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Article: Using the diastolic shock index to determine when to promptly administer vasopressors in patients with septic shock.

Ospina-Tascón, Gustavo A / García-Gallardo, Gustavo / Orozco, Nicolás

Clinical and experimental emergency medicine

2022 Volume 9, Issue 4, Page(s) 367–369

Language	English
Publishing date	2022-12-08
Publishing country	Korea (South)
Document type	Journal Article
ISSN	2383-4625
ISSN	2383-4625
DOI	10.15441/ceem.22.401
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Article: G-SAIP: Graphical Sequence Alignment Through Parallel Programming in the Post-Genomic Era.

Piña, Johan S / Orozco-Arias, Simon / Tobón-Orozco, Nicolas / Camargo-Forero, Leonardo / Tabares-Soto, Reinel / Guyot, Romain

Evolutionary bioinformatics online

2023 Volume 19, Page(s) 11769343221150585

Abstract: A common task in bioinformatics is to compare DNA sequences to identify similarities between organisms at the sequence level. An approach to such comparison is the dot-plots, a 2-dimensional graphical representation to analyze DNA or protein alignments. ... ...

Abstract	A common task in bioinformatics is to compare DNA sequences to identify similarities between organisms at the sequence level. An approach to such comparison is the dot-plots, a 2-dimensional graphical representation to analyze DNA or protein alignments. Dot-plots alignment software existed before the sequencing revolution, and now there is an ongoing limitation when dealing with large-size sequences, resulting in very long execution times. High-Performance Computing (HPC) techniques have been successfully used in many applications to reduce computing times, but so far, very few applications for graphical sequence alignment using HPC have been reported. Here, we present G-SAIP (Graphical Sequence Alignment in Parallel), a software capable of spawning multiple distributed processes on CPUs, over a supercomputing infrastructure to speed up the execution time for dot-plot generation up to 1.68× compared with other current fastest tools, improve the efficiency for comparative structural genomic analysis, phylogenetics because the benefits of pairwise alignments for comparison between genomes, repetitive structure identification, and assembly quality checking.
Language	English
Publishing date	2023-01-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2227610-5
ISSN	1176-9343
ISSN	1176-9343
DOI	10.1177/11769343221150585
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Article ; Online: Doppler identified venous congestion in septic shock: protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS).

Prager, Ross / Argaiz, Eduardo / Pratte, Michael / Rola, Philippe / Arntfield, Robert / Beaubien-Souligny, William / Denault, André Y / Haycock, Korbin / Miralles Aguiar, Francisco / Bakker, Jan / Ospina-Tascon, Gustavo / Orozco, Nicolas / Rochwerg, Bram / Lewis, Kimberley / Quazi, Ibrahim / Kattan, Eduardo / Hernandez, Glenn / Basmaji, John

BMJ open

2023 Volume 13, Issue 7, Page(s) e074843

Abstract: Introduction: Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. ... ...

Abstract	Introduction: Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. Venous congestion can be measured by Doppler ultrasound at the bedside through interrogation of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV) and intrarenal veins (IRV). The objective of this study is to quantify the association between Doppler identified venous congestion and the need for renal replacement therapy (RRT) or death for patients with septic shock. Methods and analysis: This study is a prespecified substudy of the ANDROMEDA-SHOCK 2 (AS-2) randomised control trial (RCT) assessing haemodynamic resuscitation in septic shock and will enrol at least 350 patients across multiple sites. We will include adult patients within 4 hours of fulfilling septic shock definition according to Sepsis-3 consensus conference. Using Doppler ultrasound, physicians will interrogate the IVC, HV, PV and IRV 6-12 hours after randomisation. Study investigators will provide web-based educational sessions to ultrasound operators and adjudicate image acquisition and interpretation. The primary outcome will be RRT or death within 28 days of septic shock. We will assess the hazard of RRT or death as a function of venous congestion using a Cox proportional hazards model. Sub-distribution HRs will describe the hazard of RRT given the competing risk of death. Ethics and dissemination: We obtained ethics approval for the AS-2 RCT, including this observational substudy, from local ethics boards at all participating sites. We will report the findings of this study through open-access publication, presentation at international conferences, a coordinated dissemination strategy by investigators through social media, and an open-access workshop series in multiple languages. Trial registration number: NCT05057611.
MeSH term(s)	Adult ; Humans ; Cohort Studies ; Hyperemia ; Randomized Controlled Trials as Topic ; Sepsis ; Shock, Septic ; Ultrasonography, Doppler ; Multicenter Studies as Topic
Language	English
Publishing date	2023-07-24
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-074843
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Article ; Online: Immediate Norepinephrine in Endotoxic Shock: Effects on Regional and Microcirculatory Flow.

