Novel Poly-Arginine Peptide R18D Reduces α-Synuclein Aggregation and Uptake of α-Synuclein Seeds in Cortical Neurons.

Background/objectives: The role of α-synuclein (α-syn) pathology in Parkinson's disease (PD) is well established; however, effective therapies remain elusive. Two mechanisms central to PD neurodegeneration are the intracellular aggregation of misfolded α-syn and the uptake of α-syn aggregates into neurons. Cationic arginine-rich peptides (CARPs) are an emerging class of molecule with multiple neuroprotective mechanisms of action, including protein stabilisation.

Prevention of G-Induced Effects on Vision and Consciousness During Simulated Suborbital Spaceflight.

Introduction: During centrifuge-simulated suborbital spaceplane flights, launch and re-entry frequently cause visual symptoms, and G-induced loss of consciousness can occur. G-related effects may be more prominent during re-entry from microgravity on actual flights. A modified anti-G maneuver that does not involve a breath strain and is suitable for members of the public may be effective against these effects.

Imaging flow cytometry reveals LPS-induced changes to intracellular intensity and distribution of α-synuclein in a TLR4-dependent manner in STC-1 cells.

Background: Parkinson's disease is a chronic neurodegenerative disorder, where pathological protein aggregates largely composed of phosphorylated α-synuclein are implicated in disease pathogenesis and progression. Emerging evidence suggests that the interaction between pro-inflammatory microbial factors and the gut epithelium contributes to α-synuclein aggregation in the enteric nervous system. However, the cellular sources and mechanisms for α-synuclein pathology in the gut are still unclear.

Lessons for Flying Astronauts with Disabilities Drawn from Experience in Aviation.

Accessible spaceflight may seem a distant concept. As part of a diverse European Space Agency funded Topical Team, we are working on the physiological feasibility of space missions being undertaken by people with physical disabilities. Here, the first activity of this team is presented in the form of key lessons learned from aviation to inform new work on space missions.

Computational modelling of cardiovascular pathophysiology to risk stratify commercial spaceflight.

For more than 60 years, humans have travelled into space. Until now, the majority of astronauts have been professional, government agency astronauts selected, in part, for their superlative physical fitness and the absence of disease. Commercial spaceflight is now becoming accessible to members of the public, many of whom would previously have been excluded owing to unsatisfactory fitness or the presence of cardiorespiratory diseases.

Mind over Microplastics: Exploring Microplastic-Induced Gut Disruption and Gut-Brain-Axis Consequences.

As environmental plastic waste degrades, it creates an abundance of diverse microplastic particles. Consequently, microplastics contaminate drinking water and many staple food products, meaning the oral ingestion of microplastics is an important exposure route for the human population. Microplastics have long been considered inert, however their ability to promote microbial dysbiosis as well as gut inflammation and dysfunction suggests they are more noxious than first thought.

Trait Impulsivity as a Feature of Parkinson's Disease Treatment and Progression.

Heightened trait impulsivity in both subclinical and pathological senses is becoming increasingly recognised in Parkinson's disease (PD). Impulsive behaviours and impulse control disorders (ICDs) are a consequence of perturbation to the rewards pathway leading individuals to conduct activities in a repetitive, excessive, and maladaptive fashion. Commonly linked to PD, heightened trait impulsivity has been found to primarily manifest in the forms of hypersexuality, pathological gambling, compulsive shopping, and binge eating, all of which may significantly impact social and financial standing.

The Poly-Arginine Peptide R18D Interferes with the Internalisation of α-Synuclein Pre-Formed Fibrils in STC-1 Enteroendocrine Cells.

