Notes

Calibrating physician apply, willingness and preferences for genomic medicine: a nationwide questionnaire.
Peritoneal metastasis (PM) is the major cause of recurrence in patients with gastric cancer (GC) and is associated with poor prognosis. The oncogenic role of Nicotinamide N-methyltransferase (NNMT) in GC has been reported, but the role of secreted NNMT that is transported by exosomes remains unknown. In this study, exosomes were isolated from GC patients with or without PM and from GC cell line, including GC-114, GC-026, MKN45, and SNU-16 cells. The contents of NNMT were significantly enhanced in exosomes isolated from GC patients with PM compared with those from GC patients without PM. Phlorizin Furthermore, the levels of NNMT were significantly enhanced in exosomes from GC cell lines relative to those from normal human gastric epithelial cell line GES-1 cells. These data indicate that NNMT may be involved in intercellular communication for peritoneal dissemination. Moreover, colocalization of GC-derived exosomal NNMT was found in human peritoneal mesothelial cell line HMrSV5 cells. Additionally, relative to GES-1 exosomes, SNU-16 exosomes significantly activated TGF-β/smad2 signaling in HMrSV5 cells. However, when NNMT was silenced, the activation of TGF-β/smad2 by SNU-16 exosomes was abolished in HMrSV5 cells. We propose that NNMT-containing exosomes derived from GC cells could promote peritoneal metastasis via TGF-β/smad2 signaling.Gut microbiota is known to be transferred from the mother to their offspring. This study determines whether the innate microbiota of rats selectively bred for generations as high alcohol drinkers play a role in their alcohol intake. Wistar-derived high-drinker UChB rats (intake 10-g ethanol/kg/day) administered nonabsorbable oral antibiotics before allowing access to alcohol, reducing their voluntary ethanol intake by 70%, an inhibition that remained after the antibiotic administration was discontinued. Oral administration of Lactobacillus rhamnosus Gorbach-Goldin (GG) induced the synthesis of FGF21, a vagal β-Klotho receptor agonist, and partially re-invoked a mechanism that reduces alcohol intake. The vagus nerve constitutes the main axis transferring gut microbiota information to the brain ("microbiota-gut-brain" axis). Bilateral vagotomy inhibited rat alcohol intake by 75%. Neither antibiotic treatment nor vagotomy affected total fluid intake. A microbiota-mediated marked inflammatory environment was observed in the gut of ethanol-naïve high-drinker rats, as gene expression of proinflammatory cytokines (TNF-α; IL-6; IL-1β) was significantly reduced by nonabsorbable antibiotic administration. Gut cytokines are known to activate the vagus nerve, while vagal activation induces pro-rewarding effects in nucleus accumbens. Both alcoholics and alcohol-preferring rats share a marked preference for sweet tastes-likely an evolutionary trait to seek sweet fermented fruits. Saccharin intake by UChB rats was inhibited by 75%-85% by vagotomy or oral antibiotic administration, despite saccharin-induced polydipsia. Overall, data indicate that the mechanisms that normally curtail heavy drinking are inhibited in alcohol-preferring animals and inform a gut microbiota origin. Whether it applies to other mammals and humans merits further investigation.Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.Climate warming is expected to positively alter upward and poleward treelines which are controlled by low temperature and a short growing season. Despite the importance of treelines as a bioassay of climate change, a global field assessment and posterior forecasting of tree growth at annual scales is lacking. Using annually resolved tree-ring data located across Eurasia and the Americas, we quantified and modeled the relationship between temperature and radial growth at treeline during the 20th century. We then tested whether this temperature-growth association will remain stable during the 21st century using a forward model under two climate scenarios (RCP 4.5 and 8.5). During the 20th century, growth enhancements were common in most sites, and temperature and growth showed positive trends. Interestingly, the relationship between temperature and growth trends was contingent on tree age suggesting biogeographic patterns in treeline growth are contingent on local factors besides climate warming. Simulations forecast temperature-growth decoupling during the 21st century. The growing season at treeline is projected to lengthen and growth rates would increase and become less dependent on temperature rise. These forecasts illustrate how growth may decouple from climate warming in cold regions and near the margins of tree existence. Such projected temperature-growth decoupling could impact ecosystem processes in mountain and polar biomes, with feedbacks on climate warming.
Adapalene-benzoyl peroxide (A-BPO) is a first-line topical treatment for acne vulgaris. In vivo reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) detect micromorphological changes over time and visualize transfollicular delivery.

To visualize temporal, subclinical effects of A-BPO on acne micromorphology using RCM and OCT, and evaluate their impact on transfollicular delivery of microparticulate carrier systems.

Fifteen patients with mild to moderate acne received a 6-week course of A-BPO. Micromorphological changes were evaluated at time 0, 3 and 6weeks with RCM (n=1190 images) and OCT (n=210 scans). Transfollicular delivery of microparticles was assessed at baseline and week 6.

In vivo imaging visualized steady normalization of skin micromorphology in response to A-BPO over 6weeks, including decreased hyperkeratinization of follicular borders (RCM median decrease -71.2%, P<0.05), reduced intrafollicular keratinous content (RCM median decrease -47.7%, P<0.05) and increased epidermal thickness (OCT median increase of 25.
Here's my website: https://www.selleckchem.com/products/Phlorizin(Phloridzin).html