Dynamic arterial elastance to predict arterial pressure response to volume loading in preload-dependent patients

INTRODUCTION Hemodynamic resuscitation should be aimed at achieving not only adequate cardiac output but also sufficient mean arterial pressure (MAP) to guarantee adequate tissue perfusion pressure. Since the arterial pressure response to volume expansion (VE) depends on arterial tone, knowing whether a patient is preload-dependent provides only a partial solution to the problem. The objective of this study was to assess the ability of a functional evaluation of arterial tone by dynamic arterial elastance (Ea(dyn)), defined as the pulse pressure variation (PPV) to stroke volume variation (SVV) ratio, to predict the hemodynamic response in MAP to fluid administration in hypotensive, preload-dependent patients with acute circulatory failure. METHODS We performed a prospective clinical study in an adult medical/surgical intensive care unit in a tertiary care teaching hospital, including 25 patients with controlled mechanical ventilation who were monitored with the Vigileo(®) monitor, for whom the decision to give fluids was made because of the presence of acute circulatory failure, including arterial hypotension (MAP ≤65 mmHg or systolic arterial pressure <90 mmHg) and preserved preload responsiveness condition, defined as a SVV value ≥10%. RESULTS Before fluid infusion, Ea(dyn) was significantly different between MAP responders (MAP increase ≥15% after VE) and MAP nonresponders. VE-induced increases in MAP were strongly correlated with baseline Ea(dyn) (r(2) = 0.83; P < 0.0001). The only predictor of MAP increase was Ea(dyn) (area under the curve, 0.986 ± 0.02; 95% confidence interval (CI), 0.84-1). A baseline Ea(dyn) value >0.89 predicted a MAP increase after fluid administration with a sensitivity of 93.75% (95% CI, 69.8%-99.8%) and a specificity of 100% (95% CI, 66.4%-100%). CONCLUSIONS Functional assessment of arterial tone by Ea(dyn), measured as the PVV to SVV ratio, predicted arterial pressure response after volume loading in hypotensive, preload-dependent patients under controlled mechanical ventilation.

Dissolution of Dynamic Electronic Institutions, a first approach: Relevant factors and causes

In the context of the digital business ecosystems, small organizations cooperate between them in order to achieve common goals or offer new services for expanding their markets. There are different approaches for these cooperation models such as virtual enterprises, virtual organizations or dynamic electronic institutions which in their lifecycle have in common a dissolution phase. However this phase has not been studied deeply in the current literature and it lacks formalization. In this paper a first approach for achieving and managing the dissolution phase is proposed, as well as a CBR process in order to support it in a multi-agent system

Perspectivas en el diseño y desarrollo de productos para nutrición enteral

Enteral nutrition is a technique that even though it was used in times immemorial, in the last 25 years has suffered a considerable development, from being considered a secondary therapeutic weapon destined only to feed the patient, to occupying an important status that goes beyond the single act of nourishing. The quantitative composition but overall the qualitative one, is object of an interesting argument in which a profile allowing the modulation of certain aspects of the organism response through the supplementation with different nutrients is searched. That includes from the keeping of the intestinal trophism and of the anti-bacteria intestinal barrier, so important to avoid the frightening multiple organ dysfunction, up to the lessening of the Systemic Response Inflammatory Syndrome (SRIS), going through the immuno-modulative feeding concepts, specific-feeding, pharmaco-nutrient or eco-nutrition. In this new dynamic not only certain nutrients such as glutamine, arginine, nucleotides, omega-3 fatty acids and many antioxidants have acquired importance, but also the manipulation of other molecules of a non- nutritional nature, such as hormones, cytokines and blockers. These aspects that imply passionate ways of investigation for the future are born from the better knowledge that is being acquired from such a severe pathophysiology processes such as sepsis and the organism response before fast and severe aggression; therefore, the modulation of that response through changes in the quantitative and qualitative formulas composition is being attempted.

Kinematics and dynamic complexity of postural transitions in frail elderly subjects.

