Collective Impact Approaches to Promoting Community Health and Wellbeing in a Regional Township: Learnings for Integrated Care.

This Perspective Paper explores the challenges of implementing local initiatives guided by the tenets of the Collective Impact (CI) approach. As such, it draws implications of CI for integrated health and social care efforts to improve and sustain health and social outcomes within a community-wide context, based on our efforts to deploy a CI intervention in the regional town of Muswellbrook, New South Wales (NSW) Australia. A program of health and wellbeing activities providing mental health and wellness messages and activities was implemented in the township over 2 years by the Family Action Centre (FAC), University of Newcastle, Australia. A key takeaway was the importance of authentic community engagement and active involvement as opposed to mere consultation.

Feasibility and adherence to moderate intensity cardiovascular fitness training following stroke: a pilot randomized controlled trial.

BACKGROUND: Stroke is a leading cause of disability worldwide and the cardiovascular fitness levels of stroke survivors are diminished to an extent that impairs functioning and activities of daily living performance. While cardiovascular training seems an empirically appropriate intervention, the optimal dosage and intensity of cardiovascular training in stroke survivors remains unclear. The aim was to determine the safety and feasibility of moderate-intensity cardiovascular training following stroke, including measurement of adherence to training. METHODS: A pilot, prospective, patient- and assessor-blinded randomised controlled trial conducted in a tertiary, metropolitan hospital-based community rehabilitation centre. Eligibility criteria included ambulant (> 100 m), 6 weeks-12 months post stroke. Moderate-intensity fitness training or control (low-intensity) exercise was offered biweekly for 12 weeks. Outcome measures included adverse events, peak oxygen uptake (VO2), functional exercise capacity (6-Minute Walk Test, 10-m Walk Test) and health-related quality of life (Short Form-36) and mood (Patient Health Questionnaire, PHQ9). RESULTS: Feasibility: Seventy-one (50%) of 141 screened participants were eligible (29% did not agree to participate). Twenty participants (10 intervention, 10 control) were recruited. The median (%; IQR) supervised sessions was 19.5 (81%; 12, 20); and 20 (83%; 19, 22) in the intervention and control groups, respectively. Progression of duration and intensity was limited; mean of 10 sessions to achieve target duration (30 min). There were no adverse events. Baseline peak oxygen uptake (VO2) levels were low (15.94 ml/kg/min). Significant improvements in VO2 peak in both groups were observed (p < 0.05). Although there were no significant between-group differences, this feasibility trial was not powered to detect change. CONCLUSIONS: Moderate-intensity fitness training was safe but achievement of target duration and intensity was challenging for stroke survivors. A definitive adequately-powered randomised trial is required. Alternative fitness training protocols may need to be explored. TRIAL REGISTRATION: The trial protocol was prospectively registered on the Australian New Zealand Clinical Trials Registry ( ACTRN 12613000822785 ) on 25/07/2013.

The clinical management of neck pain of novice and experienced Australian osteopaths: A secondary analysis of a nationally representative sample.

INTRODUCTION: Neck pain is one of the most common musculoskeletal disorders worldwide. Osteopaths are primary contact health professionals who predominantly manage musculoskeletal complaints. How Australian osteopaths manage neck pain is beginning to emerge in the literature and there may be differences based on clinical experience. This work presents a secondary data analysis of the Australian osteopathy practice-based research network and aims to examine the clinical management characteristics of experienced and novice osteopaths who often treat neck pain. METHODOLOGY: Secondary analysis of a cross-sectional survey of osteopaths registered with the Osteopathy Research and Innovation Network (ORION), an Australian practice-based research network. Demographic, practice and treatment characteristics of osteopaths who 'often' treat neck pain. Data was split into two groups: novice practitioners (up to nine years in clinical practice), and experienced practitioners (10 years or more in clinical practice), and clinical management was compared. RESULTS: Most (98%) of the 971 osteopaths reported that they treat neck pain often. Of those that treat neck pain often, 58% reported being male. The mean number of patient care hours per week was 28.1 ± 12.1 and the mean number of patient visits per week was 36.7 ± 18.7. There was a statistically significant difference between novice and experienced groups for discussing occupation (p < 0.01; d = 0.26) and stress (p = 0.045; d = 0.13) during their consultations, with a low to medium and low effect size, respectively. CONCLUSION: This work demonstrates differences in the management strategies of experienced and novice Australian osteopaths that includes utilisation of a multidisciplinary approach to patient management. The results support the conclusion that there are differences in the clinical management strategies employed by experienced versus novice Australian osteopaths.

