143 research outputs found
Echocardiography in the sepsis syndromes
Abstract
Purpose of the review
Non-invasiveness and instantaneous diagnostic capability are prominent features of the use of echocardiography in critical care. Sepsis and septic shock represent complex situations where early hemodynamic assessment and support are among the keys to therapeutic success. In this review, we discuss the range of applications of echocardiography in the management of the septic patient, and propose an echocardiography-based goal-oriented hemodynamic approach to septic shock.
Recent findings
Echocardiography can play a key role in the critical septic patient management, by excluding cardiac causes for sepsis, and mostly by guiding hemodynamic management of those patients in whom sepsis reaches such a severity to jeopardize cardiovascular function. In recent years, there have been both increasing evidence and diffusion of the use of echocardiography as monitoring tool in the patients with hemodynamic compromise. Also thanks to echocardiography, the features of the well-known sepsis-related myocardial dysfunction have been better characterized. Furthermore, many of the recent echocardiographic indices of volume responsiveness have been validated in populations of septic shock patients.
Conclusion
Although not proven yet in terms of patient outcome, echocardiography can be regarded as an ideal monitoring tool in the septic patient, as it allows (a) first line differential diagnosis of shock and early recognition of sepsis-related myocardial dysfunction; (b) detection of pre-existing cardiac pathology, that yields precious information in septic shock management; (c) comprehensive hemodynamic monitoring through a systematic approach based on repeated bedside assessment; (d) integration with other monitoring devices; and (e) screening for cardiac source of sepsis
Query3d: a new method for high-throughput analysis of functional residues in protein structures
BACKGROUND: The identification of local similarities between two protein structures can provide clues of a common function. Many different methods exist for searching for similar subsets of residues in proteins of known structure. However, the lack of functional and structural information on single residues, together with the low level of integration of this information in comparison methods, is a limitation that prevents these methods from being fully exploited in high-throughput analyses. RESULTS: Here we describe Query3d, a program that is both a structural DBMS (Database Management System) and a local comparison method. The method conserves a copy of all the residues of the Protein Data Bank annotated with a variety of functional and structural information. New annotations can be easily added from a variety of methods and known databases. The algorithm makes it possible to create complex queries based on the residues' function and then to compare only subsets of the selected residues. Functional information is also essential to speed up the comparison and the analysis of the results. CONCLUSION: With Query3d, users can easily obtain statistics on how many and which residues share certain properties in all proteins of known structure. At the same time, the method also finds their structural neighbours in the whole PDB. Programs and data can be accessed through the PdbFun web interface
Combined lung and brain ultrasonography for an individualized “brain-protective ventilation strategy” in neurocritical care patients with challenging ventilation needs
When intracranial hypertension and severe lung damage coexist in the same clinical scenario, their management poses a difficult challenge, especially as concerns mechanical ventilation management. The needs of combined lung and brain protection from secondary damage may conflict, as ventilation strategies commonly used in patients with ARDS are potentially associated with an increased risk of intracranial hypertension. In particular, the use of positive end-expiratory pressure, recruitment maneuvers, prone positioning, and protective lung ventilation can have undesirable effects on cerebral physiology: they may positively or negatively affect intracranial pressure, based on the final repercussions on PaO2and cerebral perfusion pressure (through changes in cardiac output, mean arterial pressure, venous return, PaO2and PaCO2), also according to the baseline conditions of cerebral autoregulation. Lung ultrasound (LUS) and brain ultrasound (BUS, as a combination of optic nerve sheath diameter assessment and cerebrovascular Doppler ultrasound) have independently proven their potential in respectively monitoring lung aeration and brain physiology at the bedside. In this narrative review, we describe how the combined use of LUS and BUS on neurocritical patients with demanding mechanical ventilation needs can contribute to ventilation management, with the aim of a tailored “brain-protective ventilation strategy.
