[How to value the work of geriatric caregivers].

Geriatric caregivers are subjected to physically and psychologically demanding situations. A geriatric short-stay service has implemented measures with a unique, creative and dynamic approach. These include participatory management, benevolence and the enhancement of the quality of work.

High-Flow Nasal Cannula in Early Emergency Department Management of Acute Hypercapnic Respiratory Failure Due to Cardiogenic Pulmonary Edema.

Background: Noninvasive ventilation (NIV) is the recommended ventilatory support for acute cardiogenic pulmonary edema (CPE) associated with acute respiratory failure or hypercapnia. High-flow nasal cannula (HFNC) has emerged as an alternative to NIV in acute hypoxemic respiratory failure. We aimed to assess the efficacy of HFNC on early changes in [Formula: see text] and respiratory parameters in patients in the emergency department with acute hypercapnic CPE and to compare it to NIV.

Dysregulated TRAF3 and BCL2 Expression Promotes Multiple Classes of Mature Non-hodgkin B Cell Lymphoma in Mice.

TNF-Receptor Associated Factor (TRAF)-3 is a master regulator of B cell homeostasis and function. TRAF3 has been shown to bind and regulate various proteins involved in the control of innate and adaptive immune responses. Previous studies showed that TRAF3 overexpression renders B cells hyper-reactive to antigens and Toll-like receptor (TLR) agonists, while TRAF3 deficiency has been implicated in the development of a variety of B cell neoplasms.

Arterial pH selectively predicts critical care needs in emergency department obese patients with acute dyspnea: A prospective comparative study.

Introduction: Obese patients with acute dyspnea may be prone to misorientation from the emergency department (ED), due to impaired gas exchange evaluation and altered basal respiratory profiles. This study aims to evaluate the prognostic value of arterial blood pH in obese ED patients with acute dyspnea in comparison to non-obese counterparts.

Methods: Single-center observational study of a cohort of 400 consecutive ED patients with acute dyspnea.

Effect of Weight Loss on Postural Changes in Pulmonary Function in Obese Subjects: A Longitudinal Study.

Background: Postural changes are known to affect normal lung volumes. A reduction in sitting to supine functional residual capacity (FRC) is well-described in non-obese subjects adopting a supine position. However, postural changes in lung volumes in the obese require further exploration.

Performances of the heart fatty acid protein assay for the rapid diagnosis of acute myocardial infarction in ED patients.

Objective: We sought to evaluate the added value of heart fatty acid protein assay (HFABP) for rapid diagnosis of acute myocardial infarction in a prospective cohort of emergency department (ED) patients with acute chest pain.

Methods: High-sensitivity cardiac troponin T (hs-cTnT; Roche Diagnostics, Meylan, France) and HFABP (Randox, Mauguio, France) were blindly assayed from venous blood samples obtained at admission. Diagnosis was made by 2 ED physicians using all available data and serial cardiac troponin I as the biochemical standard.

A systematic review and collaborative meta-analysis to determine the incremental value of copeptin for rapid rule-out of acute myocardial infarction.

Multiple studies have evaluated copeptin, a surrogate for arginine vasopressin, in the diagnosis of acute myocardial infarction (AMI) with mixed results. A systematic review and collaborative meta-analysis were performed for diagnosis of AMI and assessment of prognosis in patients presenting to the emergency department with chest pain. MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing copeptin in such patients.

Early rule out of acute myocardial infarction in ED patients: value of combined high-sensitivity cardiac troponin T and ultrasensitive copeptin assays at admission.

Objective: We sought to evaluate the added value of ultrasensitive copeptin (us-copeptin) for early rule out of acute myocardial infarction in a prospective cohort of emergency department (ED) patients with acute chest pain.

Methods: This was a prospective study including consecutive patients with acute chest pain presenting to the ED within 12 hours of symptom onset. High-sensitivity cardiac troponin T (hs-cTnT, Roche Diagnostics, Meylan, France) and us-copeptin (ThermoFisher Scientific, Clichy, France) were blindly assayed from venous blood samples obtained at admission.

In vitro activity of daptomycin against Enterococcus faecalis under various conditions of growth-phases, inoculum and pH.

