Medicine (Western Health) - Research Publications
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ItemNo Preview AvailableDetecting the vitamin D receptor (VDR) protein in mouse and human skeletal muscle: Strain-specific, species-specific and inter-individual variation(ELSEVIER IRELAND LTD, 2023-12-01)Vitamin D, and its receptor (VDR), play roles in muscle development/function, however, VDR detection in muscle has been controversial. Using different sample preparation methods and antibodies, we examined differences in muscle VDR protein abundance between two mouse strains and between mice and humans. The mouse D-6 VDR antibody was not reliable for detecting VDR in mouse muscle, but was suitable for human muscle, while the rabbit D2K6W antibody was valid for mouse and human muscle. VDR protein was generally lower in muscles from C57 B l/6 than FVB/N mice and was higher in human than mouse muscle. Two putative VDR bands were detected in human muscle, possibly representing VDR isoforms/splice variants, with marked inter-individual differences. This study provides new information on detecting VDR in muscle and on inter-mouse strain and inter-human individual differences in VDR expression. These findings may have implications for future pre-clinical and clinical studies and prompt further investigation to confirm possible VDR isoforms in human muscle.
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ItemNo Preview AvailableExploring new balance and gait factors that are associated with osteosarcopenia in patients with a previous fall and/or fracture history(ELSEVIER IRELAND LTD, 2024-02)Osteosarcopenic individuals have poor muscle function and increased bone fragility, which results in a severe detriment to health outcomes. Hence, there is a necessity to discover easily accessible factors associated with osteosarcopenia to develop timely interventions. This study aimed to determine new sensitive balance and/or gait variables that are associated with osteosarcopenia in a population of older people with a history of falls and/or fractures. In a cross-sectional cohort study, 306 men and women aged ≥65 years completed a series of questionnaires, clinical assessments and muscle strength and function tests. Subsequently, participants were separated into osteopenia, osteoporosis and osteosarcopenia, groups for comparison and further analysis. Osteosarcopenia performed worse than osteopenia and osteoporosis in grip strength, gait speed, physical function scores and in multiple gait and balance indices (p<0.001). During posturography testing, there were larger elliptical areas with eyes open (p = 0.003), and eyes closed (p = 0.043) and increased sway velocity on a firm platform (p = 0.007) in the osteosarcopenia group, compared to osteoporosis. Limits of stability and eyes open ellipse area significantly contributed to the multivariable model (p = 0.029 and p = 0.038, respectively), suggesting that these balance parameters, along with grip strength, may be useful in identifying older adults with osteosarcopenia from those with only osteopenia/osteoporosis. Older adults with osteosarcopenia and a history of falls and/or fractures demonstrated inferior strength, function, and gait characteristics. This study identified indices of balance that were sensitive discriminators for osteosarcopenia and could be easily implemented into routine assessment.
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ItemConsensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand(WILEY, 2023-02)BACKGROUND: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. METHODS: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at >80%, and five multiple-choice questions. Statements with moderate agreement (70%-80%) were revised and re-introduced in Phase 3, and statements with low agreement (<70%) were rejected. In Phase 3, topic experts responded to six revised statements and three additional questions, incorporating results from a parallel Consumer Expert Delphi study. Phase 4 involved finalization of consensus statements. RESULTS: Topic experts from Australia (n = 62, 92.5%) and New Zealand (n = 5, 7.5%) with a mean ± SD age of 45.7 ± 11.8 years participated in Phase 2; 38 (56.7%) were women, 38 (56.7%) were health professionals and 27 (40.3%) were researchers/academics. In Phase 2, 15 of 18 (83.3%) statements on sarcopenia prevention, screening, assessment, management and future research were accepted with strong agreement. The strongest agreement related to encouraging a healthy lifestyle (100%) and offering tailored resistance training to people with sarcopenia (92.5%). Forty-seven experts participated in Phase 3; 5/6 (83.3%) revised statements on prevention, assessment and management were accepted with strong agreement. A majority of experts (87.9%) preferred the revised European Working Group for Sarcopenia in Older Persons (EWGSOP2) definition. Seventeen statements with strong agreement (>80%) were confirmed by the Task Force in Phase 4. CONCLUSIONS: The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia.
