893 research outputs found

    Two-week isocaloric time-restricted feeding decreases liver inflammation without significant weight loss in obese mice with non-alcoholic fatty liver disease

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    Prolonged, isocaloric, time-restricted feeding (TRF) protocols can promote weight loss, improve metabolic dysregulation, and mitigate non-alcoholic fatty liver disease (NAFLD). In addition, 3-day, severe caloric restriction can improve liver metabolism and glucose homeostasis prior to significant weight loss. Thus, we hypothesized that short-term, isocaloric TRF would improve NAFLD and characteristics of metabolic syndrome in diet-induced obese male mice. After 26 weeks of ad libitum access to western diet, mice either continued feeding ad libitum or were provided with access to the same quantity of western diet for 8 h daily, over the course of two weeks. Remarkably, this short-term TRF protocol modestly decreased liver tissue inflammation in the absence of changes in body weight or epidydimal fat mass. There were no changes in hepatic lipid accumulation or other characteristics of NAFLD. We observed no changes in liver lipid metabolism-related gene expression, despite increased plasma free fatty acids and decreased plasma triglycerides in the TRF group. However, liver Grp78 and Txnip expression were decreased with TRF suggesting hepatic endoplasmic reticulum (ER) stress and activation of inflammatory pathways may have been diminished. We conclude that two-week, isocaloric TRF can potentially decrease liver inflammation, without significant weight loss or reductions in hepatic steatosis, in obese mice with NAFLD

    A new approach to electromagnetic wave tails on a curved spacetime

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    We present an alternative method for constructing the exact and approximate solutions of electromagnetic wave equations whose source terms are arbitrary order multipoles on a curved spacetime. The developed method is based on the higher-order Green's functions for wave equations which are defined as distributions that satisfy wave equations with the corresponding order covariant derivatives of the Dirac delta function as the source terms. The constructed solution is applied to the study of various geometric effects on the generation and propagation of electromagnetic wave tails to first order in the Riemann tensor. Generally the received radiation tail occurs after a time delay which represents geometrical backscattering by the central gravitational source. It is shown that the truly nonlocal wave-propagation correction (the tail term) takes a universal form which is independent of multipole order. In a particular case, if the radiation pulse is generated by the source during a finite time interval, the tail term after the primary pulse is entirely determined by the energy-momentum vector of the gravitational field source: the form of the tail term is independent of the multipole structure of the gravitational source. We apply the results to a compact binary system and conclude that under certain conditions the tail energy can be a noticeable fraction of the primary pulse energy. We argue that the wave tails should be carefully considered in energy calculations of such systems.Comment: RevTex, 28 pages, 5 eps figures, http://www.tpu.ee/~tony/texdocs/, 4 changes made (pp. 2, 4, 22, 24), 2 references adde

    Steps Toward Determination of the Size and Structure of the Broad-Line Region in Active Galactic Nuclei. XV. Long-Term Optical Monitoring of NGC 5548

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    We present the results of three years of ground-based observations of the Seyfert 1 galaxy NGC 5548, which combined with previously reported data, yield optical continuum and broad-line H-beta light curves for a total of eight years. The light curves consist of over 800 points, with a typical spacing of a few days between observations. During this eight-year period, the nuclear continuum has varied by more than a factor of seven, and the H-beta emission line has varied by a factor of nearly six. The H-beta emission line responds to continuum variations with a time delay or lag of 10-20 days, the precise value varying somewhat from year to year. We find some indications that the lag varies with continuum flux in the sense that the lag is larger when the source is brighter.Comment: 29 pages, 6 figures. Accepted for publication in ApJ (1999 Jan 10

    Quality of life and sexual function after high-dose or conventional chemotherapy for high-risk breast cancer

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    Three hundred and ninety women participated in the quality of life (QL) study of ACCOG1, a high-dose vs conventional adjuvant chemotherapy breast cancer trial, for patients with a high risk of relapse. Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30, questions on menopausal symptoms and the Sexual Activity Questionnaire. Pretreatment, 6,12, 24, 36, 48 and 60-month assessments were conducted. For the high dose group the median decrease in global QL at 6 months was significantly greater than in the conventional group. At 12 months, however, the median change had returned to 0 for both groups. Social functioning was also significantly lower in the high-dose group at 6 months, again returning to prebaseline levels for both groups after 12 months. The most persistent changes appear to be in the effect of treatment in both arms on sexual outcomes, reflected in problems with discomfort and pleasure. Both high-dose and conventional chemotherapy showed persisting negative effects on sexual health. This has not been previously reported as a long-term complication of high-dose chemotherapy. However, it did not have long-term affects on sexual habit, which appeared to return to pretreatment frequency and similar to that of conventional chemotherapy by about 12 months from treatment

    Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

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    It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

    Interaction of Virstatin with Human Serum Albumin: Spectroscopic Analysis and Molecular Modeling

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    Virstatin is a small molecule that inhibits Vibrio cholerae virulence regulation, the causative agent for cholera. Here we report the interaction of virstatin with human serum albumin (HSA) using various biophysical methods. The drug binding was monitored using different isomeric forms of HSA (N form ∼pH 7.2, B form ∼pH 9.0 and F form ∼pH 3.5) by absorption and fluorescence spectroscopy. There is a considerable quenching of the intrinsic fluorescence of HSA on binding the drug. The distance (r) between donor (Trp214 in HSA) and acceptor (virstatin), obtained from Forster-type fluorescence resonance energy transfer (FRET), was found to be 3.05 nm. The ITC data revealed that the binding was an enthalpy-driven process and the binding constants Ka for N and B isomers were found to be 6.09×105 M−1 and 4.47×105 M−1, respectively. The conformational changes of HSA due to the interaction with the drug were investigated from circular dichroism (CD) and Fourier Transform Infrared (FTIR) spectroscopy. For 1∶1 molar ratio of the protein and the drug the far-UV CD spectra showed an increase in α- helicity for all the conformers of HSA, and the protein is stabilized against urea and thermal unfolding. Molecular docking studies revealed possible residues involved in the protein-drug interaction and indicated that virstatin binds to Site I (subdomain IIA), also known as the warfarin binding site

    Career guidance and the changing world of work: Contesting responsibilising notions of the future.

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    Career guidance is an educational activity which helps individuals to manage their participation in learning and work and plan for their futures. Unsurprisingly career guidance practitioners are interested in how the world of work is changing and concerned about threats of technological unemployment. This chapter argues that the career guidance field is strongly influenced by a “changing world of work” narrative which is drawn from a wide body of grey literature produced by think tanks, supra-national bodies and other policy influencers. This body of literature is political in nature and describes the future of work narrowly and within the frame of neoliberalism. The ‘changing world of work’ narrative is explored through a thematic analysis of grey literature and promotional materials for career guidance conferences. The chapter concludes by arguing that career guidance needs to adopt a more critical stance on the ‘changing world of work’ and to offer more emancipatory alternatives.N/
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