Brazil is a country with continental proportions with high geographic and economic diversity. Despite its medical centers of excellence, antimicrobial resistance poses a major therapeutic challenge. ...Rates of methicillin-resistant Staphylococcus aureus are up to 60% and are related to an endemic Brazilian clone. Local resistance to vancomycin in Enterococci was first related to Enterococcus faecalis, which differs from European and American epidemiology. Also, local Klebsiella pneumoniae and Escherichia coli isolates producing extended-spectrum β-lactamases have a much higher prevalence (40%-50% and 10%-18%, respectively). Carbapenem resistance among the enterobacteriaceae group is becoming a major problem, and K. pneumoniae carbapenemase isolates have been reported in different states. Among nonfermenters, carbapenem resistance is strongly related to SPM-1 (Pseudomonasaeruginosa) and OXA-23 (Acinetobacter baumannii complex) enzymes, and a colistin-only susceptible phenotype has also emerged in these isolates, which is worrisome. Local actions without loosing the global resistance perspective will demand multidisciplinary actions, new policies, and political engagement.
The sacral autonomic outflow is sympathetic Espinosa-Medina, I; Saha, O; Boismoreau, F ...
Science (American Association for the Advancement of Science),
11/2016, Volume:
354, Issue:
6314
Journal Article
Peer reviewed
Open access
A kinship between cranial and pelvic visceral nerves of vertebrates has been accepted for a century. Accordingly, sacral preganglionic neurons are considered parasympathetic, as are their targets in ...the pelvic ganglia that prominently control rectal, bladder, and genital functions. Here, we uncover 15 phenotypic and ontogenetic features that distinguish pre- and postganglionic neurons of the cranial parasympathetic outflow from those of the thoracolumbar sympathetic outflow in mice. By every single one, the sacral outflow is indistinguishable from the thoracolumbar outflow. Thus, the parasympathetic nervous system receives input from cranial nerves exclusively and the sympathetic nervous system from spinal nerves, thoracic to sacral inclusively. This simplified, bipartite architecture offers a new framework to understand pelvic neurophysiology as well as development and evolution of the autonomic nervous system.
Cachexia has a high prevalence in cancer patients, leading to reduced tolerance/response to treatment and decreased quality of life. Results from three global surveys presented herein demonstrate a ...definite need for increased awareness and educational initiatives to improve the knowledge and understanding of cancer cachexia among physicians in order to optimize patient outcomes.
Cachexia has a high prevalence in cancer patients and negatively impacts prognosis, quality of life (QOL), and tolerance/response to treatments. This study reports the results of three surveys designed to gain insights into cancer cachexia (CC) awareness, understanding, and treatment practices among health care professionals (HCPs).
Surveys were conducted globally among HCPs involved in CC management. Topics evaluated included definitions and synonyms of CC, diagnosis and treatment practices, and goals and desired improvements of CC treatment.
In total, 742 HCPs from 14 different countries participated in the surveys. The majority (97%) of participants were medical oncologists or hematologists. CC was most frequently defined as weight loss (86%) and loss of appetite (46%). The terms loss of weight and decreased appetite (51% and 34%, respectively) were often provided as synonyms of CC. Almost half (46%) of the participants reported diagnosing CC and beginning treatment if a patient experienced a weight loss of 10%. However, 48% of the participants would wait until weight loss was ≥15% to diagnose CC and start treatment. HCPs also reported that 61%–77% of cancer patients do not receive any prescription medication for CC before Stage IV of disease is reached. Ability to promote weight gain was rated as the most important factor for selecting CC treatment. Key goals of treatment included ensuring that patients can cope with the cancer and treatment and have a QOL benefit. HCPs expressed desire for treatments with a more CC-specific mode of action and therapies that enhance QOL.
These surveys underscore the need for increased awareness among HCPs of CC and its management.
