The link between amyloid β and ferroptosis pathway in Alzheimer's disease progression.

Alzheimer's disease (AD) affects millions of people worldwide and represents the most prevalent form of dementia. Treatment strategies aiming to interfere with the formation of amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs), the two major AD hallmarks, have shown modest or no effect. Recent evidence suggests that ferroptosis, a type of programmed cell death caused by iron accumulation and lipid peroxidation, contributes to AD pathogenesis.

Impaired cellular copper regulation in the presence of ApoE4.

The strongest genetic risk factor for late-onset Alzheimer's disease (AD) is allelic variation of the APOE gene, with the following risk structure: ε4 > ε3 > ε2. The biochemical basis for this risk profile is unclear. Here, we reveal a new role for the APOE gene product, apolipoprotein E (ApoE) in regulating cellular copper homeostasis, which is perturbed in the AD brain.

Site of care and factors associated with mortality in unvaccinated Australian aged care residents during COVID-19 outbreaks.

Background: Residential InReach presents an alternative to hospital admission for aged care residents swabbed for coronavirus disease 2019 (COVID-19), although relative outcomes remain unknown.

Aims: To compare rates and predictors of 28-day mortality for aged care residents seen by InReach with COVID-19, or 'suspected COVID-19' (sCOVID), including hospital versus InReach-based care.

Methods: Prospective observational study of consecutive patients referred to a Victorian InReach service meeting COVID-19 testing criteria between April and October 2020 (prevaccine availability).

Googling Boundaries for Operating Mobile Stroke Unit for Stroke Codes.

Mobile stroke units (MSU) have been proposed to expedite delivery of recombinant tissue plasminogen activator (tPA) and expedite endovascular clot retrieval (ECR). Unexplored questions in the use of MSU include: maximal distance from base, time limit with regards to the use CT imaging, CT Angiography, CT Perfusion, and Telemedicine. We developed a computational model as an app (https://gntem3.

Paroxysmal and cognitive phenotypes in Prrt2 mutant mice.

Mutations in proline-rich transmembrane protein 2 (PRRT2) cause a range of episodic disorders that include paroxysmal kinesigenic dyskinesia and benign familial infantile epilepsy. Mutations are generally loss of function and include the c649dupC frameshifting mutation that is present in around 80% of affected individuals. To investigate how Prrt2 loss of function mutations causes disease, we performed a phenotypic investigation of a transgenic Prrt2 knockout (Prrt2 KO) mouse.

The Roc-COR tandem domain of leucine-rich repeat kinase 2 forms dimers and exhibits conventional Ras-like GTPase properties.

The Parkinson's disease (PD)-causative leucine-rich repeat kinase 2 (LRRK2) belongs to the Roco family of G-proteins comprising a Ras-of-complex (Roc) domain followed by a C-terminal of Roc (COR) domain in tandem (called Roc-COR domain). Two prokaryotic Roc-COR domains have been characterized as 'G proteins activated by guanine nucleotide-dependent dimerization' (GADs), which require dimerization for activation of their GTPase activity and bind guanine nucleotides with relatively low affinities. Additionally, LRRK2 Roc domain in isolation binds guanine nucleotides with relatively low affinities.

Role of the Personal KinetiGraph in the routine clinical assessment of Parkinson's disease: recommendations from an expert panel.

Evaluation of people with Parkinson's disease (PD) is often complex due to heterogeneity of symptoms and disease course, including the variability of motor fluctuations and dyskinesia. Routine clinical evaluations may be incomplete, may not accurately capture important symptoms, and may not reflect day-to-day variability. While significant advances have been made in wearable ambulatory continuous objective monitoring (COM) technologies, many clinicians remain uncertain of how to incorporate them in clinical practice, including the value to clinical decision-making.

Refining the ischemic penumbra with topography.

It has been 40 years since the ischemic penumbra was first conceptualized through work on animal models. The topography of penumbra has been portrayed as an infarcted core surrounded by penumbral tissue and an extreme rim of oligemic tissue. This picture has been used in many review articles and textbooks before the advent of modern imaging.

Non-Neurotoxic Nanodiamond Probes for Intraneuronal Temperature Mapping.

Optical biomarkers have been used extensively for intracellular imaging with high spatial and temporal resolution. Extending the modality of these probes is a key driver in cell biology. In recent years, the nitrogen-vacancy (NV) center in nanodiamond has emerged as a promising candidate for bioimaging and biosensing with low cytotoxicity and stable photoluminescence.

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.

A pilot randomized controlled trial of a tailored cognitive behavioural therapy based intervention for depressive symptoms in those newly diagnosed with multiple sclerosis.

Background: To examine the effectiveness and acceptability of an 8-week individual tailored cognitive behavioural therapy (CBT) intervention for the treatment of depressive symptoms in those newly diagnosed with multiple sclerosis.

Methods: The current study presents a pilot, parallel group randomized controlled trial (RCT) with an allocation ratio of 1:1 conducted in a large research and teaching hospital in Melbourne, Australia. 30 individuals with a mean age of 36.

Muscarinic receptor binding changes in postmortem Parkinson's disease.

Parkinson's disease (PD) is a devastating disorder, affecting approximately 2% of people aged 60 and above. It is marked by progressive neurodegeneration that has long been known to impact dopaminergic cells and circuits, but more recently the acetylcholine system has also been implicated in the complex aetiology and symptomatology of the disease. While broad changes in cholinergic markers have been described, insight into the contribution of specific acetylcholine receptors is less clear.

Mice Lacking or , or Both, Exhibit Behaviors Consistent with Neurodevelopmental Disorders.

