Blockade of neuronal activity with tetrodotoxin reduced both the density and perisynaptic localization of GLT-1 clusters. Conversely, enhancement of neuronal activity increased the size of GLT-1 clusters and their proximity to synapses. Together, these findings indicate that neuronal activity influences both the organization of GluTs in developing astrocyte membranes and their position relative to synapses.