Physiological function of PARbZip circadian clock-controlled transcription factors.

PARbZip proteins (proline and acidic amino acid-rich basic leucine zipper) represent a subfamily of circadian transcription factors belonging to the bZip family. They are transcriptionally controlled by the circadian molecular oscillator and are suspected to accomplish output functions of the clock. In turn, PARbZip proteins control expression of genes coding for enzymes involved in metabolism, but also expression of transcription factors which control the expression of these enzymes. For example, these transcription factors control vitamin B6 metabolism, which influences neurotransmitter homeostasis in the brain, and loss of PARbZip function leads to spontaneous and sound-induced epilepsy that are frequently lethal. In liver, kidney, and small intestine, PAR bZip transcription factors regulate phase I, II, and III detoxifying enzymes in addition to the constitutive androstane receptor (CAR), one of the principal sensors of xenobiotics. Indeed, knockout mice for the three PARbZip transcription factors are deficient in xenobiotic detoxification and display high morbidity, high mortality, and accelerated aging. Finally, less than 20% of these animals reach an age of 1 year. Accumulated evidences suggest that PARbZip transcription factors play a role of relay, coupling circadian metabolism of xenobiotic and probably endobiotic substances to the core clock circuitry of local circadian oscillators.

Functional analysis of a conserved DNA methyltransferase in caulobacter crescentus

CcrM is a DNA methyltransferase that methylates the adenine in GANTC motifs in the chromo-some of the bacterial model Caulobacter crescentus. The loss of the CcrM homolog is lethal in C. crescentus and in several other species of Alphaproteobacteria. In this research, we used different experimental and bioinformatic approaches to determine why CcrM is so critical to the physiology of C. crescentus. We first showed that CcrM is a resident orphan DNA methyltransferase in non-Rickettsiales Alphaproteobacteria and that its gene is strictly conserved in this clade (with only one ex¬ception among the genomes sequenced so far). In C. crescentus, cells depleted in CcrM in rich medium quickly lose viability and present an elongated phenotype characteristic of an im¬pairment in cell division. Using minimal medium instead of rich medium as selective and main¬tenance substrate, we could generate a AccrM mutant that presents a viability comparable to the wild type strain and only mild morphological defects. On the basis of a transcriptomic ap¬proach, we determined that several genes essential for cell division were downregulated in the AccrM strain in minimal medium. We offered decisive arguments to support that the efficient transcription of two of these genes, ftsZ and mipZ, coding respectively for the Z-ring forming GTPase FtsZ and an inhibitor of FtsZ polymerization needed for the correct positioning of the Z- ring at mid-cell, requires the methylation of an adenine in a conserved GANTC motif located in their core promoter region. We propose a model, according to which the genome of C. crescentus encodes a transcriptional activator that requires a methylated adenine in a GANTC context to bind to DNA and suggest that this transcriptional regulator might be the global cell-cycle regulator GcrA. In addition, combining a classic genetic approach and in vitro evolution experiments, we showed that the mortality and cell division defects of the AccrM strain in rich medium are mainly due to limiting intracellular levels of the FtsZ protein. We also studied the dynamics of GANTC methylation in C. crescentus using the SMRT technol¬ogy developed by Pacific Biosciences. Our findings support the commonly accepted model, accord¬ing to which the methylation state of GANTC motifs varies during the cell cycle of C. crescentus: before the initiation of DNA replication, the GANTC motifs are fully-methylated (methylated on both strands); when the DNA gets replicated, the GANTC motifs become hemi-methylated (methyl¬ated on one strand only) and this occurs at different times during replication for different loci along the chromosome depending on their position relative to the origin of replication; the GANTC mo¬tifs are only remethylated after DNA replication has finished as a consequence of the massive and short-lived expression of CcrM in predivisional cells. About 30 GANTC motifs in the C. crescentus chromosome were found to be undermethylated in most of the bacterial population; these might be protected from CcrM activity by DNA binding proteins and some of them could be involved in methylation-based bistable transcriptional switches. - CcrM est une ADN méthyltransférase qui méthyle les adénines dans le contexte GANTC dans le génome de la bactérie modèle Caulobacter crescentus. La perte de l'homologue de CcrM chez C. crescentus et chez plusieurs autres espèces d'Alphaproteobactéries est létale. Dans le courant de cette recherche, nous tentons de déterminer pourquoi la protéine CcrM est cruciale pour la survie de C. crescentus. Nous démontrons d'abord que CcrM est une adénine méthyltransférase orpheline résidente, dont le gène fait partie du génome minimal partagé par les Alphaprotéobactéries non-Rickettsiales (à une exception près). Lorsqu'une souche de C. crescentus est privée de CcrM, sa viabilité décroît rapi¬dement et ses cellules présentent une morphologie allongée qui suggère que la division cellulaire est inhibée. Nous sommes parvenus à créer une souche AccrM en utilisant un milieu minimum, au lieu du milieu riche classiquement employé, comme milieu de sélection et de maintenance pour la souche. Lorsque nous avons étudié le transcriptome de cette souche de C. crescentus privée de CcrM, nous avons pu constater que plusieurs gènes essentiels pour le bon déroulement de la division cellulaire bactérienne étaient réprimés. En particulier, l'expression adéquate des gènes ftsZ et mipZ - qui codent, respectivement, pour FtsZ, la protéine qui constitue, au milieu de la cellule, un anneau protéique qui initie le processus de division et pour MipZ, un inhibiteur de la polymérisation de FtsZ qui est indispensable pour le bon positionnement de l'anneau FtsZ - est dépendante de la présence d'une adénine méthylée dans un motif GANTC conservé situé dans leur région promotrice. Nous présentons un modèle selon lequel le génome de C. crescentus code pour un facteur de transcription qui exige la présence d'une adénine méthylée dans un contexte GANTC pour s'attacher à l'ADN et nous suggérons qu'il pourrait s'agir du régulateur global du cycle cellulaire GcrA. En outre, nous montrons, en combinant la génétique classique et une approche basée sur l'évolution expérimentale, que la mortalité et l'inhibition de la division cellulaire caractéristiques de la souche àccrMeη milieu riche sont dues à des niveaux excessivement bas de protéine FtsZ. Nous avons aussi étudié la dynamique de la méthylation du chromosome de C. crescentus sur la base de la technologie SMRT développée par Pacific Biosciences. Nous confirmons le modèle communément accepté, qui affirme que l'état de méthylation des motifs GANTC change durant le cycle cellulaire de C. crescentus: les motifs GANTC sont complètement méthylés (méthylés sur les deux brins) avant de début de la réplication de l'ADN; ils deviennent hémi-méthylés (méthylés sur un brin seulement) une fois répliqués, ce qui arrive à différents moments durant la réplication pour différents sites le long du chromosome en fonction de leur position par rapport à l'origine de répli-cation; finalement, les motifs GANTC sont reméthylés après la fin de la réplication du chromosome lorsque la protéine CcrM est massivement, mais très transitoirement, produite. Par ailleurs, nous identifions dans le chromosome de C. crescentus environ 30 motifs GANTC qui restent en perma-nence non-méthylés dans une grande partie de la population bactérienne; ces motifs sont probable-ment protégés de l'action de CcrM par des protéines qui s'attachent à l'ADN et certains d'entre eux pourraient être impliqués dans des mécanismes de régulation générant une transcription bistable.

