Exploratory Prognostic Biomarkers of Complement-Mediated Thrombotic Microangiopathy (CM-TMA) in Adults with Atypical Hemolytic Uremic Syndrome (aHUS): Analysis of a Phase III Study of Ravulizumab.

Background: Clinically validated biomarkers for monitoring of patients with complement-mediated thrombotic microangiopathy (CM-TMA) including atypical hemolytic uremic syndrome (aHUS) are unavailable. Improved characterization of biomarkers in patients with aHUS may inform treatment and monitoring for patients with CM-TMA.

Methods: This analysis used data collected from 55/56 (98.

Patient-assisted incident reporting: including the patient in patient safety.

Patient Safety Reporting Systems are a commonly used method for capturing information about adverse events and near misses in the acute care setting. These event reports are almost exclusively submitted by the frontline care provider, and the patient perspective of the event is rarely captured. The authors present a case which illustrates the use of eliciting the patient's perspective to provide a complementary perspective to the provider's description of the event.

Actin filament length tunes elasticity of flexibly cross-linked actin networks.

Networks of the cytoskeletal biopolymer actin cross-linked by the compliant protein filamin form soft gels that stiffen dramatically under shear stress. We demonstrate that the elasticity of these networks shows a strong dependence on the mean length of the actin polymers, unlike networks with small, rigid cross-links. This behavior is in agreement with a model of rigid filaments connected by multiple flexible linkers.

Mutating the dileucine motif of the human beta(2)-adrenoceptor reduces the high initial rate of receptor phosphorylation by GRK without affecting postendocytic sorting.

The internalization of beta(2)-adrenoceptors after agonist activation results in a desensitized and phosphorylated receptor that either resensitizes by recycling to the cell surface or becomes degraded by postendocytic sorting to lysosomes. The duration and physiological effects of agonists therefore depend on beta(2)-adrenoceptor sorting, highlighting the importance of sorting signals. Dileucine motifs within other membrane proteins act as signals for endocytosis and/or postendocytic sorting, and the beta(2)-adrenoceptor has a dileucine motif within helix 8 that might play a role in efficient receptor recycling and/or downregulation.

Multiplexed force measurements on live cells with holographic optical tweezers.

We describe open-loop and closed-loop multiplexed force measurements using holographic optical tweezers. We quantify the performance of our novel video-based control system in a driven suspension of colloidal particles. We demonstrate our system's abilities with the measurement of the mechanical coupling between Aplysia bag cell growth cones and beads functionalized with the neuronal cell adhesion molecule, apCAM.

Rapid recycling of beta-adrenergic receptors is dependent on the actin cytoskeleton and myosin Vb.

For the beta(2)-adrenergic receptor (beta(2)AR), published evidence suggests that an intact actin cytoskeleton is required for the endocytosis of receptors and their proper sorting to the rapid recycling pathway. We have characterized the role of the actin cytoskeleton in the regulation of beta(2)AR trafficking in human embryonic kidney 293 (HEK293) cells using two distinct actin filament disrupting compounds, cytochalasin D and latrunculin B (LB). In cells pretreated with either drug, beta(2)AR internalization into transferrin-positive vesicles was not altered but both agents significantly decreased the rate at which beta(2)ARs recycled to the cell surface.

Diffusion into use of exenatide for glucose control in diabetes mellitus: a retrospective cohort study of a new therapy.

Background: Exenatide was approved by the US Food and Drug Administration (FDA) in April 2005 as adjunctive therapy to metformin or a sulfonylurea for the treatment of type 2 diabetes mellitus (DM).

Objective: We evaluated whether use of exenatide soon after its approval was consistent with the FDA- approved indications.

Methods: We assembled a retrospective cohort of patients with DM using data from a population of employed persons and their dependents, including pharmacy claims and claims for inpatient and outpatient services, provided by i3 Innovus.

Inhibitors of phosphoinositide 3-kinase cause defects in the postendocytic sorting of beta2-adrenergic receptors.

Phosphatidylinositol 3-kinase inhibitors have been shown to affect endocytosis or subsequent intracellular sorting in various receptor systems. Agonist-activated beta(2)-adrenergic receptors undergo desensitization by mechanisms that include the phosphorylation, endocytosis and degradation of receptors. Following endocytosis, most internalized receptors are sorted to the cell surface, but some proportion is sorted to lysosomes for degradation.

Surgical specimen identification errors: a new measure of quality in surgical care.

Background: Communication errors are the primary factor contributing to all types of sentinel events including those involving surgical patients. One type of communication error is mislabeled specimens. The extent to which these errors occur is poorly quantified.

Human immunodeficiency virus and hepatitis testing and prevalence among surgical patients in an urban university hospital.

Background: Human immunodeficiency virus (HIV), hepatitis B, and hepatitis C represent significant public health problems in an urban community. Early diagnosis and treatment of these infections can improve survival and allow for preventive strategies to reduce further transmission within a community. The aim of this study was to evaluate the surgical setting as a potential opportunity for early diagnosis of HIV, hepatitis B, and hepatitis C among trauma and non-trauma patients.

