Oxidative Stress and Mitochondrial Functions in the Intestinal Caco-2/15 Cell Line

Although mitochondrial dysfunction and oxidative stress are central mechanisms in various pathological conditions, they have not been extensively studied in the gastrointestinal tract, which is known to be constantly exposed to luminal oxidants from ingested foods. Key among these is the simultaneous consumption of iron salts and ascorbic acid, which can cause oxidative damage to biomolecules.The objective of the present work was to evaluate how iron-ascorbate (FE/ASC)-mediated lipid peroxidation affects mitochondrion functioning in Caco-2/15 cells. Our results show that treatment of Caco-2/15 cells with FE/ASC (0.2 mM/2 mM) (1) increased malondialdehyde levels assessed by HPLC; (2) reduced ATP production noted by luminescence assay; (3) provoked dysregulation of mitochondrial calcium homeostasis as evidenced by confocal fluorescence microscopy; (4) upregulated the protein expression of cytochrome C and apoptotic inducing factor, indicating exaggerated apoptosis; (5) affected mitochondrial respiratory chain complexes I, II, III and IV; (6) elicited mtDNA lesions as illustrated by the raised levels of 8-OHdG; (7) lowered DNA glycosylase, one of the first lines of defense against 8-OHdG mutagenicity; and (8) altered the gene expression and protein mass of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2) without any effects on RNA Polymerase. The presence of the powerful antioxidant BHT (50 microM) prevented the occurrence of oxidative stress and most of the mitochondrial abnormalities.Collectively, our findings indicate that acute exposure of Caco-2/15 cells to FE/ASC-catalyzed peroxidation produces harmful effects on mitochondrial functions and DNA integrity, which are abrogated by the powerful exogenous BHT antioxidant. Functional derangements of mitochondria may have implications in oxidative stress-related disorders such as inflammatory bowel diseases

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

PSYCHOLOGICAL-FACTORS INFLUENCING THE SURGICAL PATIENTS CONSENT TO REGIONAL ANESTHESIA

To investigate the preoperative attitude of surgical patients to regional anaesthesia, 162 subjects scheduled for elective surgery were studied. On the day before operation, patients were interviewed by an anaesthesiologist, using a semi-structured schedule. Topics investigated were sociodemographic variables and clinical correlates, such as past anaesthetic experience, information about anaesthesia and surgery, as well as questions and Fears related to anaesthesia. Subjects were assessed for personality characteristics and emotional symptoms by Eysenck’s Personality Questionnaire (EPQ), Zung’s Self-rating Anxiety and Depression Rating Scales, Schalling-Sifneos’ Personality Scale and the 43-item Life Events Inventory of Holmes and Rahe. Seventy-one patients (44%) consented to regional anaesthesia. Consent to regional anaesthesia was associated with advanced age, low neuroticism and high extroversion score in the EPQ, as well as longer duration of illness. The deniers of consent asked more questions and expressed more fears about anaesthesia. It is suggested that the patients’ characteristics influence their preference, acceptance or refusal of regional anaesthesia

Preferences for shared decision making in chronic pain patients compared with patients during a premedication visit.

Contains fulltext : 49583.pdf (publisher's version ) (Closed access)BACKGROUND: There is some evidence that patients' outcomes improve if they are involved in shared decision making (SDM). A chronic pain clinic or premedication visit could be adequate settings for the implementation of SDM. So far, the patients' preference for involvement in decision making and their desire for information have not been tested in anesthesiological settings. METHODS: A group of chronic pain patients was compared with a group of patients in the premedication visit with respect to SDM, the desire for information and perceived involvement in care. The autonomy preference index (API, measuring preference for involvement and desire for information) and the perceived involvement in care scale (PICS, measuring patients' perception of easier involvement by doctors and information exchange) were administered. RESULTS: In total, 190 chronic pain patients and 151 patients of premedication were included in this study. Patient of the premedication visit had significantly higher SDM scores. Desire for information was high, but there were no differences between groups. Younger patients [B (estimate) =- 0.3; 95% CI (-0.4) - (-0.1)], women (B = 10.9; 95% CI 6.3-15.4) and patients with higher educational level (B = 10.1; 95% CI 5.6-14.6) had more desire for SDM. PICS scores were basically influenced by groups: chronic pain patients felt more facilitated by doctors [B =- 0.185; 95% CI (-0.4) - (-0.1)] and had more information exchange [B =- 19.5; 95% CI (-15.8) - (-2.4)] than patients in the premedication visit. CONCLUSION: In both anesthesiological settings, the desire for information was high, but patients in the premedication visit had higher SDM scores, especially young female patients with higher educational level. Real patient-physician interaction showed that premedication patients felt less involved by doctors and had less information exchange compared with the chronic pain patients. Therefore, premedication visits should be focussed more on adequate information exchange and involvement of the patient in the shared decision making process

Strength and directionality of surface Ruderman-Kittel-Kasuya-Yosida interaction mapped on the atomic scale

Ruderman-Kittel-Kasuya-Yosida interaction(1-3) is an indirect magnetic coupling between localized spins in a non-magnetic host mediated by conduction electrons. In diluted systems it is often the dominating magnetic interaction and has played a key part in the development of giant magnetoresistance devices(4,5), drives ferromagnetism in heavy rare-earth elements(6) aswell as in diluted magnetic semiconductors(7) and gives rise to complex magnetic phases such as spin glasses(8). For bulk systems, an isotropic and continuous model of Ruderman-Kittel-Kasuya Yosida interaction is often sufficient. However, it can be misleading in magnetic nanostructures consisting of separate magnetic atoms adsorbed on the surface of a non-magnetic material. Here, an atomically precise map of the magnetic coupling between individual adatoms in pairs is measured and directly compared with first-principles calculations, proving that Ruderman Kittel-Kasuya-Yosida interaction is strongly directional. By investigating adatomtriplets of different shapes we demonstrate that the map can serve to tailor the magnetism of larger nanostructures