The aim of this study was to propose a methodology allowing a detailed characterization of body sit-to-stand/stand-to-sit postural transition. Parameters characterizing the kinematics of the trunk movement during sit-to-stand (Si-St) postural transition were calculated using one initial sensor system fixed on the trunk and a data logger. Dynamic complexity of these postural transitions was estimated by fractal dimension of acceleration-angular velocity plot. We concluded that this method provides a simple and accurate tool for monitoring frail elderly and to objectively evaluate the efficacy of a rehabilitation program.

Update of the FANTOM web resource: from mammalian transcriptional landscape to its dynamic regulation.

The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4) research collaboration set out to better understand the transcriptional network that regulates macrophage differentiation and to uncover novel components of the transcriptome employing a series of high-throughput experiments. The primary and unique technique is cap analysis of gene expression (CAGE), sequencing mRNA 5'-ends with a second-generation sequencer to quantify promoter activities even in the absence of gene annotation. Additional genome-wide experiments complement the setup including short RNA sequencing, microarray gene expression profiling on large-scale perturbation experiments and ChIP-chip for epigenetic marks and transcription factors. All the experiments are performed in a differentiation time course of the THP-1 human leukemic cell line. Furthermore, we performed a large-scale mammalian two-hybrid (M2H) assay between transcription factors and monitored their expression profile across human and mouse tissues with qRT-PCR to address combinatorial effects of regulation by transcription factors. These interdependent data have been analyzed individually and in combination with each other and are published in related but distinct papers. We provide all data together with systematic annotation in an integrated view as resource for the scientific community (http://fantom.gsc.riken.jp/4/). Additionally, we assembled a rich set of derived analysis results including published predicted and validated regulatory interactions. Here we introduce the resource and its update after the initial release.

Blood-brain barrier disruption associated with topiramate-induced angle-closure glaucoma of acute onset.

BACKGROUND: Topiramate (Topamax(R)) is an anti-epileptic drug of the sulfamate group used secondarily for bipolar disease. HISTORY AND SIGNS: One week after initiation of topiramate treatment for a bipolar disorder, a 57-year-old man presented with blurred vision. Clinical examination revealed a bilateral conjunctivitis, areflexic mydriasis, severe anterior chamber shallowing, with a myopic shift and vitritis. THERAPY AND OUTCOME: A spinal tap revealed an increased protein content of 1581 mg/L on cerebrospinal fluid (CSF) analysis, being compatible with a rupture of the blood-brain barrier (BBB). UBM exposed bilateral ciliochoroidal effusions with secondary angle-closure. Topiramate was promptly discontinued, whereas visual acuity, intraocular pressure (IOP), and anterior and posterior segments anatomy normalized within 1 week. One month later, bilateral iris atrophy was present. CONCLUSION: The presence of BBB disruption with increased protein content in CSF with simultaneous blood ocular barrier breakdown may suggest a common inflammatory mechanism.

Are there positive emotions in short-term dynamic psychotherapy or is it all Freude-less ?

Psychodynamic therapists are often suspicious of positive emotions and consider them to be nothing more than a form of denial or of another defense aiming to diminish painful or difficult affects. Positive emotions seem to exist only through the absence of negative emotions or as something that may happen outside of therapy. On the other hand, clinicians also agree that psychoanalytic work could not be successful without such positive emotions as interest, pleasure, surprise and creativity. Contemporary psychoanalytic thinking and new research findings in the area of relationship regulation are likely to give positive emotions an increasingly prominent place in dynamically oriented therapies. With today's emphasis on the therapeutic relationship and intersubjectivity, the time appears right to integrate positive emotions more formally into psychodynamic clinical theories.

Combined simulation and mutagenesis analyses reveal the involvement of key residues for peroxisome proliferator-activated receptor alpha helix 12 dynamic behavior.

