Prediction of transition from ultra-high risk to first-episode psychosis using a probabilistic model combining history, clinical assessment and fatty-acid biomarkers.

Current criteria identifying patients with ultra-high risk of psychosis (UHR) have low specificity, and less than one-third of UHR cases experience transition to psychosis within 3 years of initial assessment. We explored whether a Bayesian probabilistic multimodal model, combining baseline historical and clinical risk factors with biomarkers (oxidative stress, cell membrane fatty acids, resting quantitative electroencephalography (qEEG)), could improve this specificity. We analyzed data of a UHR cohort (n=40) with a 1-year transition rate of 28%.

Endothelial Dysfunction, and A Prothrombotic, Proinflammatory Phenotype Is Caused by Loss of Mitochondrial Thioredoxin Reductase in Endothelium.

Objective: Although the investigation on the importance of mitochondria-derived reactive oxygen species (ROS) in endothelial function has been gaining momentum, little is known on the precise role of the individual components involved in the maintenance of a delicate ROS balance. Here we studied the impact of an ongoing dysregulated redox homeostasis by examining the effects of endothelial cell-specific deletion of murine thioredoxin reductase 2 (Txnrd2), a key enzyme of mitochondrial redox control.

Approach And Results: We analyzed the impact of an inducible, endothelial cell-specific deletion of Txnrd2 on vascular remodeling in the adult mouse after femoral artery ligation.

Bilateral muscle strength symmetry and performance are improved following walk training with restricted blood flow in an elite paralympic sprint runner: Case study.

Objectives: Investigate the influence of 4 weeks of walk training with blood flow restriction (BFR) on muscle strength, metabolic responses, 100-m and 400-m performances in an athlete with cerebral palsy.

Methods: An elite Paralympic sprinter (20 years, 176 cm, 64.8 kg) who presented with moderate hemiplegic cerebral palsy (right side impaired) completed four visits before and after 4 weeks of the BFR training: 1) anthropometric measurements, familiarization of maximal voluntary contraction (MVC), and an incremental test; 2) MVC measurements; 3) 400-m performance, and 4) 100-m performance.

The use of MALDI-MSI in the investigation of psychiatric and neurodegenerative disorders: A review.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a mass spectrometry technique used for the analysis of macromolecules on an intact tissue of interest, thereby allowing the assessment of molecular signatures in health and disease in the anatomical context. MALDI-MSI is increasingly used to investigate neurodegenerative and psychiatric disorders at the molecular level, including Alzheimer's disease (AD), Parkinson's disease (PD), and schizophrenia (SCZ). These illnesses are characterized by complex neuropathological processes, and conventional proteomic techniques investigating brain tissue homogenates have inherent limitations in determining the precise anatomical or cellular location of proteomic findings.

A Fast Experimental Scanner for Proton CT: Technical Performance and First Experience with Phantom Scans.

We report on the design, fabrication, and first tests of a tomographic scanner developed for proton computed tomography (pCT) of head-sized objects. After extensive preclinical testing, pCT is intended to be employed in support of proton therapy treatment planning and pre-treatment verification in patients undergoing particle-beam therapy. The scanner consists of two silicon-strip telescopes that track individual protons before and after the phantom, and a novel multistage scintillation detector that measures a combination of the residual energy and range of the proton, from which we derive the water equivalent path length (WEPL) of the protons in the scanned object.

Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

Podosomes are dynamic cytoskeletal membrane structures with local adhesive and proteolytic activity. They are critically involved in angiogenesis and vascular adaptive growth. Here, we studied in HUVECs and murine small vessels whether shear stress controls podosome assembly and local proteolytic activity.

A multi-centre open-label randomised non-inferiority trial comparing watchful waiting to antibiotic treatment for acute otitis media without perforation in low-risk urban Aboriginal and Torres Strait Islander children (the WATCH trial): study protocol for a randomised controlled trial.

