Composition Biomarkers Research Articles

Effects of Intermittent Energy Restriction Alone and in Combination with Sprint Interval Training on Body Composition and Cardiometabolic Biomarkers in Individuals with Overweight and Obesity.

The popularity of intermittent fasting (IF) and high intensity (sprint) interval training (SIT) has increased in recent years amongst the general public due to their purported health benefits and feasibility of incorporation into daily life. The number of scientific studies investigating these strategies has also increased, however, very few have examined the combined effects, especially on body composition and cardiometabolic biomarkers, which is the primary aim of this investigation. A total of thirty-four male and female participants (age: 35.4 ± 8.4 y, body mass index (BMI): 31.3 ± 3.5 kg/m2, aerobic capacity (VO2peak) 27.7 ± 7.0 mL·kg−1·min−1) were randomized into one of three 16-week interventions: (1) 5:2 IF (2 non-consecutive days of fasting per week, 5 days on ad libitum eating), (2) supervised SIT (3 bouts per week of 20s cycling at 150% VO2peak followed by 40 s of active rest, total 10 min duration), and (3) a combination of both interventions. Body composition, haemodynamic and VO2peak were measured at 0, 8 and 16 weeks. Blood samples were also taken and analysed for lipid profiles and markers of glucose regulation. Both IF and IF/SIT significantly decreased body weight, fat mass and visceral fat compared to SIT only (p < 0.05), with no significant differences between diet and diet + exercise combined. The effects of diet and/or exercise on cardiometabolic biomarkers were mixed. Only exercise alone or with IF significantly increased cardiorespiratory fitness. The results suggest that energy restriction was the main driver of body composition enhancement, with little effect from the low volume SIT. Conversely, to achieve benefits in cardiorespiratory fitness, exercise is required.

Effects of intermittent energy restriction alone and in combina-tion with sprint interval training on body composition and cardiometabolic biomarkers in overweight and obese individuals

Effects of intermittent energy restriction alone and in combina-tion with sprint interval training on body composition and cardiometabolic biomarkers in overweight and obese individuals

Greater ectopic fat deposition and liver fibroinflammation and lower skeletal muscle mass in people with type 2 diabetes.

ObjectiveType 2 diabetes (T2D) is associated with significant end‐organ damage and ectopic fat accumulation. Multiparametric magnetic resonance imaging (MRI) can provide a rapid, noninvasive assessment of multiorgan and body composition. The primary objective of this study was to investigate differences in visceral adiposity, ectopic fat accumulation, body composition, and relevant biomarkers between people with and without T2D.MethodsParticipant demographics, routine biochemistry, and multiparametric MRI scans of the liver, pancreas, visceral and subcutaneous adipose tissue, and skeletal muscle were analyzed from 266 participants (131 with T2D and 135 without T2D) who were matched for age, gender, and BMI. Wilcoxon and χ 2 tests were performed to calculate differences between groups.ResultsParticipants with T2D had significantly elevated liver fat (7.4% vs. 5.3%, p = 0.011) and fibroinflammation (as assessed by corrected T1 [cT1]; 730 milliseconds vs. 709 milliseconds, p = 0.019), despite there being no differences in liver biochemistry, serum aspartate aminotransferase (p = 0.35), or alanine transaminase concentration (p = 0.11). Significantly lower measures of skeletal muscle index (45.2 cm2/m2 vs. 50.6 cm2/m2, p = 0.003) and high‐density lipoprotein cholesterol (1.1 mmol/L vs. 1.3 mmol/L, p < 0.0001) were observed in participants with T2D.ConclusionsMultiparametric MRI revealed significantly elevated liver fat and fibroinflammation in participants with T2D, despite normal liver biochemistry. This study corroborates findings of significantly lower measures of skeletal muscle and high‐density lipoprotein cholesterol in participants with T2D versus those without T2D.