Sox genes in C. elegans: sox-2 role in postembryonic development

Report for the scientific sojourn carried out at the Columbia University, United States, from 2010 to 2012. Expression of SoxB genes correlates with the commitment of cells to a neural fate; however, the relevance of SoxB proteins in early vertebrate neurogenesis has been difficult to prove genetically due to embryonic lethality and presumed redundant functions. The nematode C. Elegants has only 5 sox genes: sox-2 and sox-3 form the SoxB group while sem-2, sox-4 and egl-13 belong to other Sox groups. Our results show that sox-2 and sem-2 are the sox genes expressed earliest and in a broader manner during embryogenesis, being expressed in several neuronal progenitors. sox-3, sox-4 and egl-13 are expressed in few cells during late embryogenesis, when most neurons are already born. Both sox-2 and sem-2 null mutants are early larval lethal but do not show neuronal specification defects during embryonic development as indicated by quantification of a panneuronal reporter. Potential redundancy or compensatory mechanisms between different sox genes have been ruled out, strongly suggesting that sox genes are not required for specification of embryonically-derived neurons. However, at the first larval stage there are still several blast cells that will give rise to different postembryonic lineages, which generate several neurons amongst other cell types. nterestingly, sox-2 is expressed in many of these progenitor cells. Using mosaic analysis we have so far identified neurons derived from two different postembryonic lineages which fail to be generated in C. elegans sox-2 mutants. These results support the idea that postembryonic progenitor competence is compromised in the absence of sox-2.

