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Medicine and Science in Sports and... Apr 2024Physical activity level has been identified as an important factor in the development and progression of various types of cancer. In this study, we determined the impact... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Physical activity level has been identified as an important factor in the development and progression of various types of cancer. In this study, we determined the impact of a low versus high physical activity level on skeletal muscle, healthy prostate, and prostate tumor protein synthesis rates in vivo in prostate cancer patients.
METHODS
Thirty prostate cancer patients (age, 66 ± 5 yr; body mass index, 27.4 ± 2.9 kg·m -2 ) were randomized to a low (<4000 steps per day, n = 15) or high (>14,000 steps per day, n = 15) physical activity level for 7 d before their scheduled radical prostatectomy. Daily deuterium oxide administration was combined with the collection of plasma, skeletal muscle, nontumorous prostate, and prostate tumor tissue during the surgical procedure to determine tissue protein synthesis rates throughout the intervention period.
RESULTS
Daily step counts averaged 3610 ± 878 and 17,589 ± 4680 steps in patients subjected to the low and high physical activity levels, respectively ( P < 0.001). No differences were observed between tissue protein synthesis rates of skeletal muscle, healthy prostate, or prostate tumor between the low (1.47% ± 0.21%, 2.74% ± 0.70%, and 4.76% ± 1.23% per day, respectively) and high (1.42% ± 0.16%, 2.64% ± 0.58%, and 4.72% ± 0.80% per day, respectively) physical activity group (all P > 0.4). Tissue protein synthesis rates were nearly twofold higher in prostate tumor compared with nontumorous prostate tissue.
CONCLUSIONS
A short-term high or low physical activity level does not modulate prostate or prostate tumor protein synthesis rates in vivo in prostate cancer patients. More studies on the impact of physical activity level on tumor protein synthesis rates and tumor progression are warranted to understand the potential impact of lifestyle interventions in the prevention and treatment of cancer.
Topics: Male; Humans; Middle Aged; Aged; Prostate; Prostatic Neoplasms; Prostatectomy; Body Mass Index; Exercise
PubMed: 38079310
DOI: 10.1249/MSS.0000000000003349 -
Journal of Biomedical Optics Nov 2023Changes in lipid, water, and collagen (LWC) content in tissue are associated with numerous medical abnormalities (cancer, atherosclerosis, and Alzheimer's disease)....
SIGNIFICANCE
Changes in lipid, water, and collagen (LWC) content in tissue are associated with numerous medical abnormalities (cancer, atherosclerosis, and Alzheimer's disease). Standard imaging modalities are limited in resolution, specificity, and/or penetration for quantifying these changes. Short-wave infrared (SWIR) photoacoustic imaging (PAI) has the potential to overcome these challenges by exploiting the unique optical absorption properties of .
AIM
This study's aim is to harness SWIR PAI for mapping LWC changes in tissue. The focus lies in devising a reflection-mode PAI technique that surmounts current limitations related to SWIR light delivery.
APPROACH
To enhance light delivery for reflection-mode SWIR PAI, we designed a deuterium oxide (, "heavy water") gelatin (HWG) interface for opto-acoustic coupling, intended to significantly improve light transmission above 1200 nm.
RESULTS
HWG permits light delivery up to 1850 nm, which was not possible with water-based coupling ( light delivery up to 1350 nm). PAI using the HWG interface and the Visualsonics Vevo LAZR-X reveals a signal increase up to 24 dB at 1720 nm in lipid-rich regions.
CONCLUSIONS
By overcoming barriers related to light penetration, the HWG coupling interface enables accurate quantification/monitoring of biomarkers like LWC using reflection-mode PAI. This technological stride offers potential for tracking changes in chronic diseases () and evaluating their responses to therapeutic interventions.
Topics: Deuterium Oxide; Photoacoustic Techniques; Diagnostic Imaging; Water; Lipids
PubMed: 38078156
DOI: 10.1117/1.JBO.28.11.116001 -
The Journal of Physiology Dec 2023
PubMed: 38051758
DOI: 10.1113/JP285616 -
Talanta Mar 2024Lipid monitoring plays a crucial role in biomedical research, particularly in the areas of cardiovascular health, metabolic disorders and nutrition. However, direct and...
Lipid monitoring plays a crucial role in biomedical research, particularly in the areas of cardiovascular health, metabolic disorders and nutrition. However, direct and highly sensitive detection of lipids poses significant challenges due to the interference of high SERS background noise in lipid samples. In this study, we present a SERS platform for the quantitative analysis of lipids. By harnessing the Surface Plasmon Resonance (SPR) effect of nanostructured grooves and leveraging deuterium oxide, a remarkable enhancement of in-situ Raman signals originating from cholesterol is achieved. This approach yielded an impressive average enhancement factor of 7.3 × 10 and a detection limit of 1.9 × 10 mg/mL, highlighting the exceptional sensitivity and precision of our method. We have obtained high quality, in-situ SERS signals for six distinct lipid molecules. Rapid identification of lipid samples in mixed systems has been achieved through the combination of characteristic peak analysis and PCA-LDA, including the detection of SERS signals from lipids in milk. Notably, univariate monitoring of in-situ cholesterol in human serum was successfully achieved for the first time using deuterium water as an internal standard. In addition, silver substrate demonstrated outstanding reproducibility, maintaining consistent SERS activity even after more than 10 repetitions. Therefore, this platform offers the distinct advantages of high sensitivity, specificity and cost-effectiveness for lipid detection. These findings enable dietary management and blood lipid monitoring, and therefore hold crucial implications for the early prevention of lipid-related disorders and diseases.
