Dysregulation of the Kynurenine Pathway in Relapsing Remitting Multiple Sclerosis and Its Correlations With Progressive Neurodegeneration.

Background And Objectives: Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through the production of neurotoxic metabolites. Among the 8 KP metabolites, six of them, namely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration.

Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study.

Background: Ulcerative colitis (UC) is a chronic inflammatory condition requiring continuous treatment and monitoring. There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.

Aim: To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.

The Future Hospital in Global Health Systems: The Future Hospital as an Entity.

Health care is changing rapidly. Hospitals are, and will remain, an essential setting to deliver it. We discuss how to maximise the benefits of hospitals in the future in different geographic and health system settings, highlighting a series of cross-cutting issues.

Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research.

Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure.

Focal granule cell bilamination of the dentate gyrus-its prevalence across the human age spectrum and review of the literature.

The prevalence of focal granule cell bilamination (FGCB) in the hippocampal dentate gyrus varies from 0% to 44%, depending on age and study population. FGCB is commonly thought to be a specific feature of temporal lobe epilepsy (TLE) but its prevalence in cases without TLE is unclear. Using formalin-fixed, paraffin-embedded hippocampal sections, this retrospective postmortem study evaluated the prevalence of FGCB and other granule cell pathologies in infants (1-12 months of age, n = 16), children (4-10 years, n = 6), and adults (28-91 years, n = 15) with no known history of epilepsy or seizures.

Slow dissociation kinetics of fentanyls and nitazenes correlates with reduced sensitivity to naloxone reversal at the μ-opioid receptor.

Background And Purpose: Fentanyls and nitazenes are μ-opioid receptor agonists responsible for a large number of opioid overdose deaths. Here, we determined the potency, dissociation kinetics and antagonism by naloxone at the μ receptor of several fentanyl and nitazene analogues, compared to morphine and DAMGO.

Experimental Approach: In vitro assays of G protein activation and signalling and arrestin recruitment were performed.

Therapeutic potential of 18-β-glycyrrhetinic acid-loaded poly (lactic-co-glycolic acid) nanoparticles on cigarette smoke-induced in-vitro model of COPD.

Chronic obstructive pulmonary disease (COPD) is strongly linked to cigarette smoke, which contains toxins that induce oxidative stress and airway inflammation, ultimately leading to premature airway epithelial cell senescence and exacerbating COPD progression. Current treatments for COPD are symptomatic and hampered by limited efficacy and severe side effects. This highlights the need to search for an optimal therapeutic candidate to address the root causes of these conditions.

Longitudinal associations between exercise and biomarkers in autosomal dominant Alzheimer's disease.

Introduction: We investigated longitudinal associations between self-reported exercise and Alzheimer's disease (AD)-related biomarkers in individuals with autosomal dominant AD (ADAD) mutations.

Methods: Participants were 308 ADAD mutation carriers aged 39.7 ± 10.

Theory and tests for coordination among hydraulic and photosynthetic traits in co-occurring woody species.

Co-occurring plants show wide variation in their hydraulic and photosynthetic traits. Here, we extended 'least-cost' optimality theory to derive predictions for how variation in key hydraulic traits potentially affects the cost of acquiring and using water in photosynthesis and how this, in turn, should drive variation in photosynthetic traits. We tested these ideas across 18 woody species at a temperate woodland in eastern Australia, focusing on hydraulic traits representing different aspects of plant water balance, that is storage (sapwood capacitance, C), demand vs supply (branch leaf : sapwood area ratio, A : A and leaf : sapwood mass ratio and M : M), access to soil water (proxied by predawn leaf water potential, Ψ) and physical strength (sapwood density, WD).

Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.

Background: Obstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment.

Methods: We conducted two phase 3, double-blind, randomized, controlled trials involving adults with moderate-to-severe obstructive sleep apnea and obesity.

Expanding the π-system of Fatty Acid-Anion Transporter Conjugates Modulates Their Mechanism of Proton Transport and Mitochondrial Uncoupling Activity.

Mitochondrial uncoupling by small molecule protonophores is a promising strategy for developing novel anticancer agents. Recently, aryl urea substituted fatty acids (aryl ureas) were identified as a new class of protonophoric anticancer agents. To mediate proton transport these molecules self-assemble into membrane-permeable anionic dimers in which intermolecular hydrogen bonds between the carboxylate and aryl-urea anion receptor delocalise the negative charge across the aromatic π-system.

Adaptation of COMPASS for use in Autism-Specific Schools in Australia: A Cluster Randomized Trial.

Autistic students are educated in Australia across a variety of contexts and almost all educators use individualized goal-setting as a way of ensuring appropriate accommodations and curriculum modifications. Educators experience similar challenges when developing individualized goals for students, including lack of a standardized process for goal setting, inconsistent support networks, and challenges with data-driven goal-setting. The purpose of our research was to adapt and trial the Collaborative Model for Competence and Success (COMPASS), a research-based intervention aimed at improving the individualized goal-setting process for autistic students.

[Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

Background: Enzalutamide and lutetium-177 [Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer.

18-β-glycyrrhetinic acid-loaded polymeric nanoparticles attenuate cigarette smoke-induced markers of impaired antiviral response in vitro.

Tobacco smoking is a leading cause of preventable mortality, and it is the major contributor to diseases such as COPD and lung cancer. Cigarette smoke compromises the pulmonary antiviral immune response, increasing susceptibility to viral infections. There is currently no therapy that specifically addresses the problem of impaired antiviral response in cigarette smokers and COPD patients, highlighting the necessity to develop novel treatment strategies.

Forest top canopy bacterial communities are influenced by elevation and host tree traits.

Background: The phyllosphere microbiome is crucial for plant health and ecosystem functioning. While host species play a determining role in shaping the phyllosphere microbiome, host trees of the same species that are subjected to different environmental conditions can still exhibit large degrees of variation in their microbiome diversity and composition. Whether these intra-specific variations in phyllosphere microbiome diversity and composition can be observed over the broader expanse of forest landscapes remains unclear.

3D Printing of Alginate/Chitosan-Based Scaffold Empowered by Tyrosol-Loaded Niosome for Wound Healing Applications: In Vitro and In Vivo Performances.

This study introduces a tyrosol-loaded niosome integrated into a chitosan-alginate scaffold (Nio-Tyro@CS-AL), employing advanced electrospinning and 3D printing techniques for wound healing applications. The niosomes, measuring 185.40 ± 6.

Institutionalizing health technology assessment in Ethiopia: seizing the window of opportunity.

Ethiopia's commitment to achieving universal health coverage (UHC) requires an efficient and equitable health priority-setting practice. The Ministry of Health aims to institutionalize health technology assessment (HTA) to support evidence-based decision making. This commentary highlights key considerations for successful formulation, adoption, and implementation of HTA policies and practices in Ethiopia, based on a review of international evidence and published normative principles and guidelines.

Cell-specific MAPT gene expression is preserved in neuronal and glial tau cytopathologies in progressive supranuclear palsy.

Microtubule-associated protein tau (MAPT) aggregates in neurons, astrocytes and oligodendrocytes in a number of neurodegenerative diseases, including progressive supranuclear palsy (PSP). Tau is a target of therapy and the strategy includes either the elimination of pathological tau aggregates or reducing MAPT expression, and thus the amount of tau protein made to prevent its aggregation. Disease-associated tau affects brain regions in a sequential manner that includes cell-to-cell spreading.

Treatment with the copper compound CuATSM has no significant effect on motor neuronal pathology in patients with ALS.

Aims: Although the orally available brain-penetrant copper compound CuATSM has demonstrated promising effects in SOD1-linked mouse models, the impact of CuATSM on disease pathology in patients with amyotrophic lateral sclerosis (ALS) remains unknown.

Methods: The present study set out to address this deficit by performing the first pilot comparative analysis of ALS pathology in patients that had been administered CuATSM and riluzole [N = 6 cases composed of ALS-TDP (n = 5) and ALS-SOD1 (n = 1)] versus riluzole only [N = 6 cases composed of ALS-TDP (n = 4) and ALS-SOD1 (n = 2)].

Results: Our results revealed no significant difference in neuron density or TDP-43 burden in the motor cortex and spinal cord of patients that had received CuATSM compared with patients that had not.

The health care and societal costs of inherited retinal diseases in Australia: a microsimulation modelling study.

Objectives: To estimate the health care and societal costs of inherited retinal diseases (IRDs) in Australia.

Design, Setting, Participants: Microsimulation modelling study based on primary data - collected in interviews of people with IRDs who had ophthalmic or genetic consultations at the Children's Hospital at Westmead or the Save Sight Institute (both Sydney) during 1 January 2019 - 31 December 2020, and of their carers and spouses - and linked Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Schedule (PBS) data.

Main Outcome Measures: Annual and lifetime costs for people with IRDs and for their carers and spouses, grouped by payer (Australian government, state governments, individuals, private health insurance) and type (health care costs; societal costs: social support, National Disability Insurance Scheme (NDIS), income and taxation, costs associated with caring for family members with IRDs); estimated annual national cost of IRDs.

Retinal arterial Aβ deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients.

Introduction: Vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that the retinal vascular tight junctions (TJs) were compromised and linked to disease status.

Methods: TJ components and Aβ expression in capillaries and larger blood vessels were determined in post mortem retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology.

First report of cereal yellow dwarf virus RPS infecting wheat in Australia.

Yellow dwarf viruses (YDVs) reduce grain yield in a wide range of cereal hosts worldwide. Cereal yellow dwarf virus RPV (CYDV RPV) and cereal yellow dwarf virus RPS (CYDV RPS) are members of the genus within the family (Scheets et al. 2020; Sõmera et al.