Capsules hélicoïdales auto-organisées par repliement d'oligoamides aromatiques pour la reconnaissance moléculaire

La reconnaissance moléculaire constitue l une des questions fondamentales les plus discutées dans le domaine de la chimie supramoléculaire. Cette thèse présente la conception, la synthèse et l étude des propriétés de capsules hélicoïdales auto-organisées par repliement d oligoamides aromatiques. Ces récepteurs sont constitués d une chaîne oligomérique se repliant en hélice et comprenant une séquence d unités codant pour des diamètres différents. Le repliement de l oligomère donne naissance à une cavité pouvant accueillir des molécules invitées. La grande modularité des séquences, permettant une évolution contrôlée des structures des foldamères, donne lieu à la reconnaissance sélective et anticipée de substrats d intérêts biologiques. Le phénomène d encapsulation a été mis en évidence en solution par spectroscopie RMN et CD, et dans le solide par diffraction des rayons X.Molecular recognition is one of the major challenges of supramolecular chemistry. Here, we present the design, synthesis and study of helical capsules properties self-organised by aromatic oligoamide folding. These receptors consist of oligomeric chains that fold into a helical conformation and comprise of a sequence of units which code for different diameters. Oligomeric folding defines a cavity which can recognize guests. The great modularity of the sequences has allowed a controlled evolution of foldamer structure resulting in the selective and predict recognition of biological substrates. The phenomenon of encapsulation was demonstrated in solution by NMR and CD spectroscopy and in the solid state by X-ray diffraction.BORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF

Detection of decreased glomerular filtration rate in intensive care units: serum cystatin C versus serum creatinine

Peer reviewe

Multiple-center evaluation of mortality associated with acute kidney injury in critically ill patients: a competing risks analysis

International audienceINTRODUCTION: In this study, we aimed to assess the association between acute kidney injury (AKI) and mortality in critically ill patients using an original competing risks approach. METHODS: Unselected patients admitted between 1997 and 2009 to 13 French medical or surgical intensive care units were included in this observational cohort study. AKI was defined according to the RIFLE criteria. The following data were recorded: baseline characteristics, daily serum creatinine level, daily Sequential Organ Failure Assessment (SOFA) score, vital status at hospital discharge and length of hospital stay. Patients were classified according to the maximum RIFLE class reached during their ICU stay. The association of AKI with hospital mortality with "discharge alive" considered as a competing event was assessed according to the Fine and Gray model. RESULTS: Of the 8,639 study patients, 32.9% had AKI, of whom 19.1% received renal replacement therapy. Patients with AKI had higher crude mortality rates and longer lengths of hospital stay than patients without AKI. In the Fine and Gray model, independent risk factors for hospital mortality were the RIFLE classes Risk (sub-hazard ratio (SHR) 1.58 and 95% confidence interval (95% CI) 1.32 to 1.88; P < 0.0001), Injury (SHR 3.99 and 95% CI 3.43 to 4.65; P < 0.0001) and Failure (SHR 4.12 and 95% CI 3.55 to 4.79; P < 0.0001); nonrenal SOFA score (SHR 1.19 per point and 95% CI 1.18 to 1.21; P < 0.0001); McCabe class 3 (SHR 2.71 and 95% CI 2.34 to 3.15; P < 0.0001); and respiratory failure (SHR 3.08 and 95% CI 1.36 to 7.01; P < 0.01). CONCLUSIONS: By using a competing risks approach, we confirm in this study that AKI affecting critically ill patients is associated with increased in-hospital mortality

Family members’ experiences of “wait and see” as a communication strategy in end-of-life decisions

The aim of this study is to examine family members’ experiences of end-of-life decision-making processes in Norwegian intensive care units (ICUs) to ascertain the degree to which they felt included in the decision-making process and whether they received necessary information. Were they asked about the patient’s preferences, and how did they view their role as family members in the decision-making process? A constructivist interpretive approach to the grounded theory method of qualitative research was employed with interviews of 27 bereaved family members of former ICU patients 3–12 months after the patient’s death. The core finding is that relatives want a more active role in end-of-life decision-making in order to communicate the patient’s wishes. However, many consider their role to be unclear, and few study participants experienced shared decision-making. The clinician’s expression “wait and see” hides and delays the communication of honest and clear information. When physicians finally address their decision, there is no time for family participation. Our results also indicate that nurses should be more involved in family–physician communication. Families are uncertain whether or how they can participate in the decision-making process. They need unambiguous communication and honest information to be able to take part in the decision-making process. We suggest that clinicians in Norwegian ICUs need more training in the knowledge and skills of effective communication with families of dying patients

Intensive care bereavement practices across New Zealand and Australian intensive care units: a qualitative content analysis.