Enterococcus faecalis (E. faecalis) has become a major leading cause of nosocomial endocarditis. Treatment of such infections remains problematic and new therapeutic options are needed.

Emergency department management of suspected carbon monoxide poisoning: role of pulse CO-oximetry.

Background: The RAD-57 pulse CO-oximeter is a lightweight device allowing noninvasive measurement of blood carboxyhemoglobin (S(pCO)). We assessed the diagnostic value of pulse CO-oximetry, comparing S(pCO) values from the RAD-57 to standard laboratory blood carboxyhemoglobin (COHb) measurement in emergency department patients with suspected carbon monoxide (CO) poisoning.

Methods: This was a prospective, diagnostic accuracy study according to the Standards for the Reporting of Diagnostic Accuracy Studies criteria in consecutive adult emergency department patients with suspected CO poisoning.

Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator.

A novel series of alkoxyimino derivatives as S1P1 agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure-activity relationship studies led to the discovery of (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic acid (32, BAF312, Siponimod), which has recently completed phase 2 clinical trials in patients with relapsing-remitting multiple sclerosis.

Proadrenomedullin, a useful tool for risk stratification in high Pneumonia Severity Index score community acquired pneumonia.

The aim of the present study was, first, to evaluate the prognostic value of mid-regional proadrenomedullin (proADM) in emergency department (ED) patients with a diagnosis of community acquired pneumonia (CAP) and, second, to analyze the added value of proADM as a risk stratification tool in comparison with other biomarkers and clinical severity scores. We evaluated proADM, C-reactive protein and procalcitonin, along with the Pneumonia Severity Index (PSI) score in consecutive CAP patients. Ability to predict 30-day mortality was assessed using receiver operating characteristic curve analysis, logistic regression, and reclassification metrics for all patients and for patients with high PSI scores.

Analytical performances of the newly developed, fully automated Kryptor Copeptin assay: which impact factor for myocardial infarction rules out in the emergency department?

Background: We evaluated the essential assay characteristics of the newly developed, fully automated Kryptor Copeptin assay including the assay performances and the clinical implications in parallel with the dosage of the cardiac Troponin I (cTnI) in patients presenting to the Emergency Department with chest pain with or without ECG abnormalities.

Methods: Analytical performance of the B-R-A-H-M-S Copeptin Kryptor was carried out according to the CLSI protocol EP17-A, volume 24, number 34 [3] including linearity imprecision, determination of quantification, and detection limits. An evaluation of the clinical concordance between cTnI and copeptin results was performed on consecutive patients, with chest pain suggestive of acute coronary syndromes (ACS), admitted to the Emergency Department of our hospital.

Predicting peripheral venous access difficulty in the emergency department using body mass index and a clinical evaluation of venous accessibility.

Background: Peripheral venous (PV) cannulation, one of the most common technical procedures in Emergency Medicine, may prove challenging, even to experienced Emergency Department (ED) staff. Morbid obesity (body mass index [BMI] ≥ 40) has been reported as a risk factor for PV access failure in the operating room.

Objectives: We investigated PV access difficulty in the ED, across BMI categories, focusing on patient-related predicting factors.

Chest compressions performed by ED staff: a randomized cross-over simulation study on the floor and on a stretcher.

Background: Multiple factors may contribute to the observed survival variability following in-hospital cardiopulmonary resuscitation (CPR). While in-hospital CPR is most often performed on patients lying on a bed or stretcher, CPR training uses primarily manikins placed on the floor. We analyzed the quality of external chest compressions (ECC) in simulated cardiac arrest scenarios occurring both on a stretcher and on the floor.

Breath analyzer screening of emergency department patients suspected of alcohol intoxication.

Background: Acute alcohol intoxication is a frequent cause of emergency department (ED) visits. Evaluating a patient's alcohol intoxication is commonly based on both a physical examination and determination of blood alcohol concentration (BAC).

Objective: To demonstrate the feasibility and usefulness of using a last-generation infrared breath analyzer as a non-invasive and rapid screening tool for alcohol intoxication in the ED.

Potent activity against K562 cells by polyamide-seco-CBI conjugates targeting histone H4 genes.