The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, ...monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to underlie the different effects of PEA in vivo. In this study, we used cultured rat microglia and human macrophages to evaluate whether PEA affects eCB signaling. PEA was found to increase CB2 mRNA and protein expression through peroxisome proliferator-activated receptor-α (PPAR-α) activation. This novel gene regulation mechanism was demonstrated through: (i) pharmacological PPAR-α manipulation, (ii) PPAR-α mRNA silencing, (iii) chromatin immunoprecipitation. Moreover, exposure to PEA induced morphological changes associated with a reactive microglial phenotype, including increased phagocytosis and migratory activity. Our findings suggest indirect regulation of microglial CB2R expression as a new possible mechanism underlying the effects of PEA. PEA can be explored as a useful tool for preventing/treating the symptoms associated with neuroinflammation in CNS disorders.
Background and purpose:
N‐arachidonoyl‐serotonin (AA‐5‐HT) is an inhibitor of fatty acid amide hydrolase (FAAH)‐catalysed hydrolysis of the endocannabinoid/ endovanilloid compound, anandamide (AEA). ...We investigated if AA‐5‐HT antagonizes the transient receptor potential vanilloid‐1 (TRPV1) channel and, as FAAH and TRPV1 are targets for analgesic compounds, if it exerts analgesia in rodent models of hyperalgesia.
Experimental approach:
AA‐5‐HT was tested in vitro, on HEK‐293 cells overexpressing the human or the rat recombinant TRPV1 receptor, and in vivo, in rats and mice treated with formalin and in rats with chronic constriction injury of the sciatic nerve. The levels of the endocannabinoids, AEA and 2‐arachidonoylglycerol, in supraspinal (periaqueductal grey, rostral ventromedial medulla), spinal or peripheral (skin) tissues were measured.
Key results:
AA‐5‐HT behaved as an antagonist at both rat and human TRPV1 receptors (IC50=37‐40 nM against 100 nM capsaicin). It exerted strong analgesic activity in all pain models used here. This activity was partly due to FAAH inhibition, elevation of AEA tissue levels and indirect activation of cannabinoid CB1 receptors, as it was reversed by AM251, a CB1 antagonist. AA‐5‐HT also appeared to act either via activation/desensitization of TRPV1, following elevation of AEA, or as a direct TRPV1 antagonist, as suggested by the fact that its effects were either reversed by capsazepine and 5′‐iodo‐resiniferatoxin, two TRPV1 antagonists, or mimicked by these compounds administered alone.
Conclusions and implications:
Possibly due to its dual activity as a FAAH inhibitor and TRPV1 antagonist, AA‐5‐HT was highly effective against both acute and chronic peripheral pain.
British Journal of Pharmacology (2007) 150, 766–781. doi:10.1038/sj.bjp.0707145
In different human carcinoma types, mast cell infiltrate increases with respect to normal tissue and mast cell density correlates with a bad prognosis. To assess the role of mast cells in human ...thyroid cancer, we compared the density of tryptase-positive mast cells in 96 papillary thyroid carcinomas (PTCs) versus normal thyroid tissue from 14 healthy individuals. Mast cell density was higher in 95% of PTCs (n=91) than in control tissue. Mast cell infiltrate correlated with extrathyroidal extension (P=0.0005) of PTCs. We show that thyroid cancer cell-line-derived soluble factors induce mast cell activation and chemoattraction in vitro. Different mast cell lines (HMC-1 and LAD2) and primary human lung mast cells induced thyroid cancer cell invasive ability, survival and DNA synthesis in vitro. The latter effect was mainly mediated by three mast-cell-derived mediators: histamine, and chemokines CXCL1/GROα and CXCL10/IP10. We show that xenografts of thyroid carcinoma cells (8505-C) could recruit mast cells injected into the tail vein of mice. Co-injection of human mast cells accelerated the growth of thyroid cancer cell (8505-C) xenografts in athymic mice. This effect was mediated by increased tumor vascularization and proliferation, and was reverted by treating mice with sodium cromoglycate (Cromolyn), a specific mast cell inhibitor. In conclusion, our study data suggest that mast cells are recruited into thyroid carcinomas and promote proliferation, survival and invasive ability of cancer cells, thereby contributing to thyroid carcinoma growth and invasiveness.
