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"Murphy, Kate"
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You're not listening : what you're missing and why it matters
\"At work, we're taught to lead the conversation. On social media, we shape our personal narratives. At parties, we talk over one another. So do our politicians. We're not listening. And no one is listening to us. Despite living in a world where technology allows constant digital communication and opportunities to connect, it seems no one is really listening or even knows how. And it's making us lonelier, more isolated, and less tolerant than ever before. A listener by trade, [the author] wanted to know how we got here ... [She] explains why we're not listening, what it's doing to us, and how we can reverse the trend. She makes accessible the psychology, neuroscience, and sociology of listening while also introducing us to some of the best listeners out there\"-- Provided by publisher.
Book
Impaired skeletal muscle health in Parkinsonian syndromes: clinical implications, mechanisms and potential treatments
There is increasing evidence that neurodegenerative disorders including the Parkinsonian syndromes are associated with impaired skeletal muscle health, manifesting as wasting and weakness. Many of the movement problems, lack of muscle strength and reduction in quality of life that are characteristic of these syndromes can be attributed to impairments in skeletal muscle health, but this concept has been grossly understudied and represents an important area of unmet clinical need. This review describes the changes in skeletal muscle health in idiopathic Parkinson's disease and in two atypical Parkinsonian syndromes, the most aggressive synucleinopathy multiple system atrophy, and the tauopathy progressive supranuclear palsy. The pathogenesis of the skeletal muscle changes is described, including the contribution of impairments to the central and peripheral nervous system and intrinsic alterations. Pharmacological interventions targeting the underlying molecular mechanisms with therapeutic potential to improve skeletal muscle health in affected patients are also discussed. Although little is known about the mechanisms underlying these conditions, current evidence implicates multiple pathways and processes, highlighting the likely need for combination therapies to protect muscle health and emphasizing the merit of personalized interventions for patients with different physical capacities at different stages of their disease. As muscle fatigue is often experienced by patients prior to diagnosis, the identification and measurement of this symptom and related biomarkers to identify early signs of disease require careful interrogation, especially for multiple system atrophy and progressive supranuclear palsy where diagnosis is often made several years after onset of symptoms and only confirmed post‐mortem. We propose a multidisciplinary approach for early diagnosis and implementation of personalized interventions to preserve muscle health and improve quality of life for patients with typical and atypical Parkinsonian syndromes.
Journal Article
Something borrowed
Rachel is a generous and loyal pal to her engaged best friend Darcy. But after celebrating her 30th birthday, perpetual good girl Rachel unexpectedly ends up in the arms of Dex, the guy she's had a crush on since law school, and who happens to be Darcy's fiancé. In the frantic weeks leading up to Darcy's wedding, Rachel finds herself caught between her longtime friendship with Darcy and the prospect of losing the love of her life.
DVD
ADP-ribosylation factor 6 expression increase in oesophageal adenocarcinoma suggests a potential biomarker role for it
ADP-ribosylation factor 6 small GTPase plays an important role in cell migration, invasion and angiogenesis, which are the hallmarks of cancer. Although alterations in ARF6 expression and activity have been linked to metastatic cancer in one or two tissues, the expression of ARF6 in cancers over a wide range of tissues has not been studied so far. In this report, we analysed the expression of ARF6 mRNA in cancers and corresponding healthy controls from 17 different tissues by real-time qualitative polymerase chain reaction (RT-qPCR). We further evaluated ARF6 protein expression in oesophageal adenocarcinoma (EAC) tissue microarray cores by immunohistochemistry. The ARF6 gene expression levels are highly variable between healthy and cancer tissues. Our findings suggest that the ARF6 gene expression is up-regulated highest in oesophageal cancer. In EAC TMAs, ARF6 protein expression increase correlated with EAC progression. This is the first study to investigate ARF6 gene expression in a wide array of cancer tissues and demonstrate that ARF6 expression, at both mRNA and protein levels, is significantly upregulated in higher grades of EAC, which may be useful in targeting ARF6 for cancer diagnostic and therapeutic purposes.
