Dynamic changes in synaptic plasticity genes in ipsilateral and contralateral inferior colliculus following unilateral noise-induced hearing loss

Unilateral noise-induced hearing loss reduces the input to the central auditory pathway disrupting the excitatory and inhibitory inputs to the inferior colliculus (IC), an important binaural processing center. Little is known about the compensatory synaptic changes that occur in the IC as a consequence of unilateral noise-induced hearing loss. To address this issue, Sprague–Dawley rats underwent unilateral noise exposure resulting in severe unilateral hearing loss. IC tissues from the contralateral and ipsilateral IC were evaluated for acute (2-d) and chronic (28-d) changes in the expression of 84 synaptic plasticity genes on a PCR array. Arc and Egr1 genes were further visualized by in situ hybridization to validate the PCR results. None of the genes were upregulated, but many were downregulated post-exposure. At 2-d post-exposure, more than 75% of the genes were significantly downregulated in the contralateral IC, while only two were downregulated in the ipsilateral IC. Many of the downregulated genes were related to long-term depression, long-term potentiation, cell adhesion, immediate early genes, neural receptors and postsynaptic density. At 28-d post-exposure, the gene expression pattern was reversed with more than 85% of genes in the ipsilateral IC now downregulated. Most genes previously downregulated in the contralateral IC 2-d post-exposure had recovered; less than 15% remained downregulated. These time-dependent, asymmetric changes in synaptic plasticity gene expression could shed new light on the perceptual deficits associated with unilateral hearing loss and the dynamic structural and functional changes that occur in the IC days and months following unilateral noise-induced hearing loss

Des(1–3)IGF-1 Treatment Normalizes Type 1 IGF Receptor and Phospho-Akt (Thr 308) Immunoreactivity in Predegenerative Retina of Diabetic Rats

Little is known about interventions that may prevent predegenerative changes in the diabetic retina. This study tested the hypothesis that immediate, systemic treatment with an insulin-like growth factor (IGF)-1 analog can prevent abnormal accumulations of type 1 IGF receptor, and phospho-Akt (Thr 308) immunoreactivity in predegenerative retinas of streptozotocin (STZ) diabetic rats. Type 1 IGF receptor immunoreactivity increased approximately 3-fold in both inner nuclear layer (INL) and ganglion cell layer (GCL) in retinas from STZ rats versus nondiabetic controls. Phospho-Akt (Thr 308) immunoreactivity increased 5-fold in GCL and 8-fold in INL of STZ rat retinas. In all cases, immunoreactive cells were significantly reduced in STZ des(1–3)IGF-1–treated versus STZ rats. Preliminary results suggested that vascular endothelial growth factor (VEGF) levels may also be reduced. Hyperglycemia/ failure of weight gain in diabetic rats continued despite systemic des(1–3)IGF-1. These data show that an IGF-1 analog can prevent early retinal biochemical abnormalities implicated in the progression of diabetic retinopathy, despite ongoing hyperglycemia

Zeta function regularization for a scalar field in a compact domain

We express the zeta function associated to the Laplacian operator on $S^1_r\times M$ in terms of the zeta function associated to the Laplacian on $M$, where $M$ is a compact connected Riemannian manifold. This gives formulas for the partition function of the associated physical model at low and high temperature for any compact domain $M$. Furthermore, we provide an exact formula for the zeta function at any value of $r$ when $M$ is a $D$-dimensional box or a $D$-dimensional torus; this allows a rigorous calculation of the zeta invariants and the analysis of the main thermodynamic functions associated to the physical models at finite temperature.Comment: 19 pages, no figures, to appear in J. Phys.

Personal identity (de)formation among lifestyle travellers: A double-edged sword?

This article explores the personal identity work of lifestyle travellers – individuals for whom extended leisure travel is a preferred lifestyle that they return to repeatedly. Qualitative findings from in-depth semi-structured interviews with lifestyle travellers in northern India and southern Thailand are interpreted in light of theories on identity formation in late modernity that position identity as problematic. It is suggested that extended leisure travel can provide exposure to varied cultural praxes that may contribute to a sense of social saturation. Whilst a minority of the respondents embraced a saturation of personal identity in the subjective formation of a cosmopolitan cultural identity, several of the respondents were paradoxically left with more identity questions than answers as the result of their travels

Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

A cross-sectional exploratory analysis between pet ownership and sleep, exercise, health and neighborhood perceptions : The Whitehall II cohort study

A cross-sectional exploratory analysis between pet ownership and sleep, exercise, health and neighbourhood perceptions: The Whitehall II cohort study Gill Mein (corresponding author), Robert Grant. Faculty of Health, Social Care and Education. Kingston University and St George’s University of London Background: To explore associations between pets, and specifically dog ownership and sleep, health, exercise and neighbourhood. Methods: Cross sectional examination of 6575 participants of the Whitehall II study aged between 59-79 years. We used self-assessed measurement scales of the Short Form (SF36), General Health Questionnaire (GHQ), Control, Autonomy, Self-realisation and Pleasure (CASP), Centre for Epidemiologic Studies Depression Scale (CES-D), sleep, exercise, and perceptions of local neighbourhood. In addition the Mini Mental State Examination which is administered to test global cognitive status (MMSE) Results: We found 2/7 people owned a pet and of those 64% were “very” attached to their pet. Mild exercise in metabolic equivalents (MET-hours) was significantly higher in pet owners than non-owners (median 27.8 (IQR 18.1 to 41.8) vs 25.7 (IQR 16.8 to 38.7), p=0.0001), and in dog owners than other pets (median 32.3 (IQR 20.8 to 46.1) vs 25.6 (IQR 16.8 to 38.5), p<0.0001). Moderate exercise was also significantly higher in pet owners than non pet owners (median 11.8 (IQR 4.2 to 21.9) vs 9.8 (IQR 2.8 to 19.5), p<0.0001), and dog owners than owners of other pets (median 12.3 (IQR 4.2 to 22.2) vs 10.1 (3.1 to 20.0), p=0.0002) but there were no significant differences with vigorous exercise. We found that pet owners were significantly more positive about their neighbourhood than non-owners on 8/9 questions, while dog owners were (significantly) even more positive than owners of other pets on 8/9 questions. Associations with sleep were mixed, although dog owners had less trouble falling asleep than non-dog owners, with borderline statistical significance. Conclusion: Dog owners feel more positive about their neighbourhood, do more exercise, and fall asleep more easily than non-dog owners. These results suggest that dog owners could be more likely to exercise by walking their dogs and therefore may be more familiar and positive about the area in which they walk their dog

Saints and lovers: myths of the avant-garde in Michel Georges-Michel's Les Montparnos

This article examines Michel Georges-Michel’s 1924 novel Les Montparnos as a study of the myths circulating around the Montparnasse avant-garde of the 1920s, and their function in relation to art. Key amongst these myths is the idea of art as a religion, according to which avant-garde artists are conceived as secular saints and martyrs. While this notion of artist as saint is strongly present in early-twentieth-century biographies of Van Gogh, Georges-Michel explicitly relates his fictionalized version of Modigliani’s life not to such recent models but rather to the Renaissance masters, and especially to Raphael, a link which is explained in terms of the post-war ‘retour à l’ordre’ in French artistic culture. The novel’s references to Raphael as archetypal painter-lover are also related to its construction of a myth of the artist as virile and sexually prolific, and to its identification of creative and sexual impulses