Short- term effect of probiotic Lactobacillus reuteri consumption on the salivary microbiome profile of subjects undergoing orthodontic treatment with fixed appliances

ABSTRACT Objective This prospective clinical study aim was to analyze the effect of the probiotic Lactobacillus reuteri Prodentis lozenges on salivary microbiome of subjects wearing fixed orthodontic appliances. Methods Saliva samples were collected prior to consumption and 14th-day post probiotic lozenges consumption (n=40, age 18–23). Oral hygiene index-score (OHI-S) and papilla bleeding index (PBI) were recorded. The salivary microbiome was profiled by next-generation sequencing using the V3-V4 region of 16S-rRNA. Microbial composition, diversity and taxonomic biomarkers were analysed in comparison to probiotic intervention and the clinical characteristics of the cohort using standard bioinformatics tools. Results The diversity and bacterial community structures did not change significantly in salivary microbiome of periodontally healthy subjects during short-term probiotic intervention. Probiotic consumption correlated with reduction of OHI and PBI scores (50% reduction of scores, P<0.001). The reduction of clinical indices was evident in conjunction with significantly reduced abundance of oral pathogens, such as Porphyromonas pasteri, Treponema sp., Fretibacterium fastidiosum, Kingella oralis and Propionibacterium acnes. Conclusion Short-term probiotic intervention helped maintaining good oral health in patients undergoing fixed orthodontic therapy. Although overall oral microbiome structure remained largely unchanged, a significant alteration in the abundance of health and disease-associated species highlighted the beneficial effect of probiotic.

Effects of Leisure-Time Physical Activity on Cognitive Reserve Biomarkers and Leisure Motivation in the Pre-Diabetes Elderly.

The purpose of this study was to investigate the change in cognitive reserve biomarkers of the pre-diabetic individual according to the types of leisure-time physical activity (aerobic or resistance physical activity). The research subjects (n = 184) who participated in the survey were pre-diabetic and diabetic patients who were visiting university hospitals and welfare centers. The intervention subjects (n = 36) who were elderly females with pre-diabetes volunteered to participate in the study by performing regular physical exercise (aerobic or resistance exercise). The study participants were 65 years of age or older with pre-diabetes defined by a glycated hemoglobin (HbA1c) level of (5.7–6.4)%. All research subjects performed motivation and stress questionnaire survey. All intervention subjects participated in leisure-time physical activity (LTPA) for 12 weeks. Body composition, HbA1c, and cognitive reserve biomarkers were measured at baseline, and at 6 and 12 weeks. LTPA motivation confirmed that the LTPA participants had a high level of motivation. Stress confirmed that the stress level of LTPA participants was low. Two-way within-factor ANOVA revealed significant group × time interaction for weight (p < 0.05), BMI (p < 0.01), % fat (p < 0.001), SBP (p < 0.05), HbA1c (p < 0.001), BDNF (p < 0.001), and Beta-Amyloid 1–42 (p < 0.001). In both physical activity groups, HbA1c (p < 0.001), NGF (p < 0.05), BDNF (p < 0.05), and Cathepsin B (p < 0.05) improved significantly at 12 weeks, compared to baseline and 6 weeks. In the resistance physical activity group, Beta-Amyloid 1–42 (p < 0.01) and Homocysteine (p < 0.05) significantly decreased at 12 weeks, compared to baseline and at 6 weeks. The LTPA showed high levels of integrated and identified regulation among leisure motive types, and the level of stress was found to be low. The LTPA is effective in reducing the HbA1c levels of the pre-diabetes elderly. In addition, the pre-diabetes elderly were found to have increased NGF, BDNF, and cathepsin B, and decreased Beta-Amyloid 1–42 and homocysteine. Regular leisure-time physical activity has a positive effect on cognitive reserve biomarkers through improving glycemic control by reducing weight and % fat in the pre-diabetes elderly.

