Laser Speckle Contrast Imaging-based diagnosis of severe mesenteric traction syndrome: Hemodynamics and prostacyclin - A prospective cohort study.

BRIEF ABSTRACT: Today, the diagnosis and grading of mesenteric traction syndrome relies on a subjective assessment of facial flushing. However, this method has several limitations. In this study, Laser Speckle Contrast Imaging and a predefined cut-off value are assessed and validated for the objective identification of severe mesenteric traction syndrome. BACKGROUND: Severe mesenteric traction syndrome (MTS) is associated with increased postoperative morbidity. The diagnosis is based on an assessment of the developed facial flushing. Today this is performed subjectively, as no objective method exists. One possible objective method is Laser Speckle Contrast Imaging (LSCI), which has been used to show significantly higher facial skin blood flow in patients developing severe MTS. Using these data, a cut-off value has been identified. This study aimed to validate our predefined LSCI cut-off value for identifying severe MTS. METHODS: A prospective cohort study was performed on patients planned for open esophagectomy or pancreatic surgery from March 2021 to April 2022. All patients underwent continuous measurement of forehead skin blood flow using LSCI during the first hour of surgery. Using the predefined cut-off value, the severity of MTS was graded. In addition, blood samples for prostacyclin (PGI2) analysis and hemodynamics were collected at predefined time points to validate the cut-off value. MAIN RESULTS: Sixty patients were included in the study. Using our predefined LSCI cut-off value, 21 (35 %) patients were identified as developing severe MTS. These patients were found to have higher concentrations of 6-Keto-PGFaα (p = 0.002), lower SVR (p < 0.001), lower MAP (p = 0.004), and higher CO (p < 0.001) 15 min into surgery, as compared with patients not developing severe MTS. CONCLUSION: This study validated our LSCI cut-off value for the objective identification of severe MTS patients as this group developed increased concentrations of PGI2 and more pronounced hemodynamic alterations compared with patients not developing severe MTS.

Home-Based Physical Activity and Diet Intervention to Improve Physical Function in Advanced Liver Disease: A Randomized Pilot Trial.

INTRODUCTION: A decline in physical function is highly prevalent and a poor prognostic factor in cirrhosis. We assessed the benefits of a home-based physical activity program (HB-PAP) in patients with cirrhosis with a randomized pilot trial. METHODS: All participants received a personal activity tracker to monitor daily activities and were given 12 g/day of an essential amino acid supplement. The HB-PAP intervention consisted of biweekly counseling sessions to increase physical activity for 12 weeks. Six-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) assessed changes in aerobic fitness. Different anthropometric measuring tools were used for skeletal muscle and adiposity assessment. RESULTS: Seventeen patients (60% male; 29% nonalcoholic steatohepatitis/cryptogenic, 29% hepatitis C, 24% alcohol, 18% other) were randomized, 9 to HB-PAP group. There were no significant differences in MELD-sodium between HB-PAP and controls at baseline or after the 12-week intervention. By the end of study, there was a significant between-group difference in daily step count favoring the active group (2627 [992-4262], p = 0.001), with less sedentary patients in the active group (33-17% vs. 25-43%, p = 0.003). The 6MWT improved in the HB-PAP group (423 ± 26 m vs. 482 ± 35 m), while the controls had a nonsignificant drop (418 ± 26 m vs. 327 ± 74 m) with a significant between-group difference. CPET did not change. Other than an improvement in psoas muscle index, there were no differences in anthropometry, or in quality of life. CONCLUSIONS: HB-PAP maintained physical performance and improved aerobic fitness according to 6MWT but not CPET, supporting the use of personal activity trackers to monitor/guide home-based prehabilitation programs in cirrhosis.

Tile Drainage and Anthropogenic Land Use Contribute to Harmful Algal Blooms and Microbiota Shifts in Inland Water Bodies.

