Microarray analysis of endothelial differentially expressed genes in liver of cirrhotic rats

BACKGROUND & AIMS: There is a long-standing interest in the identification of endothelial-specific pathways for therapeutic targeting in cirrhosis. Therefore, the aim of this study was to evaluate differences in gene expression patterns between liver endothelial cells (LECs) from control and cirrhotic rats by using microarrays. METHODS: LECs were obtained by isopycnic centrifugation. LECs gene expression was then analyzed on high-density oligonucleotide microarrays. RESULTS: Analysis of gene expression revealed that most of the differentially expressed mRNA in cirrhosis are associated with extracellular matrix remodeling, inflammation, antioxidant/stress response, and cell signaling. CONCLUSIONS: The collective expression changes observed within some functional groups of genes indicate that LECs in cirrhotic livers may contribute to lymphangiogenesis, enhancement of fibrogenesis and inflammatory processes, changes in cell-cell interaction with up-regulation of adherens junction proteins, and alterations in the intrahepatic vascular tone because of the down-regulation of genes involved in vasodilatation.     

Association of increased phagocytic NADPH oxidase-dependent superoxide production with diminished nitric oxide generation in essential hypertension

OBJECTIVE: Oxidative stress has been implicated in the pathogenesis of hypertension and its complications through alterations in nitric oxide (NO) metabolism. This study was designed to investigate whether a relationship exists between phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide anion (*O2-) production and NO generation in patients with essential hypertension. METHODS: Superoxide production was assayed by chemiluminescence under baseline and stimulated conditions on mononuclear cells obtained from hypertensives (n=51) and normotensives (n=43). NO production was evaluated by determining serum NO metabolites, nitrate plus nitrite (NOx). RESULTS: Although there were no differences in baseline *O2- production between normotensives and hypertensives, the *O2- production in phorbol myristate acetate (PMA)-stimulated mononuclear cells was increased (P <0.05) in hypertensives compared with normotensives. The PMA-induced *O2- production was completely abolished by apocynin, a specific inhibitor of NADPH oxidase. Moreover, stimulation of *O2- production by angiotensin II and endothelin-1 was higher (P <0.05) in cells from hypertensives than in cells from normotensives. In addition, diminished (P <0.001) serum NOx was detected in hypertensives compared with normotensives. Interestingly, an inverse correlation (r=0.493, P <0.01) was found between *O2- production and NOx in hypertensives. CONCLUSIONS: Generation of *O2- mainly dependent on NADPH oxidase is abnormally enhanced in stimulated mononuclear cells from hypertensives. It is suggested that this alteration could be involved in the diminished NO production observed in these patients.     

Scaling up real networks by geometric branching growth

Real networks often grow through the sequential addition of new nodes that connect to older ones in the graph. However, many real systems evolve through the branching of fundamental units, whether those be scientific fields, countries, or species. Here, we provide empirical evidence for self-similar growth of network structure in the evolution of real systems—the journal-citation network and the world trade web—and present the geometric branching growth model, which predicts this evolution and explains the symmetries observed. The model produces multiscale unfolding of a network in a sequence of scaled-up replicas preserving network features, including clustering and community structure, at all scales. Practical applications in real instances include the tuning of network size for best response to external influence and finite-size scaling to assess critical behavior under random link failures.

In the context of network science, growth is most often modeled through the sequential addition of new nodes that connect to older ones in a graph by different attachment mechanisms (1, 2), including models of hidden variables, where nodes are characterized by intrinsic properties (3, 4). Other growth processes have also been considered, such as duplication to explain large-scale proteome evolution (5, 6). Here, we take an alternative approach and explore the relation between branching growth (7) and geometric renormalization (GR) (8) to explain self-similar network evolution. Renormalization in networks, based on the ideas of the renormalization group in statistical physics (9–11), acts as a sort of inverse branching process by coarse-graining nodes and rescaling interactions. Thus, branching growth can be seen as an inverse renormalization transformation: an idea that was introduced in ref. 12 using a purely topological approach to reproduce the structure of fractal networks, where fractality was interpreted as an evolutionary drive toward robustness. However, topological distances in networks are seriously constrained by the small-world property, while the characterization of fractality in real networks disregards fundamental features of their structure, including clustering and community organization.GR (8) is an alternative technique that can be performed by virtue of the discovery that the structure of real networks is underlain by a latent hyperbolic geometry (13, 14). Thus, the likelihood of interactions between nodes depends on their distances in the underlying space, via a universal connectivity law that operates at all scales and simultaneously encodes short- and long-range connections. This approach has been able to explain many features of the structure of real networks, including the small-world property, scale-free degree distributions, and clustering, as well as fundamental mechanisms such as preferential attachment in growing networks (4) and the emergence of communities (15, 16). Given a network map, GR produces a multiscale unfolding of the network in scaled-down replicas over progressively longer length scales. This transformation has revealed self-similarity to be a ubiquitous symmetry in real networks, whose structural properties remain scale-invariant as the observational resolution is decreased (8). This poses the question of whether this self-similarity could be related to the mechanisms driving the growth of real networks and, therefore, whether their evolution could be conceptualized within the framework of the GR group.In this work, we show that real networks—citations between scientific journals (17, 18) and international trade (19)—have evolved in a self-similar way over time spans of more than 100 y, meaning that their local, mesoscale, and global topological properties remain in a steady state as time goes by, with a moderate increase of the average degree. We demonstrate that the observations can be modeled by a geometric branching growth (GBG) process that produces a self-similar metric expansion. Beyond the capacity of the model to explain and predict the self-similar evolution of real networks effectively, the technique is flexible and allows us to generate scaled-up network replicas that, when combined with scaled-down network replicas (8), provide a full up-and-down self-similar multiscale unfolding of complex networks that covers both large and small scales. We illustrate the use of GBG multiscale unfolding in real network instances via the tuning of network size for optimal response to an external influence, referred to here as “the optimal mass,” and a finite-size scaling analysis of critical behavior under random link failures.     

