Mechanistic insights into the pH-dependent membrane peptide ATRAM.

pH-responsive peptides are promising therapeutic molecules that can specifically target the plasma membrane in the acidified extracellular medium that bathes cells in tumors. We designed the acidity-triggered rational membrane (ATRAM) peptide to have a pH-responsive membrane interaction. At physiological pH, ATRAM binds to the membrane surface in a largely unstructured conformation, while in acidic conditions it inserts into lipid bilayers forming a transmembrane helix.

Anticytomegalovirus Peptides Point to New Insights for CMV Entry Mechanisms and the Limitations of Screenings.

Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that can cause severe disease following exposure, during primary infection, or latent virus reactivation in immunocompromised populations. These complications lead to a 1- to 2-billion-dollar economic burden, making vaccine development and/or alternative treatments a high priority. Current treatments for HCMV include nucleoside analogues such as ganciclovir (GCV), foscarnet, and cidofovir.

Macrophage-Mediated Phagocytosis and Dissolution of Amyloid-Like Fibrils in Mice, Monitored by Optical Imaging.

Light chain-associated amyloidosis is characterized by the extracellular deposition of amyloid fibrils in abdominothoracic organs, skin, soft tissue, and peripheral nerves. Phagocytic cells of the innate immune system appear to be ineffective at clearing the material; however, human light chain amyloid extract, injected subcutaneously into mice, is rapidly cleared in a process that requires neutrophil activity. To better elucidate the phagocytosis of light chain fibrils, a potential method of cell-mediated dissolution, amyloid-like fibrils were labeled with the pH-sensitive dye pHrodo red and a near infrared fluorophore.

Deconstructing the Dissimilatory Sulfate Reduction Pathway: Isotope Fractionation of a Mutant Unable of Growth on Sulfate.

The sulfur isotope record provides key insight into the history of Earth's redox conditions. A detailed understanding of the metabolisms driving this cycle, and specifically microbial sulfate reduction (MSR), is crucial for accurate paleoenvironmental reconstructions. This includes a precise knowledge of the step-specific sulfur isotope effects during MSR.

A pilot study of venous flow augmentation using a novel mechanical graded intermittent sequential compression device for venous insufficiency.

Background: Guidelines as well as multiple RTCs support the use of intermittent pneumatic compression (IPC) for the treatment of venous leg ulcers when conservative measures fail. Unfortunately, the clinical usefulness of IPC is significantly limited by the physical limitations of pneumatic motors, which leads to bulky devices with slow inflation cycles, uncomfortable sleeves, lack of patient mobility, and ultimately poor patient compliance with therapy. A novel mechanical device for lower leg graded intermittent sequential compression was designed to address these limitations of IPC therapy for venous leg ulcer treatment by providing rapid compression cycles in a truly wearable device that offers the additional benefit of monitoring compression dose and patient compliance.

A Case of Opioid-Induced Hyperalgesia.

We report the case of a 76 year old lady with metastatic breast cancer, who presented to a hospice in severe distress from uncontrolled pain despite an increase in her opioid dose, alongside generalised hypersensitivity and delirium. The clinical presentation suggested opioid-induced hyperalgesia (OIH). After reduction of the opioid dose, our patient significantly improved to the extent she was discharged home a few weeks later.

A new family of transcriptional regulators of tungstoenzymes and molybdate/tungstate transport.

Bacterial genes for molybdenum-containing and tungsten-containing enzymes are often differentially regulated depending on the metal availability in the environment. Here, we describe a new family of transcription factors with an unusual DNA-binding domain related to excisionases of bacteriophages. These transcription factors are associated with genes for various molybdate and tungstate-specific transporting systems as well as molybdo/tungsto-enzymes in a wide range of bacterial genomes.

Precision medicine in COPD: review of mepolizumab for eosinophilic COPD.

http://ow.ly/uklu30m4YcU.

Assessing antibiotic stewardship using the surgical site infection prevention bundle.

Background:: Antibiotic prophylaxis is crucial in head and neck surgery to prevent infection from clean contaminated wounds. Scottish Intercollegiate Guidelines Network (SIGN) guidance, the gold standard of practice, recommends that administration of broad spectrum antibiotics is discontinued after 24 hours post-operation. A three-audit cycle quality improvement project was conducted to assess clinical practice against SIGN guidance at a large London teaching hospital.

Relationship of Hippocampal Volumes and Posttraumatic Stress Disorder Symptoms Over Early Posttrauma Periods.

Background: Smaller hippocampal volume is associated with more severe posttraumatic stress disorder (PTSD) symptoms years after traumatic experiences. Posttraumatic stress symptoms appear early following trauma, but the relationship between hippocampal volume and PTSD symptom severity during early posttrauma periods is not well understood. It is possible that the inverse relationship between hippocampal volume and PTSD symptom severity is already present soon after trauma.

Bifunctional amyloid-reactive peptide promotes binding of antibody 11-1F4 to diverse amyloid types and enhances therapeutic efficacy.

Amyloidosis is a malignant pathology associated with the formation of proteinaceous amyloid fibrils that deposit in organs and tissues, leading to dysfunction and severe morbidity. More than 25 proteins have been identified as components of amyloid, but the most common form of systemic amyloidosis is associated with the deposition of amyloid composed of Ig light chains (AL). Clinical management of amyloidosis focuses on reducing synthesis of the amyloid precursor protein.

Whole-Genome Analysis of Introgression Between the Spotted Owl and Barred Owl ( and , Respectively; Aves: Strigidae) in Western North America.