Freshwater harmful algal blooms (HABs), driven by nutrient inputs from anthropogenic sources, pose unique risks to human and ecological health worldwide. A major nutrient contributor is agricultural land use, specifically tile drainage discharge. Small lakes and ponds are at elevated risk for HAB appearance, as they are uniquely sensitive to nutrient input. HABs introduce exposure risk to microcystin (MC), hepatotoxic and potentially carcinogenic cyanotoxins. To investigate the impact of anthropogenic land use on small lakes and ponds, 24 sites in central Ohio were sampled over a 3-month period in late summer of 2015. MC concentration, microbial community structure, and water chemistry were analyzed. Land use intensity, including tile drainage systems, was the driver of clustering in principle component analysis, ultimately contributing to nutrient deposition, a driver of HABs. Relative abundance of HAB-forming genera was correlated with elevated concentrations of nitrate and soluble reactive phosphate. One location (FC) showed MC concentrations exceeding 875 µg/L and large community shifts in ciliates (Oligohymenophorea) associated with hypoxic conditions. The prokaryotic community at FC was dominated by Planktothrix sp. These results demonstrate the impact of HABs in small lakes and ponds, and that prevailing issues extend beyond cyanotoxins, such as cascading impacts on other trophic levels.

Community-driven governance of FAIRness assessment: an open issue, an open discussion.

Although FAIR Research Data Principles are targeted at and implemented by different communities, research disciplines, and research stakeholders (data stewards, curators, etc.), there is no conclusive way to determine the level of FAIRness intended or required to make research artefacts (including, but not limited to, research data) Findable, Accessible, Interoperable, and Reusable. The FAIR Principles cover all types of digital objects, metadata, and infrastructures. However, they focus their narrative on data features that support their reusability. FAIR defines principles, not standards, and therefore they do not propose a mechanism to achieve the behaviours they describe in an attempt to be technology/implementation neutral. Various FAIR assessment metrics and tools have been designed to measure FAIRness. Unfortunately, the same digital objects assessed by different tools often exhibit widely different outcomes because of these independent interpretations of FAIR. This results in confusion among the publishers, the funders, and the users of digital research objects. Moreover, in the absence of a standard and transparent definition of what constitutes FAIR behaviours, there is a temptation to define existing approaches as being FAIR-compliant rather than having FAIR define the expected behaviours. This whitepaper identifies three high-level stakeholder categories -FAIR decision and policymakers, FAIR custodians, and FAIR practitioners - and provides examples outlining specific stakeholders' (hypothetical but anticipated) needs. It also examines possible models for governance based on the existing peer efforts, standardisation bodies, and other ways to acknowledge specifications and potential benefits. This whitepaper can serve as a starting point to foster an open discussion around FAIRness governance and the mechanism(s) that could be used to implement it, to be trusted, broadly representative, appropriately scoped, and sustainable. We invite engagement in this conversation in an open Google Group fair-assessment-governance@googlegroups.com.

Novel genetic loci associated with osteoarthritis in multi-ancestry analyses in the Million Veteran Program and UK Biobank.

Osteoarthritis is a common progressive joint disease. As no effective medical interventions are available, osteoarthritis often progresses to the end stage, in which only surgical options such as total joint replacement are available. A more thorough understanding of genetic influences of osteoarthritis is essential to develop targeted personalized approaches to treatment, ideally long before the end stage is reached. To date, there have been no large multiancestry genetic studies of osteoarthritis. Here, we leveraged the unique resources of 484,374 participants in the Million Veteran Program and UK Biobank to address this gap. Analyses included participants of European, African, Asian and Hispanic descent. We discovered osteoarthritis-associated genetic variation at 10 loci and replicated findings from previous osteoarthritis studies. We also present evidence that some osteoarthritis-associated regions are robust to population ancestry. Drug repurposing analyses revealed enrichment of targets of several medication classes and provide potential insight into the etiology of beneficial effects of antiepileptics on osteoarthritis pain.

Thrombin expression in prostate: a novel finding.

INTRODUCTION: A variable repertoire of coagulation protein expression is observed in different cancers. We evaluated expression of thrombin in prostate tissue. METHODS: Detection of thrombin was performed using quantitative real-time PCR in fresh tissue and in situ hybridization (ISH) in archival prostate tissue and by immunohistochemistry of prostate tissue microarrays. RESULTS: (Pro)thrombin mRNA expression was detected in cancer tissue and localized to prostatic epithelium and stroma by ISH. Thrombin protein was detected in stroma of benign and malignant epithelium (p <.05). CONCLUSIONS: Prostate tissue is a rich reservoir of thrombin. This may have potential for developing antithrombin-based cancer therapy.

