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Severe thrombocytopenia (platelet count less then 50 x 109 / l) is the most frequent hematological disorder in patients with chronic liver disease, affecting 64%-84% of individuals with cirrhosis. The pathophysiological mechanisms that underlie thrombocytopenia are complex, but the reduction of thrombopoietin levels is considered to play a key role. Until recently, there was continuous debate about the optimal management of patients with chronic liver disease and low platelet counts needing a scheduled invasive procedure. Transfusion of platelet concentrates, considered to be the standard of treatment, has major limitations, such as its short lifespan and limited efficacy, but also relevant adverse effects. Avatrombopag is an oral thrombopoietin receptor agonist that induces megakaryocytic proliferation and differentiation, and platelet production. It has been approved by the Spanish Agency of Medicines and Health Products for the treatment of severe thrombocytopenia in adult patients with chronic liver disease before scheduled procedures to decrease the risk of bleeding. Randomized trials have demonstrated this agent to be effective in maintaining platelet counts above 50 × 109 / l over a period of more than 2 weeks, with a similar safety profile to placebo. In this article we review avatrombopag in the treatment of thrombocytopenia of patients with chronic liver disease, discussing the main differences of this intervention in comparison to the previous standard of care therapy.Vitamin B12 has been widely related to methionine metabolism, which is an essential component for biological methylation reactions, including DNA methylation. However, the relationship between vitamin B12 and DNA methylation is still controversial. In addition, there is increasing evidence for the association between vitamin B12 and the risk of colorectal cancer (CRC), although results of this association need to be assessed with caution. For this purpose, we hypothesized that serum vitamin B12 could be associated with global DNA methylation in the CRC context. To test this hypothesis, we studied the association between global DNA methylation through long interspersed nuclear element-1 (LINE1) in CRC patients under the 25th percentile of serum vitamin B12. We found that the high vitamin B12 group had low LINE1 methylation in both tumor area and peripheral blood mononuclear cells (PBMCs) than the low serum vitamin B12 group. LINE1 methylation levels were significantly lower in tumor area compared to the adjacent tumor-free area, only in the high vitamin B12 group. LINE1 methylation in visceral adipose tissue (VAT) and PBMCs were correlated with tumoral, inflammatory, and insulin metabolism markers. However, the interaction between LINE1 methylation and vitamin B12 levels was associated with neoadjuvant therapy in the regression analysis only in men, suggesting a beneficial relationship. In conclusion, our results reported an inverse association between DNA methylation and vitamin B12 in the CRC context, which suggests that vitamin B12 may be implicated in an epigenetic state or mediation in CRC.Organisms specialized to thrive in cold environments (so-called psychrophiles) produce enzymes with the remarkable ability to catalyze chemical reactions at low temperature. Cold activity relies on adaptive changes in the proteins' sequence and structural organization that result in high conformational flexibility. As a consequence of flexibility, several such enzymes are inherently heat sensitive. Cold-active enzymes are of interest for application in a number of bioprocesses, where cold activity coupled with easy thermal inactivation can be of advantage. We describe the biochemical and functional properties of two glycosyl hydrolases (named LYS177 and LYS188) of family 19 (GH19), identified in the genome of an Antarctic marine Pseudomonas. https://www.selleckchem.com/products/ici-118551-ici-118-551.html Molecular evolutionary analysis placed them in a group of characterized GH19 endolysins active on lysozyme substrates, such as peptidoglycan. Enzyme activity peaks at about 25-35 °C and 40% residual activity is retained at 5 °C. LYS177 and LYS188 are thermolabile, with Tm of 52 and 45 °C and half-lives of 48 and 12 h at 37 °C, respectively. Bioinformatics analyses suggest that low heat stability may be associated to temperature-driven increases in local flexibility occurring mainly in a specific region of the polypeptide that is predicted to contain hot spots for aggregation.Without a cure, dementia affects about 50 million people worldwide. Understanding the effects of dietary habits, a key lifestyle behavior, on memory impairment is critical to inform early behavioral modification to delay further memory loss and progression to dementia. We examined the associations of total energy intake and energy intake from macronutrients with memory impairment among older US adults using data from the nationally representative National Health and Nutrition Examination Survey study 2011-2014. A total of 3623 participants aged ≥60 years were analyzed. Comparing to those with low total energy intake, individuals with high intake were more likely to have severe memory impairment (OR 1.52, 95% CI 1.15 to 2.02; ptrend = 0.005). Specifically, higher energy intake from carbohydrate (OR 1.59, 95% CI 1.12 to 2.26) and sugar (OR 1.54, 95% CI 1.11 to 2.16) were both significantly associated with the presence of memory impairment. Additionally, higher energy intake from fat, carbohydrate and sugar were significantly associated with more server memory impairment (fat ptrend = 0.04; carbohydrate ptrend = 0.03; sugar ptrend = 0.02). High energy intake, either total or from carbohydrates, fat or sugar, is associated with memory impairment severity in the older US population. No such association was found in energy intake from protein.The development of innovative antimicrobial materials is crucial in thwarting infectious diseases caused by microbes, as drug-resistant pathogens are increasing in both number and capacity to detoxify the antimicrobial drugs used today. An ideal antimicrobial material should inhibit a wide variety of bacteria in a short period of time, be less or not toxic to normal cells, and the fabrication or synthesis process should be cheap and easy. We report a one-step microwave-assisted hydrothermal synthesis of mixed composite Cu x Fe y O z (Fe2O3/Cu2O/CuO/CuFe2O) nanoparticles (NPs) as an excellent antimicrobial material. The 1 mg/mL Cu x Fe y O z NPs with the composition 36% CuFeO2, 28% Cu2O and 36% Fe2O3 have a general antimicrobial activity greater than 5 log reduction within 4 h against nine important human pathogenic bacteria (including drug-resistant bacteria as well as Gram-positive and Gram-negative strains). For example, they induced a >9 log reduction in Escherichia coli B viability after 15 min of incubation, and an ~8 log reduction in multidrug-resistant Klebsiella pneumoniae after 4 h incubation.
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