The CNGCb and CNGCd genes from Physcomitrella patens moss encode for thermosensory calcium channels responding to fluidity changes in the plasma membrane.

Land plants need precise thermosensors to timely establish molecular defenses in anticipation of upcoming noxious heat waves. The plasma membrane-embedded cyclic nucleotide-gated Ca(2+) channels (CNGCs) can translate mild variations of membrane fluidity into an effective heat shock response, leading to the accumulation of heat shock proteins (HSP) that prevent heat damages in labile proteins and membranes. Here, we deleted by targeted mutagenesis the CNGCd gene in two Physcomitrella patens transgenic moss lines containing either the heat-inducible HSP-GUS reporter cassette or the constitutive UBI-Aequorin cassette. The stable CNGCd knockout mutation caused a hyper-thermosensitive moss phenotype, in which the heat-induced entry of apoplastic Ca(2+) and the cytosolic accumulation of GUS were triggered at lower temperatures than in wild type. The combined effects of an artificial membrane fluidizer and elevated temperatures suggested that the gene products of CNGCd and CNGCb are paralogous subunits of Ca(2+)channels acting as a sensitive proteolipid thermocouple. Depending on the rate of temperature increase, the duration and intensity of the heat priming preconditions, terrestrial plants may thus acquire an array of HSP-based thermotolerance mechanisms against upcoming, otherwise lethal, extreme heat waves.

Dose optimization approach to fast X-ray microtomography of the lung alveoli.

A basic prerequisite for in vivo X-ray imaging of the lung is the exact determination of radiation dose. Achieving resolutions of the order of micrometres may become particularly challenging owing to increased dose, which in the worst case can be lethal for the imaged animal model. A framework for linking image quality to radiation dose in order to optimize experimental parameters with respect to dose reduction is presented. The approach may find application for current and future in vivo studies to facilitate proper experiment planning and radiation risk assessment on the one hand and exploit imaging capabilities on the other.

Predicting species distributions for conservation decisions.

Species distribution models (SDMs) are increasingly proposed to support conservation decision making. However, evidence of SDMs supporting solutions for on-ground conservation problems is still scarce in the scientific literature. Here, we show that successful examples exist but are still largely hidden in the grey literature, and thus less accessible for analysis and learning. Furthermore, the decision framework within which SDMs are used is rarely made explicit. Using case studies from biological invasions, identification of critical habitats, reserve selection and translocation of endangered species, we propose that SDMs may be tailored to suit a range of decision-making contexts when used within a structured and transparent decision-making process. To construct appropriate SDMs to more effectively guide conservation actions, modellers need to better understand the decision process, and decision makers need to provide feedback to modellers regarding the actual use of SDMs to support conservation decisions. This could be facilitated by individuals or institutions playing the role of 'translators' between modellers and decision makers. We encourage species distribution modellers to get involved in real decision-making processes that will benefit from their technical input; this strategy has the potential to better bridge theory and practice, and contribute to improve both scientific knowledge and conservation outcomes.

The infected aorta.

BACKGROUND: Despite the improvements achieved in antibiotic therapy, severe aortic infection resulting in mycotic aneurysms is still a highly lethal disease and surgical management remains a challenging task. PATIENTS AND METHODS: A total of 43 patients with severe aortic infections were analyzed and separated in four groups: (1) Infections of the aortic root Ventriculo-aortic disconnection due to deep aortic infection (6 patients). Two patients were operated using homo-composit grafts. Of the 6 patients total, one died early and two died late during a mean follow-up of 6 years. The two patients with homografts are still alive. (2) Infections of the ascending aorta and the aortic arch. In situ repair for mycotic aneurysmal lesions of the ascending aorta was performed in 6 patients using synthetic graft material in 4/6, biological material in 1/6 and direct suture in 1/6. Two patients had to be reoperated; one of them died early. There was no recurrent infection during a mean follow-up of 6 years. (3) Infections of the descending thoracic and thoraco-abdominal aorta in-situ repair for mycotic aneurysmal lesions of the descending and thoraco-abdominal aorta was performed in 12 patients using homografts in five. Two patients died early and two other patients died late during a mean follow-up of 6 years. (4) Infections of the infrarenal abdominal aorta. In this series of 19 patients with mycotic infrarenal aortic aneurysms, in situ reconstruction was performed in 12 (5/12 with homografts) and extra-anatomic reconstruction (axillo-femoral bypass) was performed in 7. Hospital mortality was 5/19 patients and another 5/19 patients died during a mean follow-up of 6 years. One of the early deaths was due to aortic stump rupture. Two patients with axillo-femoral reconstructions were later converted to descending-thoracic-aortic-bifemoral bypasses. Five thromboses of axillo-femoral bypasses were observed in three of the seven patients with extra-anatomic repairs. RESULTS: Infections of the aortic root, the ascending aorta and the aortic arch are approached with total cardio-pulmonary bypass, using cardioplegic myocardial protection and deep hypothermia with circulatory arrest if necessary. Proximal unloading and distal support using partial cardiopulmonary bypass is preferred for repair of infected descending and thoracoabdominal aortic lesions, whereas no such adjuncts are required for repair of infected infrarenal aortic lesions. CONCLUSIONS: The anatomical location of the aortic infection and the availability of homologous graft material are the main factors determining the surgical strategy.

