david jimenez | UNAM Universidad Nacional Autónoma de México (original) (raw)

Papers by david jimenez

Research paper thumbnail of IGF-I regulated phosphorylation and translocation of PDK-1 in neurons

Neuroreport

3'-phosphoinositide-dependent protein kinase-1 (PDK-1) is a crucial serine/threonine kinase i... more 3'-phosphoinositide-dependent protein kinase-1 (PDK-1) is a crucial serine/threonine kinase in the insulin-like growth factor-I (IGF-I)/AKT signaling pathway, but its function and localization in the nervous system has not been fully characterized. In this study, we compared the localization of PDK-1 in adult neurons and non-neuronal PC-3 cells. We showed that PC-3 cells expressed phosphorylated and nonphosphorylated PDK-1 in the cytoplasm and nucleoplasm. In contrast, neuronal PDK-1 was located in the nucleoplasm and the phosphorylated form was located along the perinuclear region. Furthermore, we found that IGF-I transiently increased phosphorylation of neuronal PDK-1, resulting in its translocation to other cellular compartments. Our findings suggest that IGF-I may regulate neuronal PDK-1 differently than in non-neuronal cells, which may indicate a novel role for PDK-1 in IGF-I-mediated neuroprotective signaling.

Research paper thumbnail of Chronic thromboembolic pulmonary hypertension: Experience improves outcomes

Archivos de Bronconeumología

Research paper thumbnail of Short-term clinical outcome of normotensive patients with acute PE and high plasma lactate

Thorax

Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-rel... more Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-related complications remain to be defined. This prospective cohort study aimed to determine the role of plasma lactate levels in the risk assessment of normotensive patients with acute PE. Outcomes assessed over the 7 days after the diagnosis of PE included PE-related mortality and haemodynamic collapse, defined as need for cardiopulmonary resuscitation, systolic blood pressure <90 mm Hg for at least 15 min, need for catecholamine administration, or need for mechanical ventilation. Between December 2012 and January 2014, the study enrolled 496 normotensive outpatients with acute symptomatic PE. PE-related complications occurred in 20 (4.0%; 95% CI 2.5% to 6.2%) of the 496 patients. These patients had higher baseline lactate levels (median 2.66 mmol/L; IQR 1.56-5.96 mmol/L) than patients without complications (1.20 mmol/L; IQR 1.20-2.00 mmol/L) (p<0.001). Overall, 135 patients (27.2%)...

Research paper thumbnail of Embolic burden of incidental pulmonary embolism diagnosed on routinely performed contrast-enhanced CT-imaging in cancer patients

Journal of Thrombosis and Haemostasis

Since the quality of CT-imaging techniques has improved, pulmonary embolism (PE) is increasingly ... more Since the quality of CT-imaging techniques has improved, pulmonary embolism (PE) is increasingly being detected incidentally on routine CT-examinations. In particular in patients with malignancy, who are known to be at elevated risk of developing venous thromboembolic events (VTE), and who frequently undergo CT scanning for reasons as diagnosing, staging and treatment evaluation, incidental PE has become a relative common finding [1]. This article is protected by copyright. All rights reserved.

Research paper thumbnail of Computerised clinical decision support for suspected PE

Thorax

This study aimed to determine the effect of an evidence-based clinical decision support (CDS) alg... more This study aimed to determine the effect of an evidence-based clinical decision support (CDS) algorithm on the use and yield of CT pulmonary angiography (CTPA) and on outcomes of patients evaluated in the emergency department (ED) for suspected PE. The study included 1363 consecutive patients evaluated for suspected PE in an ED during 12 months before and 12 months after initiation of CDS use. Introduction of CDS was associated with decreased CTPA use (55% vs 49%; absolute difference (AD), 6.3%; 95% CI 1.0% to 11.6%; p=0.02). The use of CDS was associated with fewer symptomatic venous thromboembolic events during follow-up in patients with an initial negative diagnostic evaluation for PE (0.7% vs 3.2%; AD 2.5%; 95% CI 0.9% to 4.6%; p<0.01). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Research paper thumbnail of Trends in hospital admissions for pulmonary embolism in Spain from 2002 to 2011

