A protocol for remote collection of skeletal muscle mass via D3-creatine dilution in community-dwelling postmenopausal women from the Women's Health Initiative.

BACKGROUND: There is emerging evidence that cancer and its treatments may accelerate the normal aging process, increasing the magnitude and rate of decline in functional capacity. This accelerated aging process is hypothesized to hasten the occurrence of common adverse age-related outcomes in cancer survivors, including loss of muscle mass and decrease in physical function. However, there is no data describing age-related loss of muscle mass and its relation to physical function in the long-term in cancer survivors. METHODS: This study protocol describes the use of a novel method of muscle mass measurement, D3-creatine dilution method (D3Cr), in a large sample (n~6000) of community dwelling postmenopausal women from the Women's Health Initiative (WHI). D3Cr will be used to obtain a direct measure of muscle mass remotely. Participants will be drawn from two sub-cohorts embedded within the WHI that have recently completed an in-home visit. Cancer survivors will be drawn from the Life and Longevity After Cancer (LILAC) cohort, and cancer-free controls will be drawn from the WHI Long Life Study 2. The overall objective of this study is to examine the antecedents and consequences of low muscle mass in cancer survivors. The study aims are to: 1) create age-standardized muscle mass percentile curves and z-scores to characterize the distribution of D3- muscle mass in cancer survivors and non-cancer controls, 2) compare muscle mass, physical function, and functional decline in cancer survivors and non- cancer controls, and 3) use machine learning approaches to generate multivariate risk-prediction algorithms to detect low muscle mass. DISCUSSION: The D3Cr method will transform our ability to measure muscle mass in large-scale epidemiologic research. This study is an opportunity to advance our understanding of a key source of morbidity among older and long-term female cancer survivors. This project will fill knowledge gaps, including the antecedents and consequences of low muscle mass, and use innovative methods to overcome common sources of bias in cancer research. The results of this study will be used to develop interventions to mitigate the harmful effects of low muscle mass in older adults and promote healthy survivorship in cancer survivors in the old (>65) and oldest-old (>85) age groups.

Exploring sulfur donor atom coordination chemistry with La(II), Nd(II), and Tm(II) using a terphenylthiolate ligand.

To expand the range of donor atoms known to stabilize 4fn5d1 Ln(II) rare-earth metal (Ln) ions beyond the C, N, and O first row main group donor atoms, the Ln(III) sulfur donor terphenylthiolate iodide complexes, LnIII(SAriPr6)2I (AriPr6 = C6H3-2,6-(C6H2-2,4,6-iPr3)2, Ln = La, Nd) were reduced to form LnII(SAriPr6)2 complexes. These Ln(II) species were structurally characterized, analyzed by density functional theory (DFT) calculations, and compared to Tm(SAriPr6)2, which was synthesized from TmI2(DME)3.

Investigating Steric and Electronic Effects in the Synthesis of Square Planar 6d1 Th(III) Complexes.

