Publications by authors named "Walder K"

Context: Despite being important for health and wellbeing, people with a disability engage in tourism significantly less than people who are non-disabled. It is important to understand why this is occurring so that we can set an agenda toward accessible tourism.

Objective: To understand the tourism experiences and needs of people living with spinal cord injury.

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Article Synopsis
  • The study examines genetic variations and gene expression linked to methamphetamine use disorder, focusing on single nucleotide polymorphisms (SNPs) in four candidate genes among 59 participants.
  • Findings indicate that specific SNPs are associated with the severity of methamphetamine use and cognitive performance, with certain gene expressions being lower in individuals with the disorder.
  • The research suggests novel therapeutic targets due to identified genetic factors and altered mRNA levels in those with methamphetamine use disorder, emphasizing the potential role of these genes in treatment approaches.
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Baicalin is a flavone glycoside derived from flowering plants belonging to the Scutellaria genus. Previous studies have reported baicalin's anti-inflammatory and neuroprotective properties in rodent models, indicating the potential of baicalin in neuropsychiatric disorders where alterations in numerous processes are observed. However, the extent of baicalin's therapeutic effects remains undetermined in a human cell model, more specifically, neuronal cells to mimic the brain environment in vitro.

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Despite recent progress, the challenges in drug discovery for schizophrenia persist. However, computational drug repurposing has gained popularity as it leverages the wealth of expanding biomedical databases. Network analyses provide a comprehensive understanding of transcription factor (TF) regulatory effects through gene regulatory networks, which capture the interactions between TFs and target genes by integrating various lines of evidence.

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There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer's disease. The role of amyloid beta 42 (Aβ) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ, which is increased from adipose tissue of male mice with obesity and is associated with higher plasma Aβ.

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Background: Bipolar disorder (BD) presents significant challenges in drug discovery, necessitating alternative approaches. Drug repurposing, leveraging computational techniques and expanding biomedical data, holds promise for identifying novel treatment strategies.

Methods: This study utilized gene regulatory networks (GRNs) to identify significant regulatory changes in BD, using network-based signatures for drug repurposing.

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Schizophrenia (SCZ) is a complex neuropsychiatric disorder associated with altered bioenergetic pathways and mitochondrial dysfunction. Antipsychotic medications, both first and second-generation, are commonly prescribed to manage SCZ symptoms, but their direct impact on mitochondrial function remains poorly understood. In this study, we investigated the effects of commonly prescribed antipsychotics on bioenergetic pathways in cultured neurons.

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Lipotoxicity, the accumulation of lipids in non-adipose tissues, alters the metabolic transcriptome and mitochondrial metabolism in skeletal muscle. The mechanisms involved remain poorly understood. Here we show that lipotoxicity increased histone deacetylase 4 (HDAC4) and histone deacetylase 5 (HDAC5), which reduced the expression of metabolic genes and oxidative metabolism in skeletal muscle, resulting in increased non-oxidative glucose metabolism.

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Novel approaches are required to find new treatments for schizophrenia and other neuropsychiatric disorders. This study utilised a combination of in vitro transcriptomics and in silico analysis with the BROAD Institute's Connectivity Map to identify drugs that can be repurposed to treat psychiatric disorders. Human neuronal (NT2-N) cells were treated with a combination of atypical antipsychotic drugs commonly used to treat psychiatric disorders (such as schizophrenia, bipolar disorder, and major depressive disorder), and differential gene expression was analysed.

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Background: Poor cognitive function, a major disabling condition of older age, is often considered a prodromal feature of dementia. High mortality and the lack of a cure for dementia have necessitated a focus on the identification of potentially modifiable risk factors. Mental and physical health conditions such as mood disorders and bone loss have been previously linked with poor cognition individually although their combined effect remains largely unknown.

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Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of bipolar disorder remain incremental and have come largely from repurposing drugs used for other psychiatric conditions, a strategy that has failed to find truly revolutionary therapies, as it does not target the mood instability that characterises the condition. The lack of therapeutic innovation in the bipolar disorder field is largely due to a poor understanding of the underlying disease mechanisms and the consequent absence of validated drug targets.

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Article Synopsis
  • People with physical diseases like cardiovascular issues, cancer, and neurodegenerative disorders are at a higher risk for major depressive disorder (MDD), and those with MDD also face increased risks for various physical diseases, creating a cycle of health challenges.
  • This comorbidity leads to worse health outcomes, higher treatment costs, and more complex clinical management due to overlapping symptoms and treatments, highlighting the need for integrated care approaches.
  • The text explores shared genetic and biological factors, social influences, and effective treatment strategies for managing both MDD and common physical diseases, emphasizing the importance of lifestyle interventions and collaborative care models.
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Background: A minimally invasive blood-based assessment of cognitive function could be a promising screening strategy to identify high-risk groups for the incidence of Alzheimer's disease.

