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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.

BACKGROUND: To assess the association between body composition and the risk of adverse outcomes in Fontan patients. METHODS: Participants from the Australian and New Zealand Fontan Registry with dual-energy X-ray absorptiometry scans were included. Appendicular lean mass (ALM), appendicular lean mass index (ALM divided by height squared; ALMI) and total body fat mass percentage (%BF) were calculated. ALMI and %BF z-scores were derived using age- and sex-matched reference ranges. The primary outcome was Fontan failure (death, transplantation, New York Heart Association functional class III/IV, protein-losing enteropathy, and plastic bronchitis) or moderate-or-severe ventricular dysfunction. RESULTS: 144 patients were included. Mean %BF was 29% (SD 10) with 50% having increased adiposity. Mean ALMI z-score was -1.4 (SD 1.1); one third of patients had skeletal muscle deficiency (ALMI z-score

Objectives Sarcopenia Definitions and Outcomes Consortium (SDOC) provides cut-points based on muscle weakness (low grip strength) and slowness (poor gait speed) for low-risk populations; however, it is unknown if these criteria apply to high-risk populations. We examined the association between SDOC criteria and important health status indicators in high-risk older persons. Design Cross-sectional study. Setting and Participants 356 community-dwelling older persons (median age: 79 years, interquartile range: 73, 83; 75.2% women) attending a falls and fractures clinic in Melbourne, Australia. Methods Grip strength (hydraulic dynamometer) and gait speed (over 4 m) were used to define sarcopenia using SDOC cut-points. Health measures included falls (past 1 year) and fractures (past 5 years) by self-report, and malnutrition, depression, balance confidence, fear of falling, static balance (limits of stability), dynamic balance (Four-Square Step Test), and body composition [body mass index and lean mass, fat mass, and bone density (via dual-energy x-ray absorptiometry)] were assessed using validated procedures. Fasting vitamin D and parathyroid hormone concentrations were measured by immunoassays. Participants were categorized as nonsarcopenic or sarcopenic based on the SDOC cut-points, and multivariate models were used to examine the association between sarcopenia and health status indicators while adjusting for confounding factors. Results After adjusting for covariates, sarcopenic older persons (n = 162, 45.5%) were positively associated with malnutrition [odds ratio (OR) 3.21, 95% confidence interval (CI) 1.63, 6.32], depression (OR 4.11, 95% CI 2.31, 7.29), fear of falling (OR 1.08, 95% CI 1.06, 1.10) as well as recurrent (2 or more) falls (OR 1.62, 95% CI 1.01, 2.59) and fractures (OR 2.26, 95% CI 1.17, 4.36), and negatively associated with poor balance confidence (OR 0.96, 95% CI 0.95, 0.97) (P Conclusions and Implications SDOC criteria are strongly associated with important health status indicators in high-risk older persons, which strengthens the clinical utility of the SDOC in these populations.

Anemia is commonly associated with osteoporosis and sarcopenia in older persons. However, there is a common subset of patients identified as osteosarcopenic at a higher risk of adverse outcomes. Whether these patients are also at a higher risk of anemia remains unknown. In this study, we aimed to compare hemoglobin (Hb) levels in osteosarcopenic older subjects versus those with sarcopenia, osteopenia/osteoporosis alone and controls. Cross-sectional study in 558 community-dwelling participants older than 65 (mean age 79 ± 7.5 years) from Western Sydney, Australia. Associations of anemia with sarcopenia, osteopenia/osteoporosis and osteosarcopenia were assessed. Participants were able to mobilize independently, reported a risk/history of falls and were not cognitively impaired. We used the original (EWGOP) and revised (EWGSOP2) European consensus on definition of sarcopenia, and WHO definitions of osteoporosis and osteopenia. Based on both European definitions of sarcopenia prevalence of anemia was the highest among sarcopenic patients (39%), followed by osteosarcopenic (34%), osteoporotic/penic (26%), and controls (24%). Anemia prevalence in total was 176/553 (31.5%). Osteosarcopenic patients on average had 6.3 g/L lower Hb levels compared to controls (p = 0.001), and 3.7 g/L lower Hb than patients with osteoporosis/penia (p 0.026). Interestingly, levels of Hb did not differ between sarcopenic vs osteosarcopenic patients (p = 0.817) and between osteoporotic/osteopenic patients vs controls (p 0.259). The higher prevalence of anemia and lower hemoglobin in sarcopenic and osteosarcopenic subjects compared to osteoporotic/penic participants and controls was established. However, the previously reported associations between osteoporosis and anemia were not confirmed. A likely explanation can be inclusion of osteosarcopenic subjects as osteoporotic in previous studies.