The factors affecting the formation and crystal structures of unusual 6d1 Th(III) square planar aryloxide complexes, as exemplified by [Th(OArMe)4]1- (OArMe = OC6H2tBu2-2,6-Me-4), were explored by synthetic and reduction studies of a series of related Th(IV) tetrakis(aryloxide) complexes, Th(OArR)4 (OArR = OC6H2tBu2-2,6-R-4). Specifically, electronic, steric, and countercation effects were explored by varying the aryloxide ligand, the alkali metal reducing agent, and the alkali metal chelating agent. Salt metathesis reactions between ThBr4(DME)2 (DME = 1,2-dimethoxyethane) and 4 equiv of the appropriate potassium aryloxide salt were used to prepare a series of Th(IV) aryloxide complexes in high yields: Th(OArH)4 (OArH = OC6H3tBu2-2,6), Th(OArtBu)4 (OArtBu = OC6H2tBu3-2,4,6), Th(OArOMe)4 (OArOMe = OC6H2tBu2-2,6-OMe-4), and Th(OArPh)4 (OArPh = OC6H2tBu2-2,6-Ph-4). Th(OArH)4 can be reduced by KC8, Na, or Li in the absence or presence of 2.2.2-cryptand (crypt) or 18-crown-6 (crown) to form dark purple solutions that have EPR and UV-visible spectra similar to those of the square planar Th(III) complex, [Th(OArMe)4]1-. Hence, the para position of the aryloxide ligand does not have to be alkylated to obtain the Th(III) complexes. Furthermore, reduction of Th(OArOMe)4, Th(OArtBu)4, and Th(OArPh)4 with KC8 in THF generated purple solutions with EPR and UV-visible spectra that are similar to those of the previously reported Th(III) anion, [Th(OArMe)4]1-. Although many of these reduction reactions did not produce single crystals suitable for study by X-ray diffraction, reduction of Th(OArH)4, Th(OArtBu)4, and Th(OArOMe)4 with Li provided X-ray quality crystals whose structures had square planar coordination geometries. Reduction of Th(OArPh)4 with Li also gave a product with EPR and UV-visible spectra that matched those of [Th(OArMe)4]1-, but X-ray quality crystals of the reduction product were too unstable to provide data. Neither Th(Odipp)4(THF)2 (Odipp = OC6H3iPr2-2,6) nor Th(Odmp)4(THF)2 (Odmp = OC6H3Me2-2,6) could be reduced to Th(III) products under similar conditions. Reduction of U(OArH)3(THF) with KC8 in the presence of 2.2.2-cryptand (crypt) was examined for comparison and formed [K(crypt)][U(OArH)4], which has a tetrahedral arrangement of the aryloxide ligands. Moreover, no further reduction was observed when either [K(crypt)][U(OArH)4] or [K(crown)(THF)2][U(OArH)4] were treated with KC8 or Li.

Associations Between D3Cr Muscle Mass and Magnetic Resonance Thigh Muscle Volume With Strength, Power, Physical Performance, Fitness, and Limitations in Older Adults in the SOMMA Study.

BACKGROUND: How magnetic resonance (MR) derived thigh muscle volume and deuterated creatine dilution derived muscle mass (D3Cr muscle mass) differentially relate to strength, fitness, and other functions in older adults-and whether associations vary by sex-is not known. METHODS: Men (N = 345) and women (N = 482) aged ≥70 years from the Study of Muscle, Mobility, and Aging completed leg extension strength (1-repetition max) and cardiopulmonary exercise testing to assess fitness (VO2peak). Correlations and adjusted regression models stratified by sex were used to assess the association between muscle size measures, study outcomes, and sex interactions. RESULTS: D3Cr muscle mass and MR thigh muscle volume were correlated (men: r = 0.62, women: r = 0.51, p < .001). Each standard deviation (SD) decrement in D3Cr muscle mass was associated with lower 1-repetition max strength (-14 kg men, -4 kg women, p < .001 for both; p-interaction = .003) and lower VO2peak (-79 mL/min men, -30 mL/min women, p < .001 for both, p-interaction: .016). Each SD decrement in MR thigh muscle volume was also associated with lower strength (-32 kg men, -20 kg women, p < .001 for both; p-interaction = .139) and lower VO2peak (-217 mL/min men, -111 mL/min women, p < .001 for both, p-interaction = .010). There were associations, though less consistent, between muscle size or mass with physical performance and function; associations varied by sex. CONCLUSIONS: Less muscle-measured by either D3Cr muscle mass or MR thigh muscle volume-was associated with lower strength and fitness. Varied associations by sex and assessment method suggest consideration be given to which measurement to use in future studies.

Identification of an X-Band Clock Transition in Cp'3Pr- Enabled by a 4f25d1 Configuration.

Molecular qubits offer an attractive basis for quantum information processing, but challenges remain with regard to sustained coherence. Qubits based on clock transitions offer a method to improve the coherence times. We propose a general strategy for identifying molecules with high-frequency clock transitions in systems where a d electron is coupled to a crystal-field singlet state of an f configuration, resulting in an MJ = ±1/2 ground state with strong hyperfine coupling. Using this approach, a 9.834 GHz clock transition was identified in a molecular Pr complex, [K(crypt)][Cp'3PrII], leading to 3-fold enhancements in T2 relative to other transitions in the spectrum. This result indicates the promise of the design principles outlined here for the further development of f-element systems for quantum information applications.

Perplexing EPR Signals from 5f36d1 U(II) Complexes.