Ospina-Tascón, Gustavo A / Aldana, José L / García Marín, Alberto F / Calderón-Tapia, Luis E / Marulanda, Angela / Escobar, Elena P / García-Gallardo, Gustavo / Orozco, Nicolás / Velasco, María I / Ríos, Edwin / De Backer, Daniel / Hernández, Glenn / Bakker, Jan

Critical care medicine

2023 Volume 51, Issue 8, Page(s) e157–e168

Abstract: Objectives: To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock.: Design: Animal ... ...

Abstract	Objectives: To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock. Design: Animal experimental study. Setting: University translational research laboratory. Subjects: Fifteen Landrace pigs. Interventions: Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance. Measurements and main results: Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively). Conclusions: In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.
MeSH term(s)	Animals ; Swine ; Norepinephrine/therapeutic use ; Microcirculation ; Splanchnic Circulation ; Vasoconstrictor Agents/pharmacology ; Vasoconstrictor Agents/therapeutic use ; Shock, Septic/drug therapy ; Hemodynamics ; Lactates/pharmacology ; Lactates/therapeutic use
Chemical Substances	Norepinephrine (X4W3ENH1CV) ; Vasoconstrictor Agents ; Lactates
Language	English
Publishing date	2023-05-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000005885
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Article: TIP_finder: An HPC Software to Detect Transposable Element Insertion Polymorphisms in Large Genomic Datasets.

Orozco-Arias, Simon / Tobon-Orozco, Nicolas / Piña, Johan S / Jiménez-Varón, Cristian Felipe / Tabares-Soto, Reinel / Guyot, Romain

Biology

2020 Volume 9, Issue 9

Abstract: Transposable elements (TEs) are non-static genomic units capable of moving indistinctly from one chromosomal location to another. Their insertion polymorphisms may cause beneficial mutations, such as the creation of new gene function, or deleterious in ... ...

Abstract	Transposable elements (TEs) are non-static genomic units capable of moving indistinctly from one chromosomal location to another. Their insertion polymorphisms may cause beneficial mutations, such as the creation of new gene function, or deleterious in eukaryotes, e.g., different types of cancer in humans. A particular type of TE called LTR-retrotransposons comprises almost 8% of the human genome. Among LTR retrotransposons, human endogenous retroviruses (HERVs) bear structural and functional similarities to retroviruses. Several tools allow the detection of transposon insertion polymorphisms (TIPs) but fail to efficiently analyze large genomes or large datasets. Here, we developed a computational tool, named TIP_finder, able to detect mobile element insertions in very large genomes, through high-performance computing (HPC) and parallel programming, using the inference of discordant read pair analysis. TIP_finder inputs are (i) short pair reads such as those obtained by Illumina, (ii) a chromosome-level reference genome sequence, and (iii) a database of consensus TE sequences. The HPC strategy we propose adds scalability and provides a useful tool to analyze huge genomic datasets in a decent running time. TIP_finder accelerates the detection of transposon insertion polymorphisms (TIPs) by up to 55 times in breast cancer datasets and 46 times in cancer-free datasets compared to the fastest available algorithms. TIP_finder applies a validated strategy to find TIPs, accelerates the process through HPC, and addresses the issues of runtime for large-scale analyses in the post-genomic era. TIP_finder version 1.0 is available at https://github.com/simonorozcoarias/TIP_finder.
Language	English
Publishing date	2020-09-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology9090281
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Article: TIP_finder: An HPC Software to Detect Transposable Element Insertion Polymorphisms in Large Genomic Datasets

