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"Luján, Juan"
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P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis
2019
Sepsis is characterized by a systemic inflammatory response followed by immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with sepsis. The NLRP3 inflammasome is important for establishing an inflammatory response after activation by the purinergic P2X7 receptor. Here, we study a cohort of individuals with intra-abdominal origin sepsis and show that patient monocytes have impaired NLRP3 activation by the P2X7 receptor. Furthermore, most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered. In monocytes from sepsis patients, the P2X7 receptor is associated with mitochondrial dysfunction. Furthermore, activation of the P2X7 receptor results in mitochondrial damage, which in turn inhibits NLRP3 activation by HIF-1α. We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection.
Systemic sepsis is a potentially life-threatening illness and immunocompromised individuals are especially vulnerable. Here, using a cohort of patients with intra-abdominal origin sepsis, the authors show an important role for the NLRP3 inflammasome in establishing a host response, and NLRP3 dysfunction is a common feature of sepsis mortality.
Journal Article
A Transfer Learning Method for Pneumonia Classification and Visualization
by
Yáñez-Márquez, Cornelio
,
Luján-García, Juan
,
Villuendas-Rey, Yenny
in
Automation
,
Classification
,
convolutional
2020
Pneumonia is an infectious disease that affects the lungs and is one of the principal causes of death in children under five years old. The Chest X-ray images technique is one of the most used for diagnosing pneumonia. Several Machine Learning algorithms have been successfully used in order to provide computer-aided diagnosis by automatic classification of medical images. For its remarkable results, the Convolutional Neural Networks (models based on Deep Learning) that are widely used in Computer Vision tasks, such as classification of injuries and brain abnormalities, among others, stand out. In this paper, we present a transfer learning method that automatically classifies between 3883 chest X-ray images characterized as depicting pneumonia and 1349 labeled as normal. The proposed method uses the Xception Network pre-trained weights on ImageNet as an initialization. Our model is competitive with respect to state-of-the-art proposals. To make comparisons with other models, we have used four well-known performance measures, obtaining the following results: precision (0.84), recall (0.99), F1-score (0.91) and area under the ROC curve (0.97). These positive results allow us to consider our proposal as an alternative that can be useful in countries with a lack of equipment and specialized radiologists.
Journal Article
Glucocorticoids Affect 24 h Clock Genes Expression in Human Adipose Tissue Explant Cultures
by
Foulkes, Nicholas S
,
Garaulet, Marta
,
Luján, Juan A
in
Abdomen
,
Adipose tissue
,
Adipose Tissue - drug effects
2012
to examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock genes expression. VAT and SAT biopsies were obtained from morbid obese women (body mass index≥40 kg/m 2) (n = 6). In order to investigate rhythmic expression pattern of clock genes and the effect of DEX on CLOCK , PER2 and BMAL1 expression, control AT (without DEX) and AT explants treated with DEX (2 hours) were cultured during 24 h and gene expression was analyzed at the following times: 10:00 h, 14:00 h, 18:00 h, 22:00 h, 02:00 h and 06:00 h, using qRT-PCR. CLOCK , BMAL1 and PER2 expression exhibited circadian patterns in both VAT and SAT explants that were adjusted to a typical 24 h sinusoidal curve. PER2 expression (negative element) was in antiphase with respect to CLOCK and in phase with BMAL1 expression (both positive elements) in the SAT (situation not present in VAT). A marked effect of DEX exposure on both positive and negative clock genes expression patterns was observed. Indeed, DEX treatment modified the rhythmicity pattern towards altered patterns with a period lower than 24 hours in all genes and in both tissues. 24 h patterns in CLOCK and BMAL1 (positive clock elements) and PER2 (negative element) mRNA levels were observed in human adipose explants. These patterns were altered by dexamethasone exposure.