Topics: Humans; Surface Plasmon Resonance; Silver; Reproducibility of Results; Spectrum Analysis, Raman; Metal Nanoparticles; Lipids; Cholesterol
PubMed: 38039677
DOI: 10.1016/j.talanta.2023.125432 -
Frontiers in Pediatrics 2023The deuterium dose-to-mother (DTM) method measures the human milk intake of breastfed children. Recently, the use of this method has been expanded to classify babies...
BACKGROUND
The deuterium dose-to-mother (DTM) method measures the human milk intake of breastfed children. Recently, the use of this method has been expanded to classify babies objectively as exclusively breast fed (EBF) or not (non-EBF) based on quantification of non-milk oral water intake (NMOI). However, the calculation of NMOI estimates involves atmospheric temperature and humidity.
OBJECTIVE
To evaluate the effects of atmospheric temperature and humidity on NMOI calculation and the classification of exclusive breastfeeding.
METHODS
The effect of indoor temperature and relative humidity on NMOI and the estimated prevalence of non-EBF were examined in two existing data sets of DTM in children by varying temperature in the range of 15 to 35°C and relative humidity in the range of 20 to 80% representing the maximum span of indoor conditions expected. Population-level estimates of NMOI distributions were derived using the rstan package for R v2.21.2.
RESULTS
The NMOI decreased at a rate of -1.15 g/day per °C increase and at a rate of -1.01 g/day per percent increase in relative humidity; this was due to variations in non-oral water intake from the atmosphere, a component of the calculation of NMOI, which is dependent on temperature and humidity. For the various locations considered, the mean calculated NMOI varied between 24.6 and 53.3 g/day using the same input data. In the mixed-fed sample of babies, the prevalence of non-EBF based on the earlier defined NMOI cut-off of 86.6 g/day was reduced by 19% when relative humidity was increased by 60%.
CONCLUSIONS
Atmospheric conditions are essential factors in the computation of NMOI, used in the objective classification of babies as exclusively breast fed or not, and should be considered when the DTM method is used to classify exclusive breastfeeding.
PubMed: 38034831
DOI: 10.3389/fped.2023.1188811 -
Health Physics Mar 2024Field experiments were performed to evaluate the deposition velocity of tritium oxide within a forest environment at the Savannah River Site near Aiken, SC. Field...
Field experiments were performed to evaluate the deposition velocity of tritium oxide within a forest environment at the Savannah River Site near Aiken, SC. Field releases were designed to guide selection of deposition velocity values for use in safety-basis modeling. Six releases of deuterium oxide were conducted in 2020 and 2021 with corresponding air samples during and following each release. Samples were analyzed to determine the deuterium-to-hydrogen ratio in water and converted to concentrations of deuterium in the air during the experiment. Measurements were compared to prior model simulations to evaluate model performance and deposition velocity estimates. Field releases demonstrated vertical and horizontal mixing of a plume in a forest. Predicted deposition velocities ranged from 2.4 to 5.4 cm s -1 on average. In all cases, model simulations underpredicted deuterium concentration by 1 to 2 orders of magnitude, indicating the model does not sufficiently mix the plume into the forest. While the model underestimated the transfer of material downward through the forest, it does suggest that the model's estimates are conservative for making downwind dose estimates because of lower plume depletion, leading to higher concentration and dose estimates. While the field releases do not cover all possible meteorological conditions, we conclude it is appropriate to use a non-zero deposition velocity when performing safety-basis modeling of tritium oxide based on conservatism within the model. A recommendation of 1.0 cm s -1 as a deposition velocity is made, which is beyond the 95 th percentile value estimated from the prior modeling study.
Topics: Deuterium Oxide; Deuterium; Tritium; Forests; Water
PubMed: 38011073
DOI: 10.1097/HP.0000000000001769 -
Medicine and Science in Sports and... Apr 2024Short periods of limb immobilization lower myofibrillar protein synthesis rates. Within skeletal muscle, the extracellular matrix of connective proteins is recognized as...
PURPOSE
Short periods of limb immobilization lower myofibrillar protein synthesis rates. Within skeletal muscle, the extracellular matrix of connective proteins is recognized as an important factor determining the capacity to transmit contractile force. Little is known regarding the impact of immobilization and subsequent recovery on muscle connective protein synthesis rates. This study examined the impact of 1 wk of leg immobilization and 2 wk of subsequent ambulant recovery on daily muscle connective protein synthesis rates.
METHODS
Thirty healthy, young (24 ± 5 yr) men were subjected to 7 d of one-legged knee immobilization followed by 14 d of ambulant recovery. Deuterium oxide ingestion was applied over the entire period, and muscle biopsy samples were collected before immobilization, after immobilization, and after recovery to measure muscle connective protein synthesis rates and mRNA expression of key extracellular matrix proteins (collagen I, collagen III), glycoproteins (