Preparation for action: psychophysiological activity preceding a motor skill as a function of expertise, performance outcome, and psychological pressure.

Knowledge of the psychophysiological responses that characterize optimal motor performance is required to inform biofeedback interventions. This experiment compared cortical, cardiac, muscular, and kinematic activity in 10 experts and 10 novices as they performed golf putts in low- and high-pressure conditions. Results revealed that in the final seconds preceding movement, experts displayed a greater reduction in heart rate and EEG theta, high-alpha, and beta power, when compared to novices.

Parents' experiences and expectations of care in pregnancy after stillbirth or neonatal death: a metasynthesis.

Background: Pregnancy after perinatal death is characterised by elevated stress and anxiety, increasing the risk of adverse short-term and long-term outcomes.

Objectives: This metasynthesis aimed to improve understanding of parents' experiences of maternity care in pregnancy after stillbirth or neonatal death.

Search Strategy: Six electronic databases were searched using predefined search terms.

An Additive Manufacturing Test Artifact.

A test artifact, intended for standardization, is proposed for the purpose of evaluating the performance of additive manufacturing (AM) systems. A thorough analysis of previously proposed AM test artifacts as well as experience with machining test artifacts have inspired the design of the proposed test artifact. This new artifact is designed to provide a characterization of the capabilities and limitations of an AM system, as well as to allow system improvement by linking specific errors measured in the test artifact to specific sources in the AM system.

A comparison of alfaxalone and propofol on intraocular pressure in healthy dogs.

Objective: To compare the effects of alfaxalone and propofol on intraocular (IOP) pressure in the canine eye.

Animals Studied: Twenty-three healthy adult dogs.

Procedures: Dogs were randomized to receive intravenous propofol (n = 11) or alfaxalone (n = 12) until loss of jaw tone, 20 min after intravenous premedication (acepromazine 0.

Bicaudal-C spatially controls translation of vertebrate maternal mRNAs.

The Xenopus Cripto-1 protein is confined to the cells of the animal hemisphere during early embryogenesis where it regulates the formation of anterior structures. Cripto-1 protein accumulates only in animal cells because cripto-1 mRNA in cells of the vegetal hemisphere is translationally repressed. Here, we show that the RNA binding protein, Bicaudal-C (Bic-C), functioned directly in this vegetal cell-specific repression.

Immune mechanisms in type 1 diabetes.

There are three prerequisites for development of the autoimmune disease type 1 diabetes (T1D). First, β cell-reactive T cells need to be activated; second, the response needs to be proinflammatory; and finally, immune regulation of autoreactive responses must fail. Here, we describe our current understanding of the cell types and immune mechanisms involved in each of these steps leading to T1D.

Fatal atypical O:3 Yersinia pseudotuberculosis infection in cynomolgus macaques.

Fatal Yersinia pseudotuberculosis infection in cynomolgus macaques was diagnosed based upon pathology, microbiology and PCR for this study. Pathological findings included acute, erosive to ulcerative, necrohemorrhagic enterocolitis. Genotyping by PCR showed an O:3 pattern (gmd-fcl(+), ddhC-prt(+), manB(+), ddhA-B(+)), but an additional gene, wbyK, was detected.

Evolution of a health navigator model of care within a primary care setting: a case study.

Objective: Patient navigation originated as an approach for reducing disparities in cancer care and consequent health outcomes. Over time navigator models have evolved and been used to address various health issues in differing contexts. This case study outlines the evolution, purpose and effects of a lay-led health navigator model in a deprived, sparsely populated, New Zealand rural setting, where primary care services are frequently understaffed and routinely overstretched.

Discovery of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1: optimization of kinase selectivity and pharmacokinetics.

The kinase selectivity and pharmacokinetic optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. The intersection of insights from molecular modeling, computational prediction of metabolic sites, and in vitro metabolite identification studies resulted in a simple and unique solution to both of these problems. These efforts culminated in the discovery of compound 13a, a potent, relatively selective inhibitor of TAK1 with good pharmacokinetic properties in mice, which was active in an in vivo model of ovarian cancer.

Discovery and optimization of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1.

The discovery and potency optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. Micromolar hits taken from high-throughput screening were optimized for biochemical and cellular mechanistic potency to ~10nM, as exemplified by compound 12az. Application of structure-based drug design aided by co-crystal structures of TAK1 with inhibitors significantly shortened the number of iterations required for the optimization.

Early stage W.H.O. grade I and II follicular lymphoma treated with radiation therapy alone.

Objectives: This retrospective study was undertaken to evaluate the outcome of patients with stage I or II (limited stage), grade I-II follicular non-Hodgkin's lymphoma (FL) treated with radiation therapy (RT) alone as initial management.

Methods: Patients with stage I or II and pathologically confirmed WHO grade I or II FL treated initially with RT alone between 1982 and 2008 were identified from a population based cancer registry.

Results: Forty patients with a mean age 61.

Ethanol reversal of cellular tolerance to morphine in rat locus coeruleus neurons.

Consumption of ethanol is a considerable risk factor for death in heroin overdose. We sought to determine whether a mildly intoxicating concentration of ethanol could alter morphine tolerance at the cellular level. In rat locus coeruleus (LC) neurons, tolerance to morphine was reversed by acute exposure of the brain slice to ethanol (20 mM).