The dynamic properties of helix 12 in the ligand binding domain of nuclear receptors are a major determinant of AF-2 domain activity. We investigated the molecular and structural basis of helix 12 mobility, as well as the involvement of individual residues with regard to peroxisome proliferator-activated receptor alpha (PPARalpha) constitutive and ligand-dependent transcriptional activity. Functional assays of the activity of PPARalpha helix 12 mutants were combined with free energy molecular dynamics simulations. The agreement between the results from these approaches allows us to make robust claims concerning the mechanisms that govern helix 12 functions. Our data support a model in which PPARalpha helix 12 transiently adopts a relatively stable active conformation even in the absence of a ligand. This conformation provides the interface for the recruitment of a coactivator and results in constitutive activity. The receptor agonists stabilize this conformation and increase PPARalpha transcription activation potential. Finally, we disclose important functions of residues in PPARalpha AF-2, which determine the positioning of helix 12 in the active conformation in the absence of a ligand. Substitution of these residues suppresses PPARalpha constitutive activity, without changing PPARalpha ligand-dependent activation potential.

A dynamic view of hepatitis C virus replication complexes.

Hepatitis C virus (HCV) replicates its genome in a membrane-associated replication complex (RC). Specific membrane alterations, designated membranous webs, represent predominant sites of HCV RNA replication. The principles governing HCV RC and membranous web formation are poorly understood. Here, we used replicons harboring a green fluorescent protein (GFP) insertion in nonstructural protein 5A (NS5A) to study HCV RCs in live cells. Two distinct patterns of NS5A-GFP were observed. (i) Large structures, representing membranous webs, showed restricted motility, were stable over many hours, were partitioned among daughter cells during cell division, and displayed a static internal architecture without detectable exchange of NS5A-GFP. (ii) In contrast, small structures, presumably representing small RCs, showed fast, saltatory movements over long distances. Both populations were associated with endoplasmic reticulum (ER) tubules, but only small RCs showed ER-independent, microtubule (MT)-dependent transport. We suggest that this MT-dependent transport sustains two distinct RC populations, which are both required during the HCV life cycle.

Placental growth factor contributes to micro-vascular abnormalization and blood-retinal barrier breakdown in diabetic retinopathy.

OBJECTIVE: There are controversies regarding the pro-angiogenic activity of placental growth factor (PGF) in diabetic retinopathy (DR). For a better understanding of its role on the retina, we have evaluated the effect of a sustained PGF over-expression in rat ocular media, using ciliary muscle electrotransfer (ET) of a plasmid encoding rat PGF-1 (pVAX2-rPGF-1). MATERIALS AND METHODS: pVAX2-rPGF-1 ET in the ciliary muscle (200 V/cm) was achieved in non diabetic and diabetic rat eyes. Control eyes received saline or naked plasmid ET. Clinical follow up was carried out over three months using slit lamp examination and fluorescein angiography. After the control of rPGF-1 expression, PGF-induced effects on retinal vasculature and on the blood-external barrier were evaluated respectively by lectin and occludin staining on flat-mounts. Ocular structures were visualized through histological analysis. RESULTS: After fifteen days of rPGF-1 over-expression in normal eyes, tortuous and dilated capillaries were observed. At one month, microaneurysms and moderate vascular sprouts were detected in mid retinal periphery in vivo and on retinal flat-mounts. At later stages, retinal pigmented epithelial cells demonstrated morphological abnormalities and junction ruptures. In diabetic retinas, PGF expression rose between 2 and 5 months, and, one month after ET, rPGF-1 over-expression induced glial activation and proliferation. CONCLUSION: This is the first demonstration that sustained intraocular PGF production induces vascular and retinal changes similar to those observed in the early stages of diabetic retinopathy. PGF and its receptor Flt-1 may therefore be looked upon as a potential regulatory target at this stage of the disease.

The Öresund region: A dynamic region in Europe due to inter-regional collaboration?

El cluster Medicon Valley es troba a la regió d'Oresund binacional que s'estén per Dinamarca i Suècia, inclosa la Universitat de Lund, ciutat i tercera ciutat més gran de Suècia, Malmö (veure figura 1). El 2000, aquestes dues parts nacionals estaven connectades físicament per l'establiment dels 18 quilòmetres de longitud, enllaç fix del Øresund (ponts i túnels).