Predicting clinical scores from magnetic resonance scans in Alzheimer's disease.

Machine learning and pattern recognition methods have been used to diagnose Alzheimer's disease (AD) and mild cognitive impairment (MCI) from individual MRI scans. Another application of such methods is to predict clinical scores from individual scans. Using relevance vector regression (RVR), we predicted individuals' performances on established tests from their MRI T1 weighted image in two independent data sets. From Mayo Clinic, 73 probable AD patients and 91 cognitively normal (CN) controls completed the Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), and Auditory Verbal Learning Test (AVLT) within 3months of their scan. Baseline MRI's from the Alzheimer's disease Neuroimaging Initiative (ADNI) comprised the other data set; 113 AD, 351 MCI, and 122 CN subjects completed the MMSE and Alzheimer's Disease Assessment Scale-Cognitive subtest (ADAS-cog) and 39 AD, 92 MCI, and 32 CN ADNI subjects completed MMSE, ADAS-cog, and AVLT. Predicted and actual clinical scores were highly correlated for the MMSE, DRS, and ADAS-cog tests (P<0.0001). Training with one data set and testing with another demonstrated stability between data sets. DRS, MMSE, and ADAS-Cog correlated better than AVLT with whole brain grey matter changes associated with AD. This result underscores their utility for screening and tracking disease. RVR offers a novel way to measure interactions between structural changes and neuropsychological tests beyond that of univariate methods. In clinical practice, we envision using RVR to aid in diagnosis and predict clinical outcome.

The Toarcian in the Subbetic basin (southern Spain): Bio-events (ammonite and calcareous nannofossils) and carbon-isotope stratigraphy

A detailed carbon-isotope stratigraphic study for the uppermost Pliensbachian lowermost Aalenian interval in the Median Subbetic palaeogeographic domain (External zones of the Betic Cordillera, southern Spain) has been carried out. During the Early Jurassic, the Median Subbetic, which represents a typical basin of the Hispanic Corridor connecting the Tethys and the Eastern Pacific, was located in the westernmost Tethys. The analyzed sections encompass the entire Toarcian stage as represented in the southern Iberian palaeomargin. Rocks are mainly rhythmic sequences of grey marls and marly limestones containing a rich ammonite fauna, nannofossils, and benthic foraminifers-all these provide an accurate biostratigraphic control. The lower and upper Toarcian boundaries are well represented in some of these sections and therefore represent optimal sites to link the carbon-isotope curves to ammonite zones, and to nannofossil events. delta C-13 values of bulk carbonates from the different localities of the Subbetic basin have similar variations from the uppermost Pliensbachian to the lowermost Aalenian, suggesting changes in the original DIC carbon isotope composition along the Hispanic corridor. The transition from Pliensbachian to Toarcian is marked by increasing delta C-13 values from similar to 12 to 2.0 parts per thousand, interrupted in the Serpentinum Zone by a negative shift concomitant with the Toarcian oceanic anoxic event (T-OAE), with the major ammonite extinction event of the Toarcian, and an important turnover of calcareous nannoplankton. The negative shift observed in the Serpentinum Zone confirms the global perturbation of the carbon cycling documented along the Tethys and the palaeo-Pacific in organic material and in marine carbonates. However, the amplitude of the negative excursion (similar to - 1.5 parts per thousand) is not compatible with an isotopic homogeneous seawater DIC and/or CO2 atmospheric reservoirs. The interval from the middle to the top of the Toarcian delta C-13 shows relatively constant values, minor ammonite turnovers, and is associated with increasing diversity of calcareous nannoplankton. (c) 2012 Elsevier B.V. All rights reserved.