Use of fluorescence lifetime technology to provide efficient protection from false hits in screening applications.

This article describes novel data analysis of fluorescence lifetime-based protein kinase assays to identify and correct for compound interference in several practical cases. This ability, together with inherent advantages of fluorescence lifetime technology (FLT) as a homogeneous, antibody-free format independent of sample concentration, volume, excitation intensity, and geometry, makes fluorescence lifetime a practical alternative to the established "gold standards" of radiometric and mobility shift (Caliper) assays. The analysis is based on a photochemical model that sets constraints on the values of fluorescence lifetimes in the time responses of the assay. The addition of an exponential component with free floating lifetime to the constrained model, in which the lifetimes are constants predetermined from control measurements and the preexponential coefficients are "floating" parameters, allows the relative concentration of phosphorylated and nonphosphorylated substrates to be calculated even in the presence of compound fluorescence. The method is exemplified using both simulated data and experimental results measured from mixtures of dye-labeled phosphorylated and nonphosphorylated kinase substrates. A change of the fluorescence lifetime is achieved by the phosphorylated substrate-specific interaction with a bifunctional ligand, where one binding site interacts with the phosphate group and the other interacts with the dye.

Reduced application time for prophylactic mitomycin C in photorefractive keratectomy.

OBJECTIVE: To determine whether the duration of mitomycin C (MMC) 0.02% application affects visual outcome or the incidence of subepithelial haze in patients undergoing photorefractive keratectomy (PRK) with prophylactic administration of MMC. DESIGN: Retrospective, comparative case series. PARTICIPANTS: Two hundred sixty-nine eyes undergoing PRK. METHODS: This was a retrospective comparative case series that included 269 eyes that underwent PRK with prophylactic MMC application for 120 seconds (group 1, n = 74), 60 seconds (group 2, n = 36), or 12 seconds (group 3, n = 159). The mean preoperative spherical equivalent was -6.49 diopters (D) in group 1, -6.77 D in group 2, and -7.10 D in group 3. Photorefractive keratectomy was performed using a modified nomogram. All eyes received a single intraoperative application of MMC (0.02%) after laser ablation for the above specified durations. MAIN OUTCOME MEASURES: Best-corrected visual acuity and corneal haze score. RESULTS: Best-corrected visual acuity was 20/23 in group 1, 20/20 in group 2, and 20/21 in group 3. The mean haze score+/-standard deviation (scale, 0.00-4.00) was 0.11+/-0.31 in group 1, 0.14+/-0.28 in group 2, and 0.07+/-0.20 in group 3 throughout a mean follow-up of 31 months in group 1, 16 months in group 2, and 10 months in group 3. No eyes had a haze score of more than 1.00. CONCLUSIONS: There was no statistically significant difference in postoperative best-corrected visual acuity or haze scores among the 3 groups. Administration of prophylactic MMC 0.02% for 12 seconds after PRK seems to be equally efficacious for haze prophylaxis when compared with longer application times of 60 and 120 seconds.

Selective serotonin reuptake inhibitors-associated apathy syndrome: A cross sectional study.

Selective serotonin reuptake inhibitors (SSRIs), commonly used to treat depression, are associated with loss of motivation, anergy, and lack of curiosity often referred collectively as apathy. However, this association has not been systematically assessed using a specific rating scale for measuring apathy syndrome. Our objective was to study the association between SSRI use and apathy syndrome.We conducted a retrospective chart review of 125 patients enrolled in an outpatient psychiatry clinic. The prevalence of apathy syndrome and its clinical significance (based on standardized assessment) were compared between patients treated and not treated with SSRIs. Apathy was assessed using the Apathy Evaluation Scale-clinician version with a score ranging 18-72 with higher score for worse apathy. A score of greater than 30 is considered clinically significant apathy.Among 119 patients, the mean apathy scores were significantly higher in those treated with SSRIs compared to those not treated with SSRIs (42.5 ±â€Š9.2 vs 31.3 ±â€Š6, P < .0001). The SSRI group also had a significantly higher percentage of patients with clinically significant apathy (92% vs 61%, P < .0001). Use of all SSRIs was associated with the presence of apathy. Apathy was seen in all mental health diagnostic categories with highest Apathy evaluation scale-clinician version scores in those with dementia.SSRI use may be associated with higher rates of apathy syndrome. Clinicians should specifically inquire about iatrogenic apathy syndrome when evaluating patients on an SSRI if there is suspicion of loss of motivation. Limitations of this study included retrospective nature of this study, and that majority of the sample was males. Prospective studies are needed to elucidate information regarding the prevalence, etiology, and treatment response for SSRI-associated apathy syndrome.