Sodium nitrate co-supplementation does not exacerbate low dose metronomic doxorubicin-induced cachexia in healthy mice.

The purpose of this study was to determine whether (1) sodium nitrate (SN) treatment progressed or alleviated doxorubicin (DOX)-induced cachexia and muscle wasting; and (2) if a more-clinically relevant low-dose metronomic (LDM) DOX treatment regimen compared to the high dosage bolus commonly used in animal research, was sufficient to induce cachexia in mice. Six-week old male Balb/C mice (n = 16) were treated with three intraperitoneal injections of either vehicle (0.9% NaCl; VEH) or DOX (4 mg/kg) over one week. To test the hypothesis that sodium nitrate treatment could protect against DOX-induced symptomology, a group of mice (n = 8) were treated with 1 mM NaNO3 in drinking water during DOX (4 mg/kg) treatment (DOX + SN). Body composition indices were assessed using echoMRI scanning, whilst physical and metabolic activity were assessed via indirect calorimetry, before and after the treatment regimen. Skeletal and cardiac muscles were excised to investigate histological and molecular parameters. LDM DOX treatment induced cachexia with significant impacts on both body and lean mass, and fatigue/malaise (i.e. it reduced voluntary wheel running and energy expenditure) that was associated with oxidative/nitrostative stress sufficient to induce the molecular cytotoxic stress regulator, nuclear factor erythroid-2-related factor 2 (NRF-2). SN co-treatment afforded no therapeutic potential, nor did it promote the wasting of lean tissue. Our data re-affirm a cardioprotective effect for SN against DOX-induced collagen deposition. In our mouse model, SN protected against LDM DOX-induced cardiac fibrosis but had no effect on cachexia at the conclusion of the regimen.

Intermittent Fasting and High-Intensity Exercise Elicit Sexual-Dimorphic and Tissue-Specific Adaptations in Diet-Induced Obese Mice.

: The molecular adaptations that underpin body composition changes and health benefits of intermittent fasting (IF) and high-intensity interval training (HIIT) are unclear. The present study investigated these adaptations within the hypothalamus, white adipose and skeletal muscle tissue following 12 weeks of IF and/or HIIT in diet-induced obese mice. Mice (C57BL/6, 8-week-old, males/females) were fed high-fat (59%) and sugar (30%) water (HF/S) for 12 weeks followed by an additional 12 weeks of HF/S plus either IF, HIIT, combination (IF+HIIT) or HF/S only control (CON). Tissues were harvested at 12 and 24 weeks and analysed for various molecular markers. Hypothalamic NPY expression was significantly lower following IF+HIIT compared to CON in females. In adipose tissue, leptin expression was significantly lower following IF and IF+HIIT compared to CON in males and females. Males demonstrated increased markers of fat oxidation (HADH, FABP4) following IF+HIIT, whereas females demonstrated reduced markers of adipocyte differentiation/storage (CIDEC and FOXO1) following IF and/or IF+HIIT. In muscle, SIRT1, UCP3, PGC1α, and AS160 expression was significantly lower following IF compared to CON in males and/or females. This investigation suggests that males and females undertaking IF and HIIT may prevent weight gain via different mechanisms within the same tissue.

Exercise May Ameliorate the Detrimental Side Effects of High Vitamin D Supplementation on Muscle Function in Mice.