Tuberculosis comorbidity with communicable and non-communicable diseases: integrating health services and control efforts.

Recent data for the global burden of disease reflect major demographic and lifestyle changes, leading to a rise in non-communicable diseases. Most countries with high levels of tuberculosis face a large comorbidity burden from both non-communicable and communicable diseases. Traditional disease-specific approaches typically fail to recognise common features and potential synergies in integration of care, management, and control of non-communicable and communicable diseases. In resource-limited countries, the need to tackle a broader range of overlapping comorbid diseases is growing. Tuberculosis and HIV/AIDS persist as global emergencies. The lethal interaction between tuberculosis and HIV coinfection in adults, children, and pregnant women in sub-Saharan Africa exemplifies the need for well integrated approaches to disease management and control. Furthermore, links between diabetes mellitus, smoking, alcoholism, chronic lung diseases, cancer, immunosuppressive treatment, malnutrition, and tuberculosis are well recognised. Here, we focus on interactions, synergies, and challenges of integration of tuberculosis care with management strategies for non-communicable and communicable diseases without eroding the functionality of existing national programmes for tuberculosis. The need for sustained and increased funding for these initiatives is greater than ever and requires increased political and funder commitment.

Epigenetics in sepsis: targeting histone deacetylases.

Severe sepsis and septic shock are lethal complications of infection, characterised by dysregulated inflammatory and immune responses. Our understanding of the pathogenesis of sepsis has improved markedly in recent years, but unfortunately has not been translated into efficient treatment strategies. Epigenetic mechanisms such as covalent modification of histones by acetylation are master regulators of gene expression under physiological and pathological conditions, and strongly impact on inflammatory and host defence responses. Histone acetylation is controlled by histone acetyltransferases and histone deacetylases (HDACs), which affect gene expression also by targeting non-histone transcriptional regulators. Numerous HDAC inhibitors (HDACi) are being tested in clinical trials, primarily for the treatment of cancer. We performed the first comprehensive study of the impact of HDACi on innate immune responses in vitro and in vivo. We showed that HDACi act essentially as negative regulators of the expression of critical immune receptors and antimicrobial pathways in innate immune cells. In agreement, HDACi impaired phagocytosis and killing of bacteria by macrophages, and increased susceptibility to non-severe bacterial and fungal infections. Strikingly, proof-of-principle studies demonstrated that HDACi protect from lethal toxic shock and septic shock. Overall, our observations argue for a close monitoring of the immunological and infection status of patients treated with HDACi, especially immunocompromised cancer patients. They also support the concept of pharmacological inhibitors of HDACs as promising drugs to treat inflammatory diseases, including sepsis.

L'hémodialyse intermittente aux soins intensifs = [Intermittent hemodialysis in the intensive care setting]

Acute renal failure is a frequent and potentially lethal disease in intensive care units. Renal replacement therapy (RRT) is often required. Either intermittent or continuous methods of RRT can be used. When to start a RRT and which method to use is not always clearly defined and a global evaluation of the clinical situation is required. The choice of the modality of RRT will be up to the general clinical context, hemodynamic stability, the type of molecules to be cleared and the haemorrhagic risk as much as habits and available resources. No study currently showed a superiority of either continuous or intermittent renal replacement therapy. The collaboration between intensive care specialists and nephrologists allows an optimized choice for a given patient and allow better move from one technic to another if required.

Integrative Review: Concepts And Methods Used In Nursing


Integrative review (IR) has an international reputation in nursing research and evidence-based practice. This IR aimed at identifying and analyzing the concepts and methods recommended to undertaking IR in nursing. Nine information resources,including electronic databases and grey literature were searched. Seventeen studies were included. The results indicate that: primary studies were mostly from USA; it is possible to have several research questions or hypotheses and include primary studies in the review from different theoretical and methodological approaches; it is a type of review that can go beyond the analysis and synthesis of findings from primary studies allowing exploiting other research dimensions, and that presents potentialities for the development of new theories and new problems for research. Conclusion: IR is understood as a very complex type of review and it is expected to be developed using standardized and systematic methods to ensure the required rigor of scientific research and therefore the legitimacy of the established evidence.


Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice

Résumé : La découverte que des mutations du gène humain Jagged 1 (JAG1) sont la cause du Syndrome d'Alagille, indique que la voie de signalisation Notch joue un rôle prépondérant dans l'homéostasie des canaux biliaires. L'analyse fonctionnelle de cette voie de signalisation est rendue difficile par le fait que les mutations ciblées des gènes : Jagged1, Notch1 ou Notch2 présentent un phénotype létal. Dans un précédent travail, nous avions généré une souris permettant l'inactivation de Notch1 de manière inductible en combinant un transgéne inductible par l'interféron de la Cre-recombinase et le gène Notch1 flanqué de deux séquence loxP. Nous avons utilisé cette souris knock-out conditionnelle afin d'étudier le rôle de la voie de signalisation de Notch1 dans la prolifération et la différentiation cellulaire hépatique. La délétion de Notch1 ne conduit pas à une diminution du nombre des canaux biliaires, mais de manière surprenante, l'absence de Notch1 induit une prolifération continue des hépatocytes. En conclusion, en quelques semaines après l'inactivation de Notch1 les souris développent une hyperplasie nodulaire régénérative, sans modification vasculaire dans le foie. Abstract: The discovery that the human Jagged1 gene (JAG1) is the Alagille syndrome disease gene indicated that Notch signaling has an important role in bile duct homeostasis. The functional study of this signaling pathway has been difficult because mice with targeted mutations in Jagged1, Notch1, or Notch2 have an embryonic lethal phenotype. We have previously generated mice with inducible Notch1 disruption using an interferon-inducible Cre-recombinase transgene in combination with the loxP flanked Notch1 gene. We used this conditional Notch1 knockout mouse model to investigate the role of Notch1 signaling in liver cell proliferation and differentiation. Deletion of Notch1 did not result in bile duct paucity, but, surprisingly, resulted in a continuous proliferation of hepatocytes. In conclusion, within weeks after Notch1 inactivation, the mice developed nodular regenerative hyperplasia without vascular changes in the liver.

Predictive factors of adrenal insufficiency in patients admitted to acute medical wards: a case control study.

BACKGROUND: Adrenal insufficiency is a rare and potentially lethal disease if untreated. Several clinical signs and biological markers are associated with glucocorticoid failure but the importance of these factors for diagnosing adrenal insufficiency is not known. In this study, we aimed to assess the prevalence of and the factors associated with adrenal insufficiency among patients admitted to an acute internal medicine ward. METHODS: Retrospective, case-control study including all patients with high-dose (250 μg) ACTH-stimulation tests for suspected adrenal insufficiency performed between 2008 and 2010 in an acute internal medicine ward (n = 281). Cortisol values <550 nmol/l upon ACTH-stimulation test were considered diagnostic for adrenal insufficiency. Area under the ROC curve (AROC), sensitivity, specificity, negative and positive predictive values for adrenal insufficiency were assessed for thirteen symptoms, signs and biological variables. RESULTS: 32 patients (11.4%) presented adrenal insufficiency; the others served as controls. Among all clinical and biological parameters studied, history of glucocorticoid withdrawal was the only independent factor significantly associated with patients with adrenal insufficiency (Odds Ratio: 6.71, 95% CI: 3.08 -14.62). Using a logistic regression, a model with four significant and independent variable was obtained, regrouping history of glucocorticoid withdrawal (OR 7.38, 95% CI [3.18 ; 17.11], p-value <0.001), nausea (OR 3.37, 95% CI [1.03 ; 11.00], p-value 0.044), eosinophilia (OR 17.6, 95% CI [1.02; 302.3], p-value 0.048) and hyperkalemia (OR 2.41, 95% CI [0.87; 6.69], p-value 0.092). The AROC (95% CI) was 0.75 (0.70; 0.80) for this model, with 6.3 (0.8 - 20.8) for sensitivity and 99.2 (97.1 - 99.9) for specificity. CONCLUSIONS: 11.4% of patients with suspected adrenal insufficient admitted to acute medical ward actually do present with adrenal insufficiency, defined by an abnormal response to high-dose (250 μg) ACTH-stimulation test. A history of glucocorticoid withdrawal was the strongest factor predicting the potential adrenal failure. The combination of a history of glucocorticoid withdrawal, nausea, eosinophilia and hyperkaliemia might be of interest to suspect adrenal insufficiency.