Thermal decomposition of allantoin as probed by matrix isolation FTIR spectroscopy

The optimized geometries, energies of the possible conformers of allantoin (2,5-dioxo-4-imidazolidinyl urea, the diureide of glyoxylic acid) as well as the barriers for conformational interconversion have been calculated using the density functional theory [DFT(B3LYP)/6-311++G(d,p)] method. The calculations predicted the existence of four conformers (gC, tT, g′C, and g′T; where the first and second symbols in the name of the conformers designate the conformation around the exocyclic NHC–NHCO and CNH–CO axes, respectively), with the gC form contributing to more than 98% of the population in gas phase at room temperature. This conformer is different from that corresponding to the monomeric unit found in crystalline RS-allantoin (g′C; Mootz, D. Acta Crystallogr.1965, 19, 726), stressing the importance of intermolecular H-bonding in determining the structure of the crystal. Upon sublimation under vacuum (10−6 mbar), the compound was found to undergo extensive decomposition to urea, isocyanic acid, NH3, and carbon. The identification of the decomposition products was made by using matrix isolation infrared spectroscopy. In consonance with the theoretical predictions, the allantoin molecules surviving thermal decomposition were found to undergo conformational isomerization and be present in the cryogenic argon matrix in both the gC and g′C conformations. The solid state room temperature infrared spectrum of allantoin was also investigated and assigned

Long-term result of hybrid procedure for an extensive thoracic aortic aneurysm in Takayasu arteritis: a case report

We herein present a 60 years old woman with Takayasu arteritis and an extensive thoracic aortic aneurysm who initially underwent a total aortic arch replacement. Then, in the second stage, thoracic endovascular aortic repair was performed using the elephant trunk graft as the proximal landing zone at four weeks after aortic arch repair. The postoperative course was relatively uncomplicated, but a type II endoleak was noted. Currently, about 5 years postoperatively, the slight type II endoleak from intercostal artery persists, but aneurism dilatation has not been noted, so the patient is being followed up

An inhibitory pull-push circuit in frontal cortex.

Push-pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull-push influence on excitatory neurons-an inversion of the canonical push-pull of feedforward input

Exploring the measurement of markedness and its relationship with other linguistic variables

Antonym pair members can be differentiated by each word's markedness-that distinction attributable to the presence or absence of features at morphological or semantic levels. Morphologically marked words incorporate their unmarked counterpart with additional morphs (e.g., "unlucky" vs. "lucky"); properties used to determine semantically marked words (e.g., "short" vs. "long") are less clearly defined. Despite extensive theoretical scrutiny, the lexical properties of markedness have received scant empirical study. The current paper employs an antonym sequencing approach to measure markedness: establishing markedness probabilities for individual words and evaluating their relationship with other lexical properties (e.g., length, frequency, valence). Regression analyses reveal that markedness probability is, as predicted, related to affixation and also strongly related to valence. Our results support the suggestion that antonym sequence is reflected in discourse, and further analysis demonstrates that markedness probabilities, derived from the antonym sequencing task, reflect the ordering of antonyms within natural language. In line with the Pollyanna Hypothesis, we argue that markedness is closely related to valence; language users demonstrate a tendency to present words evaluated positively ahead of those evaluated negatively if given the choice. Future research should consider the relationship of markedness and valence, and the influence of contextual information in determining which member of an antonym pair is marked or unmarked within discourse

True Neutrality as a New Type of Flavour

A classification of leptonic currents with respect to C-operation requires the separation of elementary particles into the two classes of vector C-even and axial-vector C-odd character. Their nature has been created so that to each type of lepton corresponds a kind of neutrino. Such pairs are united in families of a different C-parity. Unlike the neutrino of a vector type, any C-noninvariant Dirac neutrino must have his Majorana neutrino. They constitute the purely neutrino families. We discuss the nature of a corresponding mechanism responsible for the availability in all types of axial-vector particles of a kind of flavour which distinguishes each of them from others by a true charge characterized by a quantum number conserved at the interactions between the C-odd fermion and the field of emission of the corresponding types of gauge bosons. This regularity expresses the unidenticality of truly neutral neutrino and antineutrino, confirming that an internal symmetry of a C-noninvariant particle is described by an axial-vector space. Thereby, a true flavour together with the earlier known lepton flavour predicts the existence of leptonic strings and their birth in single and double beta decays as a unity of flavour and gauge symmetry laws. Such a unified principle explains the availability of a flavour symmetrical mode of neutrino oscillations.Comment: 19 pages, LaTex, Published version in IJT

Fear and Exploration in European Starlings (Sturnus vulgaris): A Comparison of Hand-Reared and Wild-Caught Birds

