Pioglitazone versus Rosiglitazone: Effects on Lipids, Lipoproteins, and Apolipoproteins in Head-to-Head Randomized Clinical Studies

Peroxisome proliferator-activated receptors (PPARs) play an important role in regulating both glucose and lipid metabolism. Agonists for both PPARγ and PPARγ have been used to treat dyslipidemia and hyperglycemia, respectively. In addition to affecting glucose metabolism, PPARγ agonists also regulate lipid metabolism. In this review, we will focus on the randomized clinical trials that directly compared the lipid effects of the thiazolidinedione class of PPARγ agonists, pioglitazone and rosiglitazone, head-to-head either as monotherapy or in combination with other lipid-altering or glucose-lowering agent

TrES-3: A Nearby, Massive, Transiting Hot Jupiter in a 31-Hour Orbit

We describe the discovery of a massive transiting hot Jupiter with a very short orbital period (1.30619 d), which we name TrES-3. From spectroscopy of the host star GSC 03089-00929, we measure T_eff = 5720 +- 150 K, logg=4.6 +- 0.3, and vsini < 2 km/s, and derive a stellar mass of 0.90 +- 0.15 M_sun. We estimate a planetary mass of 1.92 +- 0.23 M_Jup, based on the sinusoidal variation of our high-precision radial velocity measurements. This variation has a period and phase consistent with our transit photometry. Our spectra show no evidence of line bisector variations that would indicate a blended eclipsing binary star. From detailed modeling of our B and z photometry of the 2.5%-deep transits, we determine a stellar radius 0.802 +- 0.046 R_sun and a planetary radius 1.295 +- 0.081 R_Jup. TrES-3 has one of the shortest orbital periods of the known transiting exoplanets, facilitating studies of orbital decay and mass loss due to evaporation, and making it an excellent target for future studies of infrared emission and reflected starlight.Comment: v1. 14 pages, 2 figures, 3 tables. Submitted to ApJL 27 April 2007. Accepted for publication in ApJL 14 May 200

Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system

<p>Abstract</p> <p>Background</p> <p>Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number of severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia and Down syndrome. Although several studies have shown that cytokines have potent effects on neural function, their role in neural development is still poorly understood. In this study, we investigated the link between abnormal cytokine levels and neural development using the <it>Xenopus laevis </it>tadpole visual system, a model frequently used to examine the anatomical and functional development of neural circuits.</p> <p>Results</p> <p>Using a test for a visually guided behavior that requires normal visual system development, we examined the long-term effects of prolonged developmental exposure to three pro-inflammatory cytokines with known neural functions: interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. We found that all cytokines affected the development of normal visually guided behavior. Neuroanatomical imaging of the visual projection showed that none of the cytokines caused any gross abnormalities in the anatomical organization of this projection, suggesting that they may be acting at the level of neuronal microcircuits. We further tested the effects of TNF-α on the electrophysiological properties of the retinotectal circuit and found that long-term developmental exposure to TNF-α resulted in enhanced spontaneous excitatory synaptic transmission in tectal neurons, increased AMPA/NMDA ratios of retinotectal synapses, and a decrease in the number of immature synapses containing only NMDA receptors, consistent with premature maturation and stabilization of these synapses. Local interconnectivity within the tectum also appeared to remain widespread, as shown by increased recurrent polysynaptic activity, and was similar to what is seen in more immature, less refined tectal circuits. TNF-α treatment also enhanced the overall growth of tectal cell dendrites. Finally, we found that TNF-α-reared tadpoles had increased susceptibility to pentylenetetrazol-induced seizures.</p> <p>Conclusions</p> <p>Taken together our data are consistent with a model in which TNF-α causes premature stabilization of developing synapses within the tectum, therefore preventing normal refinement and synapse elimination that occurs during development, leading to increased local connectivity and epilepsy. This experimental model also provides an integrative approach to understanding the effects of cytokines on the development of neural circuits and may provide novel insights into the etiology underlying some neurodevelopmental disorders.</p

A New Spectroscopic and Photometric Analysis of the Transiting Planet Systems TrES-3 and TrES-4