We sought to examine the associations of osteosarcopenia with physical performance, balance, and falls and fractures in community-dwelling older adults. Additionally, we aimed to determine which clinical outcomes are associated with specific components of osteosarcopenia.Cross-sectional study.253 participants (77% women; aged 77.9 ± 0.42 years) who presented for a falls and fractures risk assessment in Melbourne, Australia.Participants were mobile, community-dwelling older adults (≥65 years) free of cognitive impairment. Body composition (via dual-energy x-ray absorptiometry), physical performance [via Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB)], and balance [via Four-Square Step test (FSS) and posturography] were examined. Falls in the past year and fractures in the past 5 years were self-reported. Osteosarcopenia was defined as (1) low bone mineral density (BMD) [T score-1 standard deviation (SD)] combined with sarcopenia and (2) osteoporosis (BMD T score ≤-2.5 SD) combined with severe sarcopenia. For sarcopenia, we employed the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP1), the revised criteria (EWGSOP2), and that of the Foundation for the National Institutes for Health (FNIH). Kruskal-Wallis and logistic regression tests were used for statistical analysis.Osteosarcopenia was associated with worse SPPB, TUG, FSS, limit of stability, and falls and fractures history. Additionally, osteosarcopenia (using the severe sarcopenia classification) conferred an increased rate of falls [odds ratios (ORs) from 2.83 to 3.63; P .05 for all] and fractures (ORs from 3.86 to 4.38; P .05 for all) when employing the EWGSOP2 and FNIH definitions, respectively.Compared with the nonosteosarcopenic group, those with osteosarcopenia had greater impairment of physical performance and balance. The EWGSOP2 and FNIH criteria resulted in the strongest associations with physical performance and self-reported falls and fractures.

The significance and roles of marrow adipose tissue (MAT) are increasingly known, and it is no more considered a passive fat storage but a tissue with significant paracrine and endocrine activities that can cause lipotoxicity and inflammation. Changes in the MAT volume and fatty acid composition appear to drive bone and hematopoietic marrow deterioration, and studying it may open new horizons to predict bone fragility and anemia development. MAT has the potential to negatively impact bone volume and strength through several mechanisms that are partially described by inflammaging and lipotoxicity terminology. Evidence indicates paramount importance of MAT in age-associated decline of bone and red marrow structure and function. Currently, MAT measurement is being tested and validated by several techniques. However, purpose-specific adaptation of existing imaging technologies and, more importantly, development of new modalities to quantitatively measure MAT are yet to be done.

This narrative review provides a summary introduction to the relationship between stroke and physical and cognitive frailty syndromes and the neuro-inflammatory similarities (including inflammaging) between the two. The review argues the potential effects of Post COVID-19 Neurological Syndrome (PCNS, also known as Long COVID) with similar pathophysiology. Many patients who have suffered from acute stroke experience long-lasting symptoms affecting several organs including fatigue, brain fog, reduced physical activity, loss of energy, and loss of cognitive reserve, culminating in the loss of independence and poor quality of life. This is very similar to the emerging reports of PCNS from different parts of the world. Stroke, particularly in older adults with comorbidities appears to impact the health and welfare of patients by reducing central neuronal input and neuromuscular function, with muscular atrophy and neuropsychiatric complications. The cumulative effects can potentially lead to a range of physical and cognitive frailty syndromes, which, in many cases may be attributed to persistent, maladapted, low grade, chronic inflammation. Meanwhile, post-COVID-19 Neurological Syndrome (also known as Long COVID Syndrome) appears to share a similar trajectory, adding further urgency for investigations into the mechanisms underlying this constellation of symptoms.