Neuromodulation for Apathy in Alzheimer's Disease: A Double-Blind, Randomized, Sham-Controlled Pilot Study.

BACKGROUND: Apathy, a profound loss of motivation, initiation, and goal directed cognition, is a common comorbidity of Alzheimer's disease (AD). The presence of apathy is associated with rapid progression of AD, long-term impairment, disability, and higher mortality. Pharmacological treatments of apathy are limited. OBJECTIVE: The primary objective was to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) for apathy in AD. METHODS: A randomized, double-blind, parallel-arm, sham-controlled pilot study was conducted in subjects with AD and apathy (N = 20). Subjects were randomized to rTMS or sham treatment (5 days/week) for four weeks. Primary outcome, apathy evaluation scale-clinician version (AES-C), and secondary outcome measures, modified-Mini Mental State Examination (3MS), instrumental activities of daily living (IADL), and clinical global impression (CGI), were assessed at baseline and four weeks. Follow-up visits were conducted at 8 and 12 weeks to test the durability of effects of intervention. RESULTS: Mean age was 77.3 (±7.2) years, 80% were Caucasians and 10% were females. After adjusting for baseline, there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment (-10.1 (-15.9 to -4.3); t (16) â€Š= -3.69; p = 0.002) at 4 weeks. There was also significantly greater improvement in 3MS (6.9 (1.7 to 12.0); t (15) â€Š= 2.85; p = 0.012), IADL (3.4 (1.0 to 5.9); χ21 = 7.72; p = 0.006), CGI-S (1.4 (0.5 to 2.3), t (16) â€Š= 3.29; p = 0.005), and CGI-I (-2.56 (-3.5 to -1.6), t (17) â€Š= -5.72; p < 0.001) for rTMS compared to the sham at 4 weeks. The effects of rTMS were durable at 12 weeks. CONCLUSION: rTMS may be safely used in subjects with AD and may improve apathy, function, and some aspects of cognition.

Muscle expression of genes associated with inflammation, growth, and remodeling is strongly correlated in older adults with resistance training outcomes.

A group (n = 8) of healthy older (68 +/- 6 yr) adults participated in a 36-session progressive resistance exercise training program targeting the thigh muscles to determine the relationship between muscle gene expression and gains in muscle size and strength. Biopsies were obtained from the vastus lateralis at baseline 72 h after an acute bout of exercise and 72 h after completion of the training program. Training increased thigh muscle size (7%) and strength for the three exercises performed: knee extension (30%) and curl (28%) and leg press (20%). We quantified 18 transcripts encoding factors that function in inflammation, growth, and muscle remodeling that were demonstrated previously to be regulated by aging and acute exercise. The gain in extension strength and muscle size showed a high number of significant correlations with gene expression. These gains were most strongly correlated (P < or = 0.003, R > or = 0.89) with the baseline mRNA levels for insulin-like growth factor-1, matrix metalloproteinase-2 and its inhibitor TIMP1, and ciliary neurotrophic factor. Moreover, strength gains were inversely correlated with the change in these mRNA levels after training (P < or = 0.002 and R < or = -0.90). Changes in gene expression after acute exercise were not associated with training outcomes. These results suggest that higher baseline expression for key genes in muscle conveys an adaptive advantage for certain older adults. Individuals with lower baseline expression of these genes show less adaptation to exercise despite increased gene expression in response to training. These genes hold promise as useful predictors of training outcomes that could be used to design more effective exercise regimens for maintaining muscle function in older adults.

A guide for using NIH Image J for single slice cross-sectional area and composition analysis of the thigh from computed tomography.