We designed and synthesized conjugates between pyrrole-imidazole polyamides and seco-CBI that alkylate within the coding regions of the histone H4 genes. DNA alkylating activity on the histone H4 fragment and cellular effects against K562 chronic myelogenous leukemia cells were investigated. One of the conjugates, 5-CBI, showed strong DNA alkylation activity and good sequence specificity on a histone H4 gene fragment.

Lymphocyte-specific TRAF3 transgenic mice have enhanced humoral responses and develop plasmacytosis, autoimmunity, inflammation, and cancer.

Tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3) regulates both innate and adaptive immunity by modulating signaling by Toll-like receptors (TLR) and TNF receptors. TRAF3 was recently identified as a tumor suppressor in human multiple myeloma, suggesting a prominent role in plasma cell homeostasis. We have generated transgenic mice expressing human TRAF3 in lymphocytes.

Growth arrest of BCR-ABL positive cells with a sequence-specific polyamide-chlorambucil conjugate.

Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, has significantly improved the clinical outcome of patients with CML. However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML.

Targeting specific gene by alkylating pyrrole-imidazole polyamides.

Targeting specific genes or gene products by small molecules is novel approach of cancer chemotherapy. We have developed sequence-specific DNA alkylating agents, conjugates between pyrrole (Py)-imidazole (Im) polyamides and 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H benz[e]indole (seco-CBI) with an indole linker. These compounds efficiently alkylate DNA at a targeted sequence and inhibit gene expression caused by alkylation at template strand of coding region.

Targeting TRAfs for therapeutic intervention.

TNF-receptor associated factors (TRAFs) are the molecules that upon engagement of the TNF-receptor (TNFR) by a TNF-family ligand come first in contact with the activated TNFR, initially acting as docking molecules for kinases and other effector proteins that are recruited to the activated receptor. TRAFs later regulate the subcellular relocalization of the receptor-ligand complex and finally they modulate the extent of the response by controlling the degradation of key proteins in the pathway. In this chapter, we review the involvement of different TRAF family members in the etiology of a variety of pathologies and address the question of whether the use of TNFR-mimic-peptides or small molecule modulators targeting TRAFs might be suitable for therapeutic intervention, discussing the advantages and disadvantages of this strategy.

Phylogeny of the TRAF/MATH domain.

The TNF-receptor associated factor (TRAF) domain (TD), also known as the meprin and TRAF-C homology (MATH) domain is a fold of seven anti-parallel p-helices that participates in protein-protein interactions. This fold is broadly represented among eukaryotes, where it is found associated with a discrete set of protein-domains. Virtually all protein families encompassing a TRAF/MATH domain seem to be involved in the regulation of protein processing and ubiquitination, strongly suggesting a parallel evolution of the TRAF/MATH domain and certain proteolysis pathways in eukaryotes.

Triterpenoids display single agent anti-tumor activity in a transgenic mouse model of chronic lymphocytic leukemia and small B cell lymphoma.

Background: The synthetic triterpenoid 2-Cyano-3,12-Dioxooleana-1,9-Dien-28-Oic Acid (CDDO) and derivatives display anti-tumor activity against a variety of cultured tumor cell lines and in mouse xenografts. In this report, we have studied the effects of CDDO and its imidazolide derivative (CDDO-Im) on chronic lymphocytic leukemia (CLL), using patients' CLL cells and a mouse model of CLL and small B cell lymphoma (SBL).

Principal Findings: CDDO and CDDO-Im efficiently induced apoptosis of malignant human and mouse B-cells ex vivo, although CDDO-Im was over 10-fold more potent than CDDO.

Ubiquitin-conjugating enzyme Ubc13 is a critical component of TNF receptor-associated factor (TRAF)-mediated inflammatory responses.

Ubc13 is a ubiquitin-conjugating enzyme responsible for noncanonical ubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in Toll-like receptor and TNF-family cytokine receptor signaling, which are regulators of innate immunity. Gene ablation was used to study the function of Ubc13 in mice. Whereas homozygous ubc13 gene disruption resulted in embryonic lethality, heterozygous ubc13(+/-) mice appeared normal, without alterations in immune cell populations.