SK609, a novel dopamine D3 receptor agonist and norepinephrine transporter blocker with putative pro-cognitive actions, does not induce psychostimulant-like increases in risky choice during probabilistic discounting.

Rationale: Psychostimulants, such as amphetamine (AMPH) and methylphenidate (MPH), non-selectively elevate extracellular concentrations of the catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), and are common pharmacological strategies used to improve prefrontal cortex (PFC)-dependent cognitive dysfunction. However, this approach can be problematic given AMPH has been shown to increase preference for risky choices in a rodent assay of risk/reward decision making. SK609 is a novel NE reuptake blocker that selectively activates DA D3 receptors without affinity for the DA transporter.

Dynamic spatial network simulation accounting for multiple ecological factors provides practical recommendations for biosecurity early detection and rapid response (EDRR) strategies.

Background: Globally the spread of invasive pests is being facilitated by increased human mobility and climate change. Simulation modelling can help assess biosecurity strategies for early detection and rapid response (EDRR), but has struggled to account for important factors in the invasion process, such as spatial and temporal variability in habitat suitability and connectivity; population dynamics; and multiple dispersal pathways. We developed a novel dynamic spatial network simulation approach based on spatial network theory that enables integration of a wider range of spatio-temporal factors than previous studies, calibrated it against extensive historical trapping data, and applied it to comprehensively analyse the EDRR strategy for Oriental fruit fly (Bactrocera dorsalis; OFF) in northern Australia.

Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors.

The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution has woven the LC into wide-ranging neural circuits that influence functions as broad as autonomic systems, the stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility that LC activity is inherently similar across species, and furthermore that age, sex, and brain state influence LC activity similarly across species.

Sex-dependent perturbations in risky choice behavior and prefrontal tyrosine hydroxylase levels induced by repetitive mild traumatic brain injury.

Head trauma often impairs cognitive processes mediated within the prefrontal cortex (PFC), leading to impaired decision making and risk-taking behavior. Mild traumatic brain injury (mTBI) accounts for approximately 80 % of reported head injury cases. Most neurological symptoms of a single mTBI are transient; however, growing evidence suggests that repeated mTBI (rmTBI) results in more severe impairments that worsen with each subsequent injury.

In search of the locus coeruleus: guidelines for identifying anatomical boundaries and electrophysiological properties of the blue spot in mice, fish, finches, and beyond.

Our understanding of human brain function can be greatly aided by studying analogous brain structures in other organisms. One brain structure with neurochemical and anatomical homology throughout vertebrate species is the locus coeruleus (LC), a small collection of norepinephrine (NE)-containing neurons in the brainstem that project throughout the central nervous system. The LC is involved in nearly every aspect of brain function, including arousal and learning, which has been extensively examined in rats and nonhuman primates using single-unit recordings.

Repetitive mild traumatic brain injury impairs norepinephrine system function and psychostimulant responsivity.

Traumatic brain injury (TBI) is a complex pathophysiological process that results in a variety of neurotransmitter, behavioral, and cognitive deficits. The locus coeruleus-norepinephrine (LC-NE) system is a critical regulator of arousal levels and higher executive processes affected by TBI including attention, working memory, and decision making. LC-NE axon injury and impaired signaling within the prefrontal cortex (PFC) is a potential contributor to the neuropsychiatric symptoms after single, moderate to severe TBI.

Perturbations in risk/reward decision making and frontal cortical catecholamine regulation induced by mild traumatic brain injury.

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers.

Levodopa use in Australia: an analysis of Pharmaceutical Benefits Scheme 10% data.

Background: Levodopa remains the mainstay of treatment of Parkinson's disease, however, over time motor fluctuations and levodopa-induced dyskinesia develop, requiring add-on therapies to control emerging symptoms. To date, however, there is no clear consensus in Australia, or elsewhere, at which dose of levodopa that add-on therapies should be considered.