As the barred owl (; Aves: Strigiformes: Strigidae) expands throughout western North America, hybridization between barred and spotted owls ( and , respectively), if abundant, may lead to genetic swamping of the endangered spotted owl. We analyzed low-coverage, whole-genome sequence data from fifty-one barred and spotted owls to investigate recent introgression between these two species. Although we obtained genomic confirmation that these species can and do hybridize and backcross, we found no evidence of widespread introgression.

Relative skeletal distribution of proliferating marrow in the adult dog determined using 3'-deoxy-3'-[ F]fluorothymidine.

3'-deoxy-3'-[ F]fluorothymidine ( FLT) is a radiopharmaceutical tracer used with positron emission tomography (PET), often in combination with computed tomography (CT), to image DNA synthesis, and thus, cellular proliferation. Characteristic accumulation of the tracer within haematopoietic bone marrow provides a noninvasive means to assess marrow activity and distribution throughout the living animal. The present study utilizes three-dimensional analysis of FLT-PET/CT scans to quantify the relative skeletal distribution of active marrow by anatomic site in the dog.

Neurointensive care of patients with cerebral venous sinus thrombosis and intracerebral haemorrhage.

The aim was to review the neurointensive care (NIC) of cerebral venous sinus thrombosis patients with haemorrhage during a 15-year period. This is a severe condition with substantial mortality caused by increased intracranial pressure (ICP) and studies are lacking describing the complex picture of the NIC, which offers a large treatment arsenal for intracranial hypertension. Patients treated 2000-2015 were investigated.

PEG-Plasma Hydrogels Increase Epithelialization Using a Human Ex Vivo Skin Model.

In vitro cell culture methods are used extensively to study cellular migration, proliferation, and differentiation, which play major roles in wound healing but the results often do not translate to the in vivo environment. One alternative would be to establish an ex vivo model utilizing human discarded skin to evaluate therapies in a more natural setting. The purpose of this study was to institute such a model by creating 'wounds' in the center of a piece of discarded skin and treating them with three different biomaterials: collagen, polyethylene glycol (PEG)-fibrin, or PEG-platelet free plasma (PFP).

2018 Academic Emergency Medicine Consensus Conference: Advancing Pediatric Emergency Medicine Education Through Research and Scholarship.

To achieve high-quality emergency care for pediatric patients nationwide, it is necessary to define the key elements for pediatric emergency medicine (PEM) education and scholarship that would: 1) close the gaps in fundamental PEM education and 2) promote systems and standards that assure an ongoing communication of best practices between tertiary pediatric institutions, general (nonchildren's) hospital emergency departments, and urgent care centers. A working group of medical educators was formed to review the literature, develop a framework for consensus discussion at the breakout session, and then translate their findings into recommendations for future research and scholarship. The breakout session consensus discussion yielded many recommendations.

Iron- and aluminium-induced depletion of molybdenum in acidic environments impedes the nitrogen cycle.

Anthropogenic nitrate contamination is a serious problem in many natural environments. Nitrate removal by microbial action is dependent on the metal molybdenum (Mo), which is required by nitrate reductase for denitrification and dissimilatory nitrate reduction to ammonium. The soluble form of Mo, molybdate (MoO ), is incorporated into and adsorbed by iron (Fe) and aluminium (Al) (oxy) hydroxide minerals.

A Simplified Method for Three-Dimensional Optical Imaging and Measurement of Patients with Chest Wall Deformities.

Background: Pectus excavatum and carinatum are two of the most commonly observed chest wall deformities in pediatrics. The standard diagnostic evaluation for these conditions includes either chest radiograph (CXR) or computed tomography (CT). Our research aims to develop a novel and reliable way of quantifying chest wall deformities in the clinic setting without radiation exposure.

Relationships in Ongoing Structural Maintenances of the Two Cerebral Cortices of an Individual Brain.

A human brain has separate left and right cerebral cortices, each of which must be continuously structurally maintained during adulthood. There is no understanding of how ongoing structural maintenances of separate parts of a mature individual brain, including the 2 cortices, are related. To explore this issue, this study used an unconventional N-of-1 magnetic resonance imaging time-series paradigm to identify relationships between maintenances of structural thicknesses of the 2 cortices in an adult human brain over week intervals for 6 months.

A Video Surveillance System to Monitor Breeding Colonies of Common Terns (Sterna Hirundo).

Many waterbird populations have faced declines over the last century, including the common tern (Sterna hirundo), a waterbird species with a widespread breeding distribution, that has been recently listed as endangered in some habitats of its range. Waterbird monitoring programs exist to track populations through time; however, some of the more intensive approaches require entering colonies and can be disruptive to nesting populations. This paper describes a protocol that utilizes a minimally invasive surveillance system to continuously monitor common tern nesting behavior in typical ground-nesting colonies.

Transition to Adulthood as a Joint Parent-Youth Project for Young Persons With Intellectual and Developmental Disabilities.

Eight dyads ( N = 16) residing in Western Canada participated in this investigation of how young adults with intellectual and developmental disabilities (IDD) and their parents jointly construct, articulate, and act on goals pertinent to the young adults' transition to adulthood. Using the action-project method to collect and analyze conversations and video recall data, cases were grouped representing the ways goal-directed projects brought relationship ( n = 4), planning ( n = 3) or both ( n = 1) to the foreground as joint projects. Resources internal to the dyad such as emotional resources, and external to the dyad, facilitated formulation and pursuit of projects.