We report new spectroscopic and photometric observations of the parent stars of the recently discovered transiting planets TrES-3 and TrES-4. A detailed abundance analysis based on high-resolution spectra yields [Fe/H] = –0.19 ± 0.08, T_(eff) = 5650 ± 75 K, and log g = 4.4 ± 0.1 for TrES-3, and [Fe/H] = +0.14 ± 0.09, T_(eff) = 6200 ± 75 K, and log g = 4.0 ± 0.1 for TrES-4. The accuracy of the effective temperatures is supported by a number of independent consistency checks. The spectroscopic orbital solution for TrES-3 is improved with our new radial velocity measurements of that system, as are the light-curve parameters for both systems based on newly acquired photometry for TrES-3 and a reanalysis of existing photometry for TrES-4. We have redetermined the stellar parameters taking advantage of the strong constraint provided by the light curves in the form of the normalized separation a/R_* (related to the stellar density) in conjunction with our new temperatures and metallicities. The masses and radii we derive are M_* = 0.928^(+0.028)_(–0.048) M_⊙, R_* = 0.829^(+0.015)_(–0.022) R_⊙, and M_* = 1.404^(+0.066)_(–0.134) M_⊙, R_* = 1.846^(+0.096)_(–0.087) R_⊙ for TrES-3 and TrES-4, respectively. With these revised stellar parameters, we obtain improved values for the planetary masses and radii. We find M_p = 1.910^(+0.075)_(–0.080) M_(Jup), R_p = 1.336^(+0.031)_(–0.036) R_(Jup) for TrES-3, and M_p = 0.925 ± 0.082 M_(Jup), R_p = 1.783^(+0.093)_(–0.086) R_(Jup) for TrES-4. We confirm TrES-4 as the planet with the largest radius among the currently known transiting hot Jupiters

Self-perceived weather sensitivity and joint pain in older people with osteoarthritis in six European countries: Results from the European Project on OSteoArthritis (EPOSA)

People with osteoarthritis (OA) frequently report that their joint pain is influenced by weather conditions. This study aimed to examine whether there are differences in perceived joint pain between older people with OA who reported to be weather-sensitive versus those who did not in six European countries with different climates and to identify characteristics of older persons with OA that are most predictive of perceived weather sensitivity. Methods Baseline data from the European Project on OSteoArthritis (EPOSA) were used. ACR classification criteria were used to determine OA. Participants with OA were asked about their perception of weather as influencing their pain. Using a two-week follow-up pain calendar, average self-reported joint pain was assessed (range: 0 (no pain)-10 (greatest pain intensity)). Linear regression analyses, logistic regression analyses and an independent t-test were used. Analyses were adjusted for several confounders. Results The majority of participants with OA (67.2%) perceived the weather as affecting their pain. Weather-sensitive participants reported more pain than non-weather-sensitive participants (M = 4.1, SD = 2.4 versus M = 3.1, SD = 2.4; p < 0.001). After adjusting for several confounding factors, the association between self-perceived weather sensitivity and joint pain remained present (B = 0.37, p = 0.03). Logistic regression analyses revealed that women and more anxious people were more likely to report weather sensitivity. Older people with OA from Southern Europe were more likely to indicate themselves as weather-sensitive persons than those from Northern Europe. Conclusions Weather (in)stability may have a greater impact on joint structures and pain perception in people from Southern Europe. The results emphasize the importance of considering weather sensitivity in daily life of older people with OA and may help to identify weather-sensitive older people with OA.The Indicators for Monitoring COPD and Asthma - Activity and Function in the Elderly in Ulm study (IMCA - ActiFE) is supported by the European Union (No.: 2005121) and the Ministry of Science, Baden-Württemberg. The Italian cohort study is part of the National Research Council Project on Aging (PNR). The Longitudinal Aging Study Amsterdam (LASA) is financially supported by the Dutch Ministry of Health, Welfare and Sports. The Peñagrande study was partially supported by the National Fund for Health Research (Fondo de Investigaciones en Salud) of Spain (project numbers FIS PI 05/1898; FIS RETICEF RD06/0013/1013 and FIS PS09/02143). The Swedish Twin Registry is supported in part by the Swedish Ministry of Higher Education. The Hertfordshire Cohort Study was supported by the Medical Research Council, UK

Health and prolonging working lives: an advisory report of the Health Council of The Netherlands

Objective This paper summarizes the main findings and recommendations of an advisory report on health and prolonging working life, which was requested by the Dutch Minister of Social Affairs and Employment. Methods The advisory report was compiled by a multidisciplinary committee of ten scientists appointed by the Health Council of The Netherlands. The committee's aims were to (i) describe the health of the ageing population, (ii) describe how prolonging working life influences health, (iii) describe determinants, besides health, for prolonging working lives, and (iv) review the literature on interventions aimed at retaining or improving employability of older workers. Results The report was presented to the Minister on 26 June 2018. As the likelihood of health problems increases with age, prolonging working life may be difficult. In general, life expectancy increases and gains in life years and health seem mainly attributable to people aged >75 years. Work is good for mental health. However, it may be beneficial for mental health to stop working around the retirement age. Besides health, financial factors, lifestyle, motivation to work, and working conditions play a role in prolonging working life. A systematic review of the evidence indicated that interventions such as worksite health promotion or career development workshops can support older workers in this matter. Conclusions The Health Council advised the Dutch Government to focus on worksite health promotion and career development interventions as well as the improvement of their implementation. This requires a tailored approach as there is a large diversity in health among older workers and particularly between low- and higheducated people. With this in mind, it was further recommended to explore whether flexible pension schemes might better suit this diversit