Vitamin D is commonly prescribed to normalize deficiencies and to treat osteoporosis. However, the effect vitamin D supplements have on skeletal muscle health is equivocal. Although vitamin D is known to play a role in the various processes that maintain muscle integrity and function, recent studies utilizing high bolus dose vitamin D supplementation has demonstrated an increased risk of falls. Thus, the aim of this study was to investigate the effects of high vitamin D supplementation on skeletal muscle function with and without exercise enrichment. Four-week old C57BL/10 mice (n = 48) were separated into either normal vitamin D (1500 IU/kg diet; unsupplemented) or high vitamin D (20,000 IU/kg diet; supplemented) treatment groups. Each dietary group was further separated into interventional subgroups where mice either remained sedentary or received exercise-enrichment for 8 weeks in the form of voluntary running. Following the intervention period, whole body in vivo and ex vivo contractile analysis were performed. High vitamin D supplementation decreased force production in the slow-twitch soleus muscles of sedentary mice (p < .01); however, exercise normalized this effect. Eight weeks of exercise did not improve fatigue resistance of the extensor digitorum longus (EDL) or soleus muscles in unsupplemented mice, likely due to low levels of activation in these muscles. In contrast, fatigability was improved in the EDL (p < .01) and even more so in the soleus (p < .001) in the supplemented exercise-enriched group. Our data highlights that increasing vitamin D levels above normal reduces postural muscle force as seen in the soleus. Thus, unnecessary vitamin D supplementation may contribute to the increased risk of falls observed in some studies. Interestingly, when vitamin D supplementation was combined with exercise, force production was effectively restored, and fatigue resistance improved, even in muscles lowly activated. Regular exercise may modulate the effects of vitamin D on skeletal muscle, and be recommended for individuals receiving vitamin D supplements. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Adenylosuccinic acid therapy ameliorates murine Duchenne Muscular Dystrophy.

Arising from the ablation of the cytoskeletal protein dystrophin, Duchenne Muscular Dystrophy (DMD) is a debilitating and fatal skeletal muscle wasting disease underpinned by metabolic insufficiency. The inability to facilitate adequate energy production may impede calcium (Ca2+) buffering within, and the regenerative capacity of, dystrophic muscle. Therefore, increasing the metabogenic potential could represent an effective treatment avenue. The aim of our study was to determine the efficacy of adenylosuccinic acid (ASA), a purine nucleotide cycle metabolite, to stimulate metabolism and buffer skeletal muscle damage in the mdx mouse model of DMD. Dystrophin-positive control (C57BL/10) and dystrophin-deficient mdx mice were treated with ASA (3000 µg.mL-1) in drinking water. Following the 8-week treatment period, metabolism, mitochondrial density, viability and superoxide (O2-) production, as well as skeletal muscle histopathology, were assessed. ASA treatment significantly improved the histopathological features of murine DMD by reducing damage area, the number of centronucleated fibres, lipid accumulation, connective tissue infiltration and Ca2+ content of mdx tibialis anterior. These effects were independent of upregulated utrophin expression in the tibialis anterior. ASA treatment also increased mitochondrial viability in mdx flexor digitorum brevis fibres and concomitantly reduced O2- production, an effect that was also observed in cultured immortalised human DMD myoblasts. Our data indicates that ASA has a protective effect on mdx skeletal muscles.

The Effect of Vitamin D Supplementation on Skeletal Muscle in the mdx Mouse Model of Duchenne Muscular Dystrophy.

Vitamin D (VitD) has shown to be beneficial in reversing muscle weakness and atrophy associated with VitD deficiency. Duchenne muscular dystrophy is characterized by worsening muscle weakness and muscle atrophy, with VitD deficiency commonly observed. This study aimed to investigate the effect of VitD supplementation on dystrophic skeletal muscle. Eight-week old female control (C57BL/10; n = 29) and dystrophic (C57BL/mdx; n = 23) mice were randomly supplemented with one of three VitD enriched diets (1000, 8000 & 20,000 IU/kg chow). Following a four-week feeding period, the extensor digitorum longus (EDL) and soleus muscles contractile and fatigue properties were tested ex vivo, followed by histological analysis. As expected, mdx muscles displayed higher mass yet lower specific forces and a rightward shift in their force frequency relationship consistent with dystrophic pathology. There was a trend for mdx muscle mass to be larger following the 20,000 IU/kg diet, but this did not result in improved force production. Fiber area in the EDL was larger in mdx compared to controls, and there were higher amounts of damage in both muscles, with VitD supplementation having no effect. Four weeks of VitD supplementation did not appear to have any impact upon dystrophic skeletal muscle pathology at this age.

The Effect of Yearly-Dose Vitamin D Supplementation on Muscle Function in Mice.