Diagnosis of diastolic dysfunction in the emergency department: really at reach for minimally trained sonologists? A call for a wise approach to heart failure with preserved ejection fraction diagnosis in the ER
pdbFun: mass selection and fast comparison of annotated PDB residues
pdbFun () is a web server for structural and functional analysis of proteins at the residue level. pdbFun gives fast access to the whole Protein Data Bank (PDB) organized as a database of annotated residues. The available data (features) range from solvent exposure to ligand binding ability, location in a protein cavity, secondary structure, residue type, sequence functional pattern, protein domain and catalytic activity. Users can select any residue subset (even including any number of PDB structures) by combining the available features. Selections can be used as probe and target in multiple structure comparison searches. For example a search could involve, as a query, all solvent-exposed, hydrophylic residues that are not in alpha-helices and are involved in nucleotide binding. Possible examples of targets are represented by another selection, a single structure or a dataset composed of many structures. The output is a list of aligned structural matches offered in tabular and also graphical format
SH3-Hunter: discovery of SH3 domain interaction sites in proteins
SH3-Hunter (http://cbm.bio.uniroma2.it/SH3-Hunter/) is a web server for the recognition of putative SH3 domain interaction sites on protein sequences. Given an input query consisting of one or more protein sequences, the server identifies peptides containing poly-proline binding motifs and associates them to a list of SH3 domains, in order to compose peptide–domain pairs. The server can accept a list of peptides and allows users to upload an input file in a proper format. An accurate selection of SH3 domains is available and users can also submit their own SH3 domain sequence
Phospho3D: a database of three-dimensional structures of protein phosphorylation sites
Phosphorylation is the most common protein post-translational modification. Phosphorylated residues (serine, threonine and tyrosine) play critical roles in the regulation of many cellular processes. Since the amount of data produced by screening assays is growing continuously, the development of computational tools for collecting and analysing experimental data has become a pivotal task for unravelling the complex network of interactions regulating eukaryotic cell life. Here we present Phospho3D, , a database of 3D structures of phosphorylation sites, which stores information retrieved from the phospho.ELM database and is enriched with structural information and annotations at the residue level. The database also collects the results of a large-scale structural comparison procedure providing clues for the identification of new putative phosphorylation sites
3dLOGO:a web server for the identification, analysis and use of conserved protein substructures
3dLOGO is a web server for the identification and analysis of conserved protein 3D substructures. Given a set of residues in a PDB (Protein Data Bank) chain, the server detects the matching substructure(s) in a set of user-provided protein structures, generates a multiple structure alignment centered on the input substructures and highlights other residues whose structural conservation becomes evident after the defined superposition. Conserved residues are proposed to the user for highlighting functional areas, deriving refined structural motifs or building sequence patterns. Residue structural conservation can be visualized through an expressly designed Java application, 3dProLogo, which is a 3D implementation of a sequence logo. The 3dLOGO server, with related documentation, is available at http://3dlogo.uniroma2.it
Development of Computational Tools for the Inference of Protein Interaction Specificity Rules and Functional Annotation Using Structural Information
Relatively few protein structures are known, compared to the enormous amount of sequence data produced in the sequencing of different genomes, and relatively few
protein complexes are deposited in the PDB with respect to the great amount of
interaction data coming from high-throughput experiments (two-hybrid or affinity
purification of protein complexes and mass spectrometry). Nevertheless, we can rely
on computational techniques for the extraction of high-quality and information-rich
data from the known structures and for their spreading in the protein sequence space.
We describe here the ongoing research projects in our group: we analyse the protein
complexes stored in the PDB and, for each complex involving one domain belonging
to a family of interaction domains for which some interaction data are available, we
can calculate its probability of interaction with any protein sequence. We analyse the
structures of proteins encoding a function specified in a PROSITE pattern, which
exhibits relatively low selectivity and specificity, and build extended patterns. To
this aim, we consider residues that are well-conserved in the structure, even if their
conservation cannot easily be recognized in the sequence alignment of the proteins
holding the function. We also analyse protein surface regions and, through the
annotation of the solvent-exposed residues, we annotate protein surface patches via a
structural comparison performed with stringent parameters and independently of the
residue order in the sequence. Local surface comparison may also help in identifying
new sequence patterns, which could not be highlighted with other sequence-based
methods
Local comparison of protein structures highlights cases of convergent evolution in analogous functional sites
We performed an exhaustive search for local structural similarities in an ensemble of non-redundant protein functional sites. With the purpose of finding new examples of convergent evolution, we selected only those matching sites composed of structural regions whose residue order is inverted in the relative protein sequences
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