Metal complexes with unpaired electrons in orbitals of different angular momentum quantum numbers (e.g., f and d orbitals) are unusual and opportunities to study the interactions among these electrons are rare. X-band electron paramagnetic resonance (EPR) data were collected at <10 and 77 K on 10 U(II) complexes with 5f36d1 electron configurations and on some analogous Ce(II), Pr(II), and Nd(II) complexes with 4fn5d1 electron configurations. The U(II) compounds unexpectedly display similar two-line axial signals with g|| = 2.04 and g⊥ = 2.00 at 77 K. In contrast, U(II) complexes with 5f4 configurations are EPR-silent. Unlike U(II), the congenic 4f35d1 Nd(II) complex is EPR-silent. The Ce(II) complex with a 4f15d1 configuration is also EPR-silent, but a signal is observed for the Pr(II) complex, which has a 4f25d1 configuration. Whether or not an EPR signal is expected for these complexes depends on the coupling between f and d electrons. Since the coupling in U(II) systems is expected to be sufficiently strong to preclude an EPR signal from compounds with a 5f36d1 configuration, the results are viewed as unexplained phenomena. However, they do show that 5f36d1 U(II) samples can be differentiated from 5f4 U(II) complexes by EPR spectroscopy.

Synthesis of Crystallographically Characterizable Bis(cyclopentadienyl) Sc(II) Complexes: (C5H2tBu3)2Sc and {[C5H3(SiMe3)2]2ScI}1.

The synthesis of previously unknown bis(cyclopentadienyl) complexes of the first transition metal, i.e., Sc(II) scandocene complexes, has been investigated using C5H2(tBu)3 (Cpttt), C5Me5 (Cp*), and C5H3(SiMe3)2 (Cp″) ligands. Cpttt2ScI, 1, formed from ScI3 and KCpttt, can be reduced with potassium graphite (KC8) in hexanes to generate dark-red crystals of the first crystallographically characterizable bis(cyclopentadienyl) scandium(II) complex, Cpttt2Sc, 2. Complex 2 has a 170.6° (ring centroid)-Sc-(ring centroid) angle and exhibits an eight-line EPR spectrum characteristic of Sc(II) with Aiso = 82.6 MHz (29.6 G). It sublimes at 200 °C at 10-4 Torr and has a melting point of 268-271 °C. Reductions of Cp*2ScI and Cp″2ScI under analogous conditions in hexanes did not provide new Sc(II) complexes, and reduction of Cp*2ScI in benzene formed the Sc(III) phenyl complex, Cp*2Sc(C6H5), 3, by C-H bond activation. However, in Et2O and toluene, reduction of Cp*2ScI at -78 °C gives a dark-red solution, 4, which displays an eight-line EPR pattern like that of 1, but it did not provide thermally stable crystals. Reduction of Cp″2ScI, in THF or Et2O at -35 °C in the presence of 2.2.2-cryptand, yields the green Sc(II) metallocene iodide complex, [K(crypt)][Cp″2ScI], 5, which was identified by X-ray crystallography and EPR spectroscopy and is thermally unstable. The analogous reaction of Cp*2ScI with KC8 and 18-crown-6 in Et2O gave the ligand redistribution product, [Cp*2Sc(18-crown-6-κ2O,O')][Cp*2ScI2], 6, as the only crystalline product. Density functional theory calculations on the electronic structure of these compounds are reported in addition to a steric analysis using the Guzei method.

D3Creatine Dilution as a Direct, Non-invasive and Accurate Measurement of Muscle Mass for Aging Research.

Initial definitions of sarcopenia included the age-associated loss of skeletal muscle mass that was presumed to be associated with late-life reduced functional capacity, disability and loss of independence. Because no method for determination of muscle mass was available for large cohort studies of aging men and women, lean body mass determined by dual X-ray absorptiometry or bioelectrical impedance was used as a surrogate measure of muscle mass. The data from these studies showed either no or a poor relationship between LBM and functional capacity and health related outcomes, leading to the conclusion of many that the amount of muscle may not be associated with these age-associated outcomes. It was assumed that some undefined index of muscle quality is the critical contributor. These studies also consistently showed that muscle strength is lost more quickly than lean mass. Total body muscle mass can now be measured directly, accurately and non-invasively using the D3creatine (D3Cr) dilution method. D3Cr muscle mass, but not DXA derived LBM, is strongly associated with functional capacity, falls and insulin resistance in older men and women. In addition, D3Cr muscle mass is associated with risk of disability, hip fracture and mortality. New and emerging data demonstrate that low muscle mass may serve as a diagnostic criterion for sarcopenia.