Accelerated turnover of MHC class II molecules in nonobese diabetic mice is developmentally and environmentally regulated in vivo and dispensable for autoimmunity.

The H2-A(g7) (A(g7)) MHC class II (MHCII) allele is required for type 1 diabetes (T1D) in NOD mice. A(g7) not only has a unique peptide-binding profile, it was reported to exhibit biochemical defects, including accelerated protein turnover. Such defects were proposed to impair Ag presentation and, thus, self-tolerance.

Butyrophilin Btn2a2 inhibits TCR activation and phosphatidylinositol 3-kinase/Akt pathway signaling and induces Foxp3 expression in T lymphocytes.

The butyrophilin-related protein Btn2a2 was upregulated on murine APC including CD19(+) B cells, CD11b(+)F4/80(+) peritoneal macrophages, and CD11c(+) bone marrow-derived dendritic cells after activation with LPS or Pam3CysK4, suggesting a role in modulation of T lymphocytes. Consistent with this, binding of mouse Btn2a2-Fc to CD3(+) primary mouse T cells stimulated with anti-CD3 and anti-CD28 reduced the number of proliferating cells and entry of cells into the cell cycle. Binding of Btn2a2-Fc to anti-CD3-stimulated T cells inhibited CD3ε, Zap70, and subsequent Erk1/2 activation.

The effects of individual and team competitions on performance, emotions, and effort.

It is well documented that competition can affect performance and emotion in sport. However, our understanding of the comparative effects of individual and team competitions on performance and emotion is limited. We also know little about emotion-based mechanisms underlying the effects of different types of competition on performance.

Type 1 diabetes: translating mechanistic observations into effective clinical outcomes.

Type 1 diabetes (T1D) remains an important health problem, particularly in western countries, where the incidence has been increasing in younger children. In 1986, Eisenbarth described T1D as a chronic autoimmune disease. Work over the past three-and-a-half decades has identified many of the genetic, immunological and environmental factors that are involved in the disease and have led to hypotheses concerning its pathogenesis.

Vaccine against autoimmune disease: can helminths or their products provide a therapy?

There is an increasing interest in exploiting the immunomodulatory effects of helminths and their products in treatment of diseases such as allergy, autoimmunity and inflammatory bowel disease. Detailed examination of the ways in which helminth derived products interact with the host immune system and with host physiology has revealed that these may be multifaceted and have almost certainly arisen following co-evolution of helminths and their hosts. Clinical trials have been initiated with encouraging results in the treatment of inflammatory bowel disease and also Multiple Sclerosis.

Th17-cell plasticity in Helicobacter hepaticus-induced intestinal inflammation.

Bacterial-induced intestinal inflammation is crucially dependent on interleukin (IL)-23 and is associated with CD4(+) T helper type 1 (Th1) and Th17 responses. However, the relative contributions of these subsets during the induction and resolution of colitis in T-cell-sufficient hosts remain unknown. We report that Helicobacter hepaticus-induced typhlocolitis in specific pathogen-free IL-10(-/-) mice is associated with elevated frequencies and numbers of large intestinal interferon (IFN)-γ(+) and IFN-γ(+)IL-17A(+) CD4(+) T cells.

The nonconventional MHC class II molecule DM governs diabetes susceptibility in NOD mice.

The spontaneous destruction of insulin producing pancreatic beta cells in non-obese diabetic (NOD) mice provides a valuable model of type 1 diabetes. As in humans, disease susceptibility is controlled by the classical MHC class II genes that guide CD4(+) T cell responses to self and foreign antigens. It has long been suspected that the dedicated class II chaperone designated HLA-DM in humans or H-2M in mice also makes an important contribution, but due to tight linkage within the MHC, a possible role played by DM peptide editing has not been previously tested by conventional genetic approaches.

Differential endosomal sorting of a novel P2Y12 purinoreceptor mutant.

P2Y12 receptor internalization and recycling play an essential role in ADP-induced platelet activation. Recently, we identified a patient with a mild bleeding disorder carrying a heterozygous mutation of P2Y12 (P341A) whose P2Y12 receptor recycling was significantly compromised. Using human cell line models, we identified key proteins regulating wild-type (WT) P2Y12 recycling and investigated P2Y12 -P341A receptor traffic.

Discovery of potent, selective and orally bioavailable imidazo[1,5-a]pyrazine derived ACK1 inhibitors.

This Letter describes the medicinal chemistry effort towards a series of novel imidazo[1,5-a]pyrazine derived inhibitors of ACK1. Virtual screening led to the discovery of the initial hit, and subsequent exploration of structure-activity relationships and optimization of drug metabolism and pharmacokinetic properties led to the identification of potent, selective and orally bioavailable ACK1 inhibitors.

Helminth mediated modulation of Type 1 diabetes (T1D).

Type 1 diabetes is increasing dramatically in incidence in the developed world. While there may be several reasons for this, improved sanitation and public health measures have altered our interactions with certain infectious agents such as helminths. There is increasing interest in the use of helminths or their products to alleviate inflammatory or allergic conditions.