In Parkinson's disease (PD), gut inflammation is hypothesised to contribute to α-synuclein aggregation, but gastrointestinal α-synuclein expression is poorly characterised. Cationic arginine-rich peptides (CARPs) are an emerging therapeutic option that exerts various neuroprotective effects and may target the transmission of protein aggregates. This study aimed to investigate endogenous α-synuclein expression in enteroendocrine STC-1 cells and the potential of the CARP, R18D (18-mer of D-arginine), to prevent internalisation of pre-formed α-synuclein fibrils (PFFs) in enteroendocrine cells in vitro.

Corrigendum to "Microglia are both a source and target of extracellular cyclophilin A" [Heliyon 5(9) August 2019 e02390].

[This corrects the article DOI: 10.1016/j.heliyon.

Lower gut dysbiosis and mortality in acute critical illness: a systematic review and meta-analysis.

Background: The human gastrointestinal tract harbours a complex multi-kingdom community known as the microbiome. Dysbiosis refers to its disruption and is reportedly extreme in acute critical illness yet its clinical implications are unresolved. The review systematically evaluates the association between gut dysbiosis and clinical outcomes of patients early in critical illness.

Quality of life implications for elevated trait impulsivity in people with Parkinson's disease.

Background: Several non-motor features of Parkinson's disease (PD) are known to adversely affect patient health-related quality of life (HRQL). However, the specific impact of neuropsychiatric complications, such as impulsive behaviour, is yet to be elucidated.

Objectives: The present cross-sectional, observational study aimed to investigate the effects of heightened trait impulsivity on HRQL in individuals with PD.

The role of the microbiota-gut-brain axis in long-term neurodegenerative processes following traumatic brain injury.

Traumatic brain injury (TBI) can be a devastating and debilitating disease to endure. Due to improvements in clinical practice, declining mortality rates have led to research into the long-term consequences of TBI. For example, the incidence and severity of TBI have been associated with an increased susceptibility of developing neurodegenerative disorders, such as Parkinson's or Alzheimer's disease.

Impact of Gastrointestinal Symptoms on Health-Related Quality of Life in an Australian Parkinson's Disease Cohort.

Background: Gastrointestinal symptoms (GIS) in people with Parkinson's disease (PwP) are often underreported and may remain untreated. Constipation is a common nonmotor symptom that can adversely affect health-related quality of life (QoL); however, the impact of other GIS has not been adequately investigated.

Objectives: To investigate the relationship between QoL and constipation using the Bristol Stool Chart, bowel movement frequency, and a perceived constipation measure; and to explore the relationship between QoL and other GIS in an Australian PD cohort.

Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset.

Neurofilament heavy (NEFH) is one of the critical proteins required for the formation of the neuronal cytoskeleton and polymorphisms in NEFH are reported as a rare cause of sporadic ALS (sALS). In the current study, a candidate tetranucleotide (TTTA) repeat variant in NEFH was selected using an in-silico short structural variant (SSV) evaluation algorithm and investigated in two cohorts of North American sALS patients, both separately and combined (Duke cohort n = 138, Coriell cohort n = 333; combined cohort n = 471), compared to a group of healthy controls from the Coriell Institute biobank (n = 496). Stratification according to site of disease onset revealed that the 9 TTTA allele was associated with reduced disease risk, specifically confined to spinal-onset sALS patients in the Duke cohort (p = 0.

The gut microbiome and cognition in Parkinson's disease: a systematic review.

Background: The pathology underlying cognitive changes in people with Parkinson's disease (PD) is not well understood. In healthy older adults, gut microbiome composition has been associated with cognitive function. In people with PD, preliminary evidence suggests that cortical spreading of abnormal alpha-synuclein aggregates may be associated with cognitive impairment.

Plasma Lipid Profiles Change with Increasing Numbers of Mild Traumatic Brain Injuries in Rats.

Mild traumatic brain injury (mTBI) causes structural, cellular and biochemical alterations which are difficult to detect in the brain and may persist chronically following single or repeated injury. Lipids are abundant in the brain and readily cross the blood-brain barrier, suggesting that lipidomic analysis of blood samples may provide valuable insight into the neuropathological state. This study used liquid chromatography-mass spectrometry (LC-MS) to examine plasma lipid concentrations at 11 days following sham (no injury), one (1×) or two (2×) mTBI in rats.

