Rodent models of intrauterine growth restriction

Demand functions generated by operant conditioning techniques may be used to assess animal priorities (Dawkins 1990, Matthews & Ladewig 1994, Sherwin & Nicol 1997, Fraser & Matthews 1997, Matthews 1998). The animal needs to perform a number of simple responses (e.g. bar-presses), to obtain one unit of a reinforcer (Lea 1978, Dawkins 1990, Matthews & Ladewig 1994). This reinforcer enables the animal to perform a certain behaviour. The relationship between the workload (traditionally set by a fixed ratio (FR) reinforcement schedule) and the amount obtained of the reinforcer is described by a curve with FR-value on the horizontal axis as the independent variable and the amount consumed as the dependent variable on the vertical axis (Hursh 1980). The resulting slope of the demand function will then provide a measure for the demand of the reinforcer. If the animal is highly motivated to obtain the reinforcer the animal will work at an increasing rate as the workload increases and thus keep its intake close to constant. The slope of the demand function will be close to zero, which indicates a high demand for the reinforcer. The steeper the demand function, the less important the reinforcer (Lea 1978, Hursh 1984). The slope of the demand function is nearly always negative and it is not influenced by e.g. the weight of the animal (Hursh 1984, Ladewig 1997). The size of an animal will influence the intercept of the demand function, but not the slope of the demand function. Using this method it should be possible to measure quantitatively to which extent an animal is motivated to obtain a given reinforcer and to compare demands for different reinforcers among different animals. It is important to note that the demand function reflects the demand for the reinforcer. The demand depends on both the internal preferences of the animal but also on the decisions made by the animal of how much to obtain of the reinforcer considering the workload imposed on the animal and the availability of alternatives.Many factors influence the slope of the demand curve; some are varied by the experimenter (e.g. FR-values and test-time), some factors might depend on the animal’s gender and genetics (e.g. sensory capacities and basic level of anxiety), and some are physiological factors influencing the motivational state (e.g. thirst, hunger, aggression, or phase in oestrous cycle). Furthermore, it is well known that, at least in rats, differences exist in performance in cognitive and operant tasks between different rat strains (Andrews et al. 1995). The purpose of this experiment was to determine if the method was able to detect differences in demand for water between two different strains.For the selection of the two strains of rats, three criteria were used. First, we wanted inbred strains in order to minimize the variation between rats in the two test groups. Second, in order to avoid any confounding influence of rats having difficulties in performing the operant response-task, we needed two strains, which were known to perform well in operant systems. Third, the strains should neither be transgenic nor spontaneous animal models of human disorders (Svendsen & Hau 1994). The two strains chosen were pigmented inbred Long Evans rats (LE/Mol) and albino inbred Wistar-Kyoto rats (WKY/Mol)

Appropriate threshold levels of cardiac beat-to-beat variation in semi-automatic analysis of equine ECG recordings

BACKGROUND: Although premature beats are a matter of concern in horses, the interpretation of equine ECG recordings is complicated by a lack of standardized analysis criteria and a limited knowledge of the normal beat-to-beat variation of equine cardiac rhythm. The purpose of this study was to determine the appropriate threshold levels of maximum acceptable deviation of RR intervals in equine ECG analysis, and to evaluate a novel two-step timing algorithm by quantifying the frequency of arrhythmias in a cohort of healthy adult endurance horses. RESULTS: Beat-to-beat variation differed considerably with heart rate (HR), and an adaptable model consisting of three different HR ranges with separate threshold levels of maximum acceptable RR deviation was consequently defined. For resting HRs <60 beats/min (bpm) the threshold level of RR deviation was set at 20%, for HRs in the intermediate range between 60 and 100 bpm the threshold was 10%, and for exercising HRs >100 bpm, the threshold level was 4%. Supraventricular premature beats represented the most prevalent arrhythmia category with varying frequencies in seven horses at rest (median 7, range 2–86) and six horses during exercise (median 2, range 1–24). CONCLUSIONS: Beat-to-beat variation of equine cardiac rhythm varies according to HR, and threshold levels in equine ECG analysis should be adjusted accordingly. Standardization of the analysis criteria will enable comparisons of studies and follow-up examinations of patients. A small number of supraventricular premature beats appears to be a normal finding in endurance horses. Further studies are required to validate the findings and determine the clinical significance of premature beats in horses