Journal Article
Digoxin and exercise effects on skeletal muscle Na+,K+‐ATPase isoform gene expression in healthy humans
In muscle, digoxin inhibits Na+,K+‐ATPase (NKA) whereas acute exercise can increase NKA gene expression, consistent with training‐induced increased NKA content. We investigated whether oral digoxin increased NKA isoform mRNA expression (qPCR) in muscle at rest, during and post‐exercise in 10 healthy adults, who received digoxin (DIG, 0.25 mg per day) or placebo (CON) for 14 days, in a randomised, double‐blind and cross‐over design. Muscle was biopsied at rest, after cycling 20 min (10 min each at 33%, then 67% V̇O2peak ${{\\dot{V}}_{{{\\mathrm{O}}}_2}{\\mathrm{peak}}}$ ), then to fatigue at 90% V̇O2peak ${{\\dot{V}}_{{{\\mathrm{O}}}_2}{\\mathrm{peak}}}$and 3 h post‐exercise. No differences were found between DIG and CON for NKA α1–3 or β1–3 isoform mRNA. Both α1 (354%, P = 0.001) and β3 mRNA (P = 0.008) were increased 3 h post‐exercise, with α2 and β1–2 mRNA unchanged, whilst α3 mRNA declined at fatigue (−43%, P = 0.045). In resting muscle, total β mRNA (∑(β1+β2+β3)) increased in DIG (60%, P = 0.025) and also when transcripts for each isoform were normalised to CON then either summed (P = 0.030) or pooled (n = 30, P = 0.034). In contrast, total α mRNA (∑(α1+α2+α3), P = 0.348), normalised then summed (P = 0.332), or pooled transcripts (n = 30, P = 0.717) did not differ with DIG. At rest, NKA α1–2 and β1–2 protein abundances were unchanged by DIG. Post‐exercise, α1 and β1–2 proteins were unchanged, but α2 declined at 3 h (19%, P = 0.020). In conclusion, digoxin did not modify gene expression of individual NKA isoforms at rest or with exercise, indicating NKA gene expression was maintained consistent with protein abundances. However, elevated resting muscle total β mRNA with digoxin suggests a possible underlying β gene‐stimulatory effect. Highlights What is the central question of this study? Na+,K+‐ATPase (NKA) in muscle is important for Na+/K+ homeostasis. We investigated whether the NKA‐inhibitor digoxin stimulates increased NKA gene expression in muscle and exacerbates NKA gene responses to exercise in healthy adults. What is the main finding and its importance? Digoxin did not modify exercise effects on muscle NKA α1–3 and β1–3 gene transcripts, which comprised increased post‐exercise α1 and β3 mRNA and reduced α3 mRNA during exercise. However, in resting muscle, digoxin increased NKA total β isoform mRNA expression. Despite inhibitory‐digoxin or acute exercise stressors, NKA gene regulation in muscle is consistent with the maintenance of NKA protein contents.
Journal Article
The case for a wound-focused multi-disciplinary ward round
The Royal Melbourne Hospital (RMH) GEM (Geriatric Evaluation Management) Wound Ward round model was developed in response to workflow changes during the COVID-19 pandemic.
Journal Article
Role for Plant-Derived Antioxidants in Attenuating Cancer Cachexia
Cancer cachexia is the progressive muscle wasting and weakness experienced by many cancer patients. It can compromise the response to gold standard cancer therapies, impair functional capacity and reduce overall quality of life. Cancer cachexia accounts for nearly one-third of all cancer-related deaths and has no effective treatment. The pathogenesis of cancer cachexia and its progression is multifactorial and includes increased oxidative stress derived from both the tumor and the host immune response. Antioxidants have therapeutic potential to attenuate cancer-related muscle loss, with polyphenols, a group of plant-derived antioxidants, being the most widely investigated. This review describes the potential of these plant-derived antioxidants for treating cancer cachexia.