Journal Article
Isoperistaltic versus antiperistaltic ileocolic anastomosis. Does it really matter? Results from a randomised clinical trial (ISOVANTI)
by
Rufete, María Dolores
,
Abrisqueta, Jesús
,
Parrilla, Pascual
in
Clinical trials
,
Colorectal cancer
,
Laparoscopy
2019
BackgroundRight hemicolectomy is a very common surgery. Many studies compare different options for laparoscopic ileocolic anastomoses: intra- or extracorporeal; handsewn or stapled; side-to-side or end-to-side. However, there are no studies about the influence that peristalsis could have on this anastomosis. The aim of this study is to compare safety and feasibility of isoperistaltic and antiperistaltic anastomosis in terms of postoperative morbidity and mortality between both groups. The secondary endpoint is to compare long-term functional outcomes (chronic diarrhoea) and quality of life (GIQLI questionnaire) after a 1-year follow-up period.MethodsA double-blind, randomised, prospective trial in patients undergoing scheduled surgery for right colon cancer with laparoscopic right hemicolectomy and isoperistaltic (ISO) or antiperistaltic (ANTI) ileocolic anastomoses.ResultsHundred and eight patients were included in the study. Patients were randomised either to isoperistaltic or antiperistaltic configuration (54 ISO/ANTI). No significant differences in baseline variables were found. No differences in surgical time (130 [120–150] min ISO vs. 140 [127–160] ANTI, p = 0.481), nor in anastomotic time (19 [17–22] vs. 20 [16–25], p = 0.207) and nor in postoperative complications: 37.0% ISO versus 40.7% ANTI, (p = 0.693) were found. There were no differences in postoperative ileus (p = 0.112) nor in anastomotic leakage (3.7% vs. 5.56%, p = 1.00). Differences in “time to first flatus” and “time to first deposition” were found in favour of the antiperistaltic group (p = 0.004 and p = 0.017). Anastomotic configuration did not influence hospital stay (3 days [2–6] isoperistaltic vs. 3 [2–4] antiperistaltic, p = 0.236). During follow-up, there were no differences between the two groups at 1, 6 and 12 months (p = 0.154, p = 0.498 and p = 0.683), nor in chronic diarrhoea rates in GIQLI scores (24% ISO vs. 31.4% ANTI, p = 0.541).ConclusionsThe isoperistaltic and antiperistaltic ileocolic anastomosis present similar results in terms of performance, safety and functionality. However, further studies must be carried out in order to assess relationship between postoperative ileus and anastomosis configuration.Trial registrationRandomised Clinical trial (Identifier: NCT02309931).
Journal Article
Full Laparoscopic Vascular Reconstruction for Portal Tumoral Invasion During a Right Hepatectomy Using the Caudal Approach
2022
BackgroundLaparoscopic liver surgery has progressively evolved. Consequently, liver procedures are increasingly performed laparoscopically, particularly in experienced centers. However, vascular resection and reconstruction still are considered a limitation for laparoscopy1 due to the risk of bleeding and the technical difficulty.MethodsA 72-year-old woman with a history of colorectal cancer had a 10 cm metastasis diagnosed in the right hemiliver with tumoral invasion of the right portal branch and tumor thrombus advancing to the portal confluence. After adjuvant chemotherapy and with stable disease, surgical resection was planned.2,3 Tips to avoid portal stenosis were carefully followed.ResultsThe operation was performed with a fully laparoscopic procedure. To minimize manipulation, an in situ right hepatectomy was performed.4 The right hepatic artery was dissected and ligated. The liver transection was guided with a caudal approach of the middle hepatic vein.5 The right biliary duct was then divided, achieving an excellent exposure of the portal bifurcation. The main and left portal trunks were occluded with vascular clamps, and the right portal vein was sharply divided with scissors. The stump was sutured to minimize backflow bleeding and to cover the tumor thrombus. Then, the portal opening was transversally sutured with a 5/0 running suture. The clamps were released, and the authors observed no bleeding and an adequate caliber with no stenosis. The procedure was completed in the standard fashion. The postoperative course was uneventful, and the woman was discharged on postoperative day 3. No early or late complications were observed.6ConclusionsIn selected cases, patients who require vascular resection and reconstruction during hepatectomies can benefit from the advantages of a laparoscopic approach.
Journal Article
Circadian transcriptome oscillations in human adipose tissue depend on napping status and link to metabolic and inflammatory pathways
by
Pérez-Sanz, Fernando
,
Scheer, Frank A J L
,
Zambrano, Carolina
in
Adipose Tissue - metabolism
,
Adipose tissues
,
Adult
2024
Abstract
Study Objectives
Napping is a common habit in many countries. Nevertheless, studies about the chronic effects of napping on obesity are contradictory, and the molecular link between napping and metabolic alterations has yet to be studied. We aim to identify molecular mechanisms in adipose tissue (AT) that may connect napping and abdominal obesity.
Methods
In this cross-sectional study, we extracted the RNA repeatedly across 24 hours from cultured AT explants and performed RNA sequencing. Circadian rhythms were analyzed using six consecutive time points across 24 hours. We also assessed global gene expression in each group (nappers vs. non-nappers).