European Respiratory Journal

The aim of our study was to analyse changes in the incidence, diagnostic procedures, comorbidity,... more The aim of our study was to analyse changes in the incidence, diagnostic procedures, comorbidity, length of hospital stay, costs and in-hospital mortality of patients hospitalised for pulmonary embolism in Spain over a 10-year period. We included all patients who were hospitalised for pulmonary embolism (ICD-9-CM codes 415.11 and 415.19) as the primary diagnosis between 2002 and 2011. Data were collected from the National Hospital Discharge Database, covering the entire Spanish population. 115 671 patients were admitted. The overall crude incidence increased from 20.44 per 100 000 inhabitants in 2002 to 32.69 in 2011 (p<0.05). In 2002, 13.3% of patients had a Charlson comorbidity index >2, and in 2011 the prevalence increased to 20.8% (p<0.05). Mean length of hospital stay was 12.7 days in 2002 and decreased to 9.99 in 2011 (p<0.05). During the study period, mean cost per patient increased from €3915 to €4372 (p<0.05). In-hospital mortality decreased from 12.9% in 200...

Research paper thumbnail of Huntington's disease: confirmation of diagnosis and presymptomatic testing in Spanish families by genetic analysis

Journal of Neurology Neurosurgery and Psychiatry, 1996

Huntington's disease is a neuropsychiatric disorder with late age of onset, caused by an elon... more Huntington's disease is a neuropsychiatric disorder with late age of onset, caused by an elongation of a (CAG)n repeat in the IT15 gene. This trinucleotide repeat has been studied by polymerase chain reaction amplification in 86 members of 43 Spanish families with Huntington's disease and in 60 unrelated subjects from the general population. The number of (CAG)n repeats in Huntington's

Research paper thumbnail of Zoledronic acid therapy for recurrent giant cell tumor of the C2 vertebra in an adolescent

The spine journal : official journal of the North American Spine Society, Jan 25, 2015

Research paper thumbnail of Comments on the 2014 ESC Guidelines on the diagnosis and management of hypertrophic cardiomyopathy. A critical view from the perspective of Spanish cardiology

Revista española de cardiología (English ed.), 2015

Grupo de Trabajo de la SEC para la guía de la ESC 2014 sobre diagnóstico y tratamiento de la pato... more Grupo de Trabajo de la SEC para la guía de la ESC 2014 sobre diagnóstico y tratamiento de la patología de la aorta , , revisores expertos para la guía de la ESC 2014 sobre diagnóstico y tratamiento de la patología de la aorta, Comité de Guías de la SEC ◊ VÉASE CONTENIDO RELACIONADO: http://dx.

Research paper thumbnail of ChemInform Abstract: First Synthesis of the Antifungal Oidiolactone C from trans-Communic Acid: Cytotoxic and Antimicrobial Activity in Podolactone-Related Compounds

ChemInform, 2002

The synthesis of the fungicide oidiolactone C starting from diterpenic trans-communic acid was ca... more The synthesis of the fungicide oidiolactone C starting from diterpenic trans-communic acid was carried out with an overall yield of 11.7%. The key step in the process consists of a new bislactonization reaction catalyzed by Pd(II), which gives rise to the podolactone-type tetracyclic skeleton from a norlabdadienedioic acid. We also carried out a study of the structure-biological activity of different natural podolactones and their synthetic precursors. Thus, the highest cytotoxic activity was found in dienic dilactones with ether-type substitutions on C-17, whereas the closure of the γ-lactone ring is not critical for presenting a maximal antimicrobial activity.

Research paper thumbnail of Abdominal pseudocyst complicating incisional hernia repair: our experience and literature review

Hernia, 2010

Giant pseudocyst is a rare complication of incisional hernia repairs whose etiology and incidence... more Giant pseudocyst is a rare complication of incisional hernia repairs whose etiology and incidence remains unknown. We have reviewed all cases of abdominal incisional hernia repair in our abdominal wall unit since its creation 6 years ago. Pseudocyst formation was observed in seven cases out of 871 incisional hernia repair operations. Four of them underwent surgical exploration with excision of the mass. To the best of our knowledge, only 18 cases of giant pseudocyst have been described in the literature. From both our personal experience and the reported literature, we understand that abdominal pseudocyst is an extremely rare or underreported late complication of hernia repair surgery. The complete excision of the cyst and its fibrous wall is the definitive treatment of choice.