Modern consumption patterns have led to a surge in waste glass accumulating in municipal landfills, contributing to environmental pollution, especially in countries that do not have well-established ...recycling standards. While glass itself is 100% recyclable, the logistics and handling involved present significant challenges. Flint and amber-colored glass, often found in high quantities in municipal waste, can serve as valuable sources of raw materials. We propose an affordable route that requires just a thermal treatment of glass waste to obtain glass-based antimicrobial materials. The thermal treatment induces crystallized nanoregions, which are the primary factor responsible for the bactericidal effect of waste glass. As a result, coarse particles of flint waste glass that undergo thermal treatment at 720 °C show superior antimicrobial activity than amber waste glass. Glass-ceramic materials from flint waste glass, obtained by thermal treatment at 720 °C during 2 h, show antimicrobial activity against Escherichia coli after just 30 min of contact time. Laser-induced breakdown spectroscopy (LIBS) was employed to monitor the elemental composition of the glass waste. The obtained glass-ceramic material was structurally characterized by transmission electron microscopy, enabling the confirmation of the presence of nanocrystals embedded within the glass matrix.
Endothelin (ET) peptides and their receptors are intimately involved in the physiological control of systemic blood pressure and body Na homeostasis, exerting these effects through alterations in a ...host of circulating and local factors. Hormonal systems affected by ET include natriuretic peptides, aldosterone, catecholamines, and angiotensin. ET also directly regulates cardiac output, central and peripheral nervous system activity, renal Na and water excretion, systemic vascular resistance, and venous capacitance. ET regulation of these systems is often complex, sometimes involving opposing actions depending on which receptor isoform is activated, which cells are affected, and what other prevailing factors exist. A detailed understanding of this system is important; disordered regulation of the ET system is strongly associated with hypertension and dysregulated extracellular fluid volume homeostasis. In addition, ET receptor antagonists are being increasingly used for the treatment of a variety of diseases; while demonstrating benefit, these agents also have adverse effects on fluid retention that may substantially limit their clinical utility. This review provides a detailed analysis of how the ET system is involved in the control of blood pressure and Na homeostasis, focusing primarily on physiological regulation with some discussion of the role of the ET system in hypertension.
The diffusion wear between a WC-10%Co tool and a Ti54M titanium alloy was investigated by studying the reaction between both the materials using a diffusion couple and studying their behavior during ...a machining test. In addition to the scanning electron microscopy (SEM) study, electron probe microanalysis (EPMA) was conducted to quantitatively analyze the chemical composition in the reactive layers after different holding times at 1100°C. The diffusion couple revealed a rapid formation of TiC carbides at the interface. The layer growth is parabolic and is mainly toward the Ti54M side. The formation of three affected zones was observed. On the tool side, the two affected zones displayed a continuous decrease in the WC content, as well as a significant enrichment in the Co amount with no WC in the Co rich zone and a decrease in the W and C contents. On the Ti54M side, the tool elements diffused into the alloy material, with the diffusion lengths of C and Co being much longer than that of W. The solubilities of C and Co remained low while that of W was almost 8–9wt%. The WC dissolution and compositional modification caused a degradation in the mechanical integrity of the tool surface, leading to crater damage. The machining experiments validated this mechanism and tool elements could be found in the adhered titanium layer.
•An innovative diffusion couple experiment between carbide and Ti alloy is proposed.•Qualitative analyzes by SEM and quantitative analyzes by EPMA were carried out.•Diffusion of tool elements was observed with different affected zones.•Machining experiments validated the diffusion mechanism.
Visual analytics systems combine machine learning or other analytic techniques with interactive data visualization to promote sensemaking and analytical reasoning. It is through such techniques that ...people can make sense of large, complex data. While progress has been made, the tactful combination of machine learning and data visualization is still under‐explored. This state‐of‐the‐art report presents a summary of the progress that has been made by highlighting and synthesizing select research advances. Further, it presents opportunities and challenges to enhance the synergy between machine learning and visual analytics for impactful future research directions.
Visual analytics systems combine machine learning or other analytic techniques with interactive data visualization to promote sensemaking and analytical reasoning. It is through such techniques that people can make sense of large, complex data. While progress has been made, the tactful combination of machine learning and data visualization is still under‐explored. This state‐of‐the‐art report presents a summary of the progress that has been made by highlighting and synthesizing select research advances. Further, it presents opportunities and challenges to enhance the synergy between machine learning and visual analytics for impactful future research directions.
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