POLYAMINE MODULATION IN ALCOHOLISM: EXAMINATION USING A NOVEL SCREENING PROCEDURE DESIGNED TO PREDICT ANTI-RELAPSE AND NEUROPROTECTIVE EFFICACY

Alcohol dependence is a major public health concern. Despite the FDA’s approval of multiple anti-relapse drugs, relapse rates remain unacceptably high. Furthermore, cognitive deficits among chronic drinkers are evident and are suggested to contribute to relapse risk. Current evidence suggests that several critical features of alcoholism and alcohol-associated neurodegeneration are mechanistically linked to glutamatergic actions; specifically, they appear positively affected by glutamatergic inhibition, particularly inhibition via polyamine modulation of a subpopulation of n-methyl-d-aspartate receptors. The current project was designed to evaluate the performance of two putative polyamine modulators (JR-220 and CP-101,606) in a variety of screens designed to identify the potential to reduce withdrawal severity, neurotoxicity and relapse risk. Screens included a complex organotypic screen designed to assess neuroprotective potential (Experiment 1), a simple behavioral screen designed to assess withdrawal severity (Experiment 2) as well as several more complex behavioral screens designed to examine cue-conditioning during withdrawal (Experiment 3), relapse behavior (Experiment 4), stress-associated consumption (Experiment 5) and binge-like consumption (Experiment 6). An additional open field experiment (Experiment 7) was conducted in order to address interpretational issues concerning activity in Experiments 2-6. Finally, as a first step in moving beyond simple screening, we expanded our binge screen to adhere more closely to an established, validated model of binge consumption (Experiment 8). While some interpretational issues were noted, taken together, the results from these experiments provide strong evidence for both drugs as potential pharmacotherapies for alcoholism and further implicate polyamines and NR2B subunits as critical mechanisms in ETOH consumption and withdrawal

Acute rotator cuff tendinopathy: does ice, low load isometric exercise, or a combination of the two produce an analgaesic effect?

This document is the Accepted Manuscript version of the following article: Parle PJ, Riddiford-Harland DL, Howitt CD, et al. 'Acute rotator cuff tendinopathy: does ice, low load isometric exercise, or a combination of the two produce an analgaesic effect?.' Br J Sports Med 2017;51:208-209, doi: http://dx.doi.org/10.1136/bjsports-2016-096107.Rotator cuff tendinopathies are the most commonly diagnosed musculoskeletal shoulder conditions and are associated with pain, weakness and loss of function.1 Tendon swelling may be associated with tendinopathy and may result from acute overload.2–3 An increase in tendon cells (tenocytes) and upregulation of large molecular weight proteoglycans, such as aggrecan, may increase tendon water content.2 There is uncertainty as to whether the swelling is related to the pain or is instead an observed but unrelated phenomenon. Weakness detected clinically may be due to pain inhibition.4–5 Early treatment of acute rotator cuff tendinopathy involves patient education and relative rest, and may include non-steroidal anti-inflammatory drugs (NSAIDs) to reduce pain, swelling and inflammation. Subacromial corticosteroid injections are also used to achieve the same purpose. These techniques show low to moderate evidence of reducing short-term pain but they do not improve function.6 The medications have side effects such as gastrointestinal tract complaints,7 and corticosteroids may damage tendon tissue.8 Identifying alternative ways to control pain and inflammation may be warranted. Two clinical procedures to manage RC tendinopathy include ice wraps and isometric exercise, however, there are no empirical data supporting their use. This pilot study, conducted at the Illawarra Sports Medicine Clinic, NSW, Australia, was designed to test (1) the short term analgaesic effect of these interventions and (2) the feasibility of a larger clinical trial for adults diagnosed with acute rotator cuff tendinopathy (<12 weeks).Peer reviewe

I am your trans patient

For the first time we are publishing a What Your Patient is Thinking article by a group of people. These transgender authors share their experiences of healthcare and the important messages they would like doctors to know

Imaging the deep structure of the San Andreas Fault south of Hollister with joint analysis of fault zone head and direct P arrivals