BACKGROUND: End-of-life and bereavement care is an important consideration in intensive care. This study describes the type of bereavement care provided in intensive care units across Australia and New Zealand. DESIGN: Inductive qualitative content analysis was conducted on free-text responses to a web-based survey exploring unit-based bereavement practice distributed to nurse managers in 229 intensive care units in New Zealand and Australia. RESULTS: A total of 153 (67%) surveys were returned with 68 respondents making free-text responses. Respondents were mainly Australian (n = 54, 85·3%), from the public sector (n = 51, 75%) and holding Nurse Unit Managers/Charge Nurse roles (n = 39, 52·9%). From the 124 free-text responses, a total of 187 individual codes were identified focussing on bereavement care practices (n = 145, 77·5%), educational provision to support staff (n = 15, 8%) and organisational challenges (n = 27, 14·4%). Bereavement care practices described use of memory boxes, cultural specificity, annual memorial services and use of community support services. Educational provision identified local in-service programmes, and national bereavement courses for specialist bereavement nurse coordinators. Organisational challenges focussed on lack of funding, especially for provision of bereavement follow-up. CONCLUSIONS: This is the first Australasian-wide survey, and one of the few international studies, describing bereavement practices within intensive care, an important aspect of nursing practice. However, with funding for new bereavement services and education for staff lacking, there are continued challenges in developing bereavement care. Given knowledge about the impact of these areas of care on bereaved family members, this requires review. RELEVANCE TO CLINICAL PRACTICE: Nurses remain committed to supporting bereaved families during and following death in intensive care. With limited resource to support bereavement care, intensive care nurses undertake a range of bereavement care practices at time of death, and after death through family bereavement follow-up

Connective tissue growth factor is a new ligand of epidermal growth factor receptor

Chronic kidney disease is reaching epidemic proportions worldwide and there is no effective treatment. Connective tissue growth factor (CCN2) has been suggested as a risk biomarker and a potential therapeutic target for renal diseases, but its specific receptor has not been identified. Epidermal growth factor receptor (EGFR) participates in kidney damage, but whether CCN2 activates the EGFR pathway is unknown. Here, we show that CCN2 is a novel EGFR ligand. CCN2 binding to EGFR extracellular domain was demonstrated by surface plasmon resonance. CCN2 contains four distinct structural modules. The carboxyl-terminal module (CCN2(IV)) showed a clear interaction with soluble EGFR, suggesting that EGFR-binding site is located in this module. Injection of CCN2(IV) in mice increased EGFR phosphorylation in the kidney, mainly in tubular epithelial cells. EGFR kinase inhibition decreased CCN2(IV)-induced renal changes (ERK activation and inflammation). Studies in cultured tubular epithelial cells showed that CCN2(IV) binds to EGFR leading to ERK activation and proinflammatory factors overexpression. CCN2 interacts with the neurotrophin receptor TrkA, and EGFR/TrkA receptor crosstalk was found in response to CCN2(IV) stimulation. Moreover, endogenous CCN2 blockade inhibited TGF-β-induced EGFR activation. These findings indicate that CCN2 is a novel EGFR ligand that contributes to renal damage through EGFR signalling. © 2013 The Author

Psychological response of family members of patients hospitalised for influenza A/H1N1 in Oaxaca, Mexico