Sarcopenia: no consensus, no diagnostic criteria, and no approved indication-How did we get here?

In addition to the role of skeletal muscle in movement and locomotion, muscle plays a critical role in a broad array of metabolic processes that can contribute to improved health or risk of disease. The age-associated loss of muscle has been termed sarcopenia. The muscle is the primary site of insulin-stimulated glucose disposal and the largest component of basal metabolic rate, directly and indirectly affects bone density, produces myokines with pleiotropic effect on muscle and other tissues including the brain, and stores essential amino acids essential for the maintenance of protein synthesis during periods of reduced food intake and stress. As such, not surprisingly deterioration of skeletal muscle health, typically operationalized as decline of muscle mass and muscle strength is both a powerful risk factor and main consequence of chronic diseases, disability, and loss of independence, and it is one of the strongest risk factors for mortality. However, skeletal muscle remains one of the most plastic of all tissues, with rapid changes in rates of protein synthesis and degradation in response to physical activity and inactivity, inflammation, and nutritional and hormonal status. This has made the development of pharmacological therapies to increase muscle mass (or prevent loss), an important goal for decades. However, while remarkable advances in the understanding of molecular and cellular regulation of muscle protein metabolism have occurred recently, there are no approved drugs for the treatment of sarcopenia, the loss of skeletal muscle affecting millions of older people. The goal of this paper is to describe the possible reasons for the lack of new and effective pharmacotherapies to treat one of the most important risk factors for age-associated disease and loss of independence.

Estimating Muscle Mass Using D3-Creatine Dilution: A Narrative Review of Clinical Implications and Comparison With Other Methods.

BACKGROUND: The D3-creatine (D3-Cr) dilution method is of emerging interest for estimating total-body skeletal muscle mass. This review explores the association of muscle mass estimated via D3-Cr with various clinical outcomes and provides a summary of the literature comparing D3-Cr with other body composition techniques. METHODS: A literature search was conducted on PubMed/MEDLINE and Web of Science for studies using D3-Cr to measure muscle in adult populations (ie, ≥18 years old) from inception until September 2023. RESULTS: Out of the 23 included studies, 15 investigated the correlation between D3-Cr and clinical outcomes. More consistent associations were reported for mortality (100%, n = 2), mobility disability (100%; n = 5), falls and fractures (100%; n = 3), physical performance (63.3%; n = 11), muscle strength (44.4%; n = 9), and muscle composition (33.3%; n = 3). However, conflicting findings were also reported for such correlations. Among the 23 studies, 14 compared D3-Cr-estimated muscle with other body composition techniques, including magnetic resonance imaging (MRI) as a reference method. Strong and positive correlations were found between D3-Cr and MRI. Nonetheless, variations in muscle measurements were noted, with differences in D3-Cr values ranging from 0.62 kg lower to 13.47 kg higher compared to MRI. CONCLUSIONS: D3-Cr-estimated muscle mass may be a valuable predictor of clinical outcomes showing consistent associations with falls and fractures, mobility disability, and mortality. However, less consistent associations were found with muscle strength and composition, and physical performance. Although a strong correlation exists between D3-Cr-estimated muscle mass and MRI measurements, under- or overestimation may occur.

Replacement of dietary carbohydrate with protein increases fat mass and reduces hepatic triglyceride synthesis and content in female obese Zucker rats.