Supplementation with vitamin D helps to alleviate weakness and fatigue seen with deficiency. However, large bolus doses appear to worsen the risk of falls. Whether this occurs as a direct result of muscle weakness is currently unknown. Thus, the aims of this study were to examine the muscle function following administration of high doses of vitamin D. Given the safety issues associated with bolus doses, experiments were conducted on C57BL6 mice. Mice at eight weeks of age with otherwise normal levels of vitamin D were supplemented for four weeks with a high dose (HIGH; n = 12) of vitamin D (20000 IU/kg food) designed to provide a year's worth of vitamin D. These mice were compared to another group who received that same yearly dose in a single bolus i.p. injection (YEAR; n = 12). Mice provided with standard mouse chow, which contained 1000 IU/kg food, and injected with the vitamin D vehicle were used as controls (CON; n = 16). Force and fatigue properties of hind limb fast- and slow-twitch muscles were measured. CON animals ingested vitamin D consistent with typical human supplementation. HIGH animals consumed significantly more food than the CON animals, such that they ingested more than a year's worth of vitamin D in four weeks. Despite this, there were few differences in the muscle function compared with CON. YEAR animals demonstrated lower absolute and relative forces in both muscles compared to the HIGH animals, as well as lower force during fatigue and early recovery. Large bolus doses of vitamin D appear to have detrimental effects on the skeletal muscle function, likely being a contributor to increased risk of falls observed with similar doses in humans. Mice ingesting the same amount over four weeks did not demonstrate the same deleterious effects, suggesting this may be a safe way to provide high vitamin D if required.

Myoprotective Potential of Creatine Is Greater than Whey Protein after Chemically-Induced Damage in Rat Skeletal Muscle.

The myoprotective effects of creatine monohydrate (CR) and whey protein (WP) are equivocal, with the use of proxy measures of muscle damage making interpretation of their effectiveness limited. The purpose of the study was to determine the effects of CR and WP supplementation on muscle damage and recovery following controlled, chemically-induced muscle damage. Degeneration of the extensor digitorum longus (EDL) muscle was induced by bupivacaine in rats supplemented with either CR, WP, or standard rat chow (CON). At day 7 and 14 post-myotoxic injury, injured EDL muscles were surgically removed and tested for isometric contractile properties, followed by the contralateral, non-injured EDL muscle. At the completion of testing, muscles were snap-frozen in liquid nitrogen and stored for later analysis. Data were analyzed using analysis of variance. Creatine-supplemented muscles displayed a greater proportion of non-damaged (intact) fibers (p = 0.002) and larger cross-sectional areas of regenerating and non-damaged fibers (p = 0.024) compared to CON muscles at day 7 post-injury. At day 14 post-injury, CR-supplemented muscles generated higher absolute forces concomitant with greater contractile protein levels compared to CON (p = 0.001, p = 0.008) and WP-supplemented muscles (p = 0.003, p = 0.006). Creatine supplementation appears to offer an element of myoprotection which was not observed following whey protein supplementation.

High dose dietary vitamin D3 increases bone mass and strength in mice.

Vitamin D plays a critical role in skeletal homeostasis. Vitamin D supplementation is used worldwide to maintain optimal bone health, but the most appropriate level of supplementation remains controversial. This study aimed to determine the effects of varying doses of dietary vitamin D3 on the mechanical properties and morphology of growing bone. Eight-week-old female mice were supplied with one of 3 diets, each containing a different dose of vitamin D3: 1000 IU/kg (control), 8000 IU/kg or 20,000 IU/kg. Mice had ad libitum access to the specialty diet for 4 weeks before they were culled and their tibiae collected for further analysis. The collected tibia underwent three-point bending and reference-point indentation from which their mechanical properties were determined, and cortical and trabecular morphology determined by micro computed tomography. Dietary supplementation with 20,000 IU/kg vitamin D3 resulted in greater ductility (~ 200%) and toughness (~ 150%) compared to the 1000 IU/kg control. The 20,000 IU/kg diet was also associated with significantly greater trabecular bone volume fraction and trabecular number. The 8000 IU/kg diet had no significant effect on trabecular bone mass. We conclude that vitamin D3 supplementation of 20,000 IU/kg during early adulthood leads to tougher bone that is more ductile and less brittle than that of mice supplied with standard levels of dietary vitamin D3 (1000 IU/kg) or 8000 IU/kg. This suggests that dietary vitamin D3 supplementation may increase bone health by improving bone material strength and supports the use of vitamin D3 supplementation, during adolescence, for achieving a higher peak bone mass in adulthood and thereby preventing osteoporosis.

Attenuation of Resting but Not Load-Mediated Protein Synthesis in Prostate Cancer Patients on Androgen Deprivation.