Author Posting. © Blackwell, 2007. This article is posted here by permission of Blackwell for personal use, not for redistribution. The definitive version was published in Geophysical Journal International 169 (2007): 1028–1042, doi:10.1111/j.1365-246X.2006.03319.x.We perform a joint inversion of arrival time data generated by direct P and fault zone (FZ) head waves in the San Andreas Fault south of Hollister, CA, to obtain a high-resolution local velocity structure. The incorporation of head waves allows us to obtain a sharp image of the overall velocity contrast across the fault as a function of depth, while the use of near-fault data allows us to resolve internal variations in the FZ structure. The data consist of over 9800 direct P and over 2700 head wave arrival times from 450 events at up to 54 stations of a dense temporary seismic array and the permanent northern California seismic network in the area. One set of inversions is performed upon the whole data set, and five inversion sets are performed on various data subsets in an effort to resolve details of the FZ structure. The results imply a strong contrast of P-wave velocities across the fault of ~50 per cent in the shallow section, and lower contrasts of 10–20 per cent below 3 km, with the southwest being the side with faster velocities. The presence of a shallow low velocity zone around the fault, which could corresponds to the damage structures imaged in trapped wave studies, is detected by inversions using subsets of the data made up of only stations close to the fault. The faster southwest side of the fault shows the development of a shallow low velocity FZ layer in inversions using instruments closer and closer to the fault (<5 and <2 km). Such a feature is not present in results of inversions using only stations at greater distances from the fault. On the slower northeast side of the fault, the presence of a low velocity shallow layer is only detected in the inversions using the stations within 2 km of the fault. We interpret this asymmetry across the fault as a possible indication of a preferred propagation direction of earthquake ruptures in the region. Using events from different portions of the fault, the head wave inversions also resolve small-scale features of the fault visible in the surface geology and relocated seismicity

The Paper Industry: Strategic Alliances, Joint Ventures, and Electronic Commerce Are Reshaping Our Business Models

J. Ben Reeves, MBA, is a wood and fiber procurement manager, Georgia-Pacific Corperation, Lynchburg, VA 24503. Deanna S. Stepp, MBA, CRP, is a marketing director, Lawrence Transportation, Roanoke, VA 24012. Lewis E. Wertz, Jr., MBA, MSCE, P.E., is an engineer-planner, R & K Engineering Inc., Roanoke, VA 24012. Dale A. Henderson, Ph.D., is assistant professor of management, Department of Management, Radford University, Radford, VA 24142

Cardiac taurine and principal amino acids in right and left ventricles of patients with either aortic valve stenosis or coronary artery disease:the importance of diabetes and gender

Free intracellular taurine and principal α-amino acids (glutamate, glutamine, aspartate, asparagine and alanine) are abundant in human heart. They are cellular regulators and their concentration can change in response to disease and cardiac insults and have been shown to differ between hypertrophic left ventricle (LV) and the relatively “normal” right ventricle (RV) in patients with aortic valve stenosis (AVS). This difference has not been shown for coronary artery disease (CAD) and there are no studies that have simultaneously compared amino acid content in LV and RV from different pathologies. In this study we investigated the effect of disease on taurine and principal amino acids in both LV and RV, measured in myocardial biopsies collected from patients with either AVS (n = 22) or CAD (n = 36). Amino acids were extracted and measured using HPLC. Intra- and inter-group analysis was performed as well as subgroup analysis focusing on gender in AVS and type 2 diabetes in CAD. LV of both groups has significantly higher levels of taurine compared to RV. This difference disappears in both diabetic CAD patients and in male AVS patients. Alanine was the only α-amino acid to be altered by diabetes. LV of female AVS patients had significantly more glutamate, aspartate and asparagine than corresponding RV, whilst no difference was seen between LV and RV in males. LV of females has higher glutamate and glutamine and less metabolic stress than LV of males. This work shows that in contrast to LV, RV responds differently to disease which can be modulated by gender and diabetes