Preliminary Development of the Lung Transplant Frailty Index

<h3>Purpose</h3> Existing measures of frailty developed in community dwelling older adults may misclassify frailty in lung transplant candidates. We aimed to develop a novel frailty index for lung transplantation with improved performance characteristics compared to existing measures. <h3>Methods</h3> In a three-center cohort study of lung transplant candidates, we measured the Short Physical Performance Battery (SPPB) and Fried Frailty Phenotype (FFP) measures; body composition by bioelectrical impedance; and serum biomarkers associated with frailty (hemoglobin, albumin, and C-reactive protein). We evaluated individual variable domains to identify those associated with the criterion of candidate delisting for becoming too ill or death. Next, we built composite multidimensional models by testing the addition of domain variables in clusters: (1) performance measures (gait speed, balance, grip strength, low physical activity level); (2) body composition (low skeletal muscle, high % body fat), and (3) biomarkers. Domain cut-points were determined using receiver operating curve analyses. Three threshold selection methods for variable retention were evaluated; where methods differed, we prioritized specificity for delisting/death. Logistic regression analyses then estimated the odds of death/delisting across candidate Lung Transplant Frailty Index models. <h3>Results</h3> In 533 participants, we identified two candidate Lung Transplant Frailty Index (LT-FI) measures that maximized specificity, area under the curve, and had stronger associations with delisting and death compared to either the SPPB or FFP (Table). <h3>Conclusion</h3> Candidate LT-FI measures that include measures of physical performance, body composition, and serum biomarkers have improved discrimination for candidate delisting or death compared to the SPPB and FFP. Validating these candidate LT-FI measures' capacity to identify people at risk for peri- and post-operative complications and at other centers will help to define the optimal measure of frailty in lung transplantation.

Profile of Clinical and Analytical Parameters in Bronchiectasis Patients during the COVID-19 Pandemic: A One-Year Follow-Up Pilot Study.

Whether the COVID-19 pandemic may have modified the clinical planning and course in bronchiectasis patients remains to be fully elucidated. We hypothesized that the COVID-19 pandemic may have influenced the management and clinical outcomes of bronchiectasis patients who were followed up for 12 months. In bronchiectasis patients (n = 30, 23 females, 66 years), lung function testing, disease severity [FEV1, age, colonization, radiological extension, dyspnea (FACED), exacerbation (EFACED)] and dyspnea scores, exacerbation numbers and hospitalizations, body composition, sputum microbiology, and blood analytical biomarkers were determined at baseline and after a one-year follow-up. Compared to baseline (n = 27, three patients dropped out), in bronchiectasis patients, a significant increase in FACED and EFACED scores, number of exacerbations, and erythrocyte sedimentation rate (ESR) was observed, while FEV1, ceruloplasmin, IgE, IgG, IgG aspergillus, IgM, and IgA significantly decreased. Patients presenting colonization by Pseudomonas aeruginosa (PA) remained unchanged (27%) during follow-up. In bronchiectasis patients, FEV1 declined only after a one-year follow-up along with increased exacerbation numbers and disease severity scores, but not hospitalizations. However, a significant decrease in acute phase-reactants and immunoglobulins was observed at the one-year follow-up compared to baseline. Despite the relatively small cohort, the reported findings suggest that lung function impairment may not rely entirely on the patients’ inflammatory status.

Vitamin D Deficiency, Excessive Gestational Weight Gain, and Oxidative Stress Predict Small for Gestational Age Newborns Using an Artificial Neural Network Model.

(1) Background: Size at birth is an important early determinant of health later in life. The prevalence of small for gestational age (SGA) newborns is high worldwide and may be associated with maternal nutritional and metabolic factors. Thus, estimation of fetal growth is warranted. (2) Methods: In this work, we developed an artificial neural network (ANN) model based on first-trimester maternal body fat composition, biochemical and oxidative stress biomarkers, and gestational weight gain (GWG) to predict an SGA newborn in pregnancies with or without obesity. A sensibility analysis to classify maternal features was conducted, and a simulator based on the ANN algorithm was constructed to predict the SGA outcome. Several predictions were performed by varying the most critical maternal features attained by the model to obtain different scenarios leading to SGA. (3) Results: The ANN model showed good performance between the actual and simulated data (R2 = 0.938) and an AUROC of 0.8 on an independent dataset. The top-five maternal predictors in the first trimester were protein and lipid oxidation biomarkers (carbonylated proteins and malondialdehyde), GWG, vitamin D, and total antioxidant capacity. Finally, excessive GWG and redox imbalance predicted SGA newborns in the implemented simulator. Significantly, vitamin D deficiency also predicted simulated SGA independently of GWG or redox status. (4) Conclusions: The study provided a computational model for the early prediction of SGA, in addition to a promising simulator that facilitates hypothesis-driven constructions, to be further validated as an application.