Journal Article
Importance of functional and metabolic impairments in the characterization of the C-26 murine model of cancer cachexia
Cancer cachexia describes the progressive skeletal muscle wasting and weakness that is associated with many cancers. It impairs quality of life and accounts for >20% of all cancer-related deaths. The main outcome that affects quality of life and mortality is loss of skeletal muscle function and so preclinical models should exhibit similar functional impairments in order to maximize translational outcomes. Mice bearing colon-26 (C-26) tumors are commonly used in cancer cachexia studies but few studies have provided comprehensive assessments of physiological and metabolic impairment, especially those factors that impact quality of life. Our aim was to characterize functional impairments in mildly and severely affected cachectic mice, and determine the suitability of these mice as a preclinical model. Metabolic abnormalities are also evident in cachectic patients and we investigated whether C-26-tumor-bearing mice had similar metabolic aberrations. Twelve-week-old CD2F1 mice received a subcutaneous injection of PBS (control) or C-26 tumor cells. After 18-20 days, assessments were made of grip strength, rotarod performance, locomotor activity, whole body metabolism, and contractile properties of tibialis anterior (TA) muscles (in situ) and diaphragm muscle strips (in vitro). Injection of C-26 cells reduced body and muscle mass, and epididymal fat mass. C-26-tumor-bearing mice exhibited lower grip strength and rotarod performance. Locomotor activity was impaired following C-26 injection, with reductions in movement distance, duration and speed compared with controls. TA muscles from C-26-tumor-bearing mice had lower maximum force (-27%) and were more susceptible to fatigue. Maximum specific (normalized) force of diaphragm muscle strips was reduced (-10%) with C-26 injection, and force during fatiguing stimulation was also lower. C-26-tumor-bearing mice had reduced carbohydrate oxidation and increased fat oxidation compared with controls. The range and consistency of functional and metabolic impairments in C-26-tumor-bearing mice confirm their suitability as a preclinical model for cancer cachexia. We recommend the use of these comprehensive functional assessments to maximize the translation of findings to more accurately identify effective treatments for cancer cachexia.
Journal Article
The Venom Proteome of the Ecologically Divergent Australian Elapid, Southern Death Adder Acanthophis antarcticus
The composition of Australian snake venoms is the least well-known of any continent. We characterised the venom proteome of the southern death adder Acanthophis antarcticus—one of the world’s most morphologically and ecologically divergent elapids. Using a combined bottom-up proteomic and venom gland transcriptomic approach employing reverse-phase chromatographic and gel electrophoretic fractionation strategies in the bottom-up proteomic workflow, we characterised 92.8% of the venom, comprising twelve different toxin identification hits belonging to seven toxin families. The most abundant protein family was three-finger toxins (3FTxs; 59.8% whole venom), consisting mostly of one long-chain neurotoxin, alpha-elapitoxin-Aa2b making up 59% of the venom and two proteoforms of another long-chain neurotoxin. Phospholipase A2s (PLA2s) were the second most abundant, with four different toxins making up 22.5% of the venom. One toxin was similar to two previous non-neurotoxic PLA2s, making up 16% of the venom. The remaining protein families present were CTL (3.6%), NGF (2.5%), CRiSP (1.8%), LAAO (1.4%), and AChE (0.8%). A. antarcticus is the first Australian elapid characterised that has a 3FTx dominant venom, a composition typical of elapids on other continents, particularly cobras Naja sp. The fact that A. antarcticus has a venom composition similar to cobra venom while having a viper-like ecology illustrates that similar venom expressions can evolve independently of ecology. The predominance of post-synaptic neurotoxins (3FTxs) and pre-synaptic neurotoxins (PLA2) is consistent with the neurotoxic clinical effects of envenomation in humans.
Journal Article
An Evaluation of the Design of Multimedia Patient Education Materials in Musculoskeletal Health Care: Systematic Review
Background:Educational multimedia is a cost-effective and straightforward way to administer large-scale information interventions to patient populations in musculoskeletal health care. While an abundance of health research informs the content of these interventions, less guidance exists about optimizing their design.Objective:This study aims to identify randomized controlled trials of patient populations with musculoskeletal conditions that used multimedia-based patient educational materials (PEMs) and examine how design was reported and impacted patients’ knowledge and rehabilitation outcomes. Design was evaluated using principles from the cognitive theory of multimedia learning (CTML).Methods:PubMed, CINAHL, PsycINFO, and Embase were searched from inception to September 2023 for studies examining adult patients with musculoskeletal conditions receiving multimedia PEMs compared to any other interventions. The primary outcome was knowledge retention measured via test scores. Secondary outcomes were any patient-reported measures. Retrievability was noted, and PEMs were sourced through search, purchase, and author communication.Results:A total of 160 randomized controlled trials were eligible for inclusion: 13 (8.1%) included their educational materials and 31 (19.4%) required a web search, purchase, or direct requests for educational materials. Of these 44 (27.5%) studies, none fully optimized the design of their educational materials, particularly lacking in the CTML principles of coherence, redundancy, modality, and generative activities for the learner. Of the 160 studies, the remaining 116 (72.5%) contained interventions that could not be retrieved or appraised. Learning was evaluated in 5 (3.1%) studies.Conclusions:Musculoskeletal studies should use open science principles and provide their PEMs wherever possible. The link between providing multimedia PEMs and patient learning is largely unexamined, but engagement potential may be maximized when considering design principles such as the CTML.
Journal Article