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ItemNo Preview AvailableAssessment of the tocolytic nifedipine in preclinical primary models of preterm birth(NATURE PORTFOLIO, 2023-04-06)Spontaneous preterm birth is the leading cause of perinatal morbidity and mortality. Tocolytics are drugs used in cases of imminent preterm birth to inhibit uterine contractions. Nifedipine is a calcium channel blocking agent used to delay threatened spontaneous preterm birth, however, has limited efficacy and lacks preclinical data regarding mechanisms of action. It is unknown if nifedipine affects the pro-inflammatory environment associated with preterm labour pathophysiology and we hypothesise nifedipine only targets myometrial contraction rather than also mitigating inflammation. We assessed anti-inflammatory and anti-contractile effects of nifedipine on human myometrium using in vitro and ex vivo techniques, and a mouse model of preterm birth. We show that nifedipine treatment inhibited contractions in myometrial in vitro contraction assays (P = 0.004 vs. vehicle control) and potently blocked spontaneous and oxytocin-induced contractions in ex vivo myometrial tissue in muscle myography studies (P = 0.01 vs. baseline). Nifedipine treatment did not reduce gene expression or protein secretion of pro-inflammatory cytokines in either cultured myometrial cells or ex vivo tissues. Although nifedipine could delay preterm birth in some mice, this was not consistent in all dams and was overall not statistically significant. Our data suggests nifedipine does not modulate preterm birth via inflammatory pathways in the myometrium, and this may account for its limited clinical efficacy.
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ItemNo Preview AvailableA blended learning exercise physiology theory module that supports student autonomy and improves academic performance(AMER PHYSIOLOGICAL SOC, 2022-09)A limited number of studies have explored the impact of blended exercise physiology theory curricula on student learning and experience. This study aimed to investigate the impact of an exercise physiology blended learning theory module on student performance, engagement, and perceptions. The module, which comprised a range of elements (student guide, lecturer-recorded videos, supplementary videos, formative quizzes, workshops, and discussion forum), was implemented in a third-year subject taken by students in nonspecialist undergraduate science, technology, engineering, and mathematics (STEM) degrees. Students chose which elements to engage with to support their learning. Exam performance was assessed by comparing exam marks from fully face-to-face delivery to the blended delivery with an independent t test. Student perceptions were determined via an end-of-module questionnaire comprised of Likert-scale questions and open-ended questions. Descriptive statistical analysis was conducted on the Likert-scale responses, and qualitative content analysis was conducted on the open-ended responses. Student engagement with online resources was determined through analysis of access statistics from the learning management system. Student exam marks in the blended learning student group were significantly higher (P < 0.0001) than in the face-to-face group, even though the questions were of a higher Bloom's level in the blended learning group. Students preferred blended delivery over fully face-to-face delivery. Most students accessed the student guide, lecturer-recorded videos, and quizzes, with supplementary videos, workshops, and discussion forums accessed by fewer students. In conclusion, a blended exercise physiology theory module improved student exam performance and was positively perceived by students, and engagement with the elements of the module was varied.NEW & NOTEWORTHY Few studies have explored the impact of blended delivery of exercise physiology theory curricula on student learning and experience. This study investigated the impact of a novel blended model on student learning and experience. The module comprised a range of elements (student guide, lecturer-recorded videos, supplementary videos, formative quizzes, workshops, and discussion forum), where students were able to choose which elements to engage with to support their learning.
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ItemEffect of androgen deprivation therapy on the contractile properties of type I and type II skeletal muscle fibres in men with non-metastatic prostate cancer(WILEY, 2018-02)The contractile properties of vastus lateralis muscle fibres were examined in prostate cancer (PrCa) patients undergoing androgen deprivation therapy (ADT) and in age- and activity-matched healthy male subjects (Control). Mechanically-skinned muscle fibres were exposed to a sequence of heavily Ca2+ -buffered solutions at progressively higher free [Ca2+ ] to determine their force-Ca2+ relationship. Ca2+ -sensitivity was decreased in both type I and type II muscle fibres of ADT subjects relative to Controls (by -0.05 and -0.04 pCa units, respectively, P < .02), and specific force was around 13% lower in type I fibres of ADT subjects than in Controls (P = .02), whereas there was no significant difference in type II fibres. Treatment with the reducing agent dithiothreitol slightly increased specific force in type I and type II fibres of ADT subjects (by ~2%-3%, P < .05) but not in Controls. Pure type IIx fibres were found frequently in muscle from ADT subjects but not in Controls, and the overall percentage of myosin heavy chain IIx in muscle samples was 2.5 times higher in ADT subjects (P < .01). The findings suggest that testosterone suppression can negatively impact the contractile properties by (i) reducing Ca2+ -sensitivity in both type I and type II fibres and (ii) reducing maximum specific force in type I fibres.
