Defining digital nursing.

Background: The use of technology in health care, including nursing, is growing, owing in part to the COVID-19 pandemic and in response to national policy.

Aims: To investigate nurses' perceptions of digital nursing (DN).

Methods: Community and primary care nurses from across Wales were recruited (=249) through a survey comprising open and closed questions.

Chelator PBT2 Forms a Ternary Cu Complex with β-Amyloid That Has High Stability but Low Specificity.

The metal chelator PBT2 (5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline) acts as a terdentate ligand capable of forming binary and ternary Cu complexes. It was clinically trialed as an Alzheimer's disease (AD) therapy but failed to progress beyond phase II. The β-amyloid (Aβ) peptide associated with AD was recently concluded to form a unique Cu(Aβ) complex that is inaccessible to PBT2.

Intermediate Cu(II)-Thiolate Species in the Reduction of Cu(II)GHK by Glutathione: A Handy Chelate for Biological Cu(II) Reduction.

Gly-His-Lys (GHK) is a tripeptide present in the human bloodstream that exhibits a number of biological functions. Its activity is attributed to the copper-complexed form, Cu(II)GHK. Little is known, however, about the molecular aspects of the mechanism of its action.

The Palladium(II) Complex of A as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids.

The Aβ4-42 peptide is a major beta-amyloid species in the human brain, forming toxic aggregates related to Alzheimer's Disease. It also strongly chelates Cu(II) at the N-terminal Phe-Arg-His ATCUN motif, as demonstrated in Aβ4-16 and Aβ4-9 model peptides. The resulting complex resists ROS generation and exchange processes and may help protect synapses from copper-related oxidative damage.

Aldehyde Production as a Calibrant of Ultrasonic Power Delivery During Protein Misfolding Cyclic Amplification.

The protein misfolding cyclic amplification (PMCA) technique employs repeated cycles of incubation and sonication to amplify minute amounts of misfolded protein conformers. Spontaneous (de novo) prion formation and ultrasonic power level represent two potentially interrelated sources of variation that frustrate attempts to replicate results from different laboratories. We previously established that water splitting during PMCA provides a radical-rich environment leading to oxidative damage to substrate molecules as well as the polypropylene PCR tubes used for sample containment.

Ternary Cu(II) Complex with GHK Peptide and -Urocanic Acid as a Potential Physiologically Functional Copper Chelate.

The tripeptide NH-Gly-His-Lys-COOH (GHK), -urocanic acid (-UCA) and Cu(II) ions are physiological constituents of the human body and they co-occur (e.g., in the skin and the plasma).

Pupillometry measures of autonomic nervous system regulation with advancing age in a healthy pediatric cohort.

Purpose: To determine if variables of the pupillary light response mature with age and sex in a healthy pediatric cohort and the utility of pupillometry in assessment among pediatric participants.

Methods: After 1 min in a dark room to establish baseline, pupillometry was performed on 323 healthy, pediatric participants (646 eyes; 2-21 years; 175 females). Variables included initial pupil diameter, pupil diameter after light stimulus, percent pupillary constriction, latency to onset of constriction, average constriction velocity, maximum constriction velocity, average dilation velocity, and time from light stimulus to 75% of the initial pupil diameter.

The Sub-picomolar Cu Dissociation Constant of Human Serum Albumin.

The apparent affinity of human serum albumin (HSA) for divalent copper has long been the subject of great interest, due to its presumed role as the major Cu -binding ligand in blood and cerebrospinal fluid. Using a combination of electronic absorption, circular dichroism and room-temperature electron paramagnetic resonance spectroscopies, together with potentiometric titrations, we competed the tripeptide GGH against HSA to reveal a conditional binding constant of log  =13.02±0.

Identification of the Binding Site of Apical Membrane Antigen 1 (AMA1) Inhibitors Using a Paramagnetic Probe.