Previous studies have demonstrated both energy restriction (ER) and higher protein (HP), lower carbohydrate (LC) diets downregulate hepatic de novo lipogenesis. Little is known about the independent and combined impact of ER and HP/LC diets on tissue-specific lipid kinetics in leptin receptor-deficient, obese rodents. This study investigated the effects of ER and dietary macronutrient content on body composition; hepatic, subcutaneous adipose tissue (SAT), and visceral AT (VAT) lipid metabolic flux (2 H2 O-labeling); and blood and liver measures of cardiometabolic health in six-week-old female obese Zucker rats (Leprfa+/fa+ ). Animals were randomized to a 10-week feeding intervention: ad libitum (AL)-HC/LP (76% carbohydrate/15% protein), AL-HP/LC (35% protein/56% carbohydrate), ER-HC/LP, or ER-HP/LC. ER groups consumed 60% of the feed consumed by AL. AL gained more fat mass than ER (P-energy = 0.012) and HP/LC gained more fat mass than HC/LP (P-diet = 0.025). Hepatic triglyceride (TG) concentrations (P-interaction = 0.0091) and absolute hepatic TG synthesis (P-interaction = 0.012) were lower in ER-HP/LC versus ER-HC/LP. ER had increased hepatic, SAT, and VAT de novo cholesterol fractional synthesis, absolute hepatic cholesterol synthesis, and serum cholesterol (P-energy≤0.0035). A HP/LC diet, independent of energy intake, led to greater gains in fat mass. A HP/LC diet, in the context of ER, led to reductions in absolute hepatic TG synthesis and TG content. However, ER worsened cholesterol metabolism. Increased adipose tissue TG retention with the HP/LC diet may reflect improved lipid storage capacity and be beneficial in this genetic model of obesity.

Associations between D3Cr muscle mass and MR thigh muscle volume with strength, power, physical performance, fitness, and limitations in older adults in the SOMMA study.

Background: Different measures to assess muscle size - magnetic resonance (MR) derived thigh muscle volume and d3-creatine dilution derived muscle mass (D3Cr muscle mass) - may have similar associations with strength, power, physical performance, fitness, and functional limitations in older adults. Methods: Men (N=345) and women (N=482) aged ≥70 years from the Study of Muscle, Mobility and Aging completed exams including leg extension strength (1-repetition max) and cardiopulmonary exercise testing to assess fitness (VO2peak). Correlations and adjusted regression models stratified by sex were used to assess the association between muscle size measures and study outcomes; we tested for sex interactions. Results: D3Cr muscle mass and MR thigh muscle volume were correlated (men: r=0.62, women: r=0.51, p<.001). Lower D3Cr muscle mass and lower MR thigh muscle volume were associated with lower strength and lower VO2peak in both men and women; D3Cr muscle mass was more strongly associated with strength in men than in women (p-int<0.05). There were correlations, though less consistent, between muscle size or mass with physical performance and function. Associations between the muscle size measures and the study outcomes occasionally varied by sex, and associations of MR thigh muscle volume were, at times, slightly more strongly associated with the study outcomes than was D3Cr muscle mass. Conclusions: Less muscle -measured by either D3Cr muscle mass or MR thigh muscle volume - was associated with lower strength and worse performance. Varied associations by sex and assessment method suggest consideration be given to which measurement to use in future studies.

D3-creatine dilution, computed tomography and dual-energy X-ray absorptiometry for assessing myopenia and physical function in colon cancer: A cross-sectional study.

BACKGROUND: Low skeletal muscle mass (myopenia) is common in cancer populations and is associated with functional decline and mortality, but prior oncology studies did not assess total body skeletal muscle mass. Instead, they measured surrogates such as cross-sectional area (CSA) of skeletal muscle at L3 from computed tomography (CT) or appendicular lean mass (ALM) from dual-energy X-ray absorptiometry (DXA). D3-creatine (D3Cr) dilution is a non-invasive method to assess total body skeletal muscle mass, which has been examined in a variety of populations but not in cancer. To compare the associations of D3Cr muscle mass, CT CSA, and DXA ALM with myopenia and physical function, we conducted a cross-sectional study among 119 patients with colon cancer (2018-2022). METHODS: For each technique (D3Cr, CT and DXA), myopenia was defined as the lowest sex-specific quartile of its measurement. Physical function was measured by the short physical performance battery and grip strength. We calculated Pearson correlations (r) among three techniques, computed Cohen's kappa coefficients (κ) to assess the agreement of myopenia, and estimated Pearson correlations (r) of three techniques with physical function. All analyses were sex-specific. RESULTS: Sixty-one (51.3%) participants were male, the mean (standard deviation) age was 56.6 (12.9) years, and most (68.9%) had high physical function (short physical performance battery: ≥11 points). Correlations and myopenia agreement among three techniques were greater in men than women; for example, regarding D3Cr muscle mass versus CT CSA, r was 0.73 (P < 0.001) for men versus 0.45 (P < 0.001) for women, and κ was 0.82 (95% CI: 0.65, 0.99) for men versus 0.24 (95% CI: -0.08, 0.52) for women. Among men, higher D3Cr muscle mass was significantly correlated with faster gait speed (r = 0.43, P < 0.01) and stronger grip strength (r = 0.32, P < 0.05); similar correlations were observed for CT CSA and DXA ALM. However, among women, no measure of muscle or lean mass was significantly associated with physical function. CONCLUSIONS: This is the first study using D3-creatine dilution method to assess muscle mass in a cancer population. Regardless of the techniques used for muscle or lean mass assessment, we observed stronger correlations, greater myopenia agreement, and more significant associations with physical function in men with colon cancer than women. D3Cr, CT and DXA are not interchangeable methods for assessing myopenia and physical function, especially in women with colon cancer. Future studies should consider relative advantages of these techniques and examine the D3-creatine dilution method in other cancer types.