Purpose: The prevalence of musculoskeletal tissue loss syndromes (osteoporosis and sarcopenia), as well as obesity and their combinations, is on the rise. Previous reports indicate mid-thigh dual-energy x-ray absorptiometry (DXA) is well-suited for the simultaneous assessment of bone, muscle, and fat mass in a single scan.Methods: Using DXA images of 1322 community-dwelling adults (57% women, age 58.2 ± 15.6 SD), bone, lean and fat mass were quantified in five regions of interest (ROIs): a) a 2.6 cm; and b) a 13 cm thick slice of mid-thigh; c) whole thigh; d) whole calf; and e) forearm. Conventional indices of tissue mass i.e. appendicular lean mass, hip, and spine bone mineral density (BMD) and total, gynoid and android fat mass, were also calculated. Their associations with muscle strength (handgrip strength) and performance (timed-up-and-go [TUG] and gait speed), as well as falls and fractures, were investigated.Results: Lean mass in all ROIs was well-correlated with outcomes, and according to regression analyses, lean mass explained two-thirds, a third and a quarter of the variability in the handgrip strength (r2= 0.63 to 0.64, p2= 0.34 to 0.37, p2= 0.25 to 0.27, pp=0.029). In all assessed ROIs, BMD was associated with the number of incident fractures within five years (OR= 0.72 to 0.93, p=0.034 to 2.Conclusion: Compared to the conventional indices and four other ROIs, mid-thigh tissue masses were associated with markers of muscle performance. Mid-thigh BMD and lean mass were superior and showed more consistent and more robust associations with adverse outcomes (falls and fractures), particularly in the older population.

Osteosarcopenia is defined as the concomitant occurrence of osteoporosis and sarcopenia. Current lack of consensus on sarcopenia definitions, combined with the low sensitivity and specificity of screening methodologies, has resulted in varying prevalences of sarcopenia, and consequently osteosarcopenia diagnosis. Previous research indicates that mid-thigh is a potential surrogate region for the assessment of bone, muscle, and fat mass in a single, efficient and low-radiation dual x-ray absorptiometry (DXA) scan. We hypothesized that muscle and bone mass measurements in the mid-thigh region can be used to evaluate bone and muscle health and function. A retrospective study was conducted on community-dwelling older subjects (> 65 y.o., n = 260) who were at risk of falls and fractures. Mid-thigh and mid-calf bone, lean muscle, and fat masses, as well as their association with muscle function, falls, and fractures were compared against conventional measures (hip/spine bone, appendicular lean, and gynoid/android fat masses). Mid-thigh bone, lean, and fat masses showed strong correlation with conventional measures. Mid-thigh lean mass showed similar associations with grip strength, gait speed, and timed up and go (TUG) test as appendicular lean mass. Appendicular, mid-thigh and mid-calf lean masses corrected for body mass index (BMI) showed stronger associations than when corrected for height2. None of the indices were associated with fractures; but fat mass was invariably associated with falls. Those with falls and fractures history had lower bone and muscle mass at mid-thigh. Mid-thigh is a potential new surrogate to study bone, muscle, and fat mass in older people, with comparable ability in predicting muscle performance and falls.

Malnutrition is highly prevalent in older persons with dementia. Therefore, strong predictors of malnutrition in this population are crucial to initiating early interventions. This study evaluates the association between the probability of having malnutrition with the muscle volume and intramuscular fat (iMAT) of the masseter and the tongue in magnetic resonance imaging (MRI) of community-dwelling older persons diagnosed with mild dementia followed up for 5 years. This is a longitudinal study conducted in the western part of Norway. Muscle volume and iMAT of the tongue and masseter were computed from structural head MRI obtained from 65 participants of the Dementia Study of Western Norway using Slice-O-Matic software for segmentation. Malnutrition was assessed using the Global Leadership Initiative on Malnutrition Index. Linear mixed models were conducted. Having malnutrition at baseline was associated with lower muscle volume (odds ratio [OR] 0.60, standard error [SE] 0.20; p = .010) and higher iMAT (OR 3.31, SE 0.46; p = .010) in the tongue. At 5 years follow-up, those with lower muscle volume (OR 0.55, SE 0.20; p = .002) and higher iMAT (OR 2.52, SE 0.40; p = .022) in the tongue had a higher probability of presenting malnutrition. The masseter iMAT and volume were not associated with malnutrition in any of the adjusted models. In people diagnosed with mild dementia, tongue muscle volume and iMAT were associated with baseline malnutrition and the probability of developing malnutrition in a 5-year trajectory. In the masseter, there were no significant associations after adjustments.

