Publications by authors named "HOLLOWAY H"

There is increased recognition of the need to improve post-diagnostic pathways for people with dementia and their care partners living in the community to access rehabilitation services to support independence and wellbeing. However, there is minimal evidence on implementing rehabilitation services for this population. The study aimed to present the expectations and experiences of allied health staff involved in piloting the Sustainable Personalised Interventions for Cognition, Care and Engagement (SPICE) program based at an outpatient clinic of a public rehabilitation hospital.

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Objective: Virtual reality (VR) has been used to improve upper limb function after stroke but there is little to guide product developers in building experiences that engage users in the sustained, repetitive training required. This research sought to understand the characteristics of VR scenarios best suited to engaging someone with a stroke during recovery to achieve therapeutic outcomes.

Methods: Five creative immersive VR scenarios were designed by an experienced VR content creator containing unique combinations of VR characteristics.

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Objective: Sustaining the health and well-being of older people living in residential aged care (RAC) requires new means of providing safe and stimulating recreational and therapeutic programs such as using virtual reality (VR). The aim of the scoping review was to investigate the utility of immersive VR interventions using head-mounted display technology to promote the health and well-being of people without cognitive impairment living in RAC.

Method: The following databases were searched from inception until January 2024: PubMed, PsycINFO, Scopus, Cochrane and CINAHL.

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Intergenerational programs in residential aged care may improve well-being and combat loneliness and social isolation in older people with cognitive impairment. This pilot study investigated the effects of a semi-structured intergenerational group, including children from a co-located early learning centre and people living in residential aged care with cognitive impairment. This 9-week study used a mixed methods pre- and post-program design.

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Background: Small-scale models of dementia care are a potential solution to deinstitutionalize residential aged care and have been associated with improved resident outcomes, including quality of life and reduced hospitalizations for people living with dementia.

Objective: This study aimed to generate strategies and ideas on how homes for people living with dementia in a village setting within a suburban community, could be designed and function without external boundaries. In particular, how could residents of the village and members of the surrounding community access and engage safely and equitably so that interpersonal connections might be fostered?

Methods: Twenty-one participants provided an idea for discussion at three Nominal Group Technique workshops, including people living with dementia, carers or former carers, academics, researchers, and clinicians.

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Older people living in residential aged care often experience complex persistent pain because of the presence of multiple comorbidities and geriatric syndrome. Complex persistent pain is associated with physical, psychological and emotional burdens. All of these factors can result in existential suffering.

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Article Synopsis
  • Mild blast traumatic brain injury (B-TBI) led to lasting cognitive impairments in novel object recognition and some deficits in Y-maze tasks.
  • Exendin-4 (Ex-4) treatment either before or after B-TBI successfully prevented these cognitive issues and reduced negative changes in synaptophysin levels in brain tissues.
  • In vitro experiments showed that Ex-4 reduced cell damage and preserved neurite length in neuron-derived cells affected by biaxial stretch injuries, suggesting its potential as a treatment for blast-induced brain injuries.
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Traumatic brain injury (TBI), often caused by a concussive impact to the head, affects an estimated 1.7 million Americans annually. With no approved drugs, its pharmacological treatment represents a significant and currently unmet medical need.

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Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on thedevelopmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.

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Introduction: Blast traumatic brain injury (B-TBI) affects military and civilian personnel. Presently, there are no approved drugs for blast brain injury.

Methods: Exendin-4 (Ex-4), administered subcutaneously, was evaluated as a pretreatment (48 hours) and postinjury treatment (2 hours) on neurodegeneration, behaviors, and gene expressions in a murine open field model of blast injury.

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Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs.

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Background: The first trimester of human development and the equivalent developmental period in animal models is a time when teratogenic ethanol (EtOH) exposure induces the major structural birth defects that fall within fetal alcohol spectrum disorder (FASD). Previous FASD research employing an acute high dose maternal intraperitoneal EtOH treatment paradigm has identified sensitive periods for a number of these defects. Extending this work, this investigation utilized high resolution magnetic resonance microscopy (MRM)-based analyses to examine the dysmorphology resulting from maternal dietary EtOH intake occurring during selected first trimester-equivalent time periods.

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Immunoelectron microscopy is wrought with technical limitations that complicate its use. However, advances in correlative light and electron microscopy have recently lead to improvements in this field. We report the development of a semi-correlative approach to investigate the ultrastructural location of an antiphospholipid antibody within the syncytiotrophoblast.

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Animal model-based studies have shown that ethanol exposure during early gestation induces developmental stage-specific abnormalities of the face and brain. The exposure time-dependent variability in ethanol's teratogenic outcomes is expected to contribute significantly to the wide spectrum of effects observed in humans with fetal alcohol spectrum disorder (FASD). The work presented here employs a mouse FASD model and magnetic resonance microscopy (MRM; high resolution magnetic resonance imaging) in studies designed to further our understanding of the developmental stage-specific defects of the brain that are induced by ethanol.

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A major pathological hallmark of Alzheimer disease (AD) is the appearance in the brain of senile plaques that are primarily composed of aggregated forms of β-amyloid peptide (Aβ) that derive from amyloid precursor protein (APP). Posiphen (1) tartrate is an experimental AD drug in current clinical trials that reduces Aβ levels by lowering the rate of APP synthesis without toxicity. To support the clinical development of Posiphen (1) and elucidate its efficacy, its three major metabolic products, (+)-N1-norPosiphen (15), (+)-N8-norPosiphen (17) and (+)-N1, N8-bisnorPosiphen (11), were required in high chemical and optical purity.