Decreased myostatin in response to a controlled DASH diet is associated with improved body composition and cardiometabolic biomarkers in older adults: results from a controlled-feeding diet intervention study

BackgroundElevated concentrations of myostatin inhibit muscle growth, function and strength. Myostatin is a mediator of sarcopenia and is associated with insulin resistance. For this study we tested the response of a calorie-restricted Dietary Approaches to Stop Hypertension (DASH) diet on changes in myostatin, follistatin, and mystatin:follistatin ratio levels after 12 weeks in comparison to basline in adults aged 65 years and older. Furthermore we evaluated correlations between changes in myostatin, body composition and cardiometabolic biomarkers in this cohort of older adults.MethodsThis was a controlled-feeding diet intervention study in which females (n = 17) and males (n = 11) aged 65 years and older consumed either 85 g (n = 15) or 170 g (n = 13) of fresh lean beef within a standardized DASH diet for 12-weeks. Myostatin and follistatin concentrations were measured from fasted blood samples collected at 5 timepoints throughout the 12-week feeding intervention period. Correlations were assessed between changes in myostatin and follistatin levels and measures of body composition and cardiometabolic biomarkers.ResultsThere were no differences (p > 0.05) in circulating myostatin or follistatin levels between the beef intake groups. However, with beef groups combined myostatin decreased by 17.6% (p = 0.006) and the myostatin-to-follistatin ratio decreased by 16.5% (p < 0.001) in response to the study diet. Decreased myostatin was positively correlated with reductions in waist circumference (R2 = 0.163; p = 0.033) and fat mass (R2 = 0.233; p = 0.009). There was an inverse relationship between decreased myostatin and increased strength-to-weight ratio (R2 = 0.162; p = 0.034). The change in myostatin-to-follistatin ratio was associated with the change in skeletal muscle mass-to-fat mass ratio (R2 = 0.176; p = 0.026). Decreased myostatin was positively correlated with reductions in total cholesterol (R2 = 0.193; p = 0.012), LDL-C (R2 = 0.163; p = 0.031), insulin (R2 = 0.234; p = 0.009), and HOMA-IR (R2 = 0.248; P = 0.007). There was no change (p > 0.05) in circulating follistatin concentrations in response to the diet intervention.ConclusionsThe outcomes from this study suggest that a calorie-restricted DASH diet has the potential to reduce myostatin concentrations in older adults. Furthermore these outcomes support interrelationships between myostatin, body composition and cardiometabolic health in adults aged 65 years and older.Trial registrationClinicalTrials.gov; Identifier: NCT04127240; Registration Date: 15/10/ 2019.

Whey Protein Supplementation Effects on Body Composition, Performance, and Blood Biomarkers During Army Initial Entry Training.

This study assesses if a lower dose of whey protein can provide similar benefits to those shown in previous work supplementing Army Initial Entry Training (IET) Soldiers with two servings of whey protein (WP) per day. Eighty-one soldiers consumed one WP or a calorie matched carbohydrate (CHO) serving/day during IET (WP: n = 39, height = 173 ± 8 cm, body mass = 76.8 ± 12.8 kg, age = 21 ± 3 years; CHO: n = 42, 175 ± 8 cm, 77.8 ± 15.3 kg, 23 ± 4 years). Physical performance (push-ups, sit-ups, and a two-mile run) was assessed during weeks two and eight. All other measures (dietary intake, body composition, blood biomarkers) at weeks one and nine. There was a significant group difference for fat mass (p = 0.044) as WP lost 2.1 ± 2.9 kg and had a moderate effect size (Cohen's d: −0.24), whereas the CHO group lost 0.9 ± 2.5 kg and had only a small effect size (d: −0.1). There was no significant group-by-time interaction on fat-free mass (p = 0.069). WP gained 1.2 ± 2.4 (d: 0.1) and CHO gained 0.1 ± 3 (d: 0) kg of FFM on average. There was a significant group by week 1-fat free mass interaction (p = 0.003) indicating individuals with higher initial fat-free mass benefitted more from WP. There were no group differences for push-up (p = 0.514), sit-up (p = 0.429) or run (p = 0.313) performance. For all biomarkers there was a significant effect of time as testosterone (p < 0.01), testosterone to cortisol ratio (p = 0.39), and IGF-1 (p < 0.01) increased across training and cortisol (p = 0.04) and IL-6 (p < 0.01) decreased. There were no differences in groups across IET for any of the biomarkers. We conclude one WP serving is beneficial for FM and for FFM in soldiers with high baseline FFM but may not significantly alter biomarker response or physical performance of IET soldiers who have high relative dietary protein intakes.