Stabilization of Pu(IV) in PuBr4(OPCy3)2 and Comparisons with Structurally Similar ThX4(OPR3)2 (R = Cy, Ph) Molecules.

The pursuit of a trivalent plutonium halide phosphine oxide compound, e.g., "PuBr3(OPR)3," instead led to the isolation of the tetravalent trans-PuIVBr4(OPCy3)2, PuBr/Cy, compound by spontaneous oxidation of PuIII. The donating nature of phosphine oxides has allowed the isolation and characterization of PuBr/Cy by crystallographic, multinuclear NMR, solid state, and solution phase UV-vis-NIR spectroscopic techniques. The presence of a putative plutonyl(VI) complex formulated as "trans-PuVIO2Br2(OPCy3)2" was also observed spectroscopically and tentatively by single-crystal X-ray diffraction as a cocrystal of PuBr/Cy. A series of trans-ThX4(OPCy3)2 (X = Cl, ThCl/Cy; Br, ThBr/Cy; I, ThI/Cy) complexes were synthesized for comparison to PuBr/Cy. The triphenylphosphine oxide, OPPh3, complexes, trans-AnI4(OPPh3)2 (An = Th, ThI/Ph; U, UI/Ph), were also synthesized for comparison, completing the series trans-UX4(OPPh3)2 (X = Cl, Br, I), UX/Ph. To enable the synthesis of ThI/Cy and ThI/Ph, a new nonaqueous thorium iodide starting material, ThI4(Et2O)2, was synthesized. The syntheses of organic solvent soluble ThI4L2 (L = Et2O, OPCy3, and OPPh3) are the first examples of crystallographically characterized neutral thorium tetraiodide materials beyond binary ThI4. To show the viability of ThI4(Et2O)2 as a starting material for organothorium chemistry, (C5Me4H)3ThI was synthesized and crystallographically characterized.

Application of the D3 -creatine muscle mass assessment tool to a geriatric weight loss trial: A pilot study.

