N-Terminal Modification of Gly-His-Tagged Proteins with Azidogluconolactone.

Site-specific protein modifications are vital for biopharmaceutical drug development. Gluconoylation is a non-enzymatic, post-translational modification of N-terminal HisTags. We report high-yield, site-selective in vitro α-aminoacylation of peptides, glycoproteins, antibodies, and virus-like particles (VLPs) with azidogluconolactone at pH 7.

A Cognitive Aid for Neonatal Epinephrine Dosing.

Objectives: Errors are common when preparing epinephrine for neonatal resuscitation. Epinephrine is available in two concentrations (1 mg/mL and 1 mg/10 mL) and requires weight-based calculations, which increases the risk of dosing errors. We developed a printed cognitive aid to assist with dose preparation.

Inspection of Trivalent Chromium Conversion Coatings Using Laser Light: The Unexpected Role of Interference on Cold-Rolled Aluminium.

Laser-based inspection of trivalent chromium conversion coatings on rough, cold-rolled aluminium substrates is studied from a basic physics perspective by means of angle and wavelength dependent measurements. As a result, we show that the correlation between the scattered laser light and the coating weight of the conversion layer is dominated by the phenomenon of interference. The combined experimental and numerical approach of our study is based on an appropriate layer model which was developed from a set of reference measurements of confocal microscopy, electron microscopy and X-ray photoelectron spectroscopy.

Volume Versus Mass Dosing of Epinephrine for Neonatal Resuscitation: A Randomized Trial.

Background: Intravenous epinephrine for neonatal resuscitation requires weight-based calculations. Epinephrine is available in 2 different concentrations, increasing the risk of dosing errors. Expert panels have conflicting recommendations for the ordering method.

New Routes and Opportunities for Modular Construction of Particulate Vaccines: Stick, Click, and Glue.

Vaccines based on virus-like particles (VLPs) can induce potent B cell responses. Some non-chimeric VLP-based vaccines are highly successful licensed products (e.g.

Cigarette smoke disrupts monolayer integrity by altering epithelial cell-cell adhesion and cortical tension.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Cigarette smoke (CS) drives disease development and progression. The epithelial barrier is damaged by CS with increased monolayer permeability.

Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines.

Vaccine development efforts have recently focused on enabling strong immune responses to poorly immunogenic antigens, via display on multimerisation scaffolds or virus like particles (VLPs). Typically such studies demonstrate improved antibody titer comparing monomeric and nano-arrayed antigen. There are many such studies and scaffold technologies, but minimal side-by-side evaluation of platforms for both the amount and efficacy of antibodies induced.

Dual Plug-and-Display Synthetic Assembly Using Orthogonal Reactive Proteins for Twin Antigen Immunization.

Engineering modular platforms to control biomolecular architecture can advance both the understanding and the manipulation of biological systems. Icosahedral particles uniformly displaying single antigens stimulate potent immune activation and have been successful in various licensed vaccines. However, it remains challenging to display multiple antigens on a single particle and to induce broader immunity protective across strains or even against distinct diseases.

Activity and connectivity changes of central projection areas revealed by functional magnetic resonance imaging in Na1.8-deficient mice upon cold signaling.

The voltage-gated sodium channel subtype Na1.8 is expressed in the peripheral nervous system in primary afferent nociceptive C-fibers and is essential for noxious cold signaling. We utilized functional magnetic resonance imaging on Na1.

Optical Riblet Sensor: Beam Parameter Requirements for the Probing Laser Source.

Beam parameters of a probing laser source in an optical riblet sensor are studied by considering the high demands on a sensors' precision and reliability for the determination of deviations of the geometrical shape of a riblet. Mandatory requirements, such as minimum intensity and light polarization, are obtained by means of detailed inspection of the optical response of the riblet using ray and wave optics; the impact of wavelength is studied. Novel measures for analyzing the riblet shape without the necessity of a measurement with a reference sample are derived; reference values for an ideal riblet structure obtained with the optical riblet sensor are given.

HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD). We sought to determine the effects of HIV on the lung epithelium.

Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization.

Virus-like particles (VLPs) are non-infectious self-assembling nanoparticles, useful in medicine and nanotechnology. Their repetitive molecularly-defined architecture is attractive for engineering multivalency, notably for vaccination. However, decorating VLPs with target-antigens by genetic fusion or chemical modification is time-consuming and often leads to capsid misassembly or antigen misfolding, hindering generation of protective immunity.

Characteristic Changes in Cell Surface Glycosylation Accompany Intestinal Epithelial Cell (IEC) Differentiation: High Mannose Structures Dominate the Cell Surface Glycome of Undifferentiated Enterocytes.