Research paper thumbnail of Contribution of N-linked glycans to the conformation and function of intercellular adhesion molecules (ICAMs)

The Journal of biological chemistry, Jan 18, 2005

The crystal structures of the glycosylated N-terminal two domains of ICAM-1 and ICAM-2 provided a... more The crystal structures of the glycosylated N-terminal two domains of ICAM-1 and ICAM-2 provided a framework for understanding the role of glycosylation in the structure and function of intercellular adhesion molecules (ICAMs). The most conserved glycans were less flexible in the structures, interacting with protein residues and contributing to receptor folding and expression. The first N-linked glycan in ICAM-2 contacts an exposed tryptophan residue, defining a conserved glycan-W motif critical for the conformation of the integrin binding domain. The absence of this motif in human ICAM-1 exposes regions used in receptor dimerization and rhinovirus recognition. Experiments with soluble molecules having the N-terminal two domains of human ICAMs identified glycans of the high mannose type N-linked to the second domain of the dendritic cell-specific ICAM-grabbing nonintegrin lectin-ligands ICAM-2 and ICAM-3. About 40% of those receptor molecules bear endoglycosidase H sensitive glycans ...

Research paper thumbnail of Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism

Thrombosis and haemostasis, 2013

In patients with venous thromboembolism (VTE), assessment of the risk of fatal recurrent VTE and ... more In patients with venous thromboembolism (VTE), assessment of the risk of fatal recurrent VTE and fatal bleeding during anticoagulation may help to guide intensity and duration of therapy. We aimed to provide estimates of the case-fatality rate (CFR) of recurrent VTE and major bleeding during anticoagulation in a 'real life' population, and to assess these outcomes according to the initial presentation of VTE and its etiology. The study included 41,826 patients with confirmed VTE from the RIETE registry who received different durations of anticoagulation (mean 7.8 ± 0.6 months). During 27,110 patient-years, the CFR was 12.1% (95% CI, 10.2-14.2) for recurrent VTE, and 19.7% (95% CI, 17.4-22.1) for major bleeding. During the first three months of anticoagulant therapy, the CFR of recurrent VTE was 16.1% (95% CI, 13.6-18.9), compared to 2.0% (95% CI, 0-4.2) beyond this period. The CFR of bleeding was 20.2% (95% CI, 17.5-23.1) during the first three months, compared to 18.2% (95%...

Research paper thumbnail of Rivaroxaban in the Treatment of Venous Thromboembolism and the Prevention of Recurrences: A Practical Approach

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, Jan 9, 2014

Anticoagulation therapy is the standard treatment of patients with symptomatic venous thromboembo... more Anticoagulation therapy is the standard treatment of patients with symptomatic venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Until recently, treatment of VTE was based on parenteral or low-molecular-weight heparin for initial therapy (5-10 days) and oral vitamin K antagonists for long-term therapy. Those treatments have some limitations, including parenteral administration (heparins), the need for frequent monitoring and dose adjustments, interactions with several medications, and dietary restrictions (vitamin K antagonists). Rivaroxaban is a new oral direct factor Xa inhibitor with a wide therapeutic window, predictable anticoagulant effect, no food interactions, and few drug interactions. Consequently, no periodic monitoring of anticoagulation is needed, and fixed doses can be prescribed. EINSTEIN program demonstrated that rivaroxaban was as effective as and significantly safer than standard therapy for treatment of VTE. Rivaroxaban was recen...

Research paper thumbnail of Age-adjusted hsTnT cut-off value for risk stratification of pulmonary embolism

The European respiratory journal, Jan 22, 2015

High-sensitivity troponin T (hsTnT) helps in identifying pulmonary embolism patients at low risk ... more High-sensitivity troponin T (hsTnT) helps in identifying pulmonary embolism patients at low risk of an adverse outcome. In 682 normotensive pulmonary embolism patients we investigate whether an optimised hsTnT cut-off value and adjustment for age improve the identification of patients at elevated risk. Overall, 25 (3.7%) patients had an adverse 30-day outcome. The established hsTnT cut-off value of 14 pg·mL(-1) retained its high prognostic value (OR (95% CI) 16.64 (2.24-123.74); p=0.006) compared with the cut-off value of 33 pg·mL(-1) calculated by receiver operating characteristic analysis (7.14 (2.64-19.26); p<0.001). In elderly (aged ⩾75 years) patients, an age-optimised hsTnT cut-off value of 45 pg·mL(-1) but not the established cut-off value of 14 pg·mL(-1) predicted an adverse outcome. An age-adjusted hsTnT cut-off value (⩾14 pg·mL(-1) for patients aged <75 years and ⩾45 pg·mL(-1) for patients aged ⩾75 years) provided additive and independent prognostic information on to...