Metabolic syndrome and breast cancer survivors: a follow-up analysis after completion of chemotherapy

BackgroundWe previously reported that (neo)adjuvant chemotherapy adversely altered metabolic syndrome (MetS) components, body composition, and related biomarkers after a 12 to 18-week chemotherapy treatment course in women. Here, we sought to determine whether these measures worsened within 4–5 years post-chemotherapy among the same sample of early stage breast cancer survivors.MethodsTwenty-eight breast cancer survivors were reassessed within 4–5 years post-chemotherapy. Participants were tested for MetS, lipid profile (total cholesterol; TC, low-density lipoprotein cholesterol; LDL-C), glucose metabolism (insulin, homeostatic model- insulin resistance; HOMA-IR, glycosylated hemoglobin; HbA1c), inflammation (C-reactive protein; CRP) and body composition (body weight; BW, percent body fat; BF, fat mass; FM) during follow-up physical exams. A comparison of measurements between post-chemotherapy and follow-up periods was performed using repeated measures analysis of covariance.ResultsMost study patients were Caucasian (44%) or Hispanic (30%) with a mean age of 48.2 years. Average time from completion of chemotherapy was 4.75 years. At follow-up, MetS components significantly increased (p < 0.01) compared with the post chemotherapy assessment. Additionally, BF, FM, lipids (TC, LDL), glucose metabolism (HOMA-IR, insulin, HbA1c), and inflammation (CRP) significantly increased (p < 0.01). Notably BW significantly increased; mean weight gain after chemotherapy was 6.1 kg and increased an additional 8.2% at follow-up (p < 0.01).ConclusionMetS components, body composition, and biomarkers continued to worsen within 4–5 years post-chemotherapy in breast cancer survivors. Energy balance interventions should target breast cancer patients to reduce the exacerbation of MetS.

Respiratory and Peripheral Muscle Weakness and Body Composition Abnormalities in Non-Cystic Fibrosis Bronchiectasis Patients: Gender Differences.

As demonstrated in COPD, bronchiectasis patients may experience respiratory and peripheral muscle dysfunction. We hypothesized that respiratory and peripheral (upper and lower limbs) muscle function and nutritional status may be more significantly altered in female than in males for identical age and disease severity. In mild-to-moderate bronchiectasis patients (n = 150, 114 females) and 37 controls (n = 37, 21 females), radiological extension, maximal inspiratory and expiratory pressures (MIP and MEP), sniff nasal inspiratory pressure (SNIP), hand grip and quadriceps muscle strengths, body composition, and blood analytical biomarkers were explored. Compared to the controls, in all bronchiectasis patients (males and females), BMI, fat-free mass index (FFMI), fat tissue, upper and lower limb muscle strength, and respiratory muscle strength significantly declined, and FFMI, fat tissue, and quadriceps muscle function were significantly lower in female than male patients. In patients with mild-to-moderate bronchiectasis, respiratory and peripheral muscle function is significantly impaired and only partly related to lung disease status. Quadriceps muscle strength was particularly weakened in the female patients and was negatively associated with their exercise tolerance. Muscle weakness should be therapeutically targeted in bronchiectasis patients. Body composition and peripheral muscle function determination should be part of the comprehensive clinical assessment of these patients.

Gut Microbiota Composition Is Related to AD Pathology.

