Implementation and evaluation of pharmacist-led heart failure diagnostic and guideline directed medication therapies clinic.

Background: Timely diagnosis of heart failure (HF) and rapid optimisation of guideline-directed medication therapy (GDMT) improves patients qualities of life, reducing mortality and morbidity. Previous papers describe the role of pharmacists in medication optimisation, but not in the diagnosis of HF.

Aim: To describe the development, implementation, and evaluation of pharmacist-led heart failure clinics with respect to time from referral to diagnosis, time from diagnosis to first review with a specialist, and the proportion receiving optimal GDMT 180 days after diagnosis.

Multi-endpoint in vitro toxicological assessment of snus and tobacco-free nicotine pouch extracts.

'Modern' oral tobacco-free nicotine pouches (NPs) are a nicotine containing product similar in appearance and concept to Swedish snus. A three-step approach was taken to analyse the biological effects of NPs and snus extracts in vitro. ToxTracker was used to screen for biomarkers for oxidative stress, cell stress, protein damage and DNA damage.

Complement activation and increased anaphylatoxin receptor expression are associated with cortical grey matter lesions and the compartmentalised inflammatory response of multiple sclerosis.

Background: The extent of cortical pathology is an important determinant of multiple sclerosis (MS) severity. Cortical demyelination and neurodegeneration are related to inflammation of the overlying leptomeninges, a more inflammatory CSF milieu and with parenchymal microglia and astroglia activation. These are all components of the compartmentalised inflammatory response.

Hacking techniques improve health and nutritional status of nestling White-tailed Eagles.

Birds of prey frequently feature in reintroductions and the hacking technique is typically used. Hacking involves removing large nestlings from donor populations, transferring them to captivity, feeding them ad libitum. Potentially, via the hacking method, the stress of captivity and disruption of parental feeding may be detrimental.

Factors affecting the seasonal distribution and biomass of E. pacifica and T. spinifera along the Pacific coast of Canada: A spatiotemporal modelling approach.

Euphausiids are a keystone species in coastal food webs due to their high lipid content and seasonally high biomass. Understanding the habitat and environmental drivers that lead to areas of high biomass, or 'hotspots', and their seasonal persistence, will support the identification of important foraging regions for mid- and upper- trophic level predators. We quantify the distribution of hotspots of the two dominant species of euphausiid in the north-east Pacific Ocean: Euphausia pacifica and Thysanoessa spinifera, as well as euphausiid larvae (mixed species).

Predicting the distribution of foraging seabirds during a period of heightened environmental variability.

Quantifying the links between the marine environment, prey occurrence, and predator distribution is the first step towards identifying areas of biological importance for marine spatial planning. Events such as marine heatwaves result in an anomalous change in the physical environment, which can lead to shifts in the structure, biomass, and distribution of lower trophic levels. As central-place foragers, seabirds are vulnerable to changes in their foraging grounds during the breeding season.

Factitious Disorder (Munchausen Syndrome) in Plastic Surgery: A Systematic Review of 42 Cases.

Introduction: Patients with factitious disorder (FD) or "Munchausen syndrome" intentionally fabricate or induce medical problems for psychological gratification. They may deceive plastic surgeons into performing multiple unnecessary procedures. We undertook the first systematic review of FD case reports in plastic surgery.

Meningeal inflammation and cortical demyelination in acute multiple sclerosis.

Objective: Cortical gray matter (GM) pathology, involving demyelination and neurodegeneration, associated with meningeal inflammation, could be important in determining disability progression in multiple sclerosis (MS). However, we need to know more about how cortical demyelination, neurodegeneration, and meningeal inflammation contribute to pathology at early stages of MS to better predict long-term outcome.

Methods: Tissue blocks from short disease duration MS (n = 12, median disease duration = 2 years), progressive MS (n = 21, disease duration = 25 years), non-diseased controls (n = 11), and other neurological inflammatory disease controls (n = 6) were quantitatively analyzed by immunohistochemistry, immunofluorescence, and in situ hybridization.

Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59.

Background: CD59, a broadly expressed glycosylphosphatidylinositol-anchored protein, is the principal cell inhibitor of complement membrane attack on cells. In the demyelinating disorders, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), elevated complement protein levels, including soluble CD59 (sCD59), were reported in cerebrospinal fluid (CSF).