Introduction: Increased adiposity and reduced lean mass are prevalent in Fontan patients and could be impactful because of the reliance on the peripheral muscle pump and the importance of favourable pulmonary physiology in univentricular physiology. The current study aimed to determine the impact of body fat and lean mass on the risk of adverse outcomes in Fontan patients. Methods: Patients with dual-energy X-ray absorptiometry (DXA) scans from the Australian and New Zealand Fontan Registry were included; they had been consecutively recruited for 2 previous cohort studies. Regression analysis was used to characterize the association between body composition and the composite endpoint of Fontan failure (which included death, transplantation, New York Heart Association (NYHA) functional class III/IV, protein-losing enteropathy, and plastic bronchitis) and development of moderate or worse ventricular dysfunction. Results: 131 DXA scans were analyzed, with mean follow-up of 2.5 (SD 2.2) years after DXA. Mean body fat percentage (%BF) was 29% (SD 10) with 48% having increased adiposity compared with local reference data. Mean appendicular lean mass index (ALMI) z-score was -1.5 (SD 1.1); one third of patients had skeletal muscle deficiency (defined as ALMI z-score between -1 and -2) and another third had Fontan-associated myopenia (defined as ALMI z-score &lt -2). Nine patients reached the composite endpoint during the follow-up period. Age and %BF were predictors of the endpoint in univariable regression (age: HR 1.09 per year, 95% CI 1.02-1.17, p = 0.01; %BF: HR 1.08, 95% CI 1.01-1.17, p = 0.03). On multivariable regression, %BF remained a significant predictor with every 1% increase conferring an 9% increased risk (HR 1.09, 95% CI 1.00-1.19; p = 0.045). ALMI was not a predictor of the endpoint (HR 1.40, 95% CI 0.71-2.76, p = 0.33). However, all patients who experienced a Fontan failure event (n=4) concurrently had increased adiposity and skeletal muscle deficiency. Conclusions: Increased adiposity is associated with increased risk for adverse clinical outcomes. Appropriate lifestyle interventions to optimise body composition should be an important aspect of routine care in this population.

ObjectiveWe aimed to investigate the skeletal phenotype of Winnie mouse model of spontaneous chronic colitis, which carries a mutation in the Muc2 gene and closely replicates IBD symptoms and pathophysiology. These mice have a high level of gut-derived serotonin (GDS), a potent osteoblastogenesis inhibitor. We explored the underlying mechanisms of bone loss associated with chronic intestinal inflammation.DesignWinnie male and female mice prior to colitis onset (6 weeks old) and progression (14 and 24 weeks) were compared to age- and sex-matched C57BL/6 controls. We assessed bone quality (static and dynamic histomorphometry, micro-CT, 3-point bending), intestinal inflammation (lipocalin-2), GDS levels, serum levels of calcium, phosphorus and vitamin D, ex vivo bone marrow analysis and molecular mechanisms inhibiting osteoblastogenesis.ResultsSignificant deterioration in trabecular and cortical microarchitecture, reductions in bone formation, mineral apposition rate, bone volume, osteoid volume and bone strength were observed in Winnie mice compared to C57BL/6 controls. Decreased osteoblast and increased osteoclast numbers were prominent in Winnie mice. We report for the first time that elevated GDS cross-talks with molecular pathways to inhibit bone formation in Winnie mice. Increased expression of 5-HTR1B and FOXO1 mRNAs, dissociation of FOXO1/CREB1 complex and association of FOXO1 with ATF4, promoting the transcriptional activity of FOXO1, results in suppression of osteoblast proliferation in Winnie mice compared to controls.ConclusionThese findings open avenues for the development of targeted therapies for IBD-related bone loss.Significance of this studyWhat is already known on this subject?- Osteoporosis is a common extraintestinal manifestation of inflammatory bowel disease (IBD).- Currently available treatments are not effective for IBD-associated bone loss.- The mechanisms of bone loss are poorly understood. A major limitation has been the lack of an appropriate animal model for IBD-associated bone loss.What are the new findings?- We report for the first-time the skeletal phenotype in Winnie mouse model of IBD- This study presents a novel mechanism of IBD-associated bone loss, involving elevated gut-derived serotonin crosstalk with molecular pathways inhibiting bone formation.How might it impact on clinical practice in the foreseeable future- These findings open avenues for the development of targeted therapies for IBD-related bone loss.

