EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Plasma oxytocin levels and anxiety in patients with major depression

Cerebrospinal fluid and plasmatic levels of oxytocin (OT) have been found to change in mood disorders. In post-mortem studies, the numbers of OT-expressing neurons in the paraventricular nucleus have been reported to be increased. Moreover, OT is considered as an endogenous antistress hormone. It has also revealed antidepressive effects. OT may contribute to the dysregulation of the HPA system in major depression. The aim of the study was to assess a possible relationship between anxiety and plasma oxytocin (OT) Levels in depressive patients. Severity of depression was estimated with the Hamilton Depression Rating Scale and anxiety by using the Spielberger State-Anxiety Inventory. Results showed a significant negative correlation between oxytocin and the scored symptoms depression (r = -0.58, p = 0.003) and anxiety (r = -0.61, p = 0.005). (C) 2007 Elsevier Ltd. All rights reserved

Toxicity of a Treatment Associating Dopamine and Disulfiram for Catecholaminergic Neuroblastoma SH-SY5Y Cells: Relationships with 3,4-Dihydroxyphenylacetaldehyde Formation

International audience3,4-Dihydroxyphenylacetaldehyde (DOPAL) is formed by the oxidative deamination of dopamine (DA) catalyzed by monoamine oxidases (MAO); then, the aldehyde is oxidized to 3,4-dihydroxyphenylacetic acid (DOPAC) by aldehyde dehydrogenases (ALDH) or reduced to 3,4-dihydroxyphenylethanol (DOPET) by aldose/aldehyde reductases. The present work aimed at evaluating the in vitro toxicity of DOPAL on catecholaminergic neuroblastoma SH-SY5Y cells which accumulate DA. DOPAL synthesis was stimulated by incubating cells with DA and blocking DOPAL oxidation by disulfiram, an irreversible inhibitor of ALDH. As evidenced by MTT reduction assays, DA and disulfiram treatments produced cell losses which increased with time. 10(-2)M DA reduced by 40% cell viability after a 1h treatment, when its TC(50) (concentration reducing viability by 50%) value was 7.3 x 10(-5) M after a 24 h treatment. For the same treatment periods, TC(50) values for disulfiram were 8 x 10(-5) and 8.7 x 10 (-7) M, respectively. MTT reduction assay performed after a 24h treatment followed by a 24h incubation in a drug-free medium evidenced that the toxicity of 10(-4)M DA or 10(-6)M disulfiram was potentiated by the second drug. HPLC measurements showed that DOPAL was produced at the early stages of the treatment by DA and disulfiram. This was evidenced by the significant increase in the ((DOPAL + DOPET)/DOPAC ratio observed after a combined 3h treatment by 10(-4)M DA and 10(-6)M disulfiram. Total contents in DA and DOPAL were greatly reduced at the end of a 15 h treatment, and disulfiram did not significantly enhanced the (DOPAL + DOPET)/DOPAC ratio. For both treatment durations, DOPAL and DOPET were detectable only in the extracellular medium. So, these results suggest that an early production of DOPAL could produce delayed toxic effects on SH-SY5Y cells. Production of DOPET and release of DOPAL could be important means for reducing DOPAL concentrations in dopaminergic neurons

Correlation Between Microstructure and Ageing of Iron Manganite Thermistors

Negative Temperature Coefficient (NTC) thermistors made of spinel structure transition metal manganites usually display ageing phenomena under thermal stress. Their resistance drift depends on their composition, crystal structure (cubic or tetragonal) and heat treatments. We have previously shown in iron manganite thermistors, Mn$_{3-x}$Fe$_x$O$_4$ (with $0 \leq x \leq 1.51$), that the ageing is due to the migration of Fe$^{3+}$ and Mn$^{2+}$ ions between tetrahedral and octahedral sites of the spinel structure. Iron manganites were investigated by Transmission Electron Microscopy (TEM) in order to relate microstructure to electrical stability. For iron manganites with iron content $x \leq 0.78$, two dimensional defects result in a domain microstructure (microtwins). As $x$ increases and exceeds 0.78, the domain structure gradually vanishes and transforms into a tweed microstructure ($x = 1.05$) and, for $x > 1.30$, no bidimensional defects are observed. Thus it is suggested that the microstructural disturbance plays an important role in the kinetics of the ion migration during the ageing of the studied ceramics.
Les thermistances à Coefficient de Température Négatif (CTN) élaborées à partir de manganites de métaux de transition à structure spinelle présentent, sous contrainte thermique, le phénomène de vieillissement. La dérive de leur résistance dépend de la composition chimique, de la structure cristallographique (cubique ou quadratique) et des traitements thermiques. Précédemment, nous avons montré, pour les thermistances à base de manganites de fer de composition Mn$_{3-x}$Fe$_x$O$_4$ (avec $0 \leq x \leq 1,51$), que le vieillissement est dû à une migration des ions Fe$^{3+}$ et Mn$^{2+}$ entre les sites tétraédriques et octaédriques de la structure spinelle. Une étude des manganites de fer a été réalisée par Microscopie Électronique à Transmission (MET) afin de relier la microstructure à la stabilité électrique. Pour les manganites de fer ayant une teneur en fer $x \leq 0,78$, la microstructure en forme de domaines (micromaclages) résulte de la présence de deux types de défauts bidimensionnels. Pour des teneurs supérieures, jusqu'à 0,78, cette microstructure disparaît graduellement et se transforme en une microstructure tweed ($x = 1,05$) et, pour $x > 1,30$, aucun défaut bidimensionnel n'est observé. Ces observations nous ont conduits à suggérer que ces différences dans la microstructure influencent grandement la cinétique de migration des ions durant le vieillissement des céramiques étudiées