CONTEXT: Androgen deprivation therapy (ADT) is a common prostate cancer (PCa) treatment but results in muscular atrophy. Periodic increases in muscle protein synthesis (MPS) that occur after resistance exercise or protein intake may ameliorate this muscle loss, but the impact of these anabolic stimuli during ADT is unclear. OBJECTIVE: To determine the acute MPS response to whey protein supplementation with and without resistance exercise during ADT. DESIGN: Acute response in PCa patients vs age-matched controls (CON). SETTING: Academic laboratory setting. PARTICIPANTS: PCa patients on ADT (N = 8) and CON (N = 10). INTERVENTION: A standardized diet was consumed for 2 days prior to performing unilateral knee extension resistance exercise followed by ingestion of 40 g of whey protein. MAIN OUTCOME MEASURES: Bilateral biopsies and stable isotope infusions were used to determine MPS rates at rest after protein ingestion with and without resistance exercise. RESULTS: Baseline MPS during ADT was suppressed relative to CON (P = 0.01). Protein consumption stimulated MPS in both groups (approximate twofold increase, both P < 0.001), but to a greater extent in CON (P = 0.003). Protein plus resistance exercise increased MPS (∼3.4-fold increase, both P < 0.001) to a greater extent than did protein alone (P < 0.001), but with no difference between groups (P = 0.380). CONCLUSIONS: ADT reduces basal and protein feeding-induced rises in MPS; however, combined protein ingestion with resistance exercise stimulated MPS to a similar degree as CON. Testosterone appears to play a role in maintaining muscle mass but is not necessary to initiate a robust response in MPS following resistance exercise when combined with protein ingestion.

Attempting to Compensate for Reduced Neuronal Nitric Oxide Synthase Protein with Nitrate Supplementation Cannot Overcome Metabolic Dysfunction but Rather Has Detrimental Effects in Dystrophin-Deficient mdx Muscle.

Duchenne muscular dystrophy arises from the loss of dystrophin and is characterized by calcium dysregulation, muscular atrophy, and metabolic dysfunction. The secondary reduction of neuronal nitric oxide synthase (nNOS) from the sarcolemma reduces NO production and bioavailability. As NO modulates glucose uptake, metabolism, and mitochondrial bioenergetics, we investigated whether an 8-week nitrate supplementation regimen could overcome metabolic dysfunction in the mdx mouse. Dystrophin-positive control (C57BL/10) and dystrophin-deficient mdx mice were supplemented with sodium nitrate (85 mg/l) in drinking water. Following the supplementation period, extensor digitorum longus and soleus were excised and radioactive glucose uptake was measured at rest (basal) and during contraction. Gastrocnemius was excised and mitochondrial respiration was measured using the Oroboros Oxygraph. Tibialis anterior was analyzed immunohistochemically for the presence of dystrophin, nNOS, nitrotyrosine, IgG and CD45+ cells, and histologically to assess areas of damage and regeneration. Glucose uptake in the basal and contracting states was normal in unsupplemented mdx muscles but was reduced following nitrate supplementation in mdx muscles only. The mitochondrial utilization of substrates was also impaired in mdx gastrocnemius during phosphorylating and maximal uncoupled respiration, and nitrate could not improve respiration in mdx muscle. Although nitrate supplementation reduced mitochondrial hydrogen peroxide emission, it induced mitochondrial uncoupling in red gastrocnemius, increased muscle fiber peroxynitrite (nitrotyrosine), and promoted skeletal muscle damage. Our novel data suggest that despite lower nNOS protein expression and likely lower NO production in mdx muscle, enhancing NO production with nitrate supplementation in these mice has detrimental effects on skeletal muscle. This may have important relevance for those with DMD.

The effect of taurine and ß-alanine supplementation on taurine transporter protein and fatigue resistance in skeletal muscle from mdx mice.

This study investigated the effect of taurine and ß-alanine supplementation on muscle function and muscle taurine transporter (TauT) protein expression in mdx mice. Wild-type (WT) and mdx mice (5 months) were supplemented with taurine or ß-alanine for 4 weeks, after which in vitro contractile properties, fatigue resistance and force recovery, and the expression of the TauT protein and proteins involved in excitation-contraction (E-C) coupling were examined in fast-twitch muscle. There was no difference in basal TauT protein expression or basal taurine content between mdx than WT muscle. Supplementation with taurine and ß-alanine increased and reduced taurine content, respectively, in muscle from WT and mdx mice but had no effect of TauT protein. Taurine supplementation reduced body and muscle mass, and enhanced fatigue resistance and force recovery in mdx muscle. ß-Alanine supplementation enhanced fatigue resistance in WT and mdx muscle. There was no difference in the basal expression of key E-C coupling proteins [ryanodine receptor 1 (RyR1), dihydropyridine receptor (DHPR), sarco(endo)plasmic reticulum Ca2+-ATPase 1 (SERCA1) or calsequestrin 1 (CSQ1)] between WT and mdx mice, and the expression of these proteins was not altered by taurine or ß-alanine supplementation. These findings suggest that TauT protein expression is relatively insensitive to changes in muscle taurine content in WT and mdx mice, and that taurine and ß-alanine supplementation may be viable therapeutic strategies to improve fatigue resistance of dystrophic skeletal muscle.

