A novel peptide-based tau aggregation inhibitor as a potential therapeutic for Alzheimer's disease and other tauopathies.

Introduction: As aggregation underpins Tau toxicity, aggregation inhibitor peptides may have disease-modifying potential. They are therefore currently being designed and target either the VQIVYK aggregation-promoting hotspot found in all Tau isoforms or the VQIINK aggregation-promoting hotspot found in 4R isoforms. However, for any Tau aggregation inhibitor to potentially be clinically relevant for other tauopathies, it should target both hotspots to suppress aggregation of Tau isoforms, be stable, cross the blood-brain barrier, and rescue aggregation-dependent Tau phenotypes in vivo.

Characterization of Olive Oil Phenolic Extracts and Their Effects on the Aggregation of the Alzheimer's Amyloid-β Peptide and Tau.

The dietary consumption of extra virgin olive oil (EVOO) is believed to slow the progression of Alzheimer's disease (AD) symptoms. Its protective mechanisms are unclear, but specific EVOO phenolic compounds can individually impede the aggregation of amyloid-β (Aβ) peptides and the microtubule-associated protein tau, two important pathological manifestations of AD. It is unknown, however, whether the numerous and variable phenolic compounds that are consumed in dietary EVOO can collectively alter tau and Aβ aggregation as effectively as the individual compounds.

Factors leading to diagnostic delay in tuberculosis in the tropical north of Australia.

Background: Tuberculosis (TB) incidence is decreasing in the Northern Territory (NT) but still exceeds rates elsewhere in Australia. Deaths and morbidity from advanced TB continue, with delay in diagnosis a contributor to adverse outcomes.

Aims: We aimed to describe the delay in diagnosis of TB, identify risk factors for delay and examine the associations between delay and clinical outcomes.

Unveiling the Mechanism of the Formation of 3D Fiber Macroassemblies with Controlled Properties.

Electrospinning technique is well-known for the generation of different fibers. While it is a "simple" technique, it lies in the fact that the fibers are typically produced in the form of densely packed two-dimensional (2D) mats with limited thickness, shape, and porosity. The highly demanded three-dimensional (3D) fiber assemblies have been explored by time-consuming postprocessing and/or complex setup modifications.

Asgard archaea shed light on the evolutionary origins of the eukaryotic ubiquitin-ESCRT machinery.

The ESCRT machinery, comprising of multiple proteins and subcomplexes, is crucial for membrane remodelling in eukaryotic cells, in processes that include ubiquitin-mediated multivesicular body formation, membrane repair, cytokinetic abscission, and virus exit from host cells. This ESCRT system appears to have simpler, ancient origins, since many archaeal species possess homologues of ESCRT-III and Vps4, the components that execute the final membrane scission reaction, where they have been shown to play roles in cytokinesis, extracellular vesicle formation and viral egress. Remarkably, metagenome assemblies of Asgard archaea, the closest known living relatives of eukaryotes, were recently shown to encode homologues of the entire cascade involved in ubiquitin-mediated membrane remodelling, including ubiquitin itself, components of the ESCRT-I and ESCRT-II subcomplexes, and ESCRT-III and Vps4.

Impact behaviour of 3D printed cellular structures for mouthguard applications.

Ethylene-Vinyl Acetate (EVA) is the most popular material for manufacturing mouthguards. However, EVA mouthguards are problematic, for example inconsistent thicknesses across the mouthguard. Additive manufacturing provides a promising solution to this problem, as it can manufacture mouthguards with a greater precision.

Identification of venular capillary remodelling: a possible link to the development of periodontitis?

Purpose: The present study measured changes in arteriolar and venular capillary flow and structure in the gingival tissues during the development of plaque-induced gingival inflammation by combining dynamic optical coherence tomography (OCT), laser perfusion, and capillaroscopic video imaging.

Methods: Gingival inflammation was induced in 21 healthy volunteers over a 3-week period. Gingival blood flow and capillary morphology were measured by dynamic OCT, laser perfusion imaging, and capillaroscopy, including a baseline assessment of capillary glycocalyx thickness.

F Solid-State NMR and Vibrational Raman Characterization of Corticosteroid Drug-Lipid Membrane Interactions.

Drug interactions with phospholipid bilayers underpin their behaviour in cell membranes and in liposomal delivery formulations. Liposomal drug delivery in ocular medicine can overcome the physical barriers of the eye and better enable the active molecule to reach its target. Here, Raman and F solid-state NMR spectroscopy are used to characterise the interactions of two ocular corticosteroid drugs, difluprednate (DFP) and fluorometholone (FML), with multilamellar vesicles of phosphatidylcholine (PC).

Patient-specific Extravasation Dosimetry Using Uptake Probe Measurements.

Extravasation is a common problem in radiopharmaceutical administration and can result in significant radiation dose to underlying tissue and skin. The resulting radiation effects are rarely studied and should be more fully evaluated to guide patient care and meet regulatory obligations. The purpose of this work was to show that a dedicated radiopharmaceutical injection monitoring system can help clinicians characterize extravasations for calculating tissue and skin doses.

Validation of low-dose lung cancer PET-CT protocol and PET image improvement using machine learning.

Purpose: To conduct a simplified lesion-detection task of a low-dose (LD) PET-CT protocol for frequent lung screening using 30% of the effective PETCT dose and to investigate the feasibility of increasing clinical value of low-statistics scans using machine learning.

Methods: We acquired 33 SD PET images, of which 13 had actual LD (ALD) PET, and simulated LD (SLD) PET images at seven different count levels from the SD PET scans. We employed image quality transfer (IQT), a machine learning algorithm that performs patch-regression to map parameters from low-quality to high-quality images.