Membrane adaptation limitations in Enterococcus faecalis underlie sensitivity and the inability to develop significant resistance to conjugated oligoelectrolytes

The growing problem of antibiotic resistant bacteria, along with a dearth of new antibiotics, has redirected attention to the search for alternative antimicrobial agents. Conjugated oligoelectrolytes (COEs) are an emerging class of antimicrobial agents which insert into bacterial cell membranes and are inhibitory against a range of Gram-positive and Gram-negative bacteria. In this study, the extent of COE resistance that Enterococcus faecalis could achieve was studied. Enterococci are able to grow in hostile environments and develop resistance to membrane targeting antibiotics such as daptomycin in clinical settings. Herein we expand our knowledge of the antimicrobial mechanism of action of COEs by developing COE-resistant strains of E. faecalis OG1RF. Evolution studies yielded strains with a moderate 4–16 fold increase in antimicrobial resistance relative to the wild type. The resistant isolates accumulated agent-specific mutations associated with the liaFSR operon, which is a cell envelope-associated stress-response sensing and regulating system. The COE resistant isolates displayed significantly altered membrane fatty acid composition. Subsequent, exogenous supplementation with single fatty acids, which were chosen based on those dominating the fatty acid profiles of the mutants, increased resistance of the wild-type E. faecalis to COEs. In combination, genetic, fatty acid, and uptake studies support the hypothesis that COEs function through insertion into and disruption of membranes and that the mechanism by which this occurs is specific to the disrupting agent. These results were validated by a series of biophysical experiments showing the tendency of COEs to accumulate in and perturb adapted membrane extracts. Collectively, the data support that COEs are promising antimicrobial agents for targeting E. faecalis, and that there is a high barrier to the emergence of severely resistant strains constrained by biological limits of membrane remodeling that can occur in E. faecalis.

COEs are emerging antimicrobials to combat drug resistant infections and to which bacteria develop only limited resistance.     

Rol de enfermería en los programas de recuperación intensificada (fast-track)

Rapid recovery (RR) or fast-track programmes are aimed at reducing surgical stress, leading to a reduction in nurse workload, costs and hospital stay, greater patient empowerment, early post-surgical recovery and reduced morbidity and mortality. These new protocols require the coordinated participation of a multidisciplinary team.Based on an integrative review of the literature, this paper aims to define the concept of a RR or fast track programme and show the existing evidence on the implementation of these programmes in nursing.The benefits and low incidence of damage of RR programmes in nursing justify their implementation. The programmes require greater support and diffusion in order to develop, as well as more research to increase the evidence on the effectiveness and efficiency of the protocols.     

The Impact of Prices and Taxes on the Use of Tobacco Products in Latin America and the Caribbean