Reports using computed tomography (CT) to estimate thigh skeletal muscle cross-sectional area and mean muscle attenuation are often difficult to evaluate due to inconsistent methods of quantification and/or poorly described analysis methods. This CT tutorial provides step-by-step instructions in using free, NIH Image J software to quantify both muscle size and composition in the mid-thigh, which was validated against a robust commercially available software, SliceOmatic. CT scans of the mid-thigh were analyzed from 101 healthy individuals aged 65 and older. Mean cross-sectional area and mean attenuation values are presented across seven defined Hounsfield unit (HU) ranges along with the percent contribution of each region to the total mid-thigh area. Inter-software correlation coefficients ranged from R2 = 0.92-0.99 for all specific area comparisons measured using the Image J method compared to SliceOmatic. We recommend reporting individual HU ranges for all areas measured. Although HU range 0-100 includes the majority of skeletal muscle area, HU range -29 to 150 appears to be the most inclusive for quantifying total thigh muscle. Reporting all HU ranges is necessary to determine the relative contribution of each, as they may be differentially affected by age, obesity, disease, and exercise. This standardized operating procedure will facilitate consistency among investigators reporting computed tomography characteristics of the thigh on single slice images. Trial Registration: ClinicalTrials.gov NCT02308228.

Induction of apoptosis by vinblastine via c-Jun autoamplification and p53-independent down-regulation of p21WAF1/CIP1.

Vinblastine treatment in all cell lines examined causes a robust increase in c-Jun protein expression and phosphorylation and a corresponding increase in activator protein-1 (AP-1) transcriptional activity. We show in KB-3 carcinoma cells that this is due to a strong autoamplification loop involving the proximal AP-1 site in the c-Jun promoter, resulting in highly increased c-Jun mRNA and c-Jun protein. Inhibitors of RNA transcription and protein translation blocked both vinblastine-induced c-Jun expression and apoptotic cell death, suggesting that apoptosis is dependent, at least in part, on transcription/translation. Small interfering RNA (siRNA) to c-Jun was used to interrupt the amplification cycle and was found to be highly effective, reducing vinblastine-induced c-Jun expression at both the mRNA and protein levels by 90%. Apoptosis and caspase-3 activation were significantly inhibited in c-Jun siRNA-treated cells. To uncover potential mechanisms of c-Jun-mediated cell death and protection by c-Jun siRNA, candidate target genes were examined. Chromatin immunoprecipitation revealed preferential association of c-Jun with the p21 (cyclin-dependent kinase inhibitor) gene promoter after vinblastine treatment. In KB-3 cells, which have compromised p53 function, and in p53-null cells but not in p53 wild-type cells, vinblastine caused down-regulation of p21 expression concomitant with increased c-Jun expression, suggesting a role for c-Jun in negative regulation of the p21 promoter independent of p53. These results provide strong evidence that c-Jun induction in response to vinblastine plays a proapoptotic role in part via down-regulation of p21, promoting cycling and subsequent cell death of mitotically impaired cells.

Aging alters gene expression of growth and remodeling factors in human skeletal muscle both at rest and in response to acute resistance exercise.

The purpose of this investigation was to compare expression of genes that function in inflammation and stress, cell structure and signaling, or remodeling and growth in skeletal muscle of young (32 +/- 7 yr, n = 15) and elderly (72 +/- 5 yr, n = 16) healthy subjects before and after a bout of resistance leg exercises. A real-time RT-PCR method was used to screen 100 transcripts in v. lateralis biopsies obtained before and 72 h postexercise. The screen identified 15 candidates for differential expression due to aging and/or exercise that were measured quantitatively. The median levels of four mRNAs (insulin-like growth factor-1 and its binding protein IGFBP5, ciliary neurotrophic factor, and the metallopeptidase MMP2) were significantly affected by aging and were greater (1.6- to 2.3-fold, P

Expression of tissue factor in prostate cancer correlates with malignant phenotype.

Tissue factor (TF), apart from its established role in hemostasis, has been implicated in promoting angiogenesis and metastasis in a wide array of tumors including prostate cancer. Expression of TF was evaluated in freshly-resected prostate specimens obtained from patients with localized (n=9) and androgen ablated (n=6) disease using real-time reverse transcription-polymerase chain reaction and Western blot analysis. TF was detected in all specimens in both stages of the disease. We further analyzed for correlations between TF expression and those of several angiogenic growth factors and their receptors. TF RNA expression correlated significantly with expression of vascular endothelial growth factor-A in these specimens (s=0.621, P=0.013). Eighty-one prostate specimens from patients with benign prostatic hyperplasia (n=27), localized prostate cancer (ES, n=32), and advanced disease (n=22) were also evaluated using immunohistochemistry and findings were correlated with clinical parameters. TF expression was detected on epithelial cells of the malignant glands. Furthermore, its expression levels correlated significantly with Gleason score (s=0.58, P=0.0001) and with the stage of the disease (s=0.441, P=0.0001) in these specimens. These data support the role of TF in angiogenesis and disease progression.

