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Falls in older persons are associated with muscle mass and strength alterations, which may also affect balance parameters. However, the most appropriate combined approach to assess muscle and balance components that predict falls in older persons is still lacking.We hypothesized that appendicular lean and/or mid-thigh mass and muscle strength and performance are positively associated with balance indices and fall risk in older persons.Cross-sectional analyses of retrospective data from 260 participants with risk and/or history of falls examined at a Falls and Fracture Clinic. Assessments included a comprehensive clinical exam, bone densitometry and body composition by DXA, grip strength, gait speed, posturography, timed up and go (TUG) and four-square step (FSST) tests. Retrospective falls and fracture history was collected. Associations between appendicular and mid-thigh lean mass and muscle strength/performance vs balance indicators were determined before and after adjusting for age and gender.Mean age of participants was 78 ± 6.7 (65-96) years. Both appendicular and mid-thigh lean masses corrected for BMI (but not for heightCombined with strength and performance parameters, ALM and mid-thigh estimates adjusted by BMI strongly correlate with dynamic balance parameters and could become practical elements of falls risk assessment as well as markers of therapeutic response to falls prevention interventions.

Background: Accurate quantification of bone, muscle, and their components is still an unmet need in the musculoskeletal field. Current methods to quantify tissue volumes in 3D images are expensive, labor-intensive, and time-consuming; thus, a reliable, valid, and quick application is highly needed.Methods: Tissue Compass is a standalone software for semiautomatic segmentation and automatic quantification of musculoskeletal organs. To validate the software, cross-sectional micro-CT scans images of rat femur (n=19), and CT images of hip and abdomen (n=100) from the Osteoporotic Fractures in Men (MrOS) Study were used to quantify bone, hematopoietic marrow (HBM), and marrow adipose tissue (MAT) using commercial manual software as a comparator. Also, abdominal CT scans (n=100) were used to quantify psoas muscle volumes and intermuscular adipose tissue (IMAT) using the same software. We calculated Pearson's correlation coefficients, individual intra-class correlation coefficients (ICC), and Bland-Altman limits of agreement together with Bland-Altman plots to show the inter- and intra-observer agreement between Tissue Compass and commercially available software.Results: In the animal study, the agreement between Tissue Compass and commercial software was r>0.93 and ICC>0.93 for rat femur measurements. Bland-Altman limits of agreement was -720.89 (-1.5e+04, 13074.00) for MAT, 4421.11 (-1.8e+04, 27149.73) for HBM and -6073.32 (-2.9e+04, 16388.37) for bone. The inter-observer agreement for QCT human study between two observers was r>0.99 and ICC>0.99. Bland-Altman limits of agreement was 0.01 (-0.07, 0.10) for MAT in hip, 0.02 (-0.08, 0.12) for HBM in hip, 0.05 (-0.15, 0.25) for bone in hip, 0.02 (-0.18, 0.22) for MAT in L1, 0.00 (-0.16, 0.16) for HBM in L1, 0.02 (-0.23, 0.27) for bone in L1. The intra-observer agreement for QCT human study between two applications was r>0.997 and ICC>0.99. Bland-Altman limits of agreement was 0.03 (-0.13, 0.20) for MAT in hip, 0.05 (-0.08, 0.18) for HBM in hip, 0.05 (-0.24, 0.34) for bone in hip, -0.02 (-0.34, 0.31) for MAT in L1, -0.14 (-0.44, 0.17) for HBM in L1, -0.29 (-0.62, 0.05) for bone in L1, 0.03 (-0.08, 0.15) for IMAT in psoas, and 0.02 (-0.35, 0.38) for muscle in psoas. Conclusion: Compared to a conventional application, Tissue Compass demonstrated high accuracy and non-inferiority while also facilitating easier analyses. Tissue Compass could become the tool of choice to diagnose tissue loss/gain syndromes in the future by requiring a small number of CT sections to detect tissue volumes and fat infiltration.

