The synthesis, characterization, and reactivity of a NiOH core bearing a tridentate redox-active ligand capable of reaching three molecular oxidation states is presented in this paper. The reduced complex [LNiOH] was characterized by single-crystal X-ray diffraction analysis, depicting a square-planar NiOH core stabilized by intramolecular H-bonding interactions. Cyclic voltammetry measurements indicated that [LNiOH] can be reversibly oxidized to [LNiOH] and [LNiOH] at very negative reduction potentials (-1.
View Article and Find Full Text PDFChlorine is a mineral nutrient which, in a certain amount in the form of chloride, is essential for plant development. However, the atmosphere-plant transfer of its radioactive isotope, chlorine-36, is still poorly understood. In this study, dry deposition of Cl on lettuce and maize was determined experimentally.
View Article and Find Full Text PDFThe success of healthcare reform hinges on policymaker, regulator, and administrator actions that shape policies at various levels. These policies can either facilitate or hinder the practice of healthcare professionals and collaborative work environments. It is imperative for all healthcare professionals to fully utilize their education and certification, as fostering an equitable workplace culture is vital for retaining staff and improving access to care.
View Article and Find Full Text PDFThe enzyme UDP-glucose: glycoprotein glucosyltransferase (UGGT) is the gatekeeper of protein folding within the endoplasmic reticulum (ER). One-third of the human proteome traverses the ER where folding and maturation are facilitated by a complex protein homeostasis network. Both glycan modifications and disulfide bonds are of key importance in the maturation of these ER proteins.
View Article and Find Full Text PDFChlorine 36 (Cl) is a radionuclide of natural and anthropogenic origin, mainly used as a tracer in geochemical studies. Owing to analytical constraints and its low environmental levels, knowledge of Cl behavior in the environment is still very limited. In this study, we use environmental measurements to report for the first time the wet deposition fluxes of Cl downwind an anthropogenic source, the Orano nuclear reprocessing plant, which chronically emits Cl into the environment.
View Article and Find Full Text PDFExtracorporeal Membrane Oxygenation (ECMO) is a technology that offers organ support for critically ill patients with respiratory and/or cardiac failure. Despite improvements in recent years in technology and the biocompatibility of circuits, patients on ECMO remain at high risk of hematologic complications, such as bleeding or thrombosis. Anticoagulation is required in most cases to limit the risk of clotting, but questions persist regarding the optimal anticoagulation strategy.
View Article and Find Full Text PDFAn increasing number of people are surviving cancer in Switzerland : 163,450 people were still alive in 2006 after a cancer diagnosis less than ten years prior, compared to 210,350 in 2016. However, most have to cope with debilitating emotional and physical aftereffects. A new 12-week rehabilitation program aims to restore patients' abilities.
View Article and Find Full Text PDFNursing faculty prepared with a Doctor of Nursing Practice (DNP) degree have unique needs as they transition from their clinical roles into full-time academia. As expert clinicians they share a wealth of knowledge that contributes to quality improvement and implementation of evidence-based practice in healthcare. However, they may lack the preparation needed for scholarship, a requirement for promotion, as well as retention, in many academic organizations.
View Article and Find Full Text PDFOverexpression of recombinant protein in mammalian cells is widely used for producing biologics, as protein maturation and post-translational modifications are similar to human cells. Some therapeutics, such as mRNA vaccines, target nonnative cells that may contain inefficient secretory machinery. For example, gene replacement therapies for alpha-1 antitrypsin (AAT), a glycoprotein normally produced in hepatocytes, are often targeted to muscle cells due to ease of delivery.
View Article and Find Full Text PDFN-glycans act as quality control tags by recruiting lectin chaperones to assist protein maturation in the endoplasmic reticulum. The location and composition of N-glycans (glyco-code) are key to the chaperone-selection process. Serpins, a class of serine protease inhibitors, fold non-sequentially to achieve metastable active states.
View Article and Find Full Text PDFObjective: Von Willebrand factor (VWF) antigen plays a role in vascular inflammation and thrombosis, both of which are important in the pathogenesis of ANCA-associated vasculitis (AAV). Previous work found that VWF correlates with disease activity in childhood-onset primary CNS vasculitis. We sought to determine the relationship between VWF and disease activity over time in children with AAV.