Objectives: The purpose of this study was to examine the treatment patterns of patients with Parkinson's disease in Australia, with particular focus on levodopa doses at the time of first add-on.

Video atlas of each uniportal robotic-assisted thoracic surgery lobectomy and lymphadenectomy.

It is important when evaluating new techniques that a surgeon can see and assess all the differences and similarities between their usual technique and the novel technique. Thus, we have collated a comprehensive atlas of videos of uniportal robotic lobectomies for every lobe. Surgeons who are considering embarking on a program of uniportal robotic lobectomies can accordingly see the different views and techniques that will be required for when they perform their first procedure.

The transition to uniportal robotic surgery in the second decade of uniportal surgery.

Uniportal robotic surgery was created by Dr. Diego Gonzalez-Rivas as a fusion of his decade of experience with uniportal video-assisted thoracoscopic surgery (VATS) and his recent experience with the Intuitive Robotic System. It represents, in his view, the natural evolution of the uniportal technique in the era of robotic surgery.

Probing the structure and function of locus coeruleus projections to CNS motor centers.

The brainstem nucleus locus coeruleus (LC) sends projections to the forebrain, brainstem, cerebellum and spinal cord and is a source of the neurotransmitter norepinephrine (NE) in these areas. For more than 50 years, LC was considered to be homogeneous in structure and function such that NE would be released uniformly and act simultaneously on the cells and circuits that receive LC projections. However, recent studies have provided evidence that LC is modular in design, with segregated output channels and the potential for differential release and action of NE in its projection fields.

Using the Bayesian detection of potential risk using inference on blinded safety data (BDRIBS) method to support the decision to refer an event for unblinded evaluation.

In the Sponsor Responsibilities-Safety Reporting Requirements and Safety Assessment for IND and Bioavailability/Bioequivalence Studies: Draft Guidance for Industry (June 2021) the Food and Drug Administration recommends that sponsors develop a Safety Surveillance Plan as a key element of a systematic approach to safety surveillance and describes two possible approaches to assess the aggregate safety data. One approach regularly analyzes unblinded serious adverse events (SAEs) by treatment group. The alternative approach prespecifies estimated background rates for anticipated SAEs in the study population (e.

The Importance of Culture Change Associated With Novel Surgical Approaches and Innovation: Does Perioperative Care Transcend Technical Considerations for Pulmonary Lobectomy?

Robotic thoracic surgery for pulmonary lobectomy was introduced at our unit in 2015, along with enhanced perioperative patient care pathways. We evaluated the effect of this practice change on short-term outcomes. Data on all adult patients who underwent a lobectomy in our unit between 2015 and 2019 were obtained retrospectively from our surgical database.

Quantitative evaluation and comparison of coronary artery characteristics by 3D coronary volume reconstruction.

Non-atherosclerotic abnormalities of vessel calibre, aneurysm and ectasia, are challenging to quantify and are often overlooked in qualitative reporting. Utilising a novel 3-dimensional (3D) quantitative coronary angiography (QCA) application, we have evaluated the characteristics of normal, diabetic and aneurysmal or ectatic coronary arteries. We selected 131 individuals under 50 years-of-age, who had undergone coronary angiography for suspected myocardial ischaemia between 1st January 2011 and 31st December 2015, at the Bristol Heart Institute, Bristol, UK.

A novel dopamine D3R agonist SK609 with norepinephrine transporter inhibition promotes improvement in cognitive task performance in rodent and non-human primate models of Parkinson's disease.

Mild cognitive impairment is present in a number of neurodegenerative disorders including Parkinson's disease (PD). Mild cognitive impairment in PD (PD-MCI) often manifests as deficits in executive functioning, attention, and spatial and working memory. Clinical studies have suggested that the development of mild cognitive impairment may be an early symptom of PD and may even precede the onset of motor impairment by several years.

Effect of sugar-sweetened beverages on oral health: a systematic review and meta-analysis.