Orozco-Arias, Simon / Tobon-Orozco, Nicolas / Piña, Johan S / Jiménez-Varón, Cristian Felipe / Tabares-Soto, Reinel / Guyot, Romain

Biology. 2020 Sept. 09, v. 9, no. 9

2020

Abstract	Transposable elements (TEs) are non-static genomic units capable of moving indistinctly from one chromosomal location to another. Their insertion polymorphisms may cause beneficial mutations, such as the creation of new gene function, or deleterious in eukaryotes, e.g., different types of cancer in humans. A particular type of TE called LTR-retrotransposons comprises almost 8% of the human genome. Among LTR retrotransposons, human endogenous retroviruses (HERVs) bear structural and functional similarities to retroviruses. Several tools allow the detection of transposon insertion polymorphisms (TIPs) but fail to efficiently analyze large genomes or large datasets. Here, we developed a computational tool, named TIP_finder, able to detect mobile element insertions in very large genomes, through high-performance computing (HPC) and parallel programming, using the inference of discordant read pair analysis. TIP_finder inputs are (i) short pair reads such as those obtained by Illumina, (ii) a chromosome-level reference genome sequence, and (iii) a database of consensus TE sequences. The HPC strategy we propose adds scalability and provides a useful tool to analyze huge genomic datasets in a decent running time. TIP_finder accelerates the detection of transposon insertion polymorphisms (TIPs) by up to 55 times in breast cancer datasets and 46 times in cancer-free datasets compared to the fastest available algorithms. TIP_finder applies a validated strategy to find TIPs, accelerates the process through HPC, and addresses the issues of runtime for large-scale analyses in the post-genomic era.
Keywords	Retroviridae ; Ursidae ; algorithms ; breast neoplasms ; computer software ; data collection ; databases ; detection ; eukaryotic cells ; genes ; genomics ; humans ; mutation ; retrotransposons ; transposons
Language	English
Dates of publication	2020-0909
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology9090281
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Article ; Online: Cistatina C como predictor de mortalidad en población hipertensa de Extremadura.

Garcia Gallego, Francisco / Robles, Nicolás Roberto / Matias Orozco, Nicolás / Mena, Candido / Cidoncha, Antonio

Medicina clinica

2015 Volume 145, Issue 5, Page(s) 198–200

Abstract: Background and objectives: Cystatin C has proven to be a useful parameter to evaluate renal and cardiovascular risk. Nevertheless, there are scanty reports on the utility of this test in the Spanish population. We performed a survey in a group of ... ...

Title translation	Cystatin C as a mortality predictor in a hypertensive population in Extremadura, Spain.
Abstract	Background and objectives: Cystatin C has proven to be a useful parameter to evaluate renal and cardiovascular risk. Nevertheless, there are scanty reports on the utility of this test in the Spanish population. We performed a survey in a group of patients followed up in Primary Care settings. Material and methods: Prospective follow up of Primary Care attended patients recruited in 2008 and the first half of 2009. The sample included 142 subjects (mean age 64.2±14.6 years, 59.2% men). In all cases, cystatin C was determined and glomerular filtration rate (GFR) was estimated through the Hoek formula. Serum creatinine was also quantified as it was GFR estimated using CKD-EPI equation. The primary objective was a combination of death and major cardiovascular events incidence. Results: There were 29 events registered (4 of them were deaths) and 9 non cardiovascular deaths. The odds ratio for the primary objective was 5.74 for the last quartile of cystatin C distribution (>1mg/l) (P=.002), while it was 6.44 for cystatin C derived GFR (P=.008) and 5.59 for CKD-EPI estimated GFR (P=.002, Mantel-Haenszel test). Conclusions: Cystatin C showed a good association with general mortality and the incidence of cardiovascular events in the Spanish population. Nevertheless, it was not better than the observed relationship with GFR, estimated from creatinine.
MeSH term(s)	Aged ; Cardiovascular Diseases/mortality ; Cause of Death ; Creatinine/blood ; Cystatin C/blood ; Diabetes Mellitus/epidemiology ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Hypertension/blood ; Hypertension/epidemiology ; Incidence ; Middle Aged ; Mortality ; Prognosis ; Prospective Studies ; Risk ; Spain/epidemiology
Chemical Substances	Cystatin C ; Creatinine (AYI8EX34EU)
Language	Spanish
Publishing date	2015-09-07
Publishing country	Spain
Document type	English Abstract ; Journal Article
ZDB-ID	411607-0
ISSN	1578-8989 ; 0025-7753
ISSN (online)	1578-8989
ISSN	0025-7753
DOI	10.1016/j.medcli.2015.03.012
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Article: Proliferative Neural Stem Cells Have High Endogenous ROS Levels that Regulate Self-Renewal and Neurogenesis in a PI3K/Akt-Dependant Manner

