The effects of pioglitazone, a PPARγ receptor agonist, on the abuse liability of oxycodone among nondependent opioid users

Aims: Activation of PPARγ by pioglitazone (PIO) has shown some efficacy in attenuating addictive-like responses in laboratory animals. The ability of PIO to alter the effects of opioids in humans has not been characterized in a controlled laboratory setting. The proposed investigation sought to examine the effects of PIO on the subjective, analgesic, physiological and cognitive effects of oxycodone (OXY). Methods: During this investigation, nondependent prescription opioid abusers (N = 17 completers) were maintained for 2-3 weeks on ascending daily doses of PIO (0 mg, 15 mg, 45 mg) prior to completing a laboratory session assessing the aforementioned effects of OXY [using a within-session cumulative dosing procedure (0, 10, and 20 mg, cumulative dose = 30 mg)]. Results: OXY produced typical mu opioid agonist effects: miosis, decreased pain perception, and decreased respiratory rate. OXY also produced dose-dependent increases in positive subjective responses. Yet, ratings such as: drug "liking," "high," and "good drug effect," were not significantly altered as a function of PIO maintenance dose. Discussion: These data suggest that PIO may not be useful for reducing the abuse liability of OXY. These data were obtained with a sample of nondependent opioid users and therefore may not be applicable to dependent populations or to other opioids. Although PIO failed to alter the abuse liability of OXY, the interaction between glia and opioid receptors is not well understood so the possibility remains that medications that interact with glia in other ways may show more promise

Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study

Doc number: 72 Abstract Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model. Methods/design: In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered. Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period. A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems. Trial registration: NCT0145089

A Boreing Night of Observations of the Upper Mesosphere and Lower Thermosphere Over the Andes Lidar Observatory

A very high-spatial resolution (∼21-23 m pixel at 85 km altitude) OH airglow imager at the Andes Lidar Observatory at Cerro Pach´on, Chile observed considerable ducted wave activity on the night of October 29-30, 2016. This instrument was collocated with a Na wind-temperature lidar that provided data revealing the occurrence of strong ducts. A large field of view OH and greenline airglow imager showed waves present over a vertical extent consistent with the altitudes of the ducting features identified in the lidar profiles. While waves that appeared to be ducted were seen in all imagers throughout the observation interval, the wave train seen in the OH images at earlier times had a distinct leading non-sinusoidal phase followed by several, lower-amplitude, more sinusoidal phases, suggesting a likely bore. The leading phase exhibited significant dissipation via small-scale secondary instabilities suggesting vortex rings that progressed rapidly to smaller scales and turbulence (the latter not fully resolved) thereafter. The motions of these small-scale features were consistent with their location in the duct at or below ∼83-84 km. Bore dissipation caused a momentum flux divergence and a local acceleration of the mean flow within the duct along the direction of the initial bore propagation. A number of these features are consistent with mesospheric bores observed or modeled in previous studies

Kelvin-Helmholtz Billow Interactions and Instabilities In The Mesosphere Over the Andes Lidar Observatory: 1. Observations

A very high spatial resolution (∼25 m pixel at 90 km altitude) OH airglow imager was installed at the Andes Lidar Observatory on Cerro Pachón, Chile, in February 2016. This instrument was collocated with a Na wind-temperature lidar. On 1 March 2016, the lidar data showed that the atmosphere was dynamically unstable before 0100 UT and thus conducive to the formation of Kelvin-Helmholtz instabilities (KHIs). The imager revealed the presence of a KHI and an apparent atmospheric gravity wave (AGW) propagating approximately perpendicular to the plane of primary KHI motions. The AGW appears to have induced modulations of the shear layer leading to misalignments of the emerging KHI billows. These enabled strong KHI billow interactions, as they achieved large amplitudes and a rapid transition to turbulence thereafter. The interactions manifested themselves as vortex tube and knot features that were earlier identified in laboratory studies, as discussed in Thorpe (1987, https://doi.org/10.1029/ JC092iC05p05231; 2002, https://doi.org/10.1002/qj.200212858307) and inferred to be widespread in the atmosphere based on features seen in tropospheric clouds but which have never been identified in previous upper atmospheric observations. This study presents the first high-resolution airglow imaging observation of these KHI interaction dynamics that drive rapid transitions to turbulence and suggest the potential importance of these dynamics in the mesosphere and at other altitudes. A companion paper (Fritts et al., 2020, https://doi.org/10.1029/2020JD033412) modeling these dynamics confirms that the vortex tubes and knots yield more rapid and significantly enhanced turbulence relative to the internal instabilities of individual KHI billows

Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON)

<p>Abstract</p> <p>Background</p> <p>Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia.</p> <p>Methods/Design</p> <p>One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an <it>aerobic exercise program in a rehabilitation centre</it> or a <it>flexibility and relaxation program in a rehabilitation centre</it>. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a <it>daily physical activity program set at home making use of pedometers</it>. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures.</p> <p>Discussion</p> <p>The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life.</p> <p>Trial registration</p> <p>The present study is registered within The Netherlands National Trial Register (ref: NTR2124)</p

Ultrafast Pump-Push Photocurrent Spectroscopy of Organic Photoconversion Systems

Novel optical pump-push – photocurrent probe ultrafast spectroscopy experiments on organic photoconversion systems show that excessive excitation energy in such systems is not lost but used to reach delocalised states that act as the gateway for long-range charge separation. We also show that the developed experimental approach can be generalised to inorganic and hybrid photoconversion systems

Plant electrophysiology with conformable organic electronics: Deciphering the propagation of Venus flytrap action potentials

Electrical signals in plants are mediators of long-distance signaling and correlate with plant movements and responses to stress. These signals are studied with single surface electrodes that cannot resolve signal propagation and integration, thus impeding their decoding and link to function. Here, we developed a conformable multielectrode array based on organic electronics for large-scale and high-resolution plant electrophysiology. We performed precise spatiotemporal mapping of the action potential (AP) in Venus flytrap and found that the AP actively propagates through the tissue with constant speed and without strong directionality. We also found that spontaneously generated APs can originate from unstimulated hairs and that they correlate with trap movement. Last, we demonstrate that the Venus flytrap circuitry can be activated by cells other than the sensory hairs. Our work reveals key properties of the AP and establishes the capacity of organic bioelectronics for resolving electrical signaling in plants contributing to the mechanistic understanding of long-distance responses in plants