Development of VU6036864: A Triazolopyridine-Based High-Quality Antagonist Tool Compound of the M Muscarinic Acetylcholine Receptor.

While the muscarinic acetylcholine receptor mAChR subtype 5 (M) has been studied over decades, recent findings suggest that more in-depth research is required to elucidate a thorough understanding of its physiological function related to neurological and psychiatric disorders. Our efforts to identify potent, selective, and pharmaceutically favorable next-generation M antagonist tool compounds have led to the discovery of a novel triazolopyridine-based series. In particular, () showed exquisite potency (human M IC = 20 nM), good subtype selectivity (>500 fold selectivity against human M), desirable brain exposure ( = 0.

Validation of a non-food or water motivated effort-based foraging task as a measure of motivational state in male mice.

Disorders of motivation such as apathy syndrome are highly prevalent across neurological disorders but do not yet have an agreed treatment approach. The use of translational behavioural models can provide a route through which to meaningfully screen novel drug targets. Methods that utilise food deprivation in contrived environments may lack the sensitivity to detect deficits in self-initiated behaviour, and may have limited translation to normal behaviour.

Risk Factors and Emergency Department Outcomes in Methamphetamine-Associated Cardiomyopathy: A Case-Control Study.

Background: Methamphetamine-associated cardiomyopathy (MACM) is a known complication of methamphetamine use; however, risk factors and outcomes of patients with MACM are not well understood.

Study Objectives: This study aims to identify risk factors, emergency department (ED) interventions, and outcomes for MACM.

Methods: This case-control study was conducted between 2012 and 2020 at two academic EDs.

Characterisation of behaviours relevant to apathy syndrome in the aged male rat.

Apathy is a complex psychiatric syndrome characterised by motivational deficit, emotional blunting and cognitive changes. It occurs alongside a broad range of neurological disorders, but also occurs in otherwise healthy ageing. Despite its clinical prevalence, apathy does not yet have a designated treatment strategy.

Controlling Nucleation Sites for Metal Oxide Film Growth on Glassy Carbon via Electrochemical Preoxidation.

Coating electrode materials with metal oxide thin films can improve the performance of electrocatalysts and charge storage materials. Atomic layer deposition (ALD) enables the deposition of conformal, uniform films on a wide range of electrodes; however, an even film depends on the availability of nucleation sites directly on the electrode surface. Here, we show that the electrochemical oxidation of glassy carbon electrodes prior to the deposition of alumina thin films by ALD leads to more uniform electrochemically passivating films.

Student-led pop-up health check clinics: innovative health prevention strategy for a low socioeconomic community.

Background: To improve preventative health screening in regional Victoria, Australia, a collaborative student-led health prevention strategy was initiated. The aim of this study is to evaluate the impact of four health check clinics using a free 'pop-up' format within community settings.

Methods: A mixed methods, explanatory sequential design was used to explore community health data and participant experiences in utilising the free health check clinics.

Pharmacological characterisation of the effort for reward task as a measure of motivation for reward in male mice.

Rationale: Motivational deficits are a common symptom shared across multiple psychiatric and neurodegenerative disorders. Effort-based decision-making tasks are a translatable method for assessing motivational state. Much of the preclinical validation of the task derives from acute pharmacological manipulations in rats.

"If I Can't Do It, Who Will?" Lived Experiences of Australian Emergency Nurses During the First Year of the COVID-19 Pandemic.

Introduction: The World Health Organization estimates that approximately 180,000 health care workers have died in the fight against COVID-19. Emergency nurses have experienced relentless pressure in maintaining the health and well-being of their patients, often to their detriment.

Methods: This research aimed to gain an understanding of lived experiences of Australian emergency nurses working on the frontline during the first year of the COVID-19 pandemic.

Successful Glenohumeral Shoulder Reduction With Combined Suprascapular and Axillary Nerve Block.

Background: Anterior glenohumeral dislocation is a common injury seen in the emergency department (ED) that sometimes requires procedural sedation for manual reduction. When compared with procedural sedation for dislocation reductions, peripheral nerve blocks provide similar patient satisfaction scores but have shorter ED length of stays. In this case report, we describe the first addition of an ultrasound-guided axillary nerve block to a suprascapular nerve block for reduction of an anterior shoulder dislocation in the ED.

Exploring the experiences of frontline nurses during the first 6 months of the COVID-19 pandemic: An integrated literature review.

Aim: The aim of this study was to explore the experiences of frontline nurses caring for patients during the first 6 months of the COVID-19 pandemic.

Design: The JBI manual for evidence synthesis and the PRISMA guidelines for reporting.

Data Sources: CINAHL Complete, MEDLINE, PsycINFO (EBSCO) and Scopus (Elsevier).

The importance of a multidimensional approach to the preclinical study of major depressive disorder and apathy.

Both the neuropsychiatric syndrome of apathy and major depressive disorder comprise a heterogenous cluster of symptoms which span multiple behavioural domains. Despite this heterogeneity, there is a tendency in the preclinical literature to conclude a MDD or apathy-like phenotype from a single dimensional behavioural task used in isolation, which may lead to inaccurate phenotypic interpretation. This is significant, as apathy and major depressive disorder are clinically distinct with different underlying mechanisms and treatment approaches.

Probing growth of metal-organic frameworks with X-ray scattering and vibrational spectroscopy.

Nucleation and crystallization arising from liquid to solid phase are involved in a multitude of processes in fields ranging from materials science to biology. Controlling the thermodynamics and kinetics of growth is advantageous to help tune the formation of complex morphologies. Here, we harness wide-angle X-ray scattering and vibrational spectroscopy to elucidate the mechanism for crystallization and growth of the metal-organic framework Co-MOF-74 within microscopic volumes enclosed in a capillary and an attenuated total reflection microchip reactor.

