Risk of a first clinical diagnosis of central nervous system demyelination in relation to human herpesviruses in the context of Epstein-Barr virus.

Background And Purpose: Epstein-Barr virus (EBV) is implicated in multiple sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we test blood markers of infection with human herpesvirus 6 (HHV-6), varicella zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first clinical diagnosis of central nervous system demyelination (FCD) in the context of markers of EBV infection.

Methods: In the Ausimmune case-control study, cases had an FCD, and population controls were matched on age, sex, and study region.

Antecedents to and outcomes for in-hospital cardiac arrests in Australian hospitals with mature medical emergency teams: A multicentre prospective observational study.

Background: The epidemiology and predictability of in-hospital cardiac arrests (IHCAs) in hospitals with established medical emergency teams (METs) is underinvestigated.

Objectives: We categorised IHCAs into three categories: "possible suboptimal end-of-life planning" (possible SELP), "potentially predictable", or "sudden and unexpected" using age, Charlson Comorbidity Index, place of residence, functional independence, along with documented vital signs, K and HCO in the period prior to the IHCA. We also described the differences in characteristics and outcomes amongst these three categories of IHCAs.

Respiratory strategy at birth initiates distinct lung injury phenotypes in the preterm lamb lung.

Background: A lack of clear trial evidence often hampers clinical decision-making during support of the preterm lung at birth. Protein biomarkers have been used to define acute lung injury phenotypes and improve patient selection for specific interventions in adult respiratory distress syndrome. The objective of the study was to use proteomics to provide a deeper biological understanding of acute lung injury phenotypes resulting from different aeration strategies at birth in the preterm lung.

Clinical Sphingolipids Pathway in Parkinson's Disease: From GCase to Integrated-Biomarker Discovery.

Alterations in the sphingolipid metabolism of Parkinson's Disease (PD) could be a potential diagnostic feature. Only around 10-15% of PD cases can be diagnosed through genetic alterations, while the remaining population, idiopathic PD (iPD), manifest without validated and specific biomarkers either before or after motor symptoms appear. Therefore, clinical diagnosis is reliant on the skills of the clinician, which can lead to misdiagnosis.

An intact membrane is essential for small extracellular vesicle-induced modulation of α-synuclein fibrillization.

The misfolding and fibrillization of the protein, α-synuclein (αsyn), is associated with neurodegenerative disorders referred to as the synucleinopathies. Understanding the mechanisms of αsyn misfolding is an important area of interest given that αsyn misfolding contributes to disease pathogenesis. While many studies report the ability of synthetic lipid membranes to modulate αsyn folding, there is little data pertaining to the mechanism(s) of this interaction.

Misfolded α-synuclein causes hyperactive respiration without functional deficit in live neuroblastoma cells.

The misfolding and aggregation of the largely disordered protein, α-synuclein, is a central pathogenic event that occurs in the synucleinopathies, a group of neurodegenerative disorders that includes Parkinson's disease. While there is a clear link between protein misfolding and neuronal vulnerability, the precise pathogenic mechanisms employed by disease-associated α-synuclein are unresolved. Here, we studied the pathogenicity of misfolded α-synuclein produced using the protein misfolding cyclic amplification (PMCA) assay.

The role of lipids in α-synuclein misfolding and neurotoxicity.

The misfolding and aggregation of α-synuclein (αsyn) in the central nervous system is associated with a group of neurodegenerative disorders referred to as the synucleinopathies. In addition to being a pathological hallmark of disease, it is now well-established that upon misfolding, αsyn acquires pathogenic properties, such as neurotoxicity, that can contribute to disease development. The mechanisms that produce αsyn misfolding and the molecular events underlying the neuronal damage caused by these misfolded species are not well-defined.

5-HT2A Agonists: A Novel Therapy for Functional Neurological Disorders?

Functional neurological disorders are frequently encountered in clinical practice. They have a poor prognosis and treatment options are limited. Their etiology is unknown, but leading theories propose a disturbance of somatic self-representation: the mind perceives dysfunction of a body region despite intact motor and sensory pathways.

The N-terminal pro-domain of the kalata B1 cyclotide precursor is intrinsically unstructured.

Cyclotides are plant-derived, gene-encoded, circular peptides with a range of host-defense functions, including insecticidal activity. They also have potential as pharmaceutical scaffolds and understanding their biosynthesis is important to facilitate their large-scale production. Insights into the biosynthesis of cyclotides are emerging but there are still open questions, particularly regarding the influence of the structure of the precursor proteins on processing/biosynthetic pathways.

Pathogenic mechanisms of prion protein, amyloid-β and α-synuclein misfolding: the prion concept and neurotoxicity of protein oligomers.

Proteinopathies represent a group of diseases characterized by the unregulated misfolding and aggregation of proteins. Accumulation of misfolded protein in the central nervous system (CNS) is associated with neurodegenerative diseases, such as the transmissible spongiform encephalopathies (or prion diseases), Alzheimer's disease, and the synucleinopathies (the most common of which is Parkinson's disease). Of these, the pathogenic mechanisms of prion diseases are particularly striking where the transmissible, causative agent of disease is the prion, or proteinaceous infectious particle.

Brain morphometry in blind and sighted subjects.

Previous neuroimaging studies have demonstrated structural brain alterations in blind subjects, but most have focused on primary open angle glaucoma or retinopathy of prematurity, used low-field scanners, a limited number of receive channels, or have presented uncorrected results. We recruited 10 blind and 10 age and sex-matched controls to undergo high-resolution MRI using a 3T scanner and a 32-channel receive coil. We evaluated whole-brain morphological differences between the groups as well as manual segmentation of regional hippocampal volumes.

