Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections.

Background: Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain.

Methods: In a multicenter, noninferiority trial, we randomly assigned hospitalized patients (including patients in the intensive care unit [ICU]) who had bloodstream infection to receive antibiotic treatment for 7 days or 14 days.

Small-Volume Blood Collection Tubes to Reduce Transfusions in Intensive Care: The STRATUS Randomized Clinical Trial.

Importance: Blood collection for laboratory testing in intensive care unit (ICU) patients is a modifiable contributor to anemia and red blood cell (RBC) transfusion. Most blood withdrawn is not required for analysis and is discarded.

Objective: To determine whether transitioning from standard-volume to small-volume vacuum tubes for blood collection in ICUs reduces RBC transfusion without compromising laboratory testing procedures.

Using Proteins As Markers for Anabolic Steroid Abuse: A New Perspective in Doping Control?

Drug toxicity is a major concern and has motivated numerous studies to elucidate specific adverse mechanisms, with acetaminophen being the favorite candidate in toxicology studies. Conversely, androgenic anabolic steroids (AASs) also represent a severe public health issue in sports for elite and non-elite athletes. Supraphysiological dosages of AASs are associated with various adverse effects, from cardiovascular to neurological repercussions including liver dysfunction.

Standardization of reticulocyte counts in the athlete biological passport.

Introduction: The percentage of circulating reticulocytes (RET%) is a useful marker of blood doping in the context of the Athlete Biological Passport (ABP). The viability of the ABP depends on the comparability of sample data obtained across multiple laboratories for a given athlete. With the recent introduction of a different technology for the measurement of reticulocytes, the goal of this study was to compare currently employed Sysmex XT/XE analyzers to the recently introduced Sysmex XN analyzer.

Detection of erythropoiesis stimulating agents in urine samples using a capillary Western system.

The presence of erythropoiesis stimulating agents (ESAs) in the urine samples collected from athletes is detected using traditional Western blotting following either size-based separation (SDS/SAR-PAGE) or isoelectric focusing (IEF). Although there is an important testing effort, there is little doubt that ESAs are still abused in sports and that reducing the costs of the tests might increase the number of tests and improve deterrence. The capillary electrophoresis system developed by Protein Simple may be useful to this end.

Drainage of Cerebrospinal Fluid and Blood Pressure Augmentation as Rescue Therapies for Ischemic Myelitis After Bronchial Embolization: A Case Report.

A 62-year-old man presented to the emergency department with massive hemoptysis. After bronchial artery embolization, he developed ischemic myelitis, a rare complication in this setting for which no specific therapy is currently recommended. The symptoms were managed with lumbar drainage of cerebrospinal fluid and blood pressure augmentation therapy.

Immunomagnetic beads-based isolation of erythropoietins from urine and blood for sports anti-doping control.

According to the World Anti-Doping Agency (WADA) technical document for erythropoiesis stimulating agents (ESA) analysis (TD2014EPO), double-blotting of serum/plasma samples is mandatory for all analysis by isoelectric focusing (IEF) and for the confirmation procedures (CP) performed by SDS-PAGE or SAR-PAGE. The goal is to prevent potential cross-reactions of the secondary antibody with remaining proteins in the purified samples. To this end, we have developed an immunopurification method of ESA in serum/plasma samples using a combination of streptavidin-coated immunomagnetic beads and biotinylated anti-EPO polyclonal antibodies.

Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents.

Objective: The aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function.

Methods: We measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration.

Desialylation improves the detection of recombinant erythropoietins in urine samples analyzed by SDS-PAGE.

Recombinant erythropoietin (rhEPO) has been misused for over two decades by athletes, mainly but not only in endurance sports. A direct rhEPO detection method in urine by isoelectric focusing (IEF) was introduced in 2000, but the emergence of third-generation erythropoiesis-stimulating agents and so-called biosimilar rhEPOs, together with the sensitivity of human endogenous EPO (huEPO) pattern to enzymatic activities and its modification following short strenuous exercise, prompted the development of a complementary test based on SDS-PAGE analysis. While Mircera and NESP are easily detected with the existing IEF and SDS-PAGE methods, some samples containing both epoetin-α/β and huEPO present profiles that are still difficult to interpret.

New structural determinants for c-Myc specific heterodimerization with Max and development of a novel homodimeric c-Myc b-HLH-LZ.

c-Myc must heterodimerize with Max to accomplish its functions as a transcription factor. This specific heterodimerization occurs through the b-HLH-LZ (basic region, helix 1-loop-helix 2-leucine zipper) domains. In fact, many studies have shown that the c-Myc b-HLH-LZ (c-Myc'SH) preferentially forms a heterodimer with the Max b-HLH-LZ (Max'SH).