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ItemNitric oxide is required for the insulin sensitizing effects of contraction in mouse skeletal muscle(WILEY, 2017-12-15)KEY POINTS: People with insulin resistance or type 2 diabetes can substantially increase their skeletal muscle glucose uptake during exercise and insulin sensitivity after exercise. Skeletal muscle nitric oxide (NO) is important for glucose uptake during exercise, although how prior exercise increases insulin sensitivity is unclear. In the present study, we examined whether NO is necessary for normal increases in skeletal muscle insulin sensitivity after contraction ex vivo in mouse muscle. The present study uncovers, for the first time, a novel role for NO in the insulin sensitizing effects of ex vivo contraction, which is independent of blood flow. ABSTRACT: The factors regulating the increase in skeletal muscle insulin sensitivity after exercise are unclear. We examined whether nitric oxide (NO) is required for the increase in insulin sensitivity after ex vivo contractions. Isolated C57BL/6J mouse EDL muscles were contracted for 10 min or remained at rest (basal) with or without the NO synthase (NOS) inhibition (NG -monomethyl-l-arginine; l-NMMA; 100 μm). Then, 3.5 h post contraction/basal, muscles were exposed to saline or insulin (120 μU ml-1 ) with or without l-NMMA during the last 30 min. l-NMMA had no effect on basal skeletal muscle glucose uptake. The increase in muscle glucose uptake with insulin (57%) was significantly (P < 0.05) greater after prior contraction (140% increase). NOS inhibition during the contractions had no effect on this insulin-sensitizing effect of contraction, whereas NOS inhibition during insulin prevented the increase in skeletal muscle insulin sensitivity post-contraction. Soluble guanylate cyclase inhibition, protein kinase G (PKG) inhibition or cyclic nucleotide phosphodiesterase inhibition each had no effect on the insulin-sensitizing effect of prior contraction. In conclusion, NO is required for increases in insulin sensitivity several hours after contraction of mouse skeletal muscle via a cGMP/PKG independent pathway.
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ItemHigh fat diet and associated changes in the expression of micro-RNAS in tissue: Lessons learned from animal studies(WILEY, 2017-06)Environment and genetic factors play an important role in the development of obesity, and diet is one of the main contributing factors to this disease. High fat intake is associated with body weight gain, leading to obesity and other metabolic diseases. MicroRNAs (miRNAs) are a group of small, noncoding RNAs that are important regulators of gene expression at posttranscriptional level. Studies have shown that high fat intake, independent of body weight status, can significantly impact both negatively and positively the expression of miRNAs and thus the biological function of tissues such as adipose, skeletal, and cardiac muscle, liver, neuronal, and endothelial. This review will summarize the effects of high calorie diet in the form of high fat intake on miRNA expression in various tissues of animal models and of high fat fed offspring. We will also briefly review the impact of different dietary lipids on miRNA expression. Given changes in miRNA expression have been associated with the development of many diseases including obesity, understanding their biological role could have important clinical implications and offer tangible therapeutic targets for the prevention, management, and/or treatment of obesity and other lifestyle-related disorders.
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ItemStepping strategy used to recover balance during an induced fall is associated with impaired function and strength in people with knee osteoarthritis(WILEY, 2018-10)AIM: We investigated differences in function, strength and pain in those with knee osteoarthritis (OA) who responded with a single step compared to multiple steps during balance recovery during an induced forward fall. METHOD: The stepping response of 24 participants with knee OA (50% female, age 68.6 ± 6.2 years) as they recovered balance from an induced forward fall was recorded. Participants were grouped based on their stepping response as single-stepper and multi-stepper. Comparison was made between the groups for functional and strength tests and self-reported pain, function, quality of life, fear of falls and physical activity. RESULTS: Fourteen of the participants (58%) responded with a multiple step response. Multiple steppers demonstrated greater time for the up and go (P = 0.01), the stair climb tests (P = 0.05), as well as reduced distance during the 2 min walk test (P = 0.001) and reduced isokinetic knee extension strength (P = 0.02). CONCLUSION: Those who demonstrated multiple step response had impaired function, reduced strength and were less physically active. Given the high prevalence of falls in people with knee OA, further studies are required to better understand the ability of people with knee OA to respond and avoid falls.
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