Background: Treatment guidelines recommend watchful waiting for children older than 2 years with acute otitis media (AOM) without perforation, unless they are at high risk of complications. The high prevalence of chronic suppurative otitis media (CSOM) in remote Aboriginal and Torres Strait Islander communities leads these children to be classified as high risk. Urban Aboriginal and Torres Strait Islander children are at lower risk of complications, but evidence to support the subsequent recommendation for watchful waiting in this population is lacking.

Observation of B→D(*) π^(+)π^(-)ℓ^(-)ν Decays in e^(+)e^(-) Collisions at the Υ(4S) Resonance.

We report on measurements of the decays of B¯ mesons into the semileptonic final states B¯→D^(*)π^(+)π^(-)ℓ^(-)ν¯, where D^(*) represents a D or D^(*) meson and ℓ^(-) is an electron or a muon. These measurements are based on 471×10^(6) BB ¯ pairs recorded with the BABAR detector at the SLAC asymmetric B factory PEP-II. We determine the branching fraction ratios R_{π^{+}π^{-}}^{(*)}=B(B[over ¯]→D^{(*)}π^{+}π^{-}ℓ^{-}ν[over ¯])/B(B[over ¯]→D^{(*)}ℓ^{-}ν[over ¯]) using events in which the second B meson is fully reconstructed.

Feedback activation of neurofibromin terminates growth factor-induced Ras activation.

Background: Growth factors induce a characteristically short-lived Ras activation in cells emerging from quiescence. Extensive work has shown that transient as opposed to sustained Ras activation is critical for the induction of mitogenic programs. Mitogen-induced accumulation of active Ras-GTP results from increased nucleotide exchange driven by the nucleotide exchange factor Sos.

Reactions of 2-Substituted Pyridines with Titanocenes and Zirconocenes: Coupling versus Dearomatisation.

Reactions of group 4 metallocene sources with 2-substituted pyridines were investigated to evaluate their coordination type between innocent and reductive dearomatisation as well as to probe the possibility for couplings. A dependence on the cyclopentadienyl ligands (Cp, Cp*), the metals (Ti, Zr), and the substrates (2-phenyl-, 2-acetyl-, and 2-iminopyridine) was observed. While 2-phenylpyridine is barely reactive, 2-acetylpyridine reacts vigorously with the Cp-substituted complexes and selectively with their Cp* analogues.

Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study.

Background: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified.

Precision of implementing virtual setups for orthodontic treatment using CAD/CAM-fabricated custom archwires.

Objectives: The SureSmile® process (OraMetrix®; Richardson, TX, USA) utilizes computer-aided design and computer-aided manufacturing (CAD/CAM). A virtual setup is created for treatment planning and chairside implementation using custom archwires fabricated by robots. The objective of this study was to determine the precision of this implementation.

Relating tribological stimuli to somatosensory electroencephalographic responses.

The present study deals with the extraction of neural correlates evoked by tactile stimulation of the human fingertip. A reciprocal sliding procedure was performed using a home-built tribometer while simultaneously electroencephalographic (EEG) data from the somatosensory cortex was recorded. The tactile stimuli were delivered by a sliding block with equidistant, perpendicular ridges.

Why go the extra mile? A longitudinal study on sojourn goals and their impact on sojourners' adaptation.

Although international student mobility has become a ubiquitous phenomenon in many parts of the world, the goals that student sojourners pursue when moving abroad have received little systematic attention in psychological research. Likewise, their effects on psychological outcomes such as sojourners' psychological and sociocultural adaptation abroad have not yet been examined. Hence, the purpose of the present research was twofold: First, we established the parsimonious Sojourn Goals Scale and confirmed its psychometric quality and construct validity.

Proteome and pathway effects of chronic haloperidol treatment in mouse hippocampus.

Proteomic exploration of the effects of psychotropic drugs on specific brain areas in rodents has the potential to uncover novel molecular networks and pathways affected by psychotropic medications, and may inform etiologic hypotheses on mental disorders. Haloperidol, a widely used first-generation antipsychotic, has been shown to produce structural and functional changes of the hippocampus, a brain region also implicated in the neuropathology of disorders such as schizophrenia and bipolar disorder. Seven adult male C57BL/6 mice were injected daily intraperitoneally with 0.