Salmeterol stimulation dissociates beta2-adrenergic receptor phosphorylation and internalization.

Salmeterol is a long-acting beta(2)-adrenergic receptor (beta(2)AR) agonist commonly used in the treatment of asthma and chronic obstructive pulmonary disease. It differs from other beta-agonists in that it has a very low intrinisic efficacy, especially when compared with the other available long-acting beta-agonist, formoterol. Receptor desensitization and down-regulation has been described with the chronic use of beta-agonists.

Sharpless surgery: a prospective study of the feasibility of performing operations using non-sharp techniques in an urban, university-based surgical practice.

Context: Percutaneous injuries occur frequently during surgical procedures and represent a significant occupational hazard to operating room personnel.

Objectives: To evaluate the feasibility of performing select general surgical procedures using a combination of non-sharp devices and techniques to replace the conventional use of scalpels and needles.

Design, Setting, And Participants: Candidate procedures for which sharpless techniques could replace conventional scalpels and suture needles were identified preoperatively in an urban, university-based general surgical practice over a 1-year period (June 2003-June 2004).

Operating room teamwork among physicians and nurses: teamwork in the eye of the beholder.

Background: Teamwork is an important component of patient safety. In fact, communication errors are the most common cause of sentinel events and wrong-site operations in the US. Although efforts to improve patient safety through improving teamwork are growing, there is no validated tool to scientifically measure teamwork in the surgical setting.

Patient safety in surgery.

Background: Improving patient safety is an increasing priority for surgeons and hospitals since sentinel events can be catastrophic for patients, caregivers, and institutions. Patient safety initiatives aimed at creating a safe operating room (OR) culture are increasingly being adopted, but a reliable means of measuring their impact on front-line providers does not exist.

Methods: We developed a surgery-specific safety questionnaire (SAQ) and administered it to 2769 eligible caregivers at 60 hospitals.

Role of the G protein-coupled receptor kinase site serine cluster in beta2-adrenergic receptor internalization, desensitization, and beta-arrestin translocation.

There is considerable evidence for the role of carboxyl-terminal serines 355, 356, and 364 in G protein-coupled receptor kinase (GRK)-mediated phosphorylation and desensitization of beta(2)-adrenergic receptors (beta(2)ARs). In this study we used receptors in which these serines were changed to alanines (SA3) or to aspartic acids (SD3) to determine the role of these sites in beta-arrestin-dependent beta(2)AR internalization and desensitization. Coupling efficiencies for epinephrine activation of adenylyl cyclase were similar in wild-type and mutant receptors, demonstrating that the SD3 mutant did not drive constitutive GRK desensitization.

Proton-neutron interactions and the new atomic masses.

Double differences of masses can be used to isolate specific nucleonic interactions. With the new 2003 mass tabulation a significant increase in the number of empirical average proton-neutron interactions of the last nucleons can be extracted. It is shown that they exhibit dramatic and distinctive patterns, especially near doubly magic nuclei, that these patterns can be interpreted with a simple ansatz based on overlaps of proton and neutron orbits, and that the trends in p-n interactions across entire shells can be understood if they are correlated with the fractional shell filling.

rCBF/SPECT in the evaluation of inner-city minority patients with a history of impaired memory: a pilot blind read pre- and poststudy.

Eight patients (seven women), mean +/- SD T1 age 68.57 +/- 12.43 years, average educational level 5.

Rab11 regulates the recycling and lysosome targeting of beta2-adrenergic receptors.

The pericentriolar recycling endosome (RE) may be an alternative compartment through which some beta2-adrenergic receptors (beta2ARs) recycle from early endosomes to the cell surface during prolonged exposure to agonist. For the transferrin receptor, CXCR2, and the M4-muscarinic acetylcholine receptor, trafficking through the RE and receptor recycling is regulated by the small GTPase rab11. The precise role of the RE and rab11 in regulating the cellular trafficking of the beta2AR is not understood.

Endosome sorting of beta 2-adrenoceptors is GRK5 independent.

1. We have investigated the role of G protein-coupled receptor kinase 5 (GRK5) in the regulation of endosome sorting of human beta(2)-adrenoceptors. 2.

The mental health and biosocial context of help-seeking in longitudinal perspective: the Midtown Longitudinal Study, 1954 to 1974.

This study of a representative community survivor sample of 695 respondents from the 1954 Midtown Manhattan Study found that parental socioeconomic status unequivocally predicted help-seeking. Age, gender, adult SES, and impaired mental health in 1954 predicted help-seeking interactively. The mental health of help-seekers continued to be unfavorable, or was worsening, from 1954 to 1974.

Agonist-induced sorting of human beta2-adrenergic receptors to lysosomes during downregulation.

During prolonged exposure to agonist, beta2-adrenergic receptors undergo downregulation, defined by the loss of radioligand binding sites. To determine the cellular basis for beta2-adrenergic receptor downregulation, we examined HEK293 cells stably expressing beta2-adrenergic receptors with an N-terminal epitope tag. Downregulation was blocked by leupeptin, a cysteine protease inhibitor, but not by pepstatin, an inhibitor of aspartate proteases.