Purpose The objective of this study was to compare the effects of 12 weeks of resistance training combined with either 5:2 intermittent fasting or continuous energy restriction on body composition, muscle size and quality, and upper and lower body strength. Methods Untrained individuals undertook 12 weeks of resistance training plus either continuous energy restriction [20% daily energy restriction (CERT)] or 5:2 intermittent fasting [~ 70% energy restriction 2 days/week, euenergetic consumption 5 days/week (IFT)], with both groups prescribed a mean of ≥ 1.4 g of protein per kilogram of body weight per day. Participants completed 2 supervised resistance and 1 unsupervised aerobic/resistance training combination session per week. Changes in lean body mass (LBM), thigh muscle size and quality, strength and dietary intake were assessed. Results Thirty-four participants completed the study (CERT = 17, IFT = 17). LBM was significantly increased (+ 3.7%, p p p Conclusion When combined with resistance training and moderate protein intake, continuous energy restriction and 5:2 intermittent fasting resulted in similar improvements in body composition, muscle quality, and strength. ACTRN: ACTRN12620000920998, September 2020, retrospectively registered.

Picolinic acid (PIC) is a byproduct of tryptophan catabolism through the kynurenine pathway, with anabolic effects on bone in vivo and in vitro. Hence, PIC has been nominated as a possible candidate to treat and/or prevent osteoporosis. However, the effective dose and toxicity of PIC are not known yet. To test the effect of escalating and very high doses of oral PIC, male Sprague-Dawley rats were gavaged PIC: Group 1 (n = 3) received incremental doses of 125, 250 and 500 mg/kg/day PIC on days 1, 3 and 5. Group 2 (n = 3) received 500 mg/kg BID (8 h apart; i.e. 1000 mg/kg/day) PIC on Day 1. Group 3 (n = 3) received 125 mg/kg/day PIC for seven consecutive days. Group 4 (n = 3) received 250 mg/kg/day PIC for seven consecutive days. Groups 1, 3 and 4 rats were euthanized on Day 8. Group 5 (n = 6) received 500 mg/kg/day PIC for two consecutive days and then once a week dose (Days 9, 16 and 23) of 500 mg/kg/dose PIC, until euthanasia (Day 30). Blood and cerebrospinal fluid (CSF) were sampled at euthanasia, and tissues showing abnormalities at necropsy underwent histopathology evaluation. All rats displayed some degree of mild hypercalcemia and hyperkalemia. Rats receiving high doses (500 or 1000 mg/kg/day) of PIC died or were euthanized on humane grounds within the first week after showing clinical neurological signs, with animals later revealed to have brain necrosis and hemorrhage at histopathology. Rats receiving lower doses (125 or 250 mg/kg/day) of PIC completed treatment course without apparent clinical adverse events. In summary, very high doses of PIC (≥500 mg/kg/day) were vascular-neurotoxic. Possible future experiments must consider significantly lower doses.

OBJECTIVES: Because of the nature of the Fontan physiology, patients are at an increased risk of thromboembolic complications. As such, warfarin or aspirin is generally prescribed lifelong for thromboprophylaxis. This study aimed to compare long-term rates of cerebrovascular injury, thrombosis, bleeding, bone mineral density, and quality of life in people living with Fontan circulation receiving warfarin compared with aspirin. METHODS: This was a multicenter study of a selected cohort from the Australia and New Zealand Fontan population. Participants underwent cerebral magnetic resonance imaging to detect the presence of cerebrovascular injury (n = 84) and dual-energy X-ray absorptiometry to assess bone mineral density (n = 120). Bleeding (n = 100) and quality of life (n = 90) were assessed using validated questionnaires: Warfarin and Aspirin Bleeding assessment tool and Pediatric Quality of Life Inventory, respectively. RESULTS: Stroke was detected in 33 participants (39%), with only 7 (6%) being clinically symptomatic. There was no association between stroke and Fontan type or thromboprophylaxis type. Microhemorrhage and white matter injury were detected in most participants (96% and 86%, respectively), regardless of thromboprophylaxis type. Bleeding rates were high in both groups; however, bleeding was more frequent in the warfarin group. Bone mineral density was reduced in our cohort compared with the general population; however, this was further attenuated in the warfarin group. Quality of life was similar between the warfarin and aspirin groups. Home international normalized ratio monitoring was associated with better quality of life scores in the warfarin group. CONCLUSIONS: Cerebrovascular injury is a frequent occurrence in the Australia and New Zealand Fontan population regardless of thromboprophylaxis type. No benefit of long-term warfarin prophylaxis could be demonstrated over aspirin; however, consideration must be given to important clinical features such as cardiac function and lung function. Furthermore, the association of reduced bone health in children receiving warfarin warrants further mechanistic studies.