Modelling falls in Parkinson's disease and normal ageing in mice using a complex motor task.

Falls resulting from multifactorial deficits are common in both normal ageing and Parkinson's disease. Resultant injuries can lead to increased hospitalisation and excess mortality. As the disease progresses, gait and balance deficits are relatively refractory to dopaminergic treatments suggesting another system is involved.

The use of ball pits and playpens in laboratory Lister Hooded male rats induces ultrasonic vocalisations indicating a more positive affective state and can reduce the welfare impacts of aversive procedures.

The advancement and quality of science rely on research that is robust and unbiased in its experimental design, execution, analysis, and reproducibility. In preclinical research, a better understanding of animal emotions and refinement of their husbandry, housing, and handling are important goals in providing good animal welfare in a laboratory setting which underpins rigorous research quality. Induction of positive emotional state in animals is a key component of their well-being, and one approach is to increase their environmental complexity using, for example, ball pits or playpens in rats.

Evidence for deficits in behavioural and physiological responses in aged mice relevant to the psychiatric symptom of apathy.

Apathy is widely reported in patients with neurological disorders or post viral infection but is also seen in otherwise-healthy aged individuals. This study investigated whether aged male mice express behavioural and physiological changes relevant to an apathy phenotype. Using measures of motivation to work for reward, we found deficits in the progressive ratio task related to rate of responding.

Buffered Coordination Modulation as a Means of Controlling Crystal Morphology and Molecular Diffusion in an Anisotropic Metal-Organic Framework.

Significant advances have been made in the synthesis of chemically selective environments within metal-organic frameworks, yet materials development and industrial implementation have been hindered by the inability to predictively control crystallite size and shape. One common strategy to control crystal growth is the inclusion of coordination modulators, which are molecular species designed to compete with the linker for metal coordination during synthesis. However, these modulators can simultaneously alter the pH of the reaction solution, an effect that can also significantly influence crystal morphology.

Interfacial Field-Driven Proton-Coupled Electron Transfer at Graphite-Conjugated Organic Acids.

Interfacial proton-coupled electron transfer (PCET) reactions are central to the operation of a wide array of energy conversion technologies, but molecular-level insights into interfacial PCET are limited. At carbon surfaces, designer sites for interfacial PCET can be incorporated by conjugating organic acid functional groups to graphite edges though aromatic phenazine linkages. At these graphite-conjugated catalysts (GCCs) bearing organic acid moieties, PCET is driven by complex interfacial electrostatic and field gradients that are difficult to probe experimentally.

Impaired Self-Awareness after Pediatric Traumatic Brain Injury: Protective Factor or Liability?

Children and adolescents with traumatic brain injury (TBI) can experience impaired self-awareness, or difficulty in accurately perceiving their personal abilities. This study aimed to identify the neuro-developmental and socio-environmental factors associated with self-awareness impairment and determine how self-awareness is associated with psychosocial functioning. Parents and their children age 8-16 years with TBI ( = 107, 65.

[Formula: see text] Investigation of children and adolescents' mood and self-concept after acquired brain injury.

Few studies have examined the self-reported mental health of children with an acquired brain injury (ABI). The current study aimed to: 1) identify levels of child-reported depressive and anxiety symptoms and poor self-concept, 2) investigate demographic and injury-related factors associated with children's mood and self-concept, and 3) examine associations between children's self-reported mental health and parents' reports of children's emotional and behavioral functioning in children specifically with traumatic brain injury (TBI). 122 children (66% male) aged 8-16 years with ABI of mixed etiology were consecutively recruited through an outpatient rehabilitation clinic.

Molecular Control of Heterogeneous Electrocatalysis through Graphite Conjugation.

The efficient interconversion of electrical and chemical energy requires catalysts capable of accelerating multielectron reactions at or near electrified interfaces. These reactions can be performed at metallic surface sites on heterogeneous electrocatalysts or through redox mediation at molecular electrocatalysts. The relative ease of synthesis and characterization for homogeneous catalysts has allowed for molecular-level control over the active site and permitted systematic tuning of activity and selectivity.

Graphite Conjugation Eliminates Redox Intermediates in Molecular Electrocatalysis.

The efficient interconversion of electrical and chemical energy requires the intimate coupling of electrons and small-molecule substrates at catalyst active sites. In molecular electrocatalysis, the molecule acts as a redox mediator which typically undergoes oxidation or reduction in a separate step from substrate activation. These mediated pathways introduce a high-energy intermediate, cap the driving force for substrate activation at the reduction potential of the molecule, and impede access to high rates at low overpotentials.

Graphite-Conjugated Acids Reveal a Molecular Framework for Proton-Coupled Electron Transfer at Electrode Surfaces.

Proton-coupled electron-transfer (PCET) steps play a key role in energy conversion reactions. Molecular PCET reactions are well-described by "square schemes" in which the overall thermochemistry of the reaction is broken into its constituent proton-transfer and electron-transfer components. Although this description has been essential for understanding molecular PCET, no such framework exists for PCET reactions that take place electrode surfaces.

Chemoinformatic Consideration of Novel Psychoactive Substances: Compilation and Preliminary Analysis of a Categorised Dataset.

Recent years have seen the emergence into circulation of a growing array of novel psychoactive substances (NPS). Knowledge of the pharmacological profiles and risk liability of these compounds is typically very scarce. Development of chemoinformatic tools enabling prediction of properties within uncharacterised analogues has potential be of particular use.