Background: The impact of consumption of sugar-sweetened beverages (SSB) on health outcomes such as obesity have been studied extensively, but oral health has been relatively neglected. This study aims to assess the association between SSB consumption and dental caries and erosion.

Methods: Systematic review of observational studies.

An Intersectional Viral-Genetic Method for Fluorescent Tracing of Axon Collaterals Reveals Details of Noradrenergic Locus Coeruleus Structure.

Understanding the function of broadly projecting neurons depends on comprehensive knowledge of the distribution and targets of their axon collaterals. While retrograde tracers and, more recently, retrograde viral vectors have been used to identify efferent projections, they have limited ability to reveal the full pattern of axon collaterals from complex, heterogeneous neuronal populations. Here we describe TrAC (tracing axon collaterals), an intersectional recombinase-based viral-genetic strategy that allows simultaneous visualization of axons from a genetically defined neuronal population and a projection-based subpopulation.

Three wound-dressing strategies to reduce surgical site infection after abdominal surgery: the Bluebelle feasibility study and pilot RCT.

Background: Surgical site infection (SSI) affects up to 20% of people with a primary closed wound after surgery. Wound dressings may reduce SSI.

Objective: To assess the feasibility of a multicentre randomised controlled trial (RCT) to evaluate the effectiveness and cost-effectiveness of dressing types or no dressing to reduce SSI in primary surgical wounds.

Selective vulnerability of dorsal raphe-medial prefrontal cortex projection neurons to corticosterone-induced hypofunction.

Glucocorticoid hormones and serotonin (5-HT) are strongly associated with the development and treatment of depression, respectively. Glucocorticoids regulate the function of serotonergic neurons in the dorsal raphe nucleus (DR), which are the major source of 5-HT to the forebrain. DR 5-HT neurons are electrophysiologically heterogeneous, though whether this phenotypic variation aligns with specific brain functions or neuropsychiatric disease states is largely unknown.

Selective activation of Dopamine D3 receptors and norepinephrine transporter blockade enhances sustained attention.

Catecholamine transmitters dopamine (DA) and norepinephrine (NE) regulate prefrontal cortical (PFC) circuit activity and PFC-mediated executive functions. Accordingly, pharmacological agents that influence catecholamine neurotransmission exert prominent effects on cognition. Many such agents are used clinically to treat attention disorders.

The locus coeruleus-norepinephrine system and sensory signal processing: A historical review and current perspectives.

Many studies in intact animals have shown that locally applied or synaptically released norepinephrine (NE) can enhance individual neuron and neural network responses to sensory inputs. However, a major unanswered question is how and when noradrenergically-mediated changes in sensory signal processing can influence downstream decision making, motor responding, and ultimately behavioral outcomes. Recent work using a variety of approaches in different sensory networks has started to consider this question.

Bayesian detection of potential risk using inference on blinded safety data.

Safety surveillance is a critical issue for ongoing clinical trials to actively identify and evaluate important safety information. With the new regulatory emphasis on aggregate review of safety, sponsors are faced with the challenge to develop systematic and sound quantitative methods to assess risk from blinded safety data during the pre-approval period of a new therapy. To address this challenge, a novel statistical method is proposed to monitor and detect safety signals with data from blinded ongoing clinical trials, specifically for adverse events of special interest (AESI) when historical data are available to provide background rates.

Considering noradrenergically mediated facilitation of sensory signal processing as a component of psychostimulant-induced performance enhancement.

Prescription stimulants are used to treat attention deficit hyperactivity disorder (ADHD). Psychostimulants are also used off-label by non-ADHD patients as performance-enhancing agents across academic, occupational, athletic, and social settings. Extensive work has focused on the reinforcing effects and abuse liability of psychostimulants, but understanding the mechanisms through which these agents regulate neural circuit functions that govern cognitive and sensorimotor processes to result in their performance-enhancing effects has received less attention.