Antiarrhythmic and electrophysiologic effects of flecainide on acutely induced atrial fibrillation in healthy horses

BACKGROUND: Only few pharmacologic compounds have been validated for treatment of atrial fibrillation (AF) in horses. Studies investigating the utility and safety of flecainide to treat AF in horses have produced conflicting results, and the antiarrhythmic mechanisms of flecainide are not fully understood. OBJECTIVES: To study the potential of flecainide to terminate acutely induced AF of short duration (≥15 minutes), to examine flecainide‐induced changes in AF duration and AF vulnerability, and to investigate the in vivo effects of flecainide on right atrial effective refractory period, AF cycle length, and ventricular depolarization and repolarization. ANIMALS: Nine Standardbred horses. Eight received flecainide, 3 were used as time‐matched controls, 2 of which also received flecainide. METHODS: Prospective study. The antiarrhythmic and electrophysiologic effects of flecainide were based on 5 parameters: ability to terminate acute pacing‐induced AF (≥15 minutes), and drug‐induced changes in atrial effective refractory period, AF duration, AF vulnerability, and ventricular depolarization and repolarization times. Parameters were assessed at baseline and after flecainide by programmed electrical stimulation methods. RESULTS: Flecainide terminated all acutely induced AF episodes (n = 7); (AF duration, 21 ± 5 minutes) and significantly decreased the AF duration, but neither altered atrial effective refractory period nor AF vulnerability significantly. Ventricular repolarization time was prolonged between 8 and 20 minutes after initiation of flecainide infusion, but no ventricular arrhythmias were detected. CONCLUSIONS AND CLINICAL IMPORTANCE: Flecainide had clear antiarrhythmic properties in terminating acute pacing‐induced AF, but showed no protective properties against immediate reinduction of AF. Flecainide caused temporary prolongation in the ventricular repolarization, which may be a proarrhythmic effect

Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid fatty acid composition in a muscle type specific manner in sheep.

We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty), twin offspring received a high-carbohydrate-high-fat (HCHF) or a moderate-conventional (CONV) diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults). The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4) protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α) mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins) related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced whole body insulin sensitivity in adult LOW sheep

The road not taken: international aid’s choice of Copenhagen over Beijing

A decade after the United Nations conferences on gender equality and social development, this paper explores their policy origins and discusses their differential impact on international aid since 1995. The author draws on her direct experience to consider why Copenhagen led to Poverty Reduction Strategies and the first Millennium Development Goal whereas Beijing has become largely invisible in the mainstream world of aid. She argues that the powerful influence of economic rational choice theory associated with bureaucratic modes of thought has meant that the central debate in development policy has remained that of growth versus equity. Beijing's agenda of societal transformation offered another paradigm of development that has remained marginal. The paper concludes with a proposal. If international aid policy could handle more than one paradigm and thus be more open to different ways of thinking about economy, society and politics, aid agencies would be better able to support transformative processes for social justice

Relationships between serum adiponectin and soluble TNF-α receptors and glucose and lipid oxidation in lean and obese subjects

Insulin resistance might be associated with an impaired ability of insulin to stimulate glucose oxidation and inhibit lipid oxidation. Insulin action is also inversely associated with TNF-α system and positively related to adiponectin. The aim of the present study was to analyze the associations between serum adiponectin, soluble TNF-α receptors concentrations and the whole-body insulin sensitivity, lipid and glucose oxidation, non-oxidative glucose metabolism (NOGM) and metabolic flexibility in lean and obese subjects. We examined 53 subjects: 25 lean (BMI < 25 kg × m−2) and 28 with overweight or obesity (BMI > 25 kg × m−2) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Obese subjects had lower insulin sensitivity, adiponectin and higher sTNFR1 (all P < 0.001) and sTNFR2 (P = 0.001). Insulin sensitivity was positively related to adiponectin (r = 0.49, P < 0.001) and negatively related to sTNFR1 (r = −0.40, P = 0.004) and sTNFR2 (r = −0.52, P < 0.001). Adiponectin was related to the rate of glucose (r = 0.47, P < 0.001) and lipid (r = −0.40, P = 0.003) oxidation during the clamp, NOGM (r = 0.41, P = 0.002) and metabolic flexibility (r = 0.36, P = 0.007). Serum sTNFR1 and sTNFR2 were associated with the rate of glucose (r = −0.45, P = 0.001; r = −0.51, P < 0.001, respectively) and lipid (r = 0.52, P < 0.001; r = 0.46, P = 0.001, respectively) oxidation during hyperinsulinemia, NOGM (r = −0.31, P = 0.02; r = −0.43, P = 0.002, respectively) and metabolic flexibility (r = −0.47 and r = −0.51, respectively, both P < 0.001) in an opposite manner than adiponectin. Our data suggest that soluble TNF-α receptors and adiponectin have multiple effects on glucose and lipid metabolism in obesity

