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Resistant hypertension (RH) induces higher morbidity and mortality due to cardiovascular disease and stroke than hypertension without treatment resistance. New guidelines define RH as blood pressure (BP) ≥130/80 mmHg in a patient taking ≥3 antihypertensive agents of different classes or BP less then 130/80 mmHg in a patient taking ≥4 antihypertensive drugs. According to the new definition, pseudo-resistance due to error in BP measurement, white coat effect and medication nonadherence must be excluded to make the diagnosis of RH. This 2020 update focuses on the lifestyle and antihypertensive drug management of RH and includes recent proof-of-principle trials of renal nerve ablation in hypertension. Stepwise evidence-based pharmacologic treatment of RH includes optimization of the 3-drug regimen, substitution of a thiazide-like for a thiazide diuretic and addition of a mineralocorticoid receptor antagonist as the fourth drug. Non-evidence-based recommendations include addition of a β-blocker as the fifth drug and switching to a minoxidil-based regimen as the final step in achieving BP control.Computational approaches have proved valuable in elucidating structure/function relationships in the cholinesterases in the context of their unusual three-dimensional structure. In this review we survey several recent studies that have enhanced our understanding of how these enzymes function, and have utilized computational approaches both to modulate their activity and to improve the design of lead compounds for their inhibition. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http//proteopedia.org/w/JournalNeuropharmacology2.Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced in the lateral hypothalamus and zona incerta that increases food intake. The neuronal pathways and behavioral mechanisms mediating the orexigenic effects of MCH are poorly understood, as is the extent to which MCH-mediated feeding outcomes are sex-dependent. Here we investigate the hypothesis that MCH-producing neurons act in the nucleus accumbens shell (ACBsh) to promote feeding behavior and motivation for palatable food in a sex-dependent manner. We utilized ACBsh MCH receptor (MCH1R)-directed pharmacology as well as a dual virus chemogenetic approach to selectively activate MCH neurons that project to the ACBsh. Results reveal that both ACBsh MCH1R activation and activating ACBsh-projecting MCH neurons increase consumption of standard chow and palatable sucrose in male rats without affecting motivated operant responding for sucrose, general activity levels, or anxiety-like behavior. In contrast, food intake was not affected in female rats by either ACBsh MCH1R activation or ACBsh-projecting MCH neuron activation. To determine a mechanism for this sexual dimorphism, we investigated whether the orexigenic effect of ACBsh MCH1R activation is reduced by endogenous estradiol signaling. In ovariectomized female rats on a cyclic regimen of either estradiol (EB) or oil vehicle, ACBsh MCH1R activation increased feeding only in oil-treated rats, suggesting that EB attenuates the ability of ACBsh MCH signaling to promote food intake. Collective results show that MCH ACBsh signaling promotes feeding in an estrogen- and sex-dependent manner, thus identifying novel neurobiological mechanisms through which MCH and female sex hormones interact to influence food intake.The aim of this study is to determine the best aflatoxin B1 degradation conditions which was optimized using a combination of the Plackett-Burman and Box-Behnken methods with Panus neostrigosus culture filtrate. Panus neostrigosus was grown in a modified Kirk Broth medium to determine optimal degradation conditions. As a result, aflatoxin B1 was degraded under varying culture conditions. The Plackett-Burman method was designed after sixteen different experiments with fifteen variables. The three most effective variables (Sucrose, yeast extract, wheat bran) were chosen for the Box-Behnken methodology. The aflatoxin B1 degradation rate was 49% in just 1 h exposure to culture filtrate which was obtained under optimal growth conditions; (g-ml/L) sucrose 10, yeast extract 3, wheat bran 3, soytone 5, KH2PO4 2, MgSO4.7H2O 0.5, CaCl2.H2O 0.1, ammonium tartrate 2, trace element solution 10; 28 °C of incubation temperature, medium pH 5, 7.5% inoculum rate, 125 rpm of agitation speed, and a twelve-day incubation period. The SDS-PAGE studies show that the enzyme responsible for AFB1 degradation has 38 kDa molecular weight and has no laccase or MnP activity. To the best of our knowledge, this is the first report for AFB1 degradation by Panus neostrigosus.Environmental enrichment (EE) is one experimental manipulation that induces changes in the brain. However, it is important to distinguish between physical and social components of enrichment. To this end we established four groups of rats reared in different enriched environments during the adolescent period. Our results indicate heightened social memory and increased spine density in dentate gyrus specifically in socially enriched animals. Physical enrichment increased spine density in CA1. Dopamine D2 receptor expression in hippocampus was decreased across all enrichment conditions. Altogether, our results demonstrate differing effects of physical and social enrichment, supporting an important role for environment in synaptogenesis, behavior, and dopaminergic signaling.

Medication errors are common at transitions points in care pathway. The pharmacist can secure patient care in "retrocession" (dispensing specific drugs by hospital pharmacy to outpatient) due to his prescription analysis (both regulatory and pharmacotherapeutic). The "retrocession" is a risk area in care pathway. The objective of this study is to evaluate iatrogenic and economic risks in "retrocession" dispense by identifying pharmaceutical interventions.

This is a prospective monocentric study performed during 8months in university hospital. see more All the prescriptions have been analyzed and divided into 3 categories "first prescription" (a new prescription for a new treatment or a new patient), continued therapy with new prescription and prescription renewal. Therapeutic optimizations and regulatory pharmaceutical interventions performed have been systematically recorded.

Among 7166 prescriptions analyzed, 161 pharmaceutical interventions (2.2%) are done. The highest rate of therapeutic optimizations and regulatory pharmaceutical interventions concern the "first prescription" category (9.