Changes in the rodent gut microbiome following chronic restraint stress and low-intensity rTMS.

Gut microbiome composition is associated with mood-relating behaviours, including those reflecting depression-like phenotypes. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, is an effective treatment for depression, but its effects on the gut microbiome remain largely unknown. This study assessed microbial changes from rat faecal samples longitudinally following chronic restraint stress (CRS) and 10 Hz low-intensity rTMS treatment.

ACTN3 (R577X) Genotype Is Associated With Australian Football League Players.

Jacob, Y, Hart, NH, Cochrane, JL, Spiteri, T, Laws, SM, Jones, A, Rogalski, B, Kenna, J, and Anderton, RS. ACTN3 (R577X) genotype is associated with Australian Football League players. J Strength Cond Res 36(2): 573-576, 2022-Genetic variants in the angiotensin-converting enzyme (ACE) and alpha actinin-3 (ACTN3) genes have been associated with elite sport athletic performance.

TLR2 and TLR4 in Parkinson's disease pathogenesis: the environment takes a toll on the gut.

Parkinson's disease (PD) is an incurable, devastating disorder that is characterized by pathological protein aggregation and neurodegeneration in the substantia nigra. In recent years, growing evidence has implicated the gut environment and the gut-brain axis in the pathogenesis and progression of PD, especially in a subset of people who exhibit prodromal gastrointestinal dysfunction. Specifically, perturbations of gut homeostasis are hypothesized to contribute to α-synuclein aggregation in enteric neurons, which may spread to the brain over decades and eventually result in the characteristic central nervous system manifestations of PD, including neurodegeneration and motor impairments.

Changes in the Gut Microbiome and Predicted Functional Metabolic Effects in an Australian Parkinson's Disease Cohort.

There has been increasing recognition of the importance of the gut microbiome in Parkinson's disease (PD), but the influence of geographic location has received little attention. The present study characterized the gut microbiota and associated changes in host metabolic pathways in an Australian cohort of people with PD (PwP). The study involved recruitment and assessment of 87 PwP from multiple Movement Disorders Clinics in Australia and 47 healthy controls.

Syncope in Commercial Pilots and New Regulatory Guidance.

Syncope is both incapacitating and unpredictable, presenting a significant challenge in aircrew assessment. Previous UK Civil Aviation Authority (CAA) guidance lacked transparency and relied heavily on specialist in-house cardiology and neurology opinion. A new algorithm was developed which elaborated and formalized the decision-making process.

TOMM40 '523' poly-T repeat length is a determinant of longitudinal cognitive decline in Parkinson's disease.

The translocase of outer mitochondrial membrane 40 (TOMM40) '523' polymorphism has previously been associated with age of Alzheimer's disease onset and cognitive functioning in non-pathological ageing, but has not been explored as a candidate risk marker for cognitive decline in Parkinson's disease (PD). Therefore, this longitudinal study investigated the role of the '523' variant in cognitive decline in a patient cohort from the Parkinson's Progression Markers Initiative. As such, a group of 368 people with PD were assessed annually for cognitive performance using multiple neuropsychological protocols, and were genotyped for the TOMM40 '523' variant using whole-genome sequencing data.

Elevated HDL Levels Linked to Poorer Cognitive Ability in Females With Parkinson's Disease.

Introduction: Cholesterol levels have been associated with age-related cognitive decline, however, such an association has not been comprehensively explored in people with Parkinson's disease (PD). To address this uncertainty, the current cross-sectional study examined the cholesterol profile and cognitive performance in a cohort of PD patients.

Methods: Cognitive function was evaluated using two validated assessments (ACE-R and SCOPA-COG) in 182 people with PD from the Australian Parkinson's Disease Registry.