The neighbourhood environment and use of neighbourhood resources in older adults with and without lower limb osteoarthritis:results from the Hertfordshire Cohort Study

This study aimed to examine the associations of perceptions of neighbourhood cohesion and neighbourhood problems and objectively measured neighbourhood deprivation with the use of neighbourhood resources by older adults with and without lower limb osteoarthritis (LLOA), and to assess whether these relationships are stronger in older persons with LLOA than in those without the condition. Data from the Hertfordshire Cohort Study were used. American College of Rheumatology classification criteria were used to diagnose clinical LLOA (knee and/or hip osteoarthritis). Use of neighbourhood resources was assessed using the Home and Community Environment instrument. Participants were asked about their perceptions of neighbourhood cohesion and neighbourhood problems. Objective neighbourhood deprivation was assessed using the Index of Multiple Deprivation score based on 2010 census data. Of the 401 participants (71–80 years), 74 (18.5 %) had LLOA. The neighbourhood measures were not significantly associated with use of resources in the full sample. A trend for a negative association between use of public transport and perceived neighbourhood problems was observed in participants with LLOA (OR = 0.77, 99 % CI = 0.53–1.12), whereas a trend for a positive association between perceived neighbourhood problems and use of public transport was found in participants without LLOA (OR = 1.18, 99 % CI = 1.00–1.39). The perception of more neighbourhood problems seems only to hinder older adults with LLOA to make use of public transport. Older adults with LLOA may be less able to deal with neighbourhood problems and more challenging environments than those without the condition

Social and physical neighbourhood characteristics and loneliness among older adults: Results from the MINDMAP project

Background: Loneliness is associated with several adverse mental and physical health outcomes in older adults. Previous studies have shown that a variety of individual-level and perceived area-level characteristics are associated with loneliness. This study examined the associations of objectively measured social and physical neighbourhood characteristics with loneliness. Methods: We used cross-sectional data from 1959 older adults (63-98 years) who participated in the Longitudinal Ageing Study Amsterdam (LASA; wave 2011/12) and the Health and Living Conditions of the Population of Eindhoven and Surroundings study (GLOBE; wave 2014) in the Netherlands. Study-specific loneliness scores were harmonised across both cohort studies and divided into tertiles denoting low, medium and high levels of loneliness. Objectively measured neighbourhood characteristics, including area-level percentages of low educated residents, social security beneficiaries and unoccupied dwellings, average income, crime levels and land use mix, were linked to individual-level data. Multinomial logistic regression analyses were conducted to examine the associations of interest. Results: There was no statistical evidence for

Hematological Changes as Prognostic Indicators of Survival: Similarities Between Gottingen Minipigs, Humans, and Other Large Animal Models

The animal efficacy rule addressing development of drugs for selected disease categories has pointed out the need to develop alternative large animal models. Based on this rule, the pathophysiology of the disease in the animal model must be well characterized and must reflect that in humans. So far, manifestations of the acute radiation syndrome (ARS) have been extensively studied only in two large animal models, the non-human primate (NHP) and the canine. We are evaluating the suitability of the minipig as an additional large animal model for development of radiation countermeasures. We have previously shown that the Gottingen minipig manifests hematopoietic ARS phases and symptoms similar to those observed in canines, NHPs, and humans.We establish here the LD50/30 dose (radiation dose at which 50% of the animals succumb within 30 days), and show that at this dose the time of nadir and the duration of cytopenia resemble those observed for NHP and canines, and mimic closely the kinetics of blood cell depletion and recovery in human patients with reversible hematopoietic damage (H3 category, METREPOL approach). No signs of GI damage in terms of diarrhea or shortening of villi were observed at doses up to 1.9 Gy. Platelet counts at days 10 and 14, number of days to reach critical platelet values, duration of thrombocytopenia, neutrophil stress response at 3 hours and count at 14 days, and CRP-to-platelet ratio were correlated with survival. The ratios between neutrophils, lymphocytes and platelets were significantly correlated with exposure to irradiation at different time intervals.As a non-rodent animal model, the minipig offers a useful alternative to NHP and canines, with attractive features including ARS resembling human ARS, cost, and regulatory acceptability. Use of the minipig may allow accelerated development of radiation countermeasures