• Munro William posted an update 1 week, 4 days ago

    Waist circumference, CRP, D-dimer, HIV duration and treatment with nucleoside reverse transcriptase inhibitors were associated with high NaF uptake in univariable analyses; D-dimer remained significant in multivariable analyses (OR = 1.05; p=0.02). There were no significant associations with FDG uptake. CONCLUSIONS The prevalence of coronary artery uptake was higher with NaF compared to FDG both in high and low risk patients, hence microcalcification imaging may be a more sensitive tool to detect coronary atherosclerosis than inflammation imaging. However, the uptake of each 18Fluoride tracer was similar between low and high-risk subjects, and this underscores the discordance between clinical and imaging based risk assessment. FUT-175 cell line Future investigation should address the prognostic significance of NaF coronary artery uptake. A series of 1,6-naphthyridinone-based MET kinase inhibitors bearing quinoline moiety in block A were designed and synthesized based on the structures of Cabozantinib and our reported compound IV. Extensive SAR and DMPK studies led to the identification of 20j, a potent and orally bioavailable MET kinase inhibitor with favorable kinase selectivity. More importantly, 20j exhibited statistically significant tumor growth inhibition (Tumor growth inhibition/TGI of 131%, 4/6 partial regression/PR) in the U-87 MG xeograft model, which is superior to that of Cabozantinib (TGI of 97%, 2/6 PR), and significantly better than that of compound IV (TGI of 15%, 0/6 PR) at the same dose (12.5 mg/kg). Combined with favorable in vitro potency, kinase selectivity, pharmacokinetic profile and in vivo efficacy, the promising antitumor drug candidate 20j has subsequently advanced into preclinical research. Using a classical molecular simplification approach, a series of 36 quinolines were synthesized and evaluated as in vitro inhibitors of Mycobacterium tuberculosis (M. tuberculosis) growth. Structure-activity relationship (SAR) studies leaded to potent antitubercular agents, with minimum inhibitory concentration (MIC) values as low as 0.3 μM against M. tuberculosis H37Rv reference strain. Furthermore, the lead compounds were active against multidrug-resistant strains, without cross-resistance with some first- and second-line drugs. Testing the molecules against a spontaneous mutant strain containing a single mutation in the qcrB gene (T313A) indicated that the synthesized quinolines targeted the cytochrome bc1 complex. In addition, leading compounds were devoid of apparent toxicity to HepG2 and Vero cells and showed moderate elimination rates in human liver S9 fractions. Finally, the selected structures inhibited M. tuberculosis growth in a macrophage model of tuberculosis infection. Taken together, these data indicate that this class of compounds may furnish candidates for the future development of antituberculosis drugs. The Hypothalamus-Pituitary-Gonadal (HPG)-axis, and testosterone in particular, play an important role in social motivational behavior. Socially avoidant behavior, characteristic of social anxiety disorder (SAD), has been linked to low endogenous testosterone levels, and can be alleviated by testosterone administration in SAD. Although these beneficial effects of testosterone may translate to exposure therapy, it remains unknown whether testosterone increases prior to exposure improve therapy outcomes. In this proof-of-principle study, we tested whether pre-exposure (reactive and baseline) endogenous testosterone levels were predictive of exposure outcome in SAD. Seventy-three participants (52 females) with a principal SAD diagnosis performed four speech exposures three during one standardized exposure therapy session and one at post-assessment one week later. Subjective fear levels were assessed before and after each speech exposure and social anxiety symptoms were assessed at pre- and post-treatment. Pre-treatment testosterone levels were assessed before (baseline) and in response to a pre-exposure instruction session (reactive). Pre-treatment testosterone levels were not related to fear levels during exposure therapy, but predicted pre- to post-treatment reductions in social anxiety symptom severity. Specifically, low baseline and high reactive pre-treatment testosterone levels were associated with larger reductions in social anxiety symptom severity. These findings support the role of HPG-axis in social fear reduction. Specifically, our finding that high reactive testosterone as well as low baseline testosterone predicted exposure outcome in SAD, suggests that good reactivity of the HPG-axis is a promising marker for the symptom-reducing effects of exposure therapy. In two experiments we investigated whether older adult controls (OACs) and people with mild and moderate Alzheimer’s disease (AD) benefit from false memory priming effects in subsequent problem-solving tasks. In addition, and unlike in previous false memory priming studies with older adults, we examined latency measures in the recognition phase. In Experiment 1 participants were asked to solve compound remote associate task (CRAT) problems, half of which had been preceded by the presentation of Deese/Roediger-McDermott (DRM) lists whose critical lures (CLs) were also the solutions to those problems. In Experiment 2, we used a similar paradigm but investigated whether CLs could prime solutions to subsequent analogical reasoning problems. In this latter experiment, we also examined whether these priming effects were stronger when the activation of the CL term occurred during the memory task (was presented as part of the list; i.e., true memories) or when these items were not presented but arose during encoding due to spreading activation (i.e., false memories). We found that all three groups’ performance on these tasks was facilitated only by false memories spontaneously generated from the prior presentation of DRM lists. That is, performance on CRATs and analogical reasoning tasks was better (greater accuracy and faster speed) when those problems were preceded by DRM lists whose CLs also served as the solution to those problems. These findings are consistent with previous results from studies with children, young adults, and older adults and extends them to people with more moderate AD.