Viscosity of Liquid Perfluoroalkanes and Perfluoroalkylalkane Surfactants

As part of a systematic study of the thermophysical properties of two important classes of fluorinated organic compounds (perfluoroalkanes and perfluoroalkylalkanes), viscosity measurements of four n-perfluoroalkanes and five perfluoroalkylalkanes have been carried out at atmospheric pressure and over a wide range of temperatures (278–353 K). From the experimental results the contribution to the viscosity from the CF2 and CF3 groups as a function of temperature have been estimated. Similarly, the contributions for CH2 and CH3 groups in n-alkanes have been determined using literature data. For perfluoroalkylalkanes, the viscosity results were interpreted in terms of the contributions of the constituent CF2, CF3, CH2, and CH3 groups, the deviations from ideality on mixing hydrogenated and fluorinated chains, and the contribution due to the formation of the CF2–CH2 bond. A standard empirical group contribution method (Sastri–Rao method) has also been used to estimate the viscosities of the perfluoroalkylalkanes. Finally, to obtain molecular level insight into the behavior of these molecules, all-atom molecular dynamics simulations have been performed and used to calculate the densities and viscosities of the perfluoroalkylalkanes studied. Although both quantities are underestimated compared to the experimental data, with the viscosities showing the largest deviations, the trends observed in the experimental viscosities are captured

Bioinformatics : indispensable, yet hidden in plain sight?

BACKGROUND: Bioinformatics has multitudinous identities, organisational alignments and disciplinary links. This variety allows bioinformaticians and bioinformatic work to contribute to much (if not most) of life science research in profound ways. The multitude of bioinformatic work also translates into a multitude of credit-distribution arrangements, apparently dismissing that work. RESULTS: We report on the epistemic and social arrangements that characterise the relationship between bioinformatics and life science. We describe, in sociological terms, the character, power and future of bioinformatic work. The character of bioinformatic work is such that its cultural, institutional and technical structures allow for it to be black-boxed easily. The result is that bioinformatic expertise and contributions travel easily and quickly, yet remain largely uncredited. The power of bioinformatic work is shaped by its dependency on life science work, which combined with the black-boxed character of bioinformatic expertise further contributes to situating bioinformatics on the periphery of the life sciences. Finally, the imagined futures of bioinformatic work suggest that bioinformatics will become ever more indispensable without necessarily becoming more visible, forcing bioinformaticians into difficult professional and career choices. CONCLUSIONS: Bioinformatic expertise and labour is epistemically central but often institutionally peripheral. In part, this is a result of the ways in which the character, power distribution and potential futures of bioinformatics are constituted. However, alternative paths can be imagined

The Complexity of Reasoning for Fragments of Default Logic

Default logic was introduced by Reiter in 1980. In 1992, Gottlob classified the complexity of the extension existence problem for propositional default logic as \SigmaPtwo-complete, and the complexity of the credulous and skeptical reasoning problem as SigmaP2-complete, resp. PiP2-complete. Additionally, he investigated restrictions on the default rules, i.e., semi-normal default rules. Selman made in 1992 a similar approach with disjunction-free and unary default rules. In this paper we systematically restrict the set of allowed propositional connectives. We give a complete complexity classification for all sets of Boolean functions in the meaning of Post's lattice for all three common decision problems for propositional default logic. We show that the complexity is a hexachotomy (SigmaP2-, DeltaP2-, NP-, P-, NL-complete, trivial) for the extension existence problem, while for the credulous and skeptical reasoning problem we obtain similar classifications without trivial cases.Comment: Corrected versio

Systems involving hydrogenated and fluorinated chains: Volumetric properties of Perfluoroalkanes and Perfluoroalkylalkane Surfactants

As part of a combined experimental and theoretical study of the thermodynamic properties of perfluoroalkylalkanes (PFAAs), the liquid density of perfluorobutylpentane (F4H5), perfluorobutylhexane (F4H6), and perfluorobutyloctane (F4H8) was measured as a function of temperature from 278.15 to 353.15 K and from atmospheric pressure to 70 MPa. The liquid densities of n-perfluoropentane, n-perfluorohexane, n-perfluorooctane, and n-perfluorononane were also measured at room pressure over the same temperature range. The PVT behavior of the PFAAs was also studied using the SAFT-VR equation of state. The PFAA molecules were modeled as heterosegmented diblock chains, using different parameters for the alkyl and perfluoroalkyl segments, that were developed in earlier work. Through this simple approach, we are able to predict the thermodynamic behavior of the perfluoroalkylalkanes, without fitting to any experimental data for the systems being studied. Molecular dynamics simulations have also been performed and used to calculate the densities of the perfluoroalkylalkanes studied