The revision of EU legislation will ban the use of wild-caught animals in scientific procedures. This change is partially predicated on the assumption that captive-rearing produces animals with reduced fearfulness. Previously, we have shown that hand-reared starlings (Sturnus vulgaris) indeed exhibit reduced fear of humans compared to wild-caught conspecifics. Here, we asked whether this reduction in fear in hand-reared birds is limited to fear of humans or extends more generally to fear of novel environments and novel objects. Comparing 6–8 month old birds hand-reared in the lab with age-matched birds caught from the wild as fledged juveniles a minimum of 1 month previously, we examined the birds' initial reactions in a novel environment (a small cage) and found that wild-caught starlings were faster to initiate movement compared to the hand-reared birds. We interpret this difference as evidence for greater escape motivation in the wild-caught birds. In contrast, we found no differences between hand-reared and wild-caught birds when tested in novel object tests assumed to measure neophobia and exploratory behaviour. Moreover, we found no correlations between individual bird's responses in the different tests, supporting the idea that these measure different traits (e.g. fear and exploration). In summary, our data show that developmental origin affects one measure of response to novelty in young starlings, indicative of a difference in either fear or coping style in a stressful situation. Our data contribute to a growing literature demonstrating effects of early-life experience on later behaviour in a range of species. However, since we did not find consistent evidence for reduced fearfulness in hand-reared birds, we remain agnostic about the welfare benefits of hand-rearing as a method for sourcing wild birds for behavioural and physiological research

Influence of Prior Influenza Vaccination on Antibody and B-Cell Responses

Currently two vaccines, trivalent inactivated influenza vaccine (TIV) and live attenuated influenza vaccine (LAIV), are licensed in the USA. Despite previous studies on immune responses induced by these two vaccines, a comparative study of the influence of prior influenza vaccination on serum antibody and B-cell responses to new LAIV or TIV vaccination has not been reported. During the 2005/6 influenza season, we quantified the serum antibody and B-cell responses to LAIV or TIV in adults with differing influenza vaccination histories in the prior year: LAIV, TIV, or neither. Blood samples were collected on days 0, 7–9 and 21–35 after immunization and used for serum HAI assay and B-cell assays. Total and influenza-specific circulating IgG and IgA antibody secreting cells (ASC) in PBMC were detected by direct ELISPOT assay. Memory B cells were also tested by ELISPOT after polyclonal stimulation of PBMC in vitro. Serum antibody, effector, and memory B-cell responses were greater in TIV recipients than LAIV recipients. Prior year TIV recipients had significantly higher baseline HAI titers, but lower HAI response after vaccination with either TIV or LAIV, and lower IgA ASC response after vaccination with TIV than prior year LAIV or no vaccination recipients. Lower levels of baseline HAI titer were associated with a greater fold-increase of HAI titer and ASC number after vaccination, which also differed by type of vaccine. Our findings suggest that the type of vaccine received in the prior year affects the serum antibody and the B-cell responses to subsequent vaccination. In particular, prior year TIV vaccination is associated with sustained higher HAI titer one year later but lower antibody response to new LAIV or TIV vaccination, and a lower effector B-cell response to new TIV but not LAIV vaccination

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Baseline Levels of Influenza-Specific CD4 Memory T-Cells Affect T-Cell Responses to Influenza Vaccines

BACKGROUND: Factors affecting immune responses to influenza vaccines have not been studied systematically. We hypothesized that T-cell and antibody responses to the vaccines are functions of pre-existing host immunity against influenza antigens. METHODOLOGY/PRINCIPAL FINDINGS: During the 2004 and 2005 influenza seasons, we have collected data on cellular and humoral immune reactivity to influenza virus in blood samples collected before and after immunization with inactivated or live attenuated influenza vaccines in healthy children and adults. We first used cross-validated lasso regression on the 2004 dataset to identify a group of candidate baseline correlates with T-cell and antibody responses to vaccines, defined as fold-increase in influenza-specific T-cells and serum HAI titer after vaccination. The following baseline parameters were examined: percentages of influenza-reactive IFN-gamma(+) cells in T and NK cell subsets, percentages of influenza-specific memory B-cells, HAI titer, age, and type of vaccine. The candidate baseline correlates were then tested with the independent 2005 dataset. Baseline percentage of influenza-specific IFN-gamma(+) CD4 T-cells was identified as a significant correlate of CD4 and CD8 T-cell responses, with lower baseline levels associated with larger T-cell responses. Baseline HAI titer and vaccine type were identified as significant correlates for HAI response, with lower baseline levels and the inactivated vaccine associated with larger HAI responses. Previously we reported that baseline levels of CD56(dim) NK reactivity against influenza virus inversely correlated with the immediate T-cell response to vaccination, and that NK reactivity induced by influenza virus depended on IL-2 produced by influenza-specific memory T-cells. Taken together these results suggest a novel mechanism for the homeostasis of virus-specific T-cells, which involves interaction between memory helper T-cells, CD56(dim) NK and DC. SIGNIFICANCE: These results demonstrate that assessment of baseline biomarkers may predict immunologic outcome of influenza vaccination and may reveal some of the mechanisms responsible for variable immune responses following vaccination and natural infection

Role of Esrrg in the Fibrate-Mediated Regulation of Lipid Metabolism Genes in Human ApoA-I Transgenic Mice

We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and β-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.National Institutes of Health (HL48739 and HL68216); European Union (LSHM-CT-2006-0376331, LSHG-CT-2006-037277); the Biomedical Research Foundation of the Academy of Athens; the Hellenic Cardiological Society; the John F Kostopoulos Foundatio