We examined the impact of tobacco prices or taxes on tobacco use in Latin America and Caribbean countries. We searched MEDLINE, EconLit, LILACS, unpublished literature, 6 specialty journals, and reviewed references. We calculated pooled price elasticities using random-effects models.The 32 studies we examined found that cigarette prices have a negative and statistically significant effect on cigarette consumption. A change in price is associated with a less than proportional change in the quantity of cigarettes demanded. In most Latin American countries, own-price elasticity for cigarettes is likely below  −0.5  (pooled elasticities, short-run: −0.31; 95% confidence interval = −0.39, −0.24; long-run: −0.43; 95% CI = −0.51, −0.35).Tax increases effectively reduce cigarette use. Lack of studies using household- or individual-level data limits research’s policy relevance.Among the many challenges facing health systems in low- and middle-income countries (LMICs) is the increasing burden of noncommunicable diseases. In 2010, more than one third of the 34.5 million deaths attributed to noncommunicable diseases occurred in LMICs.1 Tobacco use—a major risk factor of noncommunicable diseases—is worryingly high in many Latin American countries. Chile, for example, has one of the highest smoking prevalences in the world (in 2010, 44% of men and 38% of women were current smokers).2 The tobacco health toll is evident: in Chile, deaths attributable to tobacco use exceeded 15% of all deaths in 2009.3Increasing tobacco prices has been found to be the single most effective method to reduce smoking.4–6 Yet, it appears that relatively little work has been conducted using data from countries of Latin America and the Caribbean: a recent comprehensive review that the International Agency for Research on Cancer conducted identified only 6 studies.6 Additionally, reviews4–11 that examine the impact of prices and taxes on the use of tobacco products provide limited quality assessment of the data and methods used and have generally weaker generalizability to LMICs. There are exceptions (examples include Rice et al.,8 Bader et al.,9 and Guindon,11 who attempt to conduct some quality assessment of individual studies).We systematically searched for and critically reviewed studies that examined the impact of tobacco prices or taxes on tobacco use in countries of Latin America and the Caribbean. We paid particular attention to the data and statistical approaches used.     

Moderate to vigorous physical activity and sedentary behavior changes in self-isolating adults during the COVID-19 pandemic in Brazil: a cross-sectional survey exploring correlates

Sport Sciences for Health - The COVID-19 pandemic imposed major changes on daily-life routine worldwide. To the best of our knowledge, no study quantified the changes on moderate to vigorous...     

Nongenomic estrogen action regulates tyrosine phosphatase activity and tuberin stability

Estrogen action and tuberin function has been suggested to play a crucial role in the proliferation of lung smooth muscle-like cells and/or myofibroblasts in pulmonary lymphangioleiomyomatosis (LAM). Tuberin is a tumor suppressor phosphoprotein, which also regulates fluid phase endocytosis. Its activity, turnover and complex association with hamartin depends on its phosphorylation status. We have recently reported that nongenomic estrogen action regulates the phosphorylation status of several cytoplasmic proteins. Herein, we demonstrate that estrogen increases tyrosine phosphatase activity, which can be abrogated by antiestrogen ICI 182780 and tyrosine phosphatase inhibitor bpV(phen), but not by the protein synthesis inhibitor cyclohexamide. Furthermore, we show that estrogen transiently enhances the turnover of tuberin, which follows an inverse pattern to that observed for tyrosine phosphatase and endocytosis activity. We showed that tuberin phosphorylation protects it from degradation and induces its accumulation in female human lung fibroblasts and myofibroblasts. Our results suggest that nongenomic estrogen action induces tyrosine phosphatase activity that regulates stability of tyrosine phosphorylated proteins, including tuberin, which may play a crucial role in cellular specific functions such as endocytosis.     

Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound

OBJECTIVES: The aim of this study was to evaluate the feasibility and the ability of intravascular optical coherence tomography (OCT) to visualize the components of coronary plaques in living patients. BACKGROUND: Disruption of a vulnerable coronary plaque with subsequent thrombosis is currently recognized as the primary mechanism for acute myocardial infarction. Although such plaques are considered to have a thin fibrous cap overlying a lipid pool, imaging modalities in current clinical practice do not have sufficient resolution to identify thin (< 65 microm) fibrous caps. Optical coherence tomography is a new imaging modality capable of obtaining cross-sectional images of coronary vessels at a resolution of approximately 10 microm. METHODS: The OCT images and corresponding histology of 42 coronary plaques were compared to establish OCT criteria for different types of plaques. Atherosclerotic lesions with mild to moderate stenosis were identified on angiograms in 10 patients undergoing cardiac catheterization. Optical coherence tomography and intravascular ultrasound (IVUS) images of these sites were obtained in all patients without complication. RESULTS: Comparison between OCT and histology demonstrated that lipid-rich plaques and fibrous plaques have distinct OCT characteristics. A total of 17 IVUS and OCT image pairs obtained from patients were compared. Axial resolution measured 13 +/- 3 microm with OCT and 98 +/- 19 microm with IVUS. All fibrous plaques, macrocalcifications and echolucent regions identified by IVUS were visualized in corresponding OCT images. Intimal hyperplasia and echolucent regions, which may correspond to lipid pools, were identified more frequently by OCT than by IVUS. CONCLUSIONS: Intracoronary OCT appears to be feasible and safe. Optical coherence tomography identified most architectural features detected by IVUS and may provide additional detailed structural information.