View Article and Find Full Text PDFProtein folding, quality control, maturation, and trafficking are essential processes for proper cellular homeostasis. Around one-third of the human proteome is targeted to the endoplasmic reticulum (ER), the organelle that serves as entrance into the secretory pathway. Successful protein trafficking is paramount for proper cellular function and to that end there are many ER resident proteins that ensure efficient secretion.
View Article and Find Full Text PDFMisfolded glycoprotein recognition and endoplasmic reticulum (ER) retention are mediated by the ER glycoprotein folding quality control (ERQC) checkpoint enzyme, UDP-glucose glycoprotein glucosyltransferase (UGGT). UGGT modulation is a promising strategy for broad-spectrum antivirals, rescue-of-secretion therapy in rare disease caused by responsive mutations in glycoprotein genes, and many cancers, but to date no selective UGGT inhibitors are known. The small molecule 5-[(morpholin-4-yl)methyl]quinolin-8-ol (5M-8OH-Q) binds a UGGT "WY" conserved surface motif conserved across UGGTs but not present in other GT24 family glycosyltransferases.
View Article and Find Full Text PDFPrevious laboratory studies developed a conceptual model based on elevated non-volatile dissolved organic carbon (NVDOC) concentrations after photodegradation and subsequent dissolution of Macondo oil following the Deepwater Horizon blowout. However, those experiments did not account for the effects of ∼1 million gallons of dispersant applied to the surface oil. Here, laboratory results show photodissolution in the presence of dispersant results in > 2x increase in NVDOC concentrations after extensive photoprocessing relative to oil without dispersant.
View Article and Find Full Text PDFOil spills are devastating to seabirds, causing high levels of mortality and toxic physiological effects, especially to immune function. Sunlight exposure can further enhance the toxicity of oil to marine species by generating photodegradation products. Photo-enhanced oil toxicity to marine birds has not been studied.
View Article and Find Full Text PDFOnce released into the atmosphere, radionuclide dry deposition represents a major transfer process. It can be accurately characterized by its deposition velocity. However, this parameter is poorly constrained for most radionuclides, including chlorine 36.
View Article and Find Full Text PDFPurpose: Our objective was to determine characteristics of electrocardiograms (ECG) that predict ventricular fibrillation (VF) among prehospital patients with suspected ST-segment elevation myocardial infarction (STEMI) in Québec.
Methods: We performed a matched case-control study of prehospital adult suspected with STEMI. Patients in case group (STEMI/VF+) were matched with controls (STEMI/VF-) for age and sex and then compared for ECG characteristics, including ST-segment elevations (STE) and depressions (STD), duration of interval complexes, general characteristics, and several calculated variables.
Myelodysplastic neoplasms (MDS) are a collection of hematopoietic disorders with widely variable prognoses and treatment options. Accurate pathologic diagnoses present challenges because of interobserver variability in interpreting morphology and quantifying dysplasia. We compared local clinical site diagnoses with central, adjudicated review from 918 participants enrolled in the ongoing National Heart, Lung, and Blood Institute National MDS Natural History Study, a prospective observational cohort study of participants with suspected MDS or MDS/myeloproliferative neoplasms (MPNs).
View Article and Find Full Text PDFEndoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ERlocalised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). The enzyme recognises a mis-folded glycoprotein and flags it for ER retention by reglucosylating one of its N-linked glycans. In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant").
View Article and Find Full Text PDFObjectives: Oral or intratympanic corticosteroids are commonly used to treat sudden sensorineural hearing loss (SSHL), tinnitus, and Meniere disease. Direct intracochlear delivery has been proposed to overcome the variability in bioavailability and efficacy of systemic or middle ear delivery. In this study, we aim to characterize the physiologic consequences of microneedle-mediated direct intracochlear injection of dexamethasone through the round window membrane (RWM).
View Article and Find Full Text PDFUnlabelled: The standard operation for colon cancer resection should follow certain principles to ensure appropriate oncologic resection, such as retrieving 12 or more nodes with the specimen and adequate surgical margins. Although these principles are well documented, there is little evidence regarding the association of race and the attainment of an adequate oncologic resection.
Methods: The authors performed a retrospective cohort study of all cases of resectable colon adenocarcinoma who underwent surgical resection in the National Cancer Database between 2004 and 2018.