IntroductionSeveral studies have reported alterations in gut microbiota composition of Alzheimer’s disease (AD) patients. However, the observed differences are not consistent across studies. We aimed to investigate associations between gut microbiota composition and AD biomarkers using machine learning models in patients with AD dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD).Materials and MethodsWe included 170 patients from the Amsterdam Dementia Cohort, comprising 33 with AD dementia (66 ± 8 years, 46%F, mini-mental state examination (MMSE) 21[19-24]), 21 with MCI (64 ± 8 years, 43%F, MMSE 27[25-29]) and 116 with SCD (62 ± 8 years, 44%F, MMSE 29[28-30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing. Biomarkers of AD included cerebrospinal fluid (CSF) amyloid-beta 1-42 (amyloid) and phosphorylated tau (p-tau), and MRI visual scores (medial temporal atrophy, global cortical atrophy, white matter hyperintensities). Associations between gut microbiota composition and dichotomized AD biomarkers were assessed with machine learning classification models. The two models with the highest area under the curve (AUC) were selected for logistic regression, to assess associations between the 20 best predicting microbes and the outcome measures from these machine learning models while adjusting for age, sex, BMI, diabetes, medication use, and MMSE.ResultsThe machine learning prediction for amyloid and p-tau from microbiota composition performed best with AUCs of 0.64 and 0.63. Highest ranked microbes included several short chain fatty acid (SCFA)-producing species. Higher abundance of [Clostridium] leptum and lower abundance of [Eubacterium] ventriosum group spp., Lachnospiraceae spp., Marvinbryantia spp., Monoglobus spp., [Ruminococcus] torques group spp., Roseburia hominis, and Christensenellaceae R-7 spp., was associated with higher odds of amyloid positivity. We found associations between lower abundance of Lachnospiraceae spp., Lachnoclostridium spp., Roseburia hominis and Bilophila wadsworthia and higher odds of positive p-tau status.ConclusionsGut microbiota composition was associated with amyloid and p-tau status. We extend on recent studies that observed associations between SCFA levels and AD CSF biomarkers by showing that lower abundances of SCFA-producing microbes were associated with higher odds of positive amyloid and p-tau status.

P493 The synthetic glycan KB295 optimises microbiome composition and function in ulcerative colitis: Results from a proof of principle human study

Abstract Background Ulcerative colitis (UC) pathogenesis involves genetic susceptibility, immune-mediated tissue injury, and gut microbiota disturbances. Most approved therapies modify host immunity, rather than directly targeting the microbiota. Faecal microbiota transplantation provides encouraging evidence for the therapeutic potential of gut microbiome modulation. Gastrointestinal tract bacteria are ecologically differentiated by their ability to use specific glycans as growth substrates, making glycans a promising and safe alternative to target the microbiome. To explore this, we used an ex vivo faecal microbiota culture system to identify a synthetic glycan (KB295) with desirable microbiological activity and conducted a proof of principle study (NCT04508413) of safety and tolerability of KB295 in patients with UC. Methods In ex vivo studies, faecal microbial communities from healthy subjects were incubated anaerobically (negative control) ± KB295. Taxa counts from shotgun metagenomic sequencing data were used to evaluate microbial response to KB295. Short-chain fatty acid (SCFA) levels were also assessed. KB295 was evaluated in an open-label single-arm study in adult patients with mild to moderate UC. KB295 was ingested over an 8-wk period. Objectives included KB295 safety (primary) and effect on gut microbiota composition and faecal biomarkers. Results In ex vivo studies, KB295 increased SCFA levels across 10 faecal samples to a median of 47.0 vs 15.2 mM with negative control, including increases in acetate, propionate, and butyrate levels. Metagenomic sequencing showed pathobiont depletion in the family Enterobacteriaceae with KB295 to a median relative abundance of 10.8% vs 38.2% with negative control. Pathobiont depletion was associated with enrichments of diverse genera in the phyla Bacteroidetes and Firmicutes. In patients with UC (n=12), KB295 was well tolerated with generally mild adverse events (AEs). The most frequently occurring AEs were bowel habit changes, flatulence, and headache. Median faecal calprotectin and lactoferrin levels decreased by 69.0% (n=11) and 86.0% (n=6), respectively, from screening to end of the KB295 intake. Consistent with our ex vivo results, of the patients for whom we have data to date, the relative abundance of the faecal pathobiont family Enterobacteriaceae decreased in 5 of 5 participants, and the commensal genus Parabacteroides was enriched in 4 of 5 participants. Conclusion Our results establish a proof of principle for the glycan modulation of gut microbiome composition and function and provide insight into the potential utility of this strategy in patients with UC. The safety and tolerability of KB295, along with evidence of reduced inflammation, support a phase 2 study, which is planned.