Synthesis and biological activity of imidazopyridine anticoccidial agents: Part II.

Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Recently, we reported the synthesis and biological activity of potent imidazo[1,2-a]pyridine anticoccidial agents. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we report the synthesis and anticoccidial activity of a second set of such compounds, focusing on derivatization of the amine side chain at the imidazopyridine 7-position. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

Methylphenidate for Apathy in Community-Dwelling Older Veterans With Mild Alzheimer's Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: Apathy is a common behavioral problem in Alzheimer's disease. Apathy has profound consequences, such as functional impairment, higher service utilization, higher caregiver burden, and increased mortality. The authors' objective was to study the effects of methylphenidate on apathy in Alzheimer's disease. METHOD: A 12-week, prospective, double-blind, randomized, placebo-controlled trial (methylphenidate versus placebo) was conducted in community-dwelling veterans (N=60) with mild Alzheimer's disease. The primary outcome for apathy (Apathy Evaluation Scale-Clinician) and secondary outcomes for cognition (Mini-Mental State Examination, Modified Mini-Mental State Examination), functional status (activities of daily living, instrumental activities of daily living), improvement and severity (Clinical Global Impressions Scale [CGI]), caregiver burden (Zarit Burden Scale), and depression (Cornell Scale for Depression in Dementia) were measured at baseline and at 4, 8, and 12 weeks. RESULTS: Participants were all men (77 years old, SD=8). After adjusting for baseline, the methylphenidate group had significantly greater improvement in apathy than the placebo group at 4 weeks, 8 weeks, and 12 weeks. At 12 weeks, there was also greater improvement in cognition, functional status, caregiver burden, CGI scores, and depression in the methylphenidate group compared with the placebo group. CONCLUSIONS: Methylphenidate improved apathy in a group of community-dwelling veterans with mild Alzheimer's disease. Methylphenidate also improved cognition, functional status, caregiver burden, CGI scores, and depression.

Tutorial for using SliceOmatic to calculate thigh area and composition from computed tomography images from older adults.

OBJECTIVE: Area of muscle, fat, and bone is often measured in thigh CT scans when tissue composition is a key outcome. SliceOmatic software is commonly referenced for such analysis but published methods may be insufficient for new users. Thus, a quick start guide to calculating thigh composition using SliceOmatic has been developed. METHODS: CT images of the thigh were collected from older (69 ± 4 yrs, N = 24) adults before and after 12-weeks of resistance training. SliceOmatic was used to segment images into seven density regions encompassing fat, muscle, and bone from -190 to +2000 Hounsfield Units [HU]. The relative contributions to thigh area and the effects of tissue density overlap for skin and marrow with muscle and fat were determined. RESULTS: The largest contributors to the thigh were normal fat (-190 to -30 HU, 29.1 ± 7.4%) and muscle (35 to 100 HU, 48.9 ± 8.2%) while the smallest were high density (101 to 150 HU, 0.79 ± 0.50%) and very high density muscle (151 to 200 HU, 0.07 ± 0.02%). Training significantly (P<0.05) increased area for muscle in the very low (-29 to -1 HU, 5.5 ± 7.9%), low (0 to 34 HU, 9.6 ± 16.8%), normal (35 to 100 HU, 4.2 ± 7.9%), and high (100 to 150 HU, 70.9 ± 80.6%) density ranges for muscle. Normal fat, very high density muscle and bone did not change (P>0.05). Contributions to area were altered by ~1% or less and the results of training were not affected by accounting for skin and marrow. CONCLUSIONS: When using SliceOmatic to calculate thigh composition, accounting for skin and marrow may not be necessary. We recommend defining muscle as -29 to +200 HU but that smaller ranges (e.g. low density muscle, 0 to 34 HU) can easily be examined for relationships with the health condition and intervention of interest. TRIAL REGISTRATION: Clinicaltrials.gov NCT02261961.