Results
With napping, there was an 88% decrease in the number of rhythmic genes compared to that in non-nappers, a reduction in rhythm amplitudes of 29%, and significant phase changes from a coherent unimodal acrophase in non-nappers, towards a scattered and bimodal acrophase in nappers. Those genes that lost rhythmicity with napping were mainly involved in pathways of glucose and lipid metabolism, and of the circadian clock. Additionally, we found differential global gene expression between nappers and non-nappers with 34 genes down- and 32 genes upregulated in nappers. The top upregulated gene (IER3) and top down-regulated pseudogene (VDAC2P2) in nappers have been previously shown to be involved in inflammation.
Conclusions
These new findings have implications for our understanding of napping’s relationship with obesity and metabolic disorders.
Graphical Abstract
Graphical Abstract
Journal Article
Facing Fear and Embracing Safety: Validation of the COVID-19 Psychosocial Scales in Essential Frontline Workers During the Pandemic
by
Llorens, Susana
,
Salanova, Marisa
,
Umbert, Israel
in
Adult
,
COVID-19 - prevention & control
,
COVID-19 - psychology
2024
Background:: The study has two main aims: (1) to analyze and validate the factor structure of the Fear of COVID-19, Workplace health and safety training, and Behavioral Safety Compliance scales (Study 1) in frontline Spanish COVID-19 workers from different sectors (food sector, hospitals, and death care services); and (2) to analyze and validate the factor structure of a reduced version of these scales (Study 2) in Spanish workers in the healthcare sector. Method:: Analyses carried out using R 1.4.2. allowed us to validate the factor structure of the scales in the two studies. The sample consisted of 361 participants in study 1; and 708 participants in study 2. Results:: The results indicate that the instruments offer adequate evidence of reliability and validity. Conclusions:: The questionnaire (especially the short version) can be used by employees who were in frontline of COVID-19 in a reliable and valid way in the post-COVID-19 period, and even to prevent potential similar events that might threaten professionals’ physical and mental health in the future.
Journal Article
Circadian Rhythms in Hormone-sensitive Lipase in Human Adipose Tissue: Relationship to Meal Timing and Fasting Duration
by
Hu, Kun
,
Sánchez de Medina, Fermín
,
Scheer, Frank A J L
in
Adipose tissue
,
Adipose Tissue - metabolism
,
Adipose tissues
2020
Abstract
Background
Fat mobilization in adipose tissue (AT) has a specific timing. However, circadian rhythms in the activity of the major enzyme responsible for fat mobilization, hormone-sensitive lipase (HSL), have not been demonstrated in humans.
Objective
To analyze in a cross-sectional study whether there is an endogenous circadian rhythm in HSL activity in human AT ex vivo and whether rhythm characteristics are related to food timing or fasting duration.
Methods
Abdominal AT biopsies were obtained from 18 severely obese participants (age: 46 ± 11 years; body mass index 42 ± 6 kg/m2) who underwent laparoscopic gastric bypass. Twenty-four-hour rhythms of HSL activity and LIPE (HSL transcript in humans) expression in subcutaneous AT were analyzed together with habitual food timing and night fasting duration.
Results
HSL activity exhibited a circadian rhythm (P = .023) and reached the maximum value at circadian time 16 (CT) that corresponded to around midnight (relative local clock time. Similarly, LIPE displayed a circadian rhythm with acrophase also at night (P = .0002). Participants with longer night fasting duration >11.20 hours displayed almost double the amplitude (1.91 times) in HSL activity rhythm than those with short duration (P = .013); while habitual early diners (before 21:52 hours) had 1.60 times higher amplitude than late diners (P = .035).
Conclusions
Our results demonstrate circadian rhythms in HSL activity and may lead to a better understanding of the intricate relationships between food timing, fasting duration and body fat regulation.
Journal Article
Perspectivas y desafíos de las gerencias deportivas: un análisis sistemático
by
Armendáriz Erives, Camila Sofía
,
Quintana Arroyo, Pedro
,
Ramírez-Enríquez, Silvia Isela
in
administración comparativa
,
comparative management
,
eficiencia operativa
2024
El objetivo del estudio fue identificar, analizar y comparar la estructura organizativa, la gestión y el desempeño de las organizaciones deportivas de distintos países. Se realizó una revisión sistemática en bases de datos reconocidas. Se incluyeron documentos sobre gestión deportiva, de cualquier año, en español o inglés, de acceso abierto, y que utilizaran algún instrumento de medición o técnica para valorar la gerencia deportiva. Se encontraron 161 documentos, de los cuales se descartaron 130 y se analizó la información de 10 documentos. Los resultados muestran que hay diferencias en la gestión del deporte en diferentes países, pero también similitudes en los más profesionalizados. Lo analizado sugiere reforzar los procesos administrativos, contar con herramientas de evaluación continua y adoptar estrategias para cada realidad.
Journal Article