Apical membrane antigen 1 (AMA1) is essential for the invasion of host cells by malaria parasites. Several small-molecule ligands have been shown to bind to a conserved hydrophobic cleft in Plasmodium falciparum AMA1. However, a lack of detailed structural information on the binding pose of these molecules has hindered their further optimisation as inhibitors.

Oligopeptides Generated by Neprilysin Degradation of β-Amyloid Have the Highest Cu(II) Affinity in the Whole Aβ Family.

The catabolism of β-amyloid (Aβ) is carried out by numerous endopeptidases including neprilysin, which hydrolyzes peptide bonds preceding positions 4, 10, and 12 to yield Aβ and a minor Aβ species. Alternative processing of the amyloid precursor protein by β-secretase also generates the Aβ species. All these peptides contain a Xxx-Yyy-His sequence, also known as an ATCUN or NTS motif, making them strong chelators of Cu(II) ions.

The N-terminal 14-mer model peptide of human Ctr1 can collect Cu(ii) from albumin. Implications for copper uptake by Ctr1.

Human cells acquire copper primarily via the copper transporter 1 protein, hCtr1. We demonstrate that at extracellular pH 7.4 CuII is bound to the model peptide hCtr11-14via an ATCUN motif and such complexes are strong enough to collect CuII from albumin, supporting the potential physiological role of CuII binding to hCtr1.

Structural Insight into Redox Dynamics of Copper Bound N-Truncated Amyloid-β Peptides from in Situ X-ray Absorption Spectroscopy.

X-ray absorption spectroscopy of Cu amyloid-β peptide (Aβ) under in situ electrochemical control (XAS-EC) has allowed elucidation of the redox properties of Cu bound to truncated peptide forms. The Cu binding environment is significantly different for the Aβ and the N-truncated Aβ, Aβ, and Aβ (Aβ) peptides, where the N-truncated sequence (FRH) provides the high-affinity amino-terminal copper nickel (ATCUN) binding motif. Low temperature (ca.

Interplay between Copper, Neprilysin, and N-Truncation of β-Amyloid.

Sporadic Alzheimer's disease (AD) is associated with an inefficient clearance of the β-amyloid (Aβ) peptide from the central nervous system. The protein levels and activity of the Zn-dependent endopeptidase neprilysin (NEP) inversely correlate with brain Aβ levels during aging and in AD. The present study considered the ability of Cu ions to inhibit human recombinant NEP and the role for NEP in generating N-truncated Aβ fragments with high-affinity Cu binding motifs that can prevent this inhibition.

Prion protein cleavage fragments regulate adult neural stem cell quiescence through redox modulation of mitochondrial fission and SOD2 expression.

Neurogenesis continues in the post-developmental brain throughout life. The ability to stimulate the production of new neurones requires both quiescent and actively proliferating pools of neural stem cells (NSCs). Actively proliferating NSCs ensure that neurogenic demand can be met, whilst the quiescent pool makes certain NSC reserves do not become depleted.

The Cu(II) affinity of the N-terminus of human copper transporter CTR1: Comparison of human and mouse sequences.

Copper Transporter 1 (CTR1) is a homotrimeric membrane protein providing the main route of copper transport into eukaryotic cells from the extracellular milieu. Its N-terminal extracellular domain, rich in His and Met residues, is considered responsible for directing copper into the transmembrane channel. Most of vertebrate CTR1 proteins contain the His residue in position three from N-terminus, creating a well-known Amino Terminal Cu(II)- and Ni(II)-Binding (ATCUN) site.

Electron paramagnetic resonance microscopy using spins in diamond under ambient conditions.

Magnetic resonance spectroscopy is one of the most important tools in chemical and bio-medical research. However, sensitivity limitations typically restrict imaging resolution to ~ 10 µm. Here we bring quantum control to the detection of chemical systems to demonstrate high-resolution electron spin imaging using the quantum properties of an array of nitrogen-vacancy centres in diamond.

In Vivo-Near Infrared Imaging of Neurodegeneration.