BACKGROUND: Traditionally, weight loss (WL) trials utilize dual energy X-ray absorptiometry (DXA) to measure lean mass. This method assumes lean mass, as the sum of all non-bone and non-fat tissue, is a reasonable proxy for muscle mass. In contrast, the D3 -creatine (D3 Cr) dilution method directly measures whole body skeletal muscle mass, although this method has yet to be applied in the context of a geriatric WL trial. The purpose of this project was to (1) describe estimates of change and variability in D3 Cr muscle mass in older adults participating in an intentional WL intervention and (2) relate its change to other measures of body composition as well as muscle function and strength. METHODS: The INVEST in Bone Health trial (NCT04076618), used as a scaffold for this ancillary pilot project, is a three-armed, 12-month randomized, controlled trial designed to determine the effects of resistance training or weighted vest use during intentional WL on a battery of musculoskeletal health outcomes among 150 older adults living with obesity. A convenience sample of 24 participants (n = 8/arm) are included in this analysis. At baseline and 6 months, participants were weighed, ingested a 30 mg D3 Cr tracer dose, provided a fasted urine sample 3-6 days post-dosage, underwent DXA (total body fat and lean masses, appendicular lean mass) and computed tomography (mid-thigh and trunk muscle/intermuscular fat areas) scans, and performed 400-m walk, stair climb, knee extensor strength, and grip strength tests. RESULTS: Participants were older (68.0 ± 4.4 years), mostly White (75.0%), predominantly female (66.7%), and living with obesity (body mass index: 33.8 ± 2.7 kg/m2 ). Six month total body WL was -10.3 (95% confidence interval, CI: -12.7, -7.9) kg. All DXA and computed tomography-derived body composition measures were significantly decreased from baseline, yet D3 Cr muscle mass did not change [+0.5 (95% CI: -2.0, 3.0) kg]. Of muscle function and strength measures, only grip strength significantly changed [+2.5 (95% CI: 1.0, 4.0) kg] from baseline. CONCLUSIONS: Among 24 older adults, significant WL with or without weighted vest use or resistance training over a 6-month period was associated with significant declines in all bioimaging metrics, while D3 Cr muscle mass and muscle function and strength were preserved. Treatment assignment for the trial remains blinded; therefore, full interpretation of these findings is limited. Future work in this area will assess change in D3 Cr muscle mass by parent trial treatment group assignment in all study participants.

Graphite resistive heated diamond anvil cell for simultaneous high-pressure and high-temperature diffraction experiments.

High-pressure and high-temperature experiments using a resistively heated diamond anvil cell have the advantage of heating samples homogeneously with precise temperature control. Here, we present the design and performance of a graphite resistive heated diamond anvil cell (GRHDAC) setup for powder and single-crystal x-ray diffraction experiments developed at the Extreme Conditions Beamline (P02.2) at PETRA III, Hamburg, Germany. In the GRHDAC, temperatures up to 2000 K can be generated at high pressures by placing it in a water-cooled vacuum chamber. Temperature estimates from thermocouple measurements are within +/-35 K at the sample position up to 800 K and within +90 K between 800 and 1400 K when using a standard seat combination of cBN and WC. Isothermal compression at high temperatures can be achieved by employing a remote membrane control system. The advantage of the GRHDAC is demonstrated through the study of geophysical processes in the Earth's crust and upper mantle region.

Comparison of Bioelectrical Impedance Indices for Skeletal Muscle Mass and Intracellular Water Measurements of Physically Active Young Men and Athletes.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a minimally invasive, safe, easy, and quick technology used to determine body composition. OBJECTIVES: We compared the relationship among impedance indices obtained using single-frequency BIA, multi-frequency BIA, bioelectrical impedance spectroscopy (BIS), and skeletal muscle mass (SMM) of physically active young men and athletes using the creatine (methyl-d3) dilution method. We also compared the SMM and intracellular water (ICW) of athletes and active young men measured using a reference stable isotope dilution and BIS method, respectively. METHODS: We analyzed data from 28 men (mean age, 20 ± 2 y) who exercised regularly. Single-frequency BIA at 5 kHz and 50 kHz (R5 and R50), multi-frequency BIA (R250-5), and BIS (RICW) methods of determining the SMM were compared. The deuterium and sodium bromide dilution methods of obtaining the total body water, ICW, and extracellular water measurements were also used, and the results were compared to those acquired using bioimpedance methods. RESULTS: The correlation coefficients between SMM and L2/R5, L2/R50, L2/R250-5, and L2/RICW were 0.738, 0.762, 0.790, and 0.790, respectively (P < 0.01). The correlation coefficients between ICW and L2/R5, L2/R50, L2/R250-5, and L2/RICW were 0.660, 0.687, 0.758, and 0.730, respectively (P < 0.001). However, the correlation coefficients of L2/R50, L2/R250-5, and L2/RICW for SMM and ICW were not significantly different. CONCLUSIONS: Our findings suggest that single-frequency BIA at L2/R50, multi-frequency BIA, and BIS are valid for assessing the SMM of athletes and active young men. Additionally, we confirmed that the SMM and ICW were correlated with single-frequency BIA, multi-frequency BIA, and BIS. Bioimpedance technologies may be dependable and practical means for assessing SMM and hydration compartment status of active young adult males; however, cross-validation is needed.