Isolation of viable and functional T-cells from human palatine tonsils.

Increasing clinical evidence indicates that removal of the palatine tonsils enhances the risk for adults to suffer from severe illnesses. Together with recent experimental findings pointing to the presence of immunologically competent immune cells these findings illustrate that adult palatine tonsils likely play an appreciable role in the host immune response. T-cells are abundant in the palatine tonsil and are a pivotal entity of the adaptive immune response.

First Observation of CP Violation in B[over ¯]^{0}→D_{CP}^{(*)}h^{0} Decays by a Combined Time-Dependent Analysis of BABAR and Belle Data.

We report a measurement of the time-dependent CP asymmetry of B[over ¯]^{0}→D_{CP}^{(*)}h^{0} decays, where the light neutral hadron h^{0} is a π^{0}, η, or ω meson, and the neutral D meson is reconstructed in the CP eigenstates K^{+}K^{-}, K_{S}^{0}π^{0}, or K_{S}^{0}ω. The measurement is performed combining the final data samples collected at the ϒ(4S) resonance by the BABAR and Belle experiments at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6} BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6} BB[over ¯] pairs recorded by the Belle detector.

In-vivo administration of clozapine affects behaviour but does not reverse dendritic spine deficits in the 14-3-3ζ KO mouse model of schizophrenia-like disorders.

Clozapine is an atypical antipsychotic drug used in the treatment of schizophrenia, which has been shown to reverse behavioural and dendritic spine deficits in mice. It has recently been shown that deficiency of 14-3-3ζ has an association with schizophrenia, and that a mouse model lacking this protein displays several schizophrenia-like behavioural deficits. To test the effect of clozapine in this mouse model, 14-3-3ζ KO mice were administered clozapine (5mg/kg) for two weeks prior to being analysed in a test battery of cognition, anxiety, and despair (depression-like) behaviours.

Latent Cytomegalovirus Infection in Rheumatoid Arthritis and Increased Frequencies of Cytolytic LIR-1+CD8+ T Cells.

Objective: Leukocyte immunoglobulin-like receptor 1 (LIR-1) is up-regulated by cytomegalovirus (CMV), which in turn, has been associated with premature aging and more severe joint disease in patients with rheumatoid arthritis (RA). The aim of this study was to investigate the expression and functional significance of LIR-1 in CMV-positive RA patients.

Methods: We determined the phenotype, cytolytic potential, CMV-specific proliferation, and HLA-G-triggered, LIR-1-mediated inhibition of interferon-γ secretion of LIR-1+ T cells in RA patients and healthy controls.

Accelerated tomotherapy delivery with TomoEdge technique.

TomoEDGE is an advanced delivery form of tomotherapy which uses a dynamic secondary collimator. This plan comparison study describes the new features, their clinical applicability, and their effect on plan quality and treatment speed. For the first 45 patients worldwide that were scheduled for a treatment with TomoEdge, at least two plans were created: one with the previous "standard"mode with static jaws and 2.

The Sirt1 activator SRT3025 expands hematopoietic stem and progenitor cells and improves hematopoiesis in Fanconi anemia mice.

Fanconi anemia is a genetic bone marrow failure syndrome. The current treatment options are suboptimal and do not prevent the eventual onset of aplastic anemia requiring bone marrow transplantation. We previously showed that resveratrol, an antioxidant and an activator of the protein deacetylase Sirt1, enhanced hematopoiesis in Fancd2 mutant mice and improved the impaired stem cell quiescence observed in this disease.

AMPK Dilates Resistance Arteries via Activation of SERCA and BKCa Channels in Smooth Muscle.

The protective effects of 5'-AMP-activated protein kinase (AMPK) on the metabolic syndrome may include direct effects on resistance artery vasomotor function. However, the precise actions of AMPK on microvessels and their potential interaction are largely unknown. Thus, we set to determine the effects of AMPK activation on vascular smooth muscle tone and the underlying mechanisms.