Caffeine and cardiovascular diseases: critical review of current research.

Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains "Which dose is safe?", as the population does not appear to adhere to the strict guidelines listed on caffeine consumption. Studies in humans and animal models yield controversial results, which can be explained by population, type and dose of caffeine and low statistical power. This review will focus on comprehensive and critical review of the current literature and provide an avenue for further study.

Metabogenic and Nutriceutical Approaches to Address Energy Dysregulation and Skeletal Muscle Wasting in Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is a fatal genetic muscle wasting disease with no current cure. A prominent, yet poorly treated feature of dystrophic muscle is the dysregulation of energy homeostasis which may be associated with intrinsic defects in key energy systems and promote muscle wasting. As such, supplementative nutriceuticals that target and augment the bioenergetical expansion of the metabolic pathways involved in cellular energy production have been widely investigated for their therapeutic efficacy in the treatment of DMD. We describe the metabolic nuances of dystrophin-deficient skeletal muscle and review the potential of various metabogenic and nutriceutical compounds to ameliorate the pathological and clinical progression of the disease.

Revisiting the dystrophin-ATP connection: How half a century of research still implicates mitochondrial dysfunction in Duchenne Muscular Dystrophy aetiology.

Duchenne Muscular Dystrophy (DMD) is a fatal neuromuscular disease that is characterised by dystrophin-deficiency and chronic Ca(2+)-induced skeletal muscle wasting, which currently has no cure. DMD was once considered predominantly as a metabolic disease due to the myriad of metabolic insufficiencies evident in the musculature, however this aspect of the disease has been extensively ignored since the discovery of dystrophin. The collective historical and contemporary literature documenting these metabolic nuances has culminated in a series of studies that importantly demonstrate that metabolic dysfunction exists independent of dystrophin expression and a mild disease phenotype can be expressed even in the complete absence of dystrophin expression. Targeting and supporting metabolic pathways with anaplerotic and other energy-enhancing supplements has also shown therapeutic value. We explore the hypothesis that DMD is characterised by a systemic mitochondrial impairment that is central to disease aetiology rather than a secondary pathophysiological consequence of dystrophin-deficiency.

Reliability of Chinese medicine diagnostic variables in the examination of patients with osteoarthritis of the knee.

BACKGROUND: Chinese medicine (CM) has its own diagnostic indicators that are used as evidence of change in a patient's condition. The majority of studies investigating efficacy of Chinese herbal medicine (CHM) have utilized biomedical diagnostic endpoints. For CM clinical diagnostic variables to be incorporated into clinical trial designs, there would need to be evidence that these diagnostic variables are reliable. Previous studies have indicated that the reliability of CM syndrome diagnosis is variable. Little information is known about where the variability stems from--the basic data collection level or the synthesis of diagnostic data, or both. No previous studies have investigated systematically the reliability of all four diagnostic methods used in the CM diagnostic process (Inquiry, Inspection, Auscultation/Olfaction, and Palpation). OBJECTIVES: The objective of this study was to assess the inter-rater reliability of data collected using the four diagnostic methods of CM in Australian patients with knee osteoarthritis (OA), in order to investigate if CM variables could be used with confidence as diagnostic endpoints in a clinical trial investigating the efficacy of a CHM in treating OA. METHODS: An inter-rater reliability study was conducted as a substudy of a clinical trial investigating the treatment of knee OA with Chinese herbal medicine. Two (2) experienced CM practitioners conducted a CM examination separately, within 2 hours of each other, in 40 participants. A CM assessment form was utilized to record the diagnostic data. Cohen's κ coefficient was used as a measure of the level of agreement between 2 practitioners. RESULTS: There was a relatively good level of agreement for Inquiry and Auscultation variables, and, in general, a low level of agreement for (visual) Inspection and Palpation variables. CONCLUSIONS: There was variation in the level of agreement between 2 practitioners on clinical information collected using the Four Diagnostic Methods of a CM examination. Some aspects of CM diagnosis appear to be reliable, while others are not. Based on these results, it was inappropriate to use CM diagnostic variables as diagnostic endpoints in the main study, which was an investigation of efficacy of CHM treatment of knee OA.