<p>Abstract</p> <p>Background</p> <p>The A/H1N1 pandemic originated in Mexico in April 2009, amid high uncertainty, social and economic disruption, and media reports of panic. The aim of this research project was to evaluate the psychological response of family primary caregivers of patients hospitalised in the Intensive Care Unit (ICU) with suspected influenza A/H1N1 to establish whether there was empirical evidence of high adverse psychological response, and to identify risk factors for such a response. If such evidence was found, a secondary aim was to develop a specific early intervention of psychological support for these individuals, to reduce distress and possibly lessen the likelihood of post-traumatic stress disorder (PTSD) in the longer term.</p> <p>Methods</p> <p>Psychological assessment questionnaires were administered to the family primary caregivers of patients hospitalised in the ICU in the General Hospital of Zone 1 of the Mexican Institute for Social Security (IMSS), Oaxaca, Mexico with suspected influenza A/H1N1, during the month of November 2009. The main outcome measures were ratings of reported perceived stress (PSS-10), depression (CES-D), and death anxiety (DAQ). Data were subjected to simple and multiple linear regression analysis to identify risk factors for adverse psychological response.</p> <p>Results</p> <p>Elevated levels of perceived stress and depression, compared to population normative data, and moderate levels of death anxiety were noted. Levels of depression were similar to those found in comparable studies of family members of ICU patients admitted for other conditions. Multiple regression analysis indicated that increasing age and non-spousal family relationship were significantly associated with depression and perceived stress. Female gender, increasing age, and higher levels of education were significantly associated with high death anxiety. Comparisons with data collected in previous studies in the same hospital ICU with groups affected by a range of other medical conditions indicated that the psychological response reported in this study was generally lower.</p> <p>Conclusions</p> <p>Data indicated that, contrary to widely publicised reports of 'panic' surrounding A/H1N1, that some of those most directly affected did not report excessive psychological responses; however, we concluded that there was sufficient evidence to support provision of limited psychological support to family caregivers.</p

Flexible visiting positively impacted on patients, families and staff in an Australian Intensive Care Unit: A before-after mixed method study

Background The admission of a relative to intensive care is stressful for families. To help them support the patient, families need assurance, information and an ability to be near their sick relative. Flexible visiting enables patient access but the impact of this on patients, families and staff is not clear. Objective To assess the impact of flexible visiting from the perspective of patients, families, and Intensive Care Unit (ICU) staff. Methods A before-after mixed method study was used with interviews, focus groups and surveys. Patients were interviewed, family members completed the Family Satisfaction in ICU survey and ICU staff completed a survey and participated in focus groups following the introduction of 21 h per day visiting in a tertiary ICU. The study was conducted within a philosophy of family-centred care. Results All interviewed patients (n = 12) positively evaluated the concept of extended visiting hours. Family members’ (n = 181) overall ‘satisfaction with care’ did not change; however 85% were ‘very satisfied’ with increased visiting flexibility. Seventy-six percent of family visits continued to occur within the previous visiting hours (11 am–8 pm) with the remaining 24% taking place during the newly available visiting hours. Families recognised the priority of patient care with their personal needs being secondary. Three-quarters of ICU staff were ‘satisfied’ with flexible visiting and suggested any barriers could be overcome by role modelling family inclusion. Conclusion Patients, families and ICU staff positively evaluated flexible visiting hours in this ICU. Although only a minority of families took advantage of the increased hours they indicated appreciation for the additional opportunities. Junior staff may benefit from peer-support to develop family inclusion skills. More flexible visiting times can be incorporated into usual ICU practice in a manner that is viewed positively by all stakeholders

Increased Urinary Angiotensin-Converting Enzyme 2 in Renal Transplant Patients with Diabetes

Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n = 100) and healthy controls (age 45 yrs, 26% male, n = 50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p = 0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p = 0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients

Performance of the ROX index to predict intubation in immunocompromised patients receiving high-flow nasal cannula for acute respiratory failure

Background Delayed intubation is associated with high mortality. There is a lack of objective criteria to decide the time of intubation. We assessed a recently described combined oxygenation index (ROX index) to predict intubation in immunocompromised patients. The study is a secondary analysis of randomized trials in immunocompromised patients, including all patients who received high-flow nasal cannula (HFNC). The first objective was to evaluate the accuracy of the ROX index to predict intubation for patients with acute respiratory failure. Results In the study, 302 patients received HFNC. Acute respiratory failure was mostly related to pneumonia (n = 150, 49.7%). Within 2 (1-3) days, 115 (38.1%) patients were intubated. The ICU mortality rate was 27.4% (n = 83). At 6 h, the ROX index was lower for patients who needed intubation compared with those who did not [4.79 (3.69-7.01) vs. 6.10 (4.48-8.68), p < 0.001]. The accuracy of the ROX index to predict intubation was poor [AUC = 0.623 (0.557-0.689)], with low performance using the threshold previously found (4.88). In multivariate analysis, a higher ROX index was still independently associated with a lower intubation rate (OR = 0.89 [0.82-0.96], p = 0.04). Conclusion A ROX index greater than 4.88 appears to have a poor ability to predict intubation in immunocompromised patients with acute respiratory failure, although it remains highly associated with the risk of intubation and may be useful to stratify such risk in future studies