The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis.

Oncogenic stress induces expression of the alternate reading frame (Arf) tumor suppressor protein. Arf then stabilizes p53, which leads to cell cycle arrest or apoptosis. The mechanisms that distinguish both outcomes are incompletely understood.

The Max homodimeric b-HLH-LZ significantly interferes with the specific heterodimerization between the c-Myc and Max b-HLH-LZ in absence of DNA: a quantitative analysis.

Specific heterodimerization plays a crucial role in the regulation of the biology of the cell. For example, the specific heterodimerization between the b-HLH-LZ transcription factors c-Myc and Max is a prerequisite for c-Myc transcriptional activity that leads to cell growth, proliferation and tumorigenesis. On the other hand, the Mad proteins can compete with c-Myc for Max.

Permanent renal failure induced by pentastarch.

Background. Controversy exists with volume resuscitation using crystalloids or colloids. Renal dysfunction has been reported with some colloids and osmotic agents, but remains poorly defined.

Elucidation of the structural determinants responsible for the specific formation of heterodimeric Mxd1/Max b-HLH-LZ and its binding to E-box sequences.

The proteins of the Mxd family (formally known as Mad) are antagonists of the oncoprotein c-Myc. They compete with c-Myc for their obligate partner Max to prevent the c-Myc/Max heterodimer from binding to E-box sequences in the target gene promoters. In cancer cells, where Myc is overexpressed, the expression of Mxd proteins is usually insufficient or abrogated.

Thermodynamics of b-HLH-LZ protein binding to DNA: the energetic importance of protein-DNA contacts in site-specific E-box recognition by the complete gene product of the Max p21 transcription factor.

The Myc/Mad/Max network of dimeric basic region-helix-loop-helix-leucine zipper (b-HLH-LZ) transcription factors bind to enhancer box sequences (E-box) in the promotors of a large set of genes that control cell metabolism, proliferation, and differentiation. Max (Myc-associated factor X) is the obligate heterodimerization partner of Myc and Mad proteins. On the other hand, Max is the only member of the family capable of forming a stable homodimer.

The mechanism of discrimination between cognate and non-specific DNA by dimeric b/HLH/LZ transcription factors.

The Myc/Max/Mad proteins are basic region-helix-loop-helix-leucine zipper (b/HLH/LZ) transcription factors that regulate the transcription of numerous genes involved in cell growth and proliferation. The Max protein is the obligate heterodimeric partner of the Myc and Mad proteins. Heterodimerization and DNA binding to target gene promoters are mediated by the b/HLH/LZ domains.

Toward the elucidation of the structural determinants responsible for the molecular recognition between Mad1 and Max.

Mad1 is a member of the Mad family. This family is part of the larger Myc/Max/Mad b-HLH-LZ eukaryotic transcription-factor network. Mad1 forms a specific heterodimer with Max and acts as a transcriptional repressor when bound to an E-box sequence (CACGTG) found in the promoter of c-Myc target genes.

Structural and thermodynamical characterization of the complete p21 gene product of Max.

The b-HLH-LZ family of transcription factors contains numerous proteins including the Myc and Mad families of proteins. Max heterodimerizes with other members to bind the E-Box DNA sequence in target gene promoters. Max is the only protein in this network that recognizes and binds E-Box DNA sequences as a homodimer in vitro and represses transcription of Myc target genes in vivo.

Improving the thermodynamic stability of the leucine zipper of max increases the stability of its b-HLH-LZ:E-box complex.

Max is a member of the b-HLH-LZ (basic region-helix1-loop-helix2-leucine zipper) family of eukaryotic transcription factors. It is the obligate partner of the related b-HLH-LZ proteins, c-Myc and Mad1, with which it forms heterodimers on target DNA. While c-Myc and Mad1 require Max for DNA-binding, Max itself can form a homodimer that recognizes E-box DNA sequences (CACGTG) in gene promoters that are targeted by c-Myc.

Alteration of chemoattractant receptor expression regulates human neutrophil chemotaxis in vivo.

Objective: To elucidate the mechanisms that regulate human neutrophil delivery in vivo, as well as the mechanisms that lead to observed reduction in polymorphonuclear (PMN) delivery to remote sites in septic patients.

Methods: Alterations in human PMN chemoattractant receptor expression and chemotactic function in vivo were evaluated in two distinct experiments: exudate PMNs (PMNs that have undergone transmigration to skin window blisters in controls) and septic PMNs (circulating PMNs from septic patients in the intensive care unit) were both separately compared with control circulating PMNs.

Results: Exudate PMNs displayed increased C5a receptors and C5a chemotaxis, and reduced interleukin-8 receptors (both IL-8 RA and IL-8 RB) and IL-8 chemotaxis.