Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a/b trial.

The multimodal activities of farnesoid X receptor (FXR) agonists make this class an attractive option to treat nonalcoholic steatohepatitis. The safety and efficacy of tropifexor, an FXR agonist, in a randomized, multicenter, double-blind, three-part adaptive design, phase 2 study, in patients with nonalcoholic steatohepatitis were therefore assessed. In Parts A + B, 198 patients were randomized to receive tropifexor (10-90 μg) or placebo for 12 weeks.

The role of counter-torque holders in tightening of pedicle screw-rod constructs: a biomechanical study in a porcine model.

Background Context: Pedicle screw-rod assembly procedures following pedicle screw insertion include contouring and placing rods into screw tulips, introducing set screws into the tulip along the screw thread, applying a counter-torque holder and tightening all the set screws clockwise. Even if an appropriate pedicle screw is implanted, screw dislodgement after tightening of the tulip and set screw is not uncommon. Pedicle wall violation resulting from excessive rotational force due to inadequate use of a counter-torque holder might be the reason.

Mechanisms of Congenital Heart Disease Caused by NAA15 Haploinsufficiency.

[Figure: see text].

Reduced Tolerance and Asymmetrical Crosstolerance to Effects of the Indole Quinuclidinone Analog PNR-4-20, a G Protein-Biased Cannabinoid 1 Receptor Agonist in Mice: Comparisons with Δ-Tetrahydrocannabinol and JWH-018.

Most cannabinoid 1 receptor (CBR) agonists will signal through both G protein-dependent and -independent pathways in an unbiased manner. Recruitment of -arrestin 2 desensitizes and internalizes receptors, producing tolerance that limits therapeutic utility of cannabinoids for chronic conditions. We developed the indole quinuclidinone (IQD) analog (Z)-2-((1-(4-fluorobenzyl)-1H-indol-3-yl)methylene)quinuclidin-3-one (PNR-4-20) as a novel G protein-biased agonist at CBRs, and the present studies determine if repeated administration of PNR-4-20 produces lesser tolerance to in vivo effects compared with unbiased CBR agonists Δ-tetrahydrocannabinol (Δ-THC) and 1-pentyl-3-(1-naphthoyl)indole (JWH-018).

Genotypic Diversity within a Single Pseudomonas aeruginosa Strain Commonly Shared by Australian Patients with Cystic Fibrosis.

In cystic fibrosis (CF), Pseudomonas aeruginosa undergoes intra-strain genotypic and phenotypic diversification while establishing and maintaining chronic lung infections. As the clinical significance of these changes is uncertain, we investigated intra-strain diversity in commonly shared strains from CF patients to determine if specific gene mutations were associated with increased antibiotic resistance and worse clinical outcomes. Two-hundred-and-one P.

Topographical relationship between the human lateral circumflex femral artery and saphenous nerve.

This study was performed to investigate causes of various types of topographical relationship between the lateral circumflex femoral artery (L) and the saphenous nerve (S). Femoral artery (F), deep femoral artery (P), L and S of 186 legs of 93 Japanese adult cadavers were submitted to anatomy. Further, the levels of origin of L in thigh were measured.

Caffeine-induced behavioural stimulation is dose- and concentration-dependent.

1. The relationship between plasma and brain caffeine and metabolite concentrations and behavioural stimulation was investigated over a 4 h time course. 2.