The DIRAC code for relativistic molecular calculations

DIRAC is a freely distributed general-purpose program system for one-, two-, and four-component relativistic molecular calculations at the level of Hartree?Fock, Kohn?Sham (including range-separated theory), multiconfigurational self-consistent-field, multireference configuration interaction, electron propagator, and various flavors of coupled cluster theory. At the self-consistent-field level, a highly original scheme, based on quaternion algebra, is implemented for the treatment of both spatial and time reversal symmetry. DIRAC features a very general module for the calculation of molecular properties that to a large extent may be defined by the user and further analyzed through a powerful visualization module. It allows for the inclusion of environmental effects through three different classes of increasingly sophisticated embedding approaches: the implicit solvation polarizable continuum model, the explicit polarizable embedding model, and the frozen density embedding model.Fil: Saue, Trond. Université Paul Sabatier; Francia. Centre National de la Recherche Scientifique; FranciaFil: Bast, Radovan. Uit The Arctic University Of Norway; NoruegaFil: Gomes, André Severo Pereira. University Of Lille.; Francia. Centre National de la Recherche Scientifique; FranciaFil: Jensen, Hans Jorgen Aa.. University of Southern Denmark; DinamarcaFil: Visscher, Lucas. Vrije Universiteit Amsterdam; Países BajosFil: Aucar, Ignacio Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Modelado e Innovación Tecnológica. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Modelado e Innovación Tecnológica; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Física; ArgentinaFil: Di Remigio, Roberto. Uit The Arctic University of Norway; NoruegaFil: Dyall, Kenneth G.. Dirac Solutions; Estados UnidosFil: Eliav, Ephraim. Universitat Tel Aviv.; IsraelFil: Fasshauer, Elke. Aarhus University. Department of Bioscience; DinamarcaFil: Fleig, Timo. Université Paul Sabatier; Francia. Centre National de la Recherche Scientifique; FranciaFil: Halbert, Loïc. Centre National de la Recherche Scientifique; Francia. University Of Lille.; FranciaFil: Hedegård, Erik Donovan. Lund University; SueciaFil: Helmich-Paris, Benjamin. Max-planck-institut Für Kohlenforschung; AlemaniaFil: Ilias, Miroslav. Matej Bel University; EslovaquiaFil: Jacob, Christoph R.. Technische Universität Braunschweig; AlemaniaFil: Knecht, Stefan. Eth Zürich, Laboratorium Für Physikalische Chemie; SuizaFil: Laerdahl, Jon K.. Oslo University Hospital; NoruegaFil: Vidal, Marta L.. Department Of Chemistry; DinamarcaFil: Nayak, Malaya K.. Bhabha Atomic Research Centre; IndiaFil: Olejniczak, Malgorzata. University Of Warsaw; PoloniaFil: Olsen, Jógvan Magnus Haugaard. Uit The Arctic University Of Norway; NoruegaFil: Pernpointner, Markus. Kybeidos Gmbh; AlemaniaFil: Senjean, Bruno. Universiteit Leiden; Países BajosFil: Shee, Avijit. Department Of Chemistry; Estados UnidosFil: Sunaga, Ayaki. Tokyo Metropolitan University; JapónFil: van Stralen, Joost N. P.. Vrije Universiteit Amsterdam; Países Bajo