Body Composition, Relative Dose Intensity, and Adverse Events among Patients with Colon Cancer.

BACKGROUND: Despite evidence that low muscle increases the risk of chemotoxicity, most chemotherapies are dosed on body surface area without considering body composition. Among 178 patients with colon cancer, we assessed muscle and adipose tissue with multiple techniques and examined their associations with relative dose intensity (RDI) and adverse events. METHODS: We estimated (i) cross-sectional skeletal muscle area (SMA) and total adipose tissue (TAT) area at L3 from computed tomography (CT); (ii) appendicular lean mass (ALM) and total body fat (TBF) mass from dual-energy X-ray absorptiometry (DXA); and (iii) total body skeletal muscle mass using D3-creatine (D3Cr) dilution. We standardized each measurement by its sex-specific standard deviation (SD). The primary outcome was reduced RDI (RDI <85%). The secondary outcome was the number of moderate and severe adverse events during each cycle of chemotherapy. We estimated the associations of muscle and adipose tissue measurements (per SD increase) with reduced RDI using logistic regression and adverse events using generalized estimating equations for repeated measures. RESULTS: Higher CT SMA and DXA ALM were significantly associated with a lower risk of reduced RDI [odds ratios: 0.56 (0.38-0.81) for CT SMA; 0.56 (0.37-0.84) for DXA ALM]. No measurements of muscle or adipose tissue were associated with adverse events. CONCLUSIONS: More muscle was associated with improved chemotherapy completion among patients with colon cancer, whereas muscle and adipose tissue were not associated with adverse events. IMPACT: Considering body composition may help personalize dosing for colon cancer chemotherapy by identifying patients at risk for poor chemotherapy outcomes.

Alaska Backcountry Expeditionary Hunting Promotes Sustained Muscle Protein Synthesis.

INTRODUCTION: We have previously described negative energy balance (ie, -9.7±3.4 MJ/d) and weight loss (Δ-1.5 ± 0.7 kg) influenced by high levels of energy expenditure (ie, 17.4±2.6 MJ/d) during remote expeditionary hunting in Alaska. Despite negative energy balance, participants retained skeletal muscle. The purpose of this pilot study was to measure skeletal muscle protein synthesis and examine molecular markers of skeletal muscle protein metabolism under similar conditions of physical and nutrient stress. METHODS: The "virtual biopsy method" was used to evaluate integrated fractional synthetic rates (FSRs) of muscle protein from blood samples in 4 participants. Muscle biopsies were taken to measure molecular markers of muscle protein kinetics (ie, FSTL1, MEF2, MYOD1, B2M, and miR-1-3p, -206, -208b, 23a, and 499a) using real-time polymerase chain reaction. RESULTS: Our findings in 4 participants (2 females [28 and 62 y of age; 66.2 and 71.8 kg body weight; 25.5 and 26.7 kg/m2 body mass index] and 2 males [47 and 56 y of age; 87.5 and 91.4 kg body weight; 26.1 and 28.3 kg/m2 body mass index]) describe mean muscle FSRs of serum carbonic anhydrase (2.4%) and creatine kinase M-type (4.0%) and positive increments in molecular regulation. CONCLUSIONS: Preservation of skeletal muscle under conditions of physical and nutrient stress seems to be supported by positive inflection of skeletal muscle FSR and molecular activation.

A MHz X-ray diffraction set-up for dynamic compression experiments in the diamond anvil cell.

An experimental platform for dynamic diamond anvil cell (dDAC) research has been developed at the High Energy Density (HED) Instrument at the European X-ray Free Electron Laser (European XFEL). Advantage was taken of the high repetition rate of the European XFEL (up to 4.5 MHz) to collect pulse-resolved MHz X-ray diffraction data from samples as they are dynamically compressed at intermediate strain rates (≤103 s-1), where up to 352 diffraction images can be collected from a single pulse train. The set-up employs piezo-driven dDACs capable of compressing samples in ≥340 µs, compatible with the maximum length of the pulse train (550 µs). Results from rapid compression experiments on a wide range of sample systems with different X-ray scattering powers are presented. A maximum compression rate of 87 TPa s-1 was observed during the fast compression of Au, while a strain rate of ∼1100 s-1 was achieved during the rapid compression of N2 at 23 TPa s-1.