Le Belle, Janel E / Orozco, Nicolas M / Paucar, Andres A / Saxe, Jonathan P / Mottahedeh, Jack / Pyle, April D / Wu, Hong / Kornblum, Harley I

Cell stem cell. 2011 Jan. 7, v. 8, no. 1

2011

Abstract: The majority of research on reactive oxygen species (ROS) has focused on their cellular toxicities. Stem cells generally have been thought to maintain low levels of ROS as a protection against these processes. However, recent studies suggest that ROS can ...

Abstract	The majority of research on reactive oxygen species (ROS) has focused on their cellular toxicities. Stem cells generally have been thought to maintain low levels of ROS as a protection against these processes. However, recent studies suggest that ROS can also play roles as second messengers, activating normal cellular processes. Here, we investigated ROS function in primary brain-derived neural progenitors. Somewhat surprisingly, we found that proliferative, self-renewing multipotent neural progenitors with the phenotypic characteristics of neural stem cells (NSC) maintained a high ROS status and were highly responsive to ROS stimulation. ROS-mediated enhancements in self-renewal and neurogenesis were dependent on PI3K/Akt signaling. Pharmacological or genetic manipulations that diminished cellular ROS levels also interfered with normal NSC and/or multipotent progenitor function both in vitro and in vivo. This study has identified a redox-mediated regulatory mechanism of NSC function that may have significant implications for brain injury, disease, and repair.
Keywords	brain ; cytotoxicity ; genetic engineering ; neurogenesis ; reactive oxygen species ; second messengers ; stem cells
Language	English
Dates of publication	2011-0107
Size	p. 59-71.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2375354-7
ISSN	1934-5909
ISSN	1934-5909
DOI	10.1016/j.stem.2010.11.028
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner.

Le Belle, Janel E / Orozco, Nicolas M / Paucar, Andres A / Saxe, Jonathan P / Mottahedeh, Jack / Pyle, April D / Wu, Hong / Kornblum, Harley I

Cell stem cell

2010 Volume 8, Issue 1, Page(s) 59–71

Abstract	The majority of research on reactive oxygen species (ROS) has focused on their cellular toxicities. Stem cells generally have been thought to maintain low levels of ROS as a protection against these processes. However, recent studies suggest that ROS can also play roles as second messengers, activating normal cellular processes. Here, we investigated ROS function in primary brain-derived neural progenitors. Somewhat surprisingly, we found that proliferative, self-renewing multipotent neural progenitors with the phenotypic characteristics of neural stem cells (NSC) maintained a high ROS status and were highly responsive to ROS stimulation. ROS-mediated enhancements in self-renewal and neurogenesis were dependent on PI3K/Akt signaling. Pharmacological or genetic manipulations that diminished cellular ROS levels also interfered with normal NSC and/or multipotent progenitor function both in vitro and in vivo. This study has identified a redox-mediated regulatory mechanism of NSC function that may have significant implications for brain injury, disease, and repair.
MeSH term(s)	Animals ; Cell Proliferation ; Cells, Cultured ; Humans ; Mice ; Mice, Inbred Strains ; Neural Stem Cells/cytology ; Neural Stem Cells/metabolism ; Neurogenesis/physiology ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction
Chemical Substances	Reactive Oxygen Species ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2010-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2010.11.028
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