Changes in cell surface glycosylation occur during the development and differentiation of cells and have been widely correlated with the progression of several diseases. Because of their structural diversity and sensitivity to intra- and extracellular conditions, glycans are an indispensable tool for analyzing cellular transformations. Glycans present on the surface of intestinal epithelial cells (IEC) mediate interactions with billions of native microorganisms, which continuously populate the mammalian gut.

Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology.

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. Similar to other NSAIDs, diclofenac is associated with serious dose-dependent gastrointestinal, cardiovascular, and renal adverse effects.

New insights into the use of currently available non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs), which act via inhibition of the cyclooxygenase (COX) isozymes, were discovered more than 100 years ago. They remain a key component of the pharmacological management of acute and chronic pain. The COX-1 and COX-2 isozymes have different biological functions; analgesic activity is primarily (although not exclusively) associated with inhibition of COX-2, while different side effects result from the inhibition of COX-1 and COX-2.

Pulmonary epithelial barrier function: some new players and mechanisms.

The pulmonary epithelium serves as a barrier to prevent access of the inspired luminal contents to the subepithelium. In addition, the epithelium dictates the initial responses of the lung to both infectious and noninfectious stimuli. One mechanism by which the epithelium does this is by coordinating transport of diffusible molecules across the epithelial barrier, both through the cell and between cells.

Acetaminophen/paracetamol: A history of errors, failures and false decisions.

Acetaminophen/paracetamol is the most widely used drug of the world. At the same time, it is probably one of the most dangerous compounds in medical use, causing hundreds of deaths in all industrialized countries due to acute liver failure (ALF). Publications of the last 130 years found in the usual databases were analyzed.

[Unexpected hemorrhage complications in association with celecoxib. Spontaneously reported case series after perioperative pain treatment in gynecological operations].

A series of cases of postoperative bleeding were reported to the Drug Commission of the German Medical Association (Arzneimittelkommission der deutschen Ärzteschaft, AkdÄ) within the spontaneous reporting system after the regimen for postoperative pain treatment was changed from diclofenac (150 mg per day) to celecoxib (400 mg per day). All patients underwent elective gynecological surgery and 7 out of 11 patients with postoperative bleeding required revision surgery. Although alternative causes for the hemorrhage incidents could not be excluded, the documented circumstances could have been indicative of a possible causal association.

New problems arising from old drugs: second-generation effects of acetaminophen.

Acetaminophen (APAP)/paracetamol is one of the most commonly used over-the-counter drugs taken worldwide for treatment of pain and fever. Although considered as safe when taken in recommended doses not higher than 4 g/day, APAP overdose is currently the most important cause of acute liver failure (ALF). ALF may require liver transplantation and can be fatal.

[Evaluation and choice of imaging protocols on the Elekta XVI(®) kilovoltage cone-beam computed tomography imaging system].

Purpose: This work proposes an evaluation of the Elekta XVI(®) kilovoltage cone-beam computed tomography imaging system. The average dose delivered for each acquisition protocol proposed by default by the manufacturer was measured with several detectors and compared to theoretical dose values given by Elekta. At the same time, an evaluation of image quality for pelvic protocols correlated to dose measurements in homogeneous and heterogeneous mediums allowed to optimize the use of the XVI(®) system.

Consumption of analgesics before a marathon and the incidence of cardiovascular, gastrointestinal and renal problems: a cohort study.

Objectives: To prevent pain inhibiting their performance, many athletes ingest over-the-counter (OTC) analgesics before competing. We aimed at defining the use of analgesics and the relation between OTC analgesic use/dose and adverse events (AEs) during and after the race, a relation that has not been investigated to date.

Design: Prospective (non-interventional) cohort study, using an online questionnaire.

E-pharmacovigilance: development and implementation of a computable knowledge base to identify adverse drug reactions.

Aims: Computer-assisted signal generation is an important issue for the prevention of adverse drug reactions (ADRs). However, due to poor standardization of patients' medical data and a lack of computable medical drug knowledge the specificity of computerized decision support systems for early ADR detection is too low and thus those systems are not yet implemented in daily clinical practice. We report on a method to formalize knowledge about ADRs based on the Summary of Product Characteristics (SmPCs) and linking them with structured patient data to generate safety signals automatically and with high sensitivity and specificity.

Engineering microbial consortia to enhance biomining and bioremediation.

In natural environments microorganisms commonly exist as communities of multiple species that are capable of performing more varied and complicated tasks than clonal populations. Synthetic biologists have engineered clonal populations with characteristics such as differentiation, memory, and pattern formation, which are usually associated with more complex multicellular organisms. The prospect of designing microbial communities has alluring possibilities for environmental, biomedical, and energy applications, and is likely to reveal insight into how natural microbial consortia function.