Research paper thumbnail of Short-term clinical outcome of normotensive patients with acute PE and high plasma lactate

Thorax, Jan 6, 2015

Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-rel... more Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-related complications remain to be defined. This prospective cohort study aimed to determine the role of plasma lactate levels in the risk assessment of normotensive patients with acute PE. Outcomes assessed over the 7 days after the diagnosis of PE included PE-related mortality and haemodynamic collapse, defined as need for cardiopulmonary resuscitation, systolic blood pressure <90 mm Hg for at least 15 min, need for catecholamine administration, or need for mechanical ventilation. Between December 2012 and January 2014, the study enrolled 496 normotensive outpatients with acute symptomatic PE. PE-related complications occurred in 20 (4.0%; 95% CI 2.5% to 6.2%) of the 496 patients. These patients had higher baseline lactate levels (median 2.66 mmol/L; IQR 1.56-5.96 mmol/L) than patients without complications (1.20 mmol/L; IQR 1.20-2.00 mmol/L) (p<0.001). Overall, 135 patients (27.2%)...

Research paper thumbnail of Temporal Differences in MicroRNA Expression Patterns in Astrocytes and Neurons after Ischemic Injury

PLOS One, 2011

MicroRNAs (miRNAs) are small, non-protein-coding RNA molecules that modulate gene translation. Th... more MicroRNAs (miRNAs) are small, non-protein-coding RNA molecules that modulate gene translation. Their expression is altered in many central nervous system (CNS) injuries suggesting a role in the cellular response to stress. Current studies in brain tissue have not yet described the cell-specific temporal miRNA expression patterns following ischemic injury. In this study, we analyzed the expression alterations of a set

Research paper thumbnail of Novedades en la enfermedad tromboembólica venosa

Revista Clínica Española, 2012

This paper brings together the latest developments that have occurred in different aspects of ven... more This paper brings together the latest developments that have occurred in different aspects of venous thromboembolism (VTE): VTE prophylaxis in high-risk orthopedic surgery and acutely ill hospitalized medical patients; therapeutic advances in pulmonary embolism and superficial vein thrombosis and VTE future prospects. It summarizes the reviews that five speakers made in-depth for the Second Day in New Anticoagulant Treatment, held in Madrid on November 18, 2011, organized by the Foundation for the Study of Thromboembolic Disease in Spain and endorsed by the Spanish Society of Internal Medicine, Spanish Society of Pneumology and Thoracic Surgery, Spanish Society of Cardiology, Spanish Society of Thrombosis and Haemostasis and the Spanish Society of Angiology and Vascular Surgery.

Research paper thumbnail of Does progesterone show neuroprotective effects on traumatic brain injury through increasing phosphorylation of Akt in the hippocampus?

Neural Regeneration Research, 2014

Research paper thumbnail of Computerised clinical decision support for suspected PE

Thorax, 2015

This study aimed to determine the effect of an evidence-based clinical decision support (CDS) alg... more This study aimed to determine the effect of an evidence-based clinical decision support (CDS) algorithm on the use and yield of CT pulmonary angiography (CTPA) and on outcomes of patients evaluated in the emergency department (ED) for suspected PE. The study included 1363 consecutive patients evaluated for suspected PE in an ED during 12 months before and 12 months after initiation of CDS use. Introduction of CDS was associated with decreased CTPA use (55% vs 49%; absolute difference (AD), 6.3%; 95% CI 1.0% to 11.6%; p=0.02). The use of CDS was associated with fewer symptomatic venous thromboembolic events during follow-up in patients with an initial negative diagnostic evaluation for PE (0.7% vs 3.2%; AD 2.5%; 95% CI 0.9% to 4.6%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01).