LEVOTHYROXINE USE MAY BE ASSOCIATED WITH LONGITUDINAL QUADRICEPS ATROPHY AND SUBSEQUENT KNEE OA RISK: PRELIMINARY ANALYSIS FROM OAI COHORT

Levothyroxine, the primary treatment for hypothyroidism, is prescribed for more than 7% of Americans. Levothyroxine use, or the underlying hypothyroidism can be associated with musculoskeletal symptoms; however, no prior work has investigated this association using sensitive biomarkers. We examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in participants at-risk of knee OA and their mediatory role in subsequent knee OA radiographic and symptomatic incidence. Thighs and knees of OAI participants without established radiographic knee OA were included. Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th-year and were matched with nonusers for potential confounders using 1:2/3 propensity-score (PS) matching. We developed and validated a deep learning method for automated thigh segmentation and assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intramuscular adipose tissue (intra-MAT), contractile percentage, and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard knee OA radiographic and symptomatic incidence. Finally, we assessed whether the association between levothyroxine use and knee OA incidence is mediated via muscle changes. We included 1485 matched thighs/knees (387:1098 users:non-users; age: 62±9 years, female/male:3.1). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI:-15.46mm2/year, -25.11– -5.82) but not thigh muscles’ composition biomarkers. Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR):1.59, 1.15–2.20) and symptomatic knee OA incidence (HR:1.60, 1.12–2.29). A decrease in quadriceps CSA partially mediated the increased risk of knee OA incidence associated with levothyroxine use. Our exploratory analyses suggest that levothyroxine users might have increased risk of thigh muscle atrophy and subsequent knee OA. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier and therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal thigh muscles atrophy and associated knee OA incidence risk. NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under Award Number R01AR079620-01. AG reported receiving funding from Merck Serono, AstraZeneca, Galapagos, Pfizer, Roche, TissueGene (for consultation), and Boston Imaging Core Lab (as the president and stockholder). SD reported that he received funding from Toshiba Medical Systems (for consultation) and grants from GERRAF and Carestream Health (for a clinical trial study). Authors acknowledge OAI staff and team. CORRESPONDENCE ADDRESS: sdemehri1@jhmi.edu .

Effects of 40% of Maximum Oxygen Uptake Intensity Cycling Combined with Blood Flow Restriction Training on Body Composition and Serum Biomarkers of Chinese College Students with Obesity.

Blood flow restriction training (BFRT) is a new method for promoting muscle growth and improving muscle function, even with relatively low-intensity exercise. BFRT on patients with obesity has not been extensively studied. This study aimed to analyze the effects of cycling at 40% of maximum oxygen uptake (VO2max) combined with BFRT on body composition and serum biomarkers among college students with obesity. This pilot study included thirty-seven male college students with obesity aged 18–22 years (experimental group (EG): n = 18; control group (CG): n = 19). The EG conducted 40% VO2max cycling combined with BFRT activities and the CG conducted 40% VO2max cycling without BFRT two times per week for 12 weeks. Our results showed that in EG, there were significant differences in weight, thigh skinfold thickness (TS), waist circumference, abdominal skinfold thickness, fat mass, body fat percentage, body mass index and glucose (GLU), total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels before and after the experiment (p < 0.05, p < 0.01, and p < 0.001). After the experiment, TS, GLU, TC, HDL-C, and LDL-C in EG were significantly different than those of the CG (p < 0.05, p < 0.01, and p < 0.001). Together, our results demonstrate that cycling at 40% VO2max combined with BFRT may improve body composition and blood lipid profile of male college students with obesity. Our findings have important implications for those who cannot perform moderate- and high-intensity exercises.

Nomogram of Combining CT-Based Body Composition Analyses and Prognostic Inflammation Score: Prediction of Survival in Advanced Epithelial Ovarian Cancer Patients

To investigate the value of body composition changes measured by quantitative computer tomography (QCT) in evaluating the prognosis of advanced epithelial ovarian cancer (AEOC) patients who underwent primary debulking surgery (PDS) and adjuvant platinum-based chemotherapy, and constructed a nomogram model for predicting survival in combination with prognostic inflammation score (PIS). Fifty-seven patients with AEOC between 2012 and 2016 were retrospectively enrolled. Pre- and post-treatment CT images were used to analyze the body composition biomarkers. The subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), cross-sectional area of paraspinal skeletal muscle area (PMA), skeletal muscle density (SMD), body mineral density (BMD) were measured from two sets of CT images. In multivariate analyses, VFA gain, PMA loss, BMD loss, and PIS were independent risk factors of overall survival (OS) (HR=3.7, 3.0, 2.8, 1.9, respectively, all p < 0.05). Receiver operating characteristic (ROC) curves showed that the prognostic model combining body composition changes (BCC) and PIS had the highest predictive performance (area under the curve=0.890). The concordance index (C-index) of the prognostic nomogram was 0.779 (95% CI, 0.673-0.886). Decision curve analysis (DCA) demonstrated the prognostic nomogram had a great distinguishing performance. CT-based body composition analyses and PIS were associated with poor OS for AEOC patients who underwent PDS and adjuvant platinum-based chemotherapy. The prognostic nomogram with a combination of BCC and PIS was dependable in predicting survival for AEOC patients during treatment.