, and Astrotactins () , are members of the Membrane Attack Complex/Perforin (MACPF) superfamily that are predominantly expressed in the mammalian brain during development. Genetic variation at the human and loci has been implicated in neurodevelopmental disorders. We, and others, have previously shown that mice exhibit behavior reminiscent of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).

Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia.

Disturbed mitochondrial fusion and fission have been linked to various neurodegenerative disorders. In siblings from two unrelated families who died soon after birth with a profound neurodevelopmental disorder characterized by pontocerebellar hypoplasia and apnoea, we discovered a missense mutation and an exonic deletion in the SLC25A46 gene encoding a mitochondrial protein recently implicated in optic atrophy spectrum disorder. We performed functional studies that confirmed the mitochondrial localization and pro-fission properties of SLC25A46.

Magneto-optical imaging of thin magnetic films using spins in diamond.

Imaging the fields of magnetic materials provides crucial insight into the physical and chemical processes surrounding magnetism, and has been a key ingredient in the spectacular development of magnetic data storage. Existing approaches using the magneto-optic Kerr effect, x-ray and electron microscopy have limitations that constrain further development, and there is increasing demand for imaging and characterisation of magnetic phenomena in real time with high spatial resolution. Here we show how the magneto-optical response of an array of negatively-charged nitrogen-vacancy spins in diamond can be used to image and map the sub-micron stray magnetic field patterns from thin ferromagnetic films.

A semi-automated "blanket" method for renal segmentation from non-contrast T1-weighted MR images.

Objective: To investigate the precision and accuracy of a new semi-automated method for kidney segmentation from single-breath-hold non-contrast MRI.

Materials And Methods: The user draws approximate kidney contours on every tenth slice, focusing on separating adjacent organs from the kidney. The program then performs a sequence of fully automatic steps: contour filling, interpolation, non-uniformity correction, sampling of representative parenchyma signal, and 3D binary morphology.

Perfusion computed tomography to assist decision making for stroke thrombolysis.

The use of perfusion imaging to guide selection of patients for stroke thrombolysis remains controversial because of lack of supportive phase three clinical trial evidence. We aimed to measure the outcomes for patients treated with intravenous recombinant tissue plasminogen activator (rtPA) at a comprehensive stroke care facility where perfusion computed tomography was routinely used for thrombolysis eligibility decision assistance. Our overall hypothesis was that patients with 'target' mismatch on perfusion computed tomography would have improved outcomes with rtPA.

Single nucleotide variations in CLCN6 identified in patients with benign partial epilepsies in infancy and/or febrile seizures.

Nucleotide alterations in the gene encoding proline-rich transmembrane protein 2 (PRRT2) have been identified in most patients with benign partial epilepsies in infancy (BPEI)/benign familial infantile epilepsy (BFIE). However, not all patients harbor these PRRT2 mutations, indicating the involvement of genes other than PRRT2. In this study, we performed whole exome sequencing analysis for a large family affected with PRRT2-unrelated BPEI.

A conditioned response as a measure of impulsive-compulsive behaviours in Parkinson's disease.

Objectives: Parkinson's Disease patients wore a device on the wrist that gave reminders to take levodopa and also measured bradykinesia and dyskinesia. Consumption of medications was acknowledged by placing the thumb on the device. Some patients performed this acknowledgement repeatedly and unconsciously.

Arterial spin labeling versus bolus-tracking perfusion in hyperacute stroke.

Background And Purpose: Arterial spin labeling (ASL) is a perfusion magnetic resonance imaging (MRI) technique that does not require contrast administration and thus may be more practical in hyperacute stroke than susceptibility-weighted bolus-tracking perfusion-weighted imaging (PWI). However, a threshold for ASL measurement of the ischemic penumbra needs to be determined.

Methods: A total of 58 patients with acute hemispheric ischemic stroke were imaged within 6 hours of symptom onset with MRI including ASL, diffusion-weighted MRI (DWI), and PWI, after perfusion computed tomography (CTP).

Measuring activity levels at an acute stroke ward: comparing observations to a device.

Background: If a simple system of instrumented monitoring was possible early after stroke, therapists may be able to more readily gather information about activity and monitor progress over time. Our aim was to establish whether a device containing a dual-axis accelerometer provides similar information to behavioural mapping on physical activity patterns early after stroke.

Methods: Twenty participants with recent stroke ≤ 2 weeks and aged >18 were recruited and monitored at an acute stroke ward.

Recanalisation success is associated with good clinical outcome despite advanced age and stroke severity in patients treated with the Solitaire stentriever.

Intravenous recombinant tissue plasminogen activator is associated with significant recanalisation failure in the setting of large artery occlusion. Endovascular treatment by stentriever achieves improved rates of recanalisation but its impact on clinical outcomes remains unclear. We hypothesise that successful recanalisation, unattentuated by age and stroke severity, is associated with improved clinical outcomes in patients treated with the Solitaire stentriever (ev3 Endovascular, Plymouth, MN, USA).

Transplantation of fetal midbrain dopamine progenitors into a rodent model of Parkinson's disease.

Cell therapy is a promising experimental treatment for Parkinson's disease (PD). It is based on the idea that new dopamine neurons transplanted directly into the forebrain of the patient can structurally and functionally compensate for those lost to the disease in order to restore motor function. While there is a highly active field of research focused on the development of stem cell-based procedures, fetal tissue remains the "gold standard" as a safe and reliable source of dopamine neuron progenitors capable of structural and functional integration with existing motor circuitry following transplantation.