In vivo near-infrared (NIR) imaging of molecular processes at the preclinical stage promises to provide more valuable mechanistic information about pathological pathways involved in neurodegeneration. NIR imaging has the potential to improve in vivo therapeutic screening protocols by enabling noninvasive monitoring of presymptomatic responses to treatment. We have developed new NIR fluorescent contrast agents conjugated to markers of cell death, and using these agents we have identified molecular pathways associated with prion-induced neurodegeneration and determined the optimal window for meaningful therapeutic intervention in prion disease.

The Case for Abandoning Therapeutic Chelation of Copper Ions in Alzheimer's Disease.

The "therapeutic chelation" approach to treating Alzheimer's disease (AD) evolved from the metals hypothesis, with the premise that small molecules can be designed to prevent transition metal-induced amyloid deposition and oxidative stress within the AD brain. Over more than 20 years, countless studies have been devoted to characterizing metal binding, its effect on Aβ aggregation, ROS production, and toxicity. Despite a lack of evidence for any clinical benefit, the conjecture that therapeutic chelation is an effective approach for treating AD remains widespread.

Systematically Studying the Effect of Fluoride on the Properties of Cyclophanes Bearing Naphthalene Diimide and Dialkoxyaryl Groups.

Anion-π interactions between the Lewis basic anion fluoride and π-acidic naphthalene diimide was systematically studied in a series of cyclophanes in which the properties are modulated through the influence of a second, electron-rich aromatic unit. The systems and subsequently generated radical anions, upon addition of fluoride, were studied by absorption spectroscopic and EPR techniques. The results infer a modulation as a result of the nature and strength of the π-π interaction in the macrocyclic structure.

Interactions of α-Factor-1, a Yeast Pheromone, and Its Analogue with Copper(II) Ions and Low-Molecular-Weight Ligands Yield Very Stable Complexes.

α-Factor-1 (WHWLQLKPGQPMY), a peptidic pheromone of Saccharomyces cerevisiae yeast, contains a XHX type copper(II) binding N-terminal site. Using a soluble analogue, WHWSKNR-amide, we demonstrated that the W(1)H(2)W(3) site alone binds copper(II) with a Kd value of 0.18 pM at pH 7.

Copper Exchange and Redox Activity of a Prototypical 8-Hydroxyquinoline: Implications for Therapeutic Chelation.

The N-truncated β-amyloid (Aβ) isoform Aβ4-x is known to bind Cu(2+) via a redox-silent ATCUN motif with a conditional Kd = 30 fM at pH 7.4. This study characterizes the Cu(2+) interactions and redox activity of Aβx-16 (x = 1, 4) and 2-[(dimethylamino)-methyl-8-hydroxyquinoline, a terdentate 8-hydroxyquinoline (8HQ) with a conditional Kd(CuL) = 35 pM at pH 7.

A 2-Substituted 8-Hydroxyquinoline Stimulates Neural Stem Cell Proliferation by Modulating ROS Signalling.

Eight-hydroxyquinolines (8HQs) are a class of compounds that have been identified as potential therapeutics for a number of neurodegenerative diseases. Understanding the influence of structural modifications to the 8HQ scaffold on cellular behaviour will aid the identification of compounds that might be effective in treating dementias. In this study, we describe the action of 2-[(dimethylamino)methyl]-8-hydroxyquinoline (DMAMQ) on adult murine neural stem cells (NSCs) cultured in vitro.

Resistance of Cu(Aβ4-16) to Copper Capture by Metallothionein-3 Supports a Function for the Aβ4-42 Peptide as a Synaptic Cu(II) Scavenger.

Aβ4-42 is a major species of Aβ peptide in the brains of both healthy individuals and those affected by Alzheimer's disease. It has recently been demonstrated to bind Cu(II) with an affinity approximately 3000 times higher than the commonly studied Aβ1-42 and Aβ1-40 peptides, which are implicated in the pathogenesis of Alzheimer's disease. Metallothionein-3, a protein considered to orchestrate copper and zinc metabolism in the brain and provide antioxidant protection, was shown to extract Cu(II) from Aβ1-40 when acting in its native Zn7 MT-3 form.