Background Sarcopenia is defined as the age-related loss of muscle mass, strength, and physical performance. The original European Working Group on Sarcopenia in Older Persons (EWGSOP1) definition, and its revision (EWGSOP2), provide new cut-points and alternate measures for sarcopenia diagnosis. However, sarcopenia is rarely diagnosed in clinical settings owing to its labor-intensive diagnostic process. Given the Short Physical Performance Battery (SPPB) is a quick, easily administrable, and objective measure of muscle strength and physical performance, both of which are key components of sarcopenia, this study examined the diagnostic value of the SPPB for this muscle disease. Methods A cross-sectional analysis of 294 community-dwelling older persons (≥65 years) was conducted. Appendicular lean body mass [(ALM) divided by height squared (ALM/h2)], muscle strength (handgrip/sit to stand), and physical performance [gait speed, timed up and go (TUG) and SPPB] were assessed using validated procedures, while participants were diagnosed with sarcopenia following the EWGSOP1 and EWGSOP2 criteria. Diagnostic ability of the SPPB independently and combined with ALM/h2 for sarcopenia was determined using area under the curve (AUC). Potential cut-points were identified, and sensitivity and specificity calculated. Results Prevalence of sarcopenia ranged from 4 to 16% depending on the definition. The SPPB demonstrated moderate (AUC = 0.644–0.770) value in diagnosing sarcopenia, and a cut-point of ≤8points in SPPB performance resulted in high sensitivity (82–100%) but low specificity (36–41%) for diagnosing those with severe sarcopenia. Conclusions The SPPB displayed acceptable value in diagnosing older adults with severe sarcopenia. Moreover, the high sensitivity of the SPPB when using the cut-point of ≤8 suggests it may be a favorable screening tool for sarcopenia in clinical settings where ALM measurements are not available.

To investigate the association between bone mineral density (BMD) and the severity of sarcopenia using the revised European Working Group on Sarcopenia in Older People (EWGSOP2) definition. Osteoporosis was associated with a greater risk of sarcopenia when using the European definition. Health care professionals should screen for sarcopenia in those with osteoporosis. To investigate the association between bone mineral density (BMD) and the severity of sarcopenia using the revised European Working Group on Sarcopenia in Older People (EWGSOP2) definition. BMD [dual energy X-ray absorptiometry (DXA)], appendicular lean mass (DXA), handgrip strength (hydraulic dynamometer) and gait speed (over 4-m) were used to screen for osteoporosis and sarcopenia. Participants were categorized as osteoporotic according to the World Health Organization definition (T score ≤ − 2.5), and classified with probable sarcopenia or confirmed sarcopenia according to the EWGSOP2 criteria. Fasting biochemistry profile, fragility fractures, malnutrition index, geriatric depression scale and fear of falling, were also measured using validated procedures. A total of 484 community-dwelling older adults (69.6% women) with a median age of 76 years [Interquartile range (IQR) 70–81] were included in this study. Osteoporosis prevalence increased from 47.6% in non-sarcopenia to 65.5% in probable sarcopenia and 78.1% in those with confirmed sarcopenia (p

Marrow (MAT) and subcutaneous (SAT) adipose tissues display different metabolic profiles and varying associations with aging, bone density, and fracture risk. Using a non-invasive imaging methodology, we aimed to investigate the associations between MAT, SAT, and visceral fat (VAT) with bone volume, bone remodeling markers, insulin resistance, and circulating inflammatory mediators in a population of older men. In this cross-sectional study, 96 healthy men (mean age 67 ± 5.5) were assessed for anthropometric parameters, body composition, serum biochemistry, and inflammatory panel. Using single-energy computed tomography images, MAT (in L2 and L3 and both hips), VAT, and SAT (at the level of L2-L3 and L4-L5) were measured employing Slice-O-Matic software (Tomovision), which enables specific tissue demarcation applying previously reported Hounsfield unit thresholds. MAT volume was similar in all anatomical sites and independent of BMI. In all femoral regions of interest (ROIs) there was a strong negative association between bone and MAT volumes (r = - 0.840 to - 0.972, p

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.