Objectives: We compared sCD59 levels in CSF and matched plasma in controls and patients with MS, NMOSD and clinically isolated syndrome (CIS) and investigated the source of CSF sCD59 and whether it was microparticle associated.

Tissue microarray methodology identifies complement pathway activation and dysregulation in progressive multiple sclerosis.

The complement pathway has potential contributions to both white (WM) and grey matter (GM) pathology in Multiple Sclerosis (MS). A quantitative assessment of complement involvement is lacking. Here we describe the use of Tissue MicroArray (TMA) methodology in conjunction with immunohistochemistry to investigate the localization of complement pathway proteins in progressive MS cortical GM and subcortical WM.

Point-of-choice prompts to reduce sitting time at work: a randomized trial.

Background: Prolonged sitting is prevalent in the workplace and is associated with adverse health markers.

Purpose: Investigate the effects of point-of-choice (PoC) prompting software, on the computer used at work (PC), to reduce long uninterrupted sedentary periods and total sedentary time at work.

Design: Assessor-blinded, parallel group, active-controlled randomized trial.

Heterodimerization of ORL1 and opioid receptors and its consequences for N-type calcium channel regulation.

We have investigated the heterodimerization of ORL1 receptors and classical members of the opioid receptor family. All three classes of opioid receptors could be co-immunoprecipitated with ORL1 receptors from both transfected tsA-201 cell lysate and rat dorsal root ganglia lysate, suggesting that these receptors can form heterodimers. Consistent with this hypothesis, in cells expressing either one of the opioid receptors together with ORL1, prolonged ORL1 receptor activation via nociceptin application resulted in internalization of the opioid receptors.

Differential role of N-type calcium channel splice isoforms in pain.

N-type calcium channels are essential mediators of spinal nociceptive transmission. The core subunit of the N-type channel is encoded by a single gene, and multiple N-type channel isoforms can be generated by alternate splicing. In particular, cell-specific inclusion of an alternatively spliced exon 37a generates a novel form of the N-type channel that is highly enriched in nociceptive neurons and, as we show here, downregulated in a neuropathic pain model.

Presynaptic Ca2+ channels--integration centers for neuronal signaling pathways.

Calcium influx into presynaptic nerve terminals via voltage-gated Ca2+ channels is an essential step in neurotransmitter release. The predominant Ca2+ channel species in synaptic nerve terminals are P/Q-type and N-type channels, with their relative levels of expression varying across the nervous system. The different distributions of these two channel subtypes are reflected in their distinct physiological and pathological roles, yet their activity is regulated by common mechanisms and both function as part of larger signaling complexes that enable their precise regulation and subcellular targeting.

Functional analysis of Ca3.2 T-type calcium channel mutations linked to childhood absence epilepsy.

Purpose: Childhood absence epilepsy (CAE) is an idiopathic form of seizure disorder that is believed to have a genetic basis.

Methods: We examined the biophysical consequences of seven mutations in the Ca(v)3.2 T-type calcium channel gene linked to CAE.

ORL1 receptor-mediated internalization of N-type calcium channels.

The inhibition of N-type calcium channels by opioid receptor like receptor 1 (ORL1) is a key mechanism for controlling the transmission of nociceptive signals. We recently reported that signaling complexes consisting of ORL1 receptors and N-type channels mediate a tonic inhibition of calcium entry. Here we show that prolonged ( approximately 30 min) exposure of ORL1 receptors to their agonist nociceptin triggers an internalization of these signaling complexes into vesicular compartments.

A study comparing the actions of gabapentin and pregabalin on the electrophysiological properties of cultured DRG neurones from neonatal rats.

Background: Gabapentin and pregabalin have wide-ranging therapeutic actions, and are structurally related to the inhibitory neurotransmitter GABA. Gabapentin, pregablin and GABA can all modulate voltage-activated Ca2+ channels. In this study we have used whole cell patch clamp recording and fura-2 Ca2+ imaging to characterise the actions of pregabalin on the electrophysiological properties of cultured dorsal root ganglion (DRG) neurones from neonatal rats.

Multiple actions of anandamide on neonatal rat cultured sensory neurones.

1. We have investigated the effects of the endocannabinoid anandamide (AEA) on neuronal excitability and vanilloid TRPV1 receptors in neonatal rat cultured dorsal root ganglion neurones. 2.