Research paper thumbnail of IGF-I regulated phosphorylation and translocation of PDK-1 in neurons

Neuroreport

3'-phosphoinositide-dependent protein kinase-1 (PDK-1) is a crucial serine/threonine kinase i... more 3'-phosphoinositide-dependent protein kinase-1 (PDK-1) is a crucial serine/threonine kinase in the insulin-like growth factor-I (IGF-I)/AKT signaling pathway, but its function and localization in the nervous system has not been fully characterized. In this study, we compared the localization of PDK-1 in adult neurons and non-neuronal PC-3 cells. We showed that PC-3 cells expressed phosphorylated and nonphosphorylated PDK-1 in the cytoplasm and nucleoplasm. In contrast, neuronal PDK-1 was located in the nucleoplasm and the phosphorylated form was located along the perinuclear region. Furthermore, we found that IGF-I transiently increased phosphorylation of neuronal PDK-1, resulting in its translocation to other cellular compartments. Our findings suggest that IGF-I may regulate neuronal PDK-1 differently than in non-neuronal cells, which may indicate a novel role for PDK-1 in IGF-I-mediated neuroprotective signaling.

Research paper thumbnail of Chronic thromboembolic pulmonary hypertension: Experience improves outcomes

Archivos de Bronconeumología

Research paper thumbnail of Short-term clinical outcome of normotensive patients with acute PE and high plasma lactate

Thorax

Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-rel... more Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-related complications remain to be defined. This prospective cohort study aimed to determine the role of plasma lactate levels in the risk assessment of normotensive patients with acute PE. Outcomes assessed over the 7 days after the diagnosis of PE included PE-related mortality and haemodynamic collapse, defined as need for cardiopulmonary resuscitation, systolic blood pressure <90 mm Hg for at least 15 min, need for catecholamine administration, or need for mechanical ventilation. Between December 2012 and January 2014, the study enrolled 496 normotensive outpatients with acute symptomatic PE. PE-related complications occurred in 20 (4.0%; 95% CI 2.5% to 6.2%) of the 496 patients. These patients had higher baseline lactate levels (median 2.66 mmol/L; IQR 1.56-5.96 mmol/L) than patients without complications (1.20 mmol/L; IQR 1.20-2.00 mmol/L) (p<0.001). Overall, 135 patients (27.2%)...

Research paper thumbnail of Embolic burden of incidental pulmonary embolism diagnosed on routinely performed contrast-enhanced CT-imaging in cancer patients

Journal of Thrombosis and Haemostasis

Since the quality of CT-imaging techniques has improved, pulmonary embolism (PE) is increasingly ... more Since the quality of CT-imaging techniques has improved, pulmonary embolism (PE) is increasingly being detected incidentally on routine CT-examinations. In particular in patients with malignancy, who are known to be at elevated risk of developing venous thromboembolic events (VTE), and who frequently undergo CT scanning for reasons as diagnosing, staging and treatment evaluation, incidental PE has become a relative common finding [1]. This article is protected by copyright. All rights reserved.

Research paper thumbnail of Computerised clinical decision support for suspected PE

Thorax

This study aimed to determine the effect of an evidence-based clinical decision support (CDS) alg... more This study aimed to determine the effect of an evidence-based clinical decision support (CDS) algorithm on the use and yield of CT pulmonary angiography (CTPA) and on outcomes of patients evaluated in the emergency department (ED) for suspected PE. The study included 1363 consecutive patients evaluated for suspected PE in an ED during 12 months before and 12 months after initiation of CDS use. Introduction of CDS was associated with decreased CTPA use (55% vs 49%; absolute difference (AD), 6.3%; 95% CI 1.0% to 11.6%; p=0.02). The use of CDS was associated with fewer symptomatic venous thromboembolic events during follow-up in patients with an initial negative diagnostic evaluation for PE (0.7% vs 3.2%; AD 2.5%; 95% CI 0.9% to 4.6%; p<0.01). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Research paper thumbnail of Trends in hospital admissions for pulmonary embolism in Spain from 2002 to 2011