Background Bone and muscle are closely linked anatomically, biochemically, and metabolically. Acute exercise affects both bone and muscle, implying a crosstalk between the two systems. However, how these two systems communicate is still largely unknown. We will explore the role of undercarboxylated osteocalcin (ucOC) in this crosstalk. ucOC is involved in glucose metabolism and has a potential role in muscle maintenance and metabolism. Objective The proposed trial will determine if circulating ucOC levels in older adults at baseline and following acute exercise are associated with parameters of muscle function and if the ucOC response to exercise varies between older adults with low muscle quality and those with normal or high muscle quality. Methods A total of 54 men and women aged 60 years or older with no history of diabetes and warfarin and vitamin K use will be recruited. Screening tests will be performed, including those for functional, anthropometric, and clinical presentation. On the basis of muscle quality, a combined equation of lean mass (leg appendicular skeletal muscle mass in kg) and strength (leg press; one-repetition maximum), participants will be stratified into a high or low muscle function group and randomized into the controlled crossover acute intervention. Three visits will be performed approximately 7 days apart, and acute aerobic exercise, acute resistance exercise, and a control session (rest) will be completed in any order. Our primary outcome for this study is the effect of acute exercise on ucOC in older adults with low muscle function and those with high muscle function. Results The trial is active and ongoing. Recruitment began in February 2018, and 38 participants have completed the study as of May 26, 2019. Conclusions This study will provide novel insights into bone and muscle crosstalk in older adults, potentially identifying new clinical biomarkers and mechanistic targets for drug treatments for sarcopenia and other related musculoskeletal conditions. Trial Registration Australia New Zealand Clinical Trials Registry ACTRN12618001756213; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375925. International Registered Report Identifier (IRRID) DERR1-10.2196/18777

This is a case report of unusual lesions caused by Thelazia gulosa in cattle. After several ineffective treatments of suspected infectious keratoconjunctivitis in calves and cows, T. gulosa was found associated with retrobulbar granuloma-like masses. The masses with multiple digit-like protrusions on conjunctival surface ejected multiple worms on firm pressure on clinical examination. Samples of tissues that contained worms were surgically removed, fixed in ethanol and submitted to the parasitology and histopathology labs for morphological identification of worms and the nature of the tissue masses, respectively. The infestation was present only in young calves (

Understanding how changes in nutritional status influence musculoskeletal recovery after falling remains unclear. We explored associations between changes in nutritional status and musculoskeletal health in 106 community-dwelling older adults aged &ge, 65 years, who attended the Falls and Fractures Clinic at Sunshine Hospital in St Albans, Australia after falling. At baseline and after 6 months, individuals were assessed for Mini Nutritional Assessment (MNA&reg, ), grip strength, gait speed, Timed Up and Go (TUG) test, Short Physical Performance Battery (SPPB), and bone turnover marker levels. Associations were examined using multiple linear regression, adjusted for baseline covariates and post-fall care plans. Over 6 months, the prevalence of malnutrition or risk thereof decreased from 29% to 15% using MNA &lt, 24/30. Specifically, 20 individuals (19%) improved, 7 (7%) deteriorated, and 73 (69%) maintained nutritional status, including 65 (61%) who remained well-nourished and 8 (8%) who remained malnourished/at risk. A 1-point increase in MNA score over 6 months was associated with an increase of 0.20 points (95% confidence interval 0.10, 0.31, p &lt, 0.001) in SPPB score. Improvement in nutritional status was associated with improvement in physical performance, providing a basis for interventional studies to ascertain causality and evaluate nutritional models of care for post-fall functional recovery in older adults.