Associations between gut microbiota composition and AD biomarkers

AbstractBackgroundSeveral studies have reported alterations in gut microbiota composition of Alzheimer’s disease (AD) patients. However, the observed differences are not consistent across studies. We aimed to investigate associations between gut microbiota composition and clinical biomarkers of AD using machine learning models in patients with AD dementia, mild cognitive impairment (MCI) and controls.MethodWe included 169 patients from the NUDAD project, comprising 33 with AD dementia (66±8 years, 46%F, MMSE 21[19‐24]), 21 with MCI (64±8 years, 43%F, MMSE 27[25‐29]) and 115 controls (62±8 years, 44%F, MMSE 29[28‐30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing. Clinical parameters of AD included clinical diagnosis, cerebral spinal fluid (CSF) amyloid and phosphorylated tau (pTau) status, positron emission tomography (PET) amyloid status, and MRI visual scores. Associations between gut microbiota composition and dichotomized clinical parameters of AD were assessed with separate machine learning classification models using XGBoost with nested cross‐validation. The model with the highest area under the curve (AUC) was selected for logistic regression, to assess associations between the 20 best predicting microbes (cumulative sum scaled counts) and the outcome measure from this machine learning model while adjusting for age, sex, and BMI.ResultThe machine learning prediction for amyloid status (CSF) from microbiota composition had the highest AUC. Top predicting microbes included several short chain fatty acid (SCFA)‐producing species. In the logistic regression models, these microbes were significantly associated with lower odds of amyloid positive status, and included Eubacterium ventriosum group spp. (OR 0.49 (0.30‐0.76) per SD increase in counts, p = 0.002), Marvinbryantia spp. (OR 0.55 (0.34‐0.85), p = 0.009), Coprococcus catus (OR 0.58 (0.36‐0.89), p = 0.017), Roseburia hominis (OR 0.59 (0.38‐0.90), p = 0.018), Odoribacter splanchnicus (OR 0.51 (0.30‐0.82), p = 0.008), Lachnospiraceae spp. (OR 0.58 (0.36‐0.89), p = 0.014), and Ruminococcaceae spp. (OR 0.44 (0.25‐0.71), p = 0.002).ConclusionGut microbiota composition had the strongest association with amyloid status among the clinical biomarkers examined. We extend on recent studies that observed associations between SCFA levels and AD biomarkers by showing that higher abundances of SCFA‐producing microbes were associated with lower odds of amyloid positive status.

Lignan exposure: a worldwide perspective.

Dietary lignans are phytoestrogens that are mostly found in plant-based foods, especially whole grains, seeds, nuts, legumes and vegetables. An accurate assessment of lignan exposure is crucial to evaluate their potential health benefits and to establish future recommendations and dietary guidelines. This narrative review aimed to (i) summarize the pros and the cons of the current main assessment methods for lignan exposure─i.e., dietary questionnaires, food composition tables and biomarkers, (ii) describe the individual lignans more consumed from a worldwide perspective, as well as their main food sources, (iii) determine the lignans concentrations in both urine and blood, and explore their heterogeneity among countries, and finally (iv) discuss the main determinants of lignan exposure.

Detailed knowledge of maternal and infant factors and human milk composition could inform recommendations for optimal composition.

Breastfeeding is best for infants, but quantitative associations between specific milk components and infant biomarkers remain unclear. Methodological limitations include missing milk volume intake, variable milk composition and that standardised, fasted state blood sampling is impossible in infants. Milk protein and fat content appear marginally related to infant serum amino acid and phospholipid concentrations, with some association between milk fatty acid composition and lipid species levels. CONCLUSION: Detailed simultaneous examinations of maternal factors, milk composition and infant biomarkers or outcomes could identify the mechanistic basis of human milk effects and help develop dietary recommendations for optimal human milk composition.