COVID-19 and the importance of space in entrepreneurship research and policy.

Given the COVID-19 crisis, the importance of space in the global economic system has emerged as critical in a hitherto unprecedented way. Even as large-scale, globally operating digital platform enterprises find new ways to thrive in the midst of a crisis, small and medium-sized enterprises (SMEs) nestled in local economies have proven to be fragile to shocks, causing countless local economies to unravel in the face of severe challenges to survival. Here, we discuss the role of entrepreneurship in re-building local economies that are more resilient.

Aggregation Kinetics and Filament Structure of a Tau Fragment Are Influenced by the Sulfation Pattern of the Cofactor Heparin.

A pathological signature of Alzheimer's disease (AD) is the formation of neurofibrillary tangles comprising filamentous aggregates of the microtubule associated protein tau. Tau self-assembly is accelerated by polyanions including heparin, an analogue of heparan sulfate. Tau filaments colocalize with heparan sulfate proteoglycans (HSPGs) in vivo, and HSPGs may also assist the transcellular propagation of tau aggregates.

Raman Spectroscopy with 2D Perturbation Correlation Moving Windows for the Characterization of Heparin-Amyloid Interactions.

It has been shown extensively that glycosaminoglycan (GAG)-protein interactions can induce, accelerate, and impede the clearance of amyloid fibrils associated with systemic and localized amyloidosis. Obtaining molecular details of these interactions is fundamental to our understanding of amyloid disease. Consequently, there is a need for analytical approaches that can identify protein conformational transitions and simultaneously characterize heparin interactions.

Circular Dichroism Spectroscopy Identifies the β-Adrenoceptor Agonist Salbutamol As a Direct Inhibitor of Tau Filament Formation .

Potential drug treatments for Alzheimer's disease (AD) may be found by identifying compounds that block the assembly of the microtubule-associated protein tau into neurofibrillar tangles associated with neuron destabilization and cell death. Here, a small library of structurally diverse compounds was screened for the ability to inhibit tau aggregation, using high-throughput synchrotron radiation circular dichroism as a novel tool to monitor the structural changes in the protein as it assembles into filaments. The catecholamine epinephrine was found to be the most effective tau aggregation inhibitor of all 88 screened compounds.

Pseudo-nitzschia bloom dynamics in the Gulf of Maine: 2012-2016.

The toxic diatom genus Pseudo-nitzschia is a growing presence in the Gulf of Maine (GOM), where regionally unprecedented levels of domoic acid (DA) in 2016 led to the first Amnesic Shellfish Poisoning closures in the region. However, factors driving GOM Pseudo-nitzschia dynamics, DA concentrations, and the 2016 event are unclear. Water samples were collected at the surface and at depth in offshore transects in summer 2012, 2014, and 2015, and fall 2016, and a weekly time series of surface water samples was collected in 2013.

Brown Adipose Tissue: Multimodality Evaluation by PET, MRI, Infrared Thermography, and Whole-Body Calorimetry (TACTICAL-II).

Objective: This study aimed to compare the associations of positron emission tomography (PET), magnetic resonance (MR), and infrared thermography (IRT) imaging modalities with energy expenditure (EE) after brown adipose tissue (BAT) activation using capsinoid ingestion and cold exposure.

Methods: Twenty participants underwent PET-MR, IRT imaging, and whole-body calorimetry after capsinoid ingestion and cold exposure. Standardized uptake values (SUV) and the fat fraction (FF) of the supraclavicular brown adipose tissue regions were estimated.

Quality Improvement Initiatives to Assess and Improve PET/CT Injection Infiltration Rates at Multiple Centers.

PET/CT radiotracer infiltration is not uncommon and is often outside the imaging field of view. Infiltration can negatively affect image quality, image quantification, and patient management. Until recently, there has not been a simple way to routinely practice PET radiopharmaceutical administration quality control and quality assurance.

Low dose positron emission tomography emulation from decimated high statistics: A clinical validation study.

Purpose: The fundamental nature of positron emission tomography (PET), as an event detection system, provides some flexibility for data handling, including retrospective data manipulation. The reorganization of acquisition data allows the emulation of new scans arising from identical radiotracer spatial distributions, but with different statistical compositions, and is especially useful for evaluating the stability and reproducibility of reconstruction algorithms or when investigating extremely low count conditions. This approach is ubiquitous in the research literature but has only been validated, from the point of view of the noise properties, with numerical simulations and phantom data.

Sub-clinical abnormalities detected by PET/MRI in household tuberculosis contacts.

Background: The understanding of early events following TB exposure is limited by traditional tests that rely on detection of an immune response to infection, which is delayed, or on imaging tests with low sensitivity for early disease. We investigated for evidence of lung abnormalities in heavily exposed TB contacts using PET/MRI.

Methods: 30 household contacts of 20 index patients underwent clinical assessment, IGRA testing, chest x-ray and PET/MRI scan using 18-F-FDG.

Correlation Between Personal Health History and Depression Self-Care Practices and Depression Screening Among African Americans With Chronic Conditions.

Little is known about the influence of personal health history and depression self-care practices on screening for depression by health care providers among African Americans with chronic conditions. African Americans (N = 203) aged 18 years or older and living with at least one chronic health condition in a metropolitan city completed a 45-item community perceptions survey. The number of depression symptoms experienced per month was positively associated with screening for depression by a health care provider; perceived ability to identify depression symptoms was inversely associated with screening by a health care provider.