Reliability of the Eight Guiding Principles and Syndrome Diagnosis in Chinese Medicine Diagnosis of Patients with Knee Osteoarthritis.

Abstract Background: A Chinese medicine (CM) "Syndrome" or "pattern of disharmony" is a diagnostic subcategory of a disease/disorder or symptom, characterized by particular symptoms and signs, and indicative of the etiology and the state of pathogenesis at that point in time. In CM, treatment is aimed at addressing the disease/disorder and the underlying CM Syndrome. A few studies have assessed reliability of CM Syndrome diagnosis according to one of the major CM theories, Zang-Fu theory, but only 1 study has investigated the reliability of diagnosis according to a fundamental theory, that of the Eight Guiding Principles. Given that treatment follows diagnosis, if diagnosis is not reliable there will be lower confidence that optimal treatment is received. There have not yet been any reliability studies in osteoarthritis (OA). Little is known about the characteristics or Syndromes of OA with respect to the Eight Guiding Principles and Zang-Fu theory. Objectives: The objectives of this study were to characterize diagnostic subcategories of OA according to the Eight Guiding Principles and Zang-Fu theory and to investigate the inter-rater reliability of CM diagnosis according to these two theories. Methods: An inter-rater reliability study was conducted as a substudy of a clinical trial investigating the treatment of knee OA with Chinese herbal medicine. Two (2) experienced CM practitioners conducted a CM examination separately, within 2 hours of each other, of 40 participants. A CM assessment form was utilized to record the diagnostic data. Cohen's κ coefficient was used as a measure of reliability. Results: Results support the concept that knee OA is more likely a disease with characteristics of Interior, Deficiency, and Yin according to the Eight Guiding Principles. There was no clear agreement on CM Syndromes of knee OA according to Zang-Fu theory. The main Zang Organs involved were broadly agreed on; they were Kidney, Liver, and Spleen. Conclusions: Results lend some empirical evidence to support to the argument that OA of the knee is an Internal disease with the manifestations of Deficient symptoms according to CM theories. To establish if Syndrome diagnosis is reliable, more studies should be conducted for different clinical conditions.

Taurine supplementation increases skeletal muscle force production and protects muscle function during and after high-frequency in vitro stimulation.

Recent studies report that depletion and repletion of muscle taurine (Tau) to endogenous levels affects skeletal muscle contractility in vitro. In this study, muscle Tau content was raised above endogenous levels by supplementing male Sprague-Dawley rats with 2.5% (wt/vol) Tau in drinking water for 2 wk, after which extensor digitorum longus (EDL) muscles were examined for in vitro contractile properties, fatigue resistance, and recovery from fatigue after two different high-frequency stimulation bouts. Tau supplementation increased muscle Tau content by approximately 40% and isometric twitch force by 19%, shifted the force-frequency relationship upward and to the left, increased specific force by 4.2%, and increased muscle calsequestrin protein content by 49%. Force at the end of a 10-s (100 Hz) continuous tetanic stimulation was 6% greater than controls, while force at the end of the 3-min intermittent high-frequency stimulation bout was significantly higher than controls, with a 12% greater area under the force curve. For 1 h after the 10-s continuous stimulation, tetanic force in Tau-supplemented muscles remained relatively stable while control muscle force gradually deteriorated. After the 3-min intermittent bout, tetanic force continued to slowly recover over the next 1 h, while control muscle force again began to decline. Tau supplementation attenuated F(2)-isoprostane production (a sensitive indicator of reactive oxygen species-induced lipid peroxidation) during the 3-min intermittent stimulation bout. Finally, Tau transporter protein expression was not altered by the Tau supplementation. Our results demonstrate that raising Tau content above endogenous levels increases twitch and subtetanic and specific force in rat fast-twitch skeletal muscle. Also, we demonstrate that raising Tau protects muscle function during high-frequency in vitro stimulation and the ensuing recovery period and helps reduce oxidative stress during prolonged stimulation.