Interleukin-1β has trophic effects in microglia and its release is mediated by P2X7R pore.

Background: Enhanced expression of the purinergic P2X7 receptor (P2X7R) occurs in several neuroinflammatory conditions where increased microglial activation is a co-existing feature. P2X7 receptors can function either as a cation channel or, upon continued stimulation, a large pore. P2X7R-over-expression alone is sufficient to drive microglial activation and proliferation in a process that is P2X7R pore dependent, although the biological signaling pathway through which this occurs remains unclear.

Nucleosome levels and toll-like receptor expression during high cut-off haemofiltration: a pilot assessment.

Objectives: To measure plasma nucleosome levels and expression of toll-like receptors (TLRs) in a pilot cohort of patients with severe acute kidney injury (AKI) within a randomised controlled trial of continuous venovenous haemofiltration with high cut-off filters (CVVH-HCO) v standard filters (CVVH-std).

Methods: We measured plasma nucleosome levels using the Cell Death Detection ELISA PLUS (10X) assay kit. We analysed plasma levels for correlation with disease severity and compared the effects of CVVH-HCO and CVVH-std on plasma nucleosome levels over the first 72 hours.

Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level.

The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such as reproduction and immune responses. We here provide genetic and biochemical evidence that the metabolic and immune functions of leptin can be uncoupled at the receptor level. First, homozygous mutant fatt/fatt mice carry a spontaneous splice mutation causing deletion of the leptin receptor (LR) immunoglobulin-like domain (IGD) in all LR isoforms.

Status epilepticus after prolonged umbilical cord occlusion is associated with greater neural injury in [corrected] fetal sheep at term-equivalent.

The majority of pre-clinical studies of hypoxic-ischemic encephalopathy at term-equivalent have focused on either relatively mild insults, or on functional paradigms of cerebral ischemia or hypoxia-ischemia/hypotension. There is surprisingly little information on the responses to single, severe 'physiological' insults. In this study we examined the evolution and pattern of neural injury after prolonged umbilical cord occlusion (UCO).

Vascular endothelial growth factor and brain-derived neurotrophic factor in quetiapine treated first-episode psychosis.

Objective. It has been suggested that atypical antipsychotics confer their effects via brain-derived neurotrophic factor (BDNF). We investigated the effect of quetiapine on serum levels of BDNF and vascular endothelial growth factor (VEGF) in drug-naive first-episode psychosis subjects.

Acid-base changes after fluid bolus: sodium chloride vs. sodium octanoate.

Objectives: This study aims to test the hypothesis that fluid loading with sodium chloride (150 mmol Na and 150 mmol Cl) or sodium octanoate (150 mmol Na, 100 mmol Cl, and 50 mmol octanoate) would lead to different acid-base changes.

Design: We performed a double-blind crossover experimental study.

Setting: The study was done at a University Physiology Laboratory.

The anti-fibrotic hormone relaxin is not reno-protective, despite being active, in an experimental model of type 1 diabetes.

The end-point of diabetic renal disease is the accumulation of excess collagen (fibrosis/sclerosis). A number of studies have shown that the hormone relaxin (RLX) ameliorates progression of renal and non-renal fibrosis. This study assessed the anti-fibrotic potential of RLX in streptozotocin (STZ)-treated transgenic mRen-2 rats, an accelerated model of type 1 diabetes.

The stretcher spontaneous neurodegenerative mutation models Charcot-Marie-Tooth disease type 4D.

Mice affected by a spontaneous mutation which arose within our colony exhibited a neuromuscular phenotype involving tremor and characteristic stretching of the rear limbs. The mutant, named stretcher, was used to breed a backcross cohort for genetic mapping studies. The gene responsible for the mutant phenotype was mapped to a small region on mouse chromosome 15, with a LOD score above 20.

Novel targets for sepsis-induced kidney injury: the glomerular arterioles and the sympathetic nervous system.

Sepsis and septic shock are the most common causes of acute kidney injury (AKI) in the intensive care unit, and mortality remains high despite improvements in our ability to support vital organs. The lack of development of effective treatments is partly because there has been little advance in our understanding of the pathophysiology of septic AKI, owing to the difficulty in conducting experiments on critically ill patients and use of inappropriate experimental models. Recently, however, a number of new concepts have emerged that challenge existing dogma and give insights into the causes of AKI.

Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

Objective: Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow.

The effects of terlipressin on regional hemodynamics and kidney function in experimental hyperdynamic sepsis.

Background And Aims: Although terlipressin (TP) may improve renal function in cirrhotic patients, its use in sepsis remains controversial due to concerns about regional ischemia. We investigated the effects of TP on regional hemodynamics and kidney function in experimental hyperdynamic sepsis.

Methods: We studied thirteen merino ewes in a university physiology laboratory using a randomized controlled cross over design.

Central angiotensin type 1 receptor blockade decreases cardiac but not renal sympathetic nerve activity in heart failure.

In heart failure (HF), cardiac sympathetic nerve activity (SNA; CSNA) is increased, which has detrimental effects on the heart and promotes arrhythmias and sudden death. There is evidence that the central renin-angiotensin system plays an important role in stimulating renal SNA in HF. Because SNA to individual organs is differentially controlled, we have investigated whether central angiotensin receptor blockade decreases CSNA in HF.