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Article Synopsis
  • Prenatal ethanol exposure is the top preventable cause of congenital mental disabilities, but many affected individuals don't show the classic facial traits of fetal alcohol syndrome (FAS).
  • A study used MRI and shape analysis to investigate how ethanol exposure at different stages of pregnancy affects both facial and brain development in mouse fetuses, revealing distinct facial characteristics and brain abnormalities for each stage.
  • Early exposure on gestational day 7 led to severe facial dysmorphology similar to human FAS, while exposure on day 8.5 resulted in milder features; this indicates the need to broaden diagnostic criteria for fetal alcohol spectrum disorders to identify varying defect patterns.
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  • Mild traumatic brain injury (mTBI) is a significant public health issue, especially affecting young adults and the elderly, leading to long-term cognitive and emotional problems without clear structural damage.
  • Existing treatments are primarily supportive, with no effective drugs available, but recent research suggests the long-acting GLP-1 receptor agonist exendin-4 (Ex-4) shows promise in protecting against mTBI-related damage.
  • In mouse models, Ex-4 alleviated mTBI-induced cognitive deficits and was well-tolerated, indicating its potential as a neuroprotective therapy to combat the impairments associated with mTBI.
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In most mammalian cardiomyocytes, the transverse tubular system (t-system) is a major site for electrical signaling and excitation-contraction coupling. The t-system consists of membrane invaginations, which are decorated with various proteins involved in excitation-contraction coupling and mechano-electric feedback. Remodeling of the t-system has been reported for cells in culture and various types of heart disease.

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Article Synopsis
  • Neuroinflammation, particularly through the action of the cytokine TNF-α, is linked to the progression of neurodegenerative diseases like Alzheimer's disease (AD), raising questions about its causative role versus its impact on disease progression.
  • Researchers tested a new agent, 3,6'-dithiothalidomide, for its ability to lower TNF-α in both cellular and rodent models of neuroinflammation related to AD.
  • Results showed that 3,6'-dithiothalidomide effectively reduced TNF-α levels, markers of neuroinflammation, and improved memory function in AD models, indicating potential therapeutic benefits for cognitive decline in Alzheimer's disease.
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Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by a progressive loss of lower motor neurons in the spinal cord. The incretin hormone, glucagon-like peptide-1 (GLP-1), facilitates insulin signaling, and the long acting GLP-1 receptor agonist exendin-4 (Ex-4) is currently used as an anti-diabetic drug. GLP-1 receptors are widely expressed in the brain and spinal cord, and our prior studies have shown that Ex-4 is neuroprotective in several neurodegenerative disease rodent models, including stroke, Parkinson's disease and Alzheimer's disease.

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Eight novel 2-(2,6-dioxopiperidin-3-yl)phthalimidine EM-12 dithiocarbamates 9 and 10, N-substituted 3-(phthalimidin-2-yl)-2,6-dioxopiperidines 11-14 and 3-substituted 2,6-dioxopiperidines 16 and 18 were synthesized as tumor necrosis factor-α (TNF-α) synthesis inhibitors. Synthesis involved utilization of a novel condensation approach, a one-pot reaction involving addition, iminium rearrangement and elimination, to generate the phthalimidine ring required for the creation of compounds 9-14. Agents were, thereafter, quantitatively assessed for their ability to suppress the synthesis on TNF-α in a lipopolysaccharide (LPS)-challenged mouse macrophage-like cellular screen, utilizing cultured RAW 264.

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It is estimated that the adult human brain contains 100 billion neurons with 5-10 times as many astrocytes. Although it has been generally considered that the astrocyte is a simple supportive cell to the neuron, recent research has revealed new functionality of the astrocyte in the form of information transfer to neurons of the brain. In our previous work we developed a protocol to pattern the hNT neuron (derived from the human teratocarcinoma cell line (hNT)) on parylene-C/SiO(2) substrates.

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As a clinical medication for the treatment of hyperkinetic movement disorders, in conditions such as Huntington's disease, tetrabenazine (TBZ) has been always used in its racemic form. To establish whether or not its beneficial therapeutic actions are enantiospecific, a practical total synthetic route was developed to yield each enantiomeric form to allow their chemical and pharmacological characterization. We briefly summarize the total synthesis of TBZ and report a detailed procedure for resolution of TBZ into its enantiomers, (+)-TBZ and (-)-TBZ.

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The N-monophenylcarbamate analogues of neostigmine methyl sulfate (6) and pyridostigmine bromide (8) together with their precursors (5), (7), and the N(1)-methylammonium analogues of (-)-phenserine (12), (-)-tolserine (14), (-)-cymserine (16) and (-)-phenethylcymserine (18) were synthesized to produce long-acting peripheral inhibitors of acetylcholinesterase or butyrylcholinesterase. Evaluation of their cholinesterase inhibition against human enzyme ex vivo demonstrated that, whereas compounds 5-8 possessed only marginal activity, 12, 14, 16 and 18 proved to be potent anticholinesterases. An extended duration of cholinesterase inhibition was determined in rodent, making them of potential interest as long-acting agents for myasthenia gravis.

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Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability.

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