Methods: The study included 448 cognitively unimpaired men (mean age 64.1 years) drawn from the Geelong Osteoporosis Study.

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Objective: This study aimed to identify priority self-management skills and behaviours in partnership with stroke survivors, and to co-create approaches to support self-management during inpatient stroke rehabilitation.

Methods: Three stroke survivors and two communication partners participated in the three-stage Participatory Action Research project with embedded co-design processes after undertaking inpatient rehabilitation at a metropolitan tertiary hospital.

Results: Participants identified key factors influencing self-management during inpatient rehabilitation including motivation, emotional well-being, and fatigue.

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Systems genetics has begun to tackle the complexity of insulin resistance by capitalising on computational advances to study high-diversity populations. 'Diversity Outbred in Australia (DOz)' is a population of genetically unique mice with profound metabolic heterogeneity. We leveraged this variance to explore skeletal muscle's contribution to whole-body insulin action through metabolic phenotyping and skeletal muscle proteomics of 215 DOz mice.

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  • Bipolar disorder is characterized by severe mood swings and can disrupt thinking and behavior, with various inherited and environmental factors contributing to its complexity.
  • The text reviews the underlying molecular mechanisms of bipolar depression, such as mitochondrial dysfunction, inflammation, and oxidative stress, and discusses the potential of trimetazidine as a treatment.
  • Trimetazidine, initially used for angina pectoris, shows promise due to its anti-inflammatory and antioxidant effects, as well as its ability to normalize mitochondrial function, warranting further clinical trials for treating bipolar depression.
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Minocycline has anti-inflammatory, antioxidant, and anti-apoptotic properties that explain the renewed interest in its use as an adjunctive treatment for psychiatric and neurological conditions. Following the completion of several new clinical trials using minocycline, we proposed an up-to-date systematic review and meta-analysis of the data available. The PICO (patient/population, intervention, comparison and outcomes) framework was used to search 5 databases aiming to identify randomized controlled trials that used minocycline as an adjunctive treatment for psychiatric and neurological conditions.

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Article Synopsis
  • The study aimed to find a new use for the drug trimetazidine in treating bipolar depression by analyzing how various drugs affect gene expression in neuronal-like cells.
  • Researchers screened a library of 960 approved drugs and identified trimetazidine, which boosts ATP production and showed increased mitochondrial respiration in lab tests.
  • In animal studies, trimetazidine demonstrated antidepressant-like effects, indicating its potential as a treatment for bipolar depression.
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Background: Immune system dysfunction is considered to play an aetiological role in schizophrenia spectrum disorders, with substantial alterations in the concentrations of specific peripheral inflammatory proteins, such as cytokines. However, there are inconsistencies in the literature over which inflammatory proteins are altered throughout the course of illness. Through conducting a systematic review and network meta-analysis, this study aimed to investigate the patterns of alteration that peripheral inflammatory proteins undergo in both acute and chronic stages of schizophrenia spectrum disorders, relative to a healthy control population.

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Targeting β-cell failure could prevent, delay or even partially reverse Type 2 diabetes. However, development of such drugs is limited as the molecular pathogenesis is complex and incompletely understood. Further, while β-cell failure can be modeled experimentally, only some of the molecular changes will be pathogenic.

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Background: Adjunctive minocycline shows promise in treating affective and psychotic disorders; however, the therapeutic mechanism remains unclear. Identifying relevant biomarkers may enhance the efficacy of novel adjunctive treatment candidates. We thus investigated the peripheral immune-inflammatory profile in a randomized controlled trial (RCT) of minocycline in major depressive disorder (MDD).

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Although several genetic polymorphisms have been linked with the risk of Alzheimer's disease, less is known about their impact on cognitive performance among cognitively healthy individuals. Our aim was to investigate the association of the genetic variant, rs744373 in the bridging integrator 1 gene (BIN1), the strongest genetic risk factor for Alzheimer's disease after the APOE ε4 allele, with different cognitive domains among non-demented older men. Cognitive function was measured using the CogState Brief Battery, which assessed cognitive performance across four domains: psychomotor function, visual attention, recognition memory and working memory.

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Advances in psychopharmacology have been significantly slower to evolve than in other disciplines of medicine and therefore investigation into novel therapeutic approaches is required. Additionally, concurrent metabolic conditions are prevalent among people with mental disorders. Metformin is a widely used hypoglycaemic agent that is now being studied for use beyond diabetes management.

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Introduction: Mood disorders are a major cause of disability, and current treatment options are inadequate for reducing the burden on a global scale. The aim of this project was to identify drugs suitable for repurposing to treat mood disorders.

Methods: This mixed-method study utilized gene expression signature technology and pharmacoepidemiology to investigate drugs that may be suitable for repurposing to treat mood disorders.

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