Purpose: Marrow adipose tissue (MAT) expansion and associated lipotoxicity are important drivers of age-related bone loss and hematopoietic bone marrow (HBM) atrophy. Fish oil and borage oil (rich in ω3 fatty acids) can partially prevent aged-related bone loss in SAMP8 mice. However, whether preservation of bone mass in this progeria model is associated with MAT volumes remains unknown. Results: MAT volume fraction (MAT%) showed a negative association with hematopoietic bone marrow (HBM%;r=-0.836, p9 /group) were allocated into 4 categories and fed a control ration, FO-, sunflower oil (SFO)- and borage oil-enriched diets for lifetime. Femurs were scanned using microcomputed tomography (μCT) and bone, MAT, and HBM volumes were determined using an image analysis software.

Context Androgen deprivation therapy (ADT) for prostate cancer (PCa) leads to a selective loss of leg muscle function during walking. Rodent models of ADT have demonstrated that the levator ani is exquisitely androgen sensitive. Objective To determine whether the high androgen responsiveness of the levator ani muscle documented in rodents is evolutionarily conserved and ADT is associated with a selective loss in leg muscle volume. Design Prospective longitudinal case-control study. Setting Tertiary referral hospital. Participants Thirty-four men newly beginning ADT and 29 age-matched controls with PCa. Main outcome measures The muscle volumes in liters of the levator ani and primary muscles involved in walking (iliopsoas, quadriceps, gluteus maximus, gluteus medius, calf). Results Compared with controls, during a 12-month period, men receiving ADT experienced a mean reduction in total testosterone from 14.1 to 0.4 nmol/L and demonstrated greater decreases in levator ani [mean adjusted difference (MAD), -0.005 L; 95% CI, -0.007 to -0.002; P = 0.002; -16% of initial median value], gluteus maximus (MAD, -0.032 L; 95% CI, -0.063 to -0.002; P = 0.017; -5% of initial median value), iliopsoas (MAD, -0.005 L; 95% CI, -0.001 to 0.000; P = 0.013; -5% of initial median value), and quadriceps (MAD, -0.050 L; 95% CI, -0.088 to -0.012; P = 0.031; -3% of initial median value). No substantial differences were observed in the gluteus medius and calf muscles. Conclusions The androgen responsiveness of the levator ani appears to be evolutionarily conserved in humans. ADT selectively decreases the volume of muscles that support body weight. Interventional strategies to reduce ADT-related sarcopenia and sexual dysfunction should assess whether targeting these muscle groups, including the pelvic floor, will improve clinical outcomes.

Osteosarcopenia is a newly defined geriatric syndrome with serious consequences in the older population. Therefore, early identification of this syndrome and accurate prediction of poor outcomes and response to treatment are crucial. However, the diagnostic methods for sarcopenia and osteoporosis have several limitations. In this review, we briefly discuss the pathogenesis of osteosarcopenia in the light of new discoveries on the importance of local lipotoxicity induced by intramuscular and marrow fat. We also discuss the current and possible future diagnostic methods for osteosarcopenia focusing on the identification and quantification of tissue-embedded fat.

Objective—To evaluate the effect of parenteral administration of ivermectin and erythromycin on abomasal emptying rate in suckling calves. Animals—6 male Holstein-Friesian calves < 15 days old. Procedures—In a crossover study, calves were administered each of 3 treatments (control treatment, 2 mL of saline [0.9% NaCl] solution, IM; erythromycin, 8.8 mg/kg, IM; and ivermectin, 200 μg/kg, IV). Thirty minutes later, calves were bottle-fed 2 L of fresh cow's milk containing acetaminophen (50 mg/kg). Blood samples were collected from a jugular vein at various periods after suckling of milk. Abomasal emptying rate was assessed by use of the time to pharmacokinetically determined maximal plasma acetaminophen concentration. Results—Administration of erythromycin and ivermectin caused a significant increase in abomasal emptying rate, compared with results for the control treatment, as determined on the basis of time to maximal plasma acetaminophen concentration. Conclusions and Clinical Relevance—Parenteral administration of erythromycin and ivermectin increased the abomasal emptying rate. The macrolide erythromycin can be an effective prokinetic agent in calves and other animals. Ivermectin is classified as a macrolide but has a number of structural differences from erythromycin. The clinical importance of a slight increase in abomasal emptying rate after IV administration of ivermectin remains to be determined because ivermectin is only labeled for SC, oral, and topical administration.