European Respiratory Journal

The aim of our study was to analyse changes in the incidence, diagnostic procedures, comorbidity,... more The aim of our study was to analyse changes in the incidence, diagnostic procedures, comorbidity, length of hospital stay, costs and in-hospital mortality of patients hospitalised for pulmonary embolism in Spain over a 10-year period. We included all patients who were hospitalised for pulmonary embolism (ICD-9-CM codes 415.11 and 415.19) as the primary diagnosis between 2002 and 2011. Data were collected from the National Hospital Discharge Database, covering the entire Spanish population. 115 671 patients were admitted. The overall crude incidence increased from 20.44 per 100 000 inhabitants in 2002 to 32.69 in 2011 (p<0.05). In 2002, 13.3% of patients had a Charlson comorbidity index >2, and in 2011 the prevalence increased to 20.8% (p<0.05). Mean length of hospital stay was 12.7 days in 2002 and decreased to 9.99 in 2011 (p<0.05). During the study period, mean cost per patient increased from €3915 to €4372 (p<0.05). In-hospital mortality decreased from 12.9% in 200...

Research paper thumbnail of Huntington's disease: confirmation of diagnosis and presymptomatic testing in Spanish families by genetic analysis

Journal of Neurology Neurosurgery and Psychiatry, 1996

Huntington's disease is a neuropsychiatric disorder with late age of onset, caused by an elon... more Huntington's disease is a neuropsychiatric disorder with late age of onset, caused by an elongation of a (CAG)n repeat in the IT15 gene. This trinucleotide repeat has been studied by polymerase chain reaction amplification in 86 members of 43 Spanish families with Huntington's disease and in 60 unrelated subjects from the general population. The number of (CAG)n repeats in Huntington's

Research paper thumbnail of Zoledronic acid therapy for recurrent giant cell tumor of the C2 vertebra in an adolescent

The spine journal : official journal of the North American Spine Society, Jan 25, 2015

Research paper thumbnail of Comments on the 2014 ESC Guidelines on the diagnosis and management of hypertrophic cardiomyopathy. A critical view from the perspective of Spanish cardiology

Revista española de cardiología (English ed.), 2015

Grupo de Trabajo de la SEC para la guía de la ESC 2014 sobre diagnóstico y tratamiento de la pato... more Grupo de Trabajo de la SEC para la guía de la ESC 2014 sobre diagnóstico y tratamiento de la patología de la aorta , , revisores expertos para la guía de la ESC 2014 sobre diagnóstico y tratamiento de la patología de la aorta, Comité de Guías de la SEC ◊ VÉASE CONTENIDO RELACIONADO: http://dx.

Research paper thumbnail of ChemInform Abstract: First Synthesis of the Antifungal Oidiolactone C from trans-Communic Acid: Cytotoxic and Antimicrobial Activity in Podolactone-Related Compounds

ChemInform, 2002

The synthesis of the fungicide oidiolactone C starting from diterpenic trans-communic acid was ca... more The synthesis of the fungicide oidiolactone C starting from diterpenic trans-communic acid was carried out with an overall yield of 11.7%. The key step in the process consists of a new bislactonization reaction catalyzed by Pd(II), which gives rise to the podolactone-type tetracyclic skeleton from a norlabdadienedioic acid. We also carried out a study of the structure-biological activity of different natural podolactones and their synthetic precursors. Thus, the highest cytotoxic activity was found in dienic dilactones with ether-type substitutions on C-17, whereas the closure of the γ-lactone ring is not critical for presenting a maximal antimicrobial activity.

Research paper thumbnail of Abdominal pseudocyst complicating incisional hernia repair: our experience and literature review

Hernia, 2010

Giant pseudocyst is a rare complication of incisional hernia repairs whose etiology and incidence... more Giant pseudocyst is a rare complication of incisional hernia repairs whose etiology and incidence remains unknown. We have reviewed all cases of abdominal incisional hernia repair in our abdominal wall unit since its creation 6 years ago. Pseudocyst formation was observed in seven cases out of 871 incisional hernia repair operations. Four of them underwent surgical exploration with excision of the mass. To the best of our knowledge, only 18 cases of giant pseudocyst have been described in the literature. From both our personal experience and the reported literature, we understand that abdominal pseudocyst is an extremely rare or underreported late complication of hernia repair surgery. The complete excision of the cyst and its fibrous wall is the definitive treatment of choice.

Research paper thumbnail of Contribution of N-linked glycans to the conformation and function of intercellular adhesion molecules (ICAMs)

The Journal of biological chemistry, Jan 18, 2005

The crystal structures of the glycosylated N-terminal two domains of ICAM-1 and ICAM-2 provided a... more The crystal structures of the glycosylated N-terminal two domains of ICAM-1 and ICAM-2 provided a framework for understanding the role of glycosylation in the structure and function of intercellular adhesion molecules (ICAMs). The most conserved glycans were less flexible in the structures, interacting with protein residues and contributing to receptor folding and expression. The first N-linked glycan in ICAM-2 contacts an exposed tryptophan residue, defining a conserved glycan-W motif critical for the conformation of the integrin binding domain. The absence of this motif in human ICAM-1 exposes regions used in receptor dimerization and rhinovirus recognition. Experiments with soluble molecules having the N-terminal two domains of human ICAMs identified glycans of the high mannose type N-linked to the second domain of the dendritic cell-specific ICAM-grabbing nonintegrin lectin-ligands ICAM-2 and ICAM-3. About 40% of those receptor molecules bear endoglycosidase H sensitive glycans ...

Research paper thumbnail of Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism

Thrombosis and haemostasis, 2013

In patients with venous thromboembolism (VTE), assessment of the risk of fatal recurrent VTE and ... more In patients with venous thromboembolism (VTE), assessment of the risk of fatal recurrent VTE and fatal bleeding during anticoagulation may help to guide intensity and duration of therapy. We aimed to provide estimates of the case-fatality rate (CFR) of recurrent VTE and major bleeding during anticoagulation in a 'real life' population, and to assess these outcomes according to the initial presentation of VTE and its etiology. The study included 41,826 patients with confirmed VTE from the RIETE registry who received different durations of anticoagulation (mean 7.8 ± 0.6 months). During 27,110 patient-years, the CFR was 12.1% (95% CI, 10.2-14.2) for recurrent VTE, and 19.7% (95% CI, 17.4-22.1) for major bleeding. During the first three months of anticoagulant therapy, the CFR of recurrent VTE was 16.1% (95% CI, 13.6-18.9), compared to 2.0% (95% CI, 0-4.2) beyond this period. The CFR of bleeding was 20.2% (95% CI, 17.5-23.1) during the first three months, compared to 18.2% (95%...

Research paper thumbnail of Rivaroxaban in the Treatment of Venous Thromboembolism and the Prevention of Recurrences: A Practical Approach

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, Jan 9, 2014

Anticoagulation therapy is the standard treatment of patients with symptomatic venous thromboembo... more Anticoagulation therapy is the standard treatment of patients with symptomatic venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Until recently, treatment of VTE was based on parenteral or low-molecular-weight heparin for initial therapy (5-10 days) and oral vitamin K antagonists for long-term therapy. Those treatments have some limitations, including parenteral administration (heparins), the need for frequent monitoring and dose adjustments, interactions with several medications, and dietary restrictions (vitamin K antagonists). Rivaroxaban is a new oral direct factor Xa inhibitor with a wide therapeutic window, predictable anticoagulant effect, no food interactions, and few drug interactions. Consequently, no periodic monitoring of anticoagulation is needed, and fixed doses can be prescribed. EINSTEIN program demonstrated that rivaroxaban was as effective as and significantly safer than standard therapy for treatment of VTE. Rivaroxaban was recen...

Research paper thumbnail of Age-adjusted hsTnT cut-off value for risk stratification of pulmonary embolism

The European respiratory journal, Jan 22, 2015

High-sensitivity troponin T (hsTnT) helps in identifying pulmonary embolism patients at low risk ... more High-sensitivity troponin T (hsTnT) helps in identifying pulmonary embolism patients at low risk of an adverse outcome. In 682 normotensive pulmonary embolism patients we investigate whether an optimised hsTnT cut-off value and adjustment for age improve the identification of patients at elevated risk. Overall, 25 (3.7%) patients had an adverse 30-day outcome. The established hsTnT cut-off value of 14 pg·mL(-1) retained its high prognostic value (OR (95% CI) 16.64 (2.24-123.74); p=0.006) compared with the cut-off value of 33 pg·mL(-1) calculated by receiver operating characteristic analysis (7.14 (2.64-19.26); p<0.001). In elderly (aged ⩾75 years) patients, an age-optimised hsTnT cut-off value of 45 pg·mL(-1) but not the established cut-off value of 14 pg·mL(-1) predicted an adverse outcome. An age-adjusted hsTnT cut-off value (⩾14 pg·mL(-1) for patients aged <75 years and ⩾45 pg·mL(-1) for patients aged ⩾75 years) provided additive and independent prognostic information on to...

Research paper thumbnail of Short-term clinical outcome of normotensive patients with acute PE and high plasma lactate

Thorax, Jan 6, 2015

Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-rel... more Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-related complications remain to be defined. This prospective cohort study aimed to determine the role of plasma lactate levels in the risk assessment of normotensive patients with acute PE. Outcomes assessed over the 7 days after the diagnosis of PE included PE-related mortality and haemodynamic collapse, defined as need for cardiopulmonary resuscitation, systolic blood pressure <90 mm Hg for at least 15 min, need for catecholamine administration, or need for mechanical ventilation. Between December 2012 and January 2014, the study enrolled 496 normotensive outpatients with acute symptomatic PE. PE-related complications occurred in 20 (4.0%; 95% CI 2.5% to 6.2%) of the 496 patients. These patients had higher baseline lactate levels (median 2.66 mmol/L; IQR 1.56-5.96 mmol/L) than patients without complications (1.20 mmol/L; IQR 1.20-2.00 mmol/L) (p<0.001). Overall, 135 patients (27.2%)...

Research paper thumbnail of Temporal Differences in MicroRNA Expression Patterns in Astrocytes and Neurons after Ischemic Injury

PLOS One, 2011

MicroRNAs (miRNAs) are small, non-protein-coding RNA molecules that modulate gene translation. Th... more MicroRNAs (miRNAs) are small, non-protein-coding RNA molecules that modulate gene translation. Their expression is altered in many central nervous system (CNS) injuries suggesting a role in the cellular response to stress. Current studies in brain tissue have not yet described the cell-specific temporal miRNA expression patterns following ischemic injury. In this study, we analyzed the expression alterations of a set

Research paper thumbnail of Novedades en la enfermedad tromboembólica venosa

Revista Clínica Española, 2012

This paper brings together the latest developments that have occurred in different aspects of ven... more This paper brings together the latest developments that have occurred in different aspects of venous thromboembolism (VTE): VTE prophylaxis in high-risk orthopedic surgery and acutely ill hospitalized medical patients; therapeutic advances in pulmonary embolism and superficial vein thrombosis and VTE future prospects. It summarizes the reviews that five speakers made in-depth for the Second Day in New Anticoagulant Treatment, held in Madrid on November 18, 2011, organized by the Foundation for the Study of Thromboembolic Disease in Spain and endorsed by the Spanish Society of Internal Medicine, Spanish Society of Pneumology and Thoracic Surgery, Spanish Society of Cardiology, Spanish Society of Thrombosis and Haemostasis and the Spanish Society of Angiology and Vascular Surgery.

Research paper thumbnail of Does progesterone show neuroprotective effects on traumatic brain injury through increasing phosphorylation of Akt in the hippocampus?

Neural Regeneration Research, 2014

Research paper thumbnail of Computerised clinical decision support for suspected PE

Thorax, 2015

This study aimed to determine the effect of an evidence-based clinical decision support (CDS) alg... more This study aimed to determine the effect of an evidence-based clinical decision support (CDS) algorithm on the use and yield of CT pulmonary angiography (CTPA) and on outcomes of patients evaluated in the emergency department (ED) for suspected PE. The study included 1363 consecutive patients evaluated for suspected PE in an ED during 12 months before and 12 months after initiation of CDS use. Introduction of CDS was associated with decreased CTPA use (55% vs 49%; absolute difference (AD), 6.3%; 95% CI 1.0% to 11.6%; p=0.02). The use of CDS was associated with fewer symptomatic venous thromboembolic events during follow-up in patients with an initial negative diagnostic evaluation for PE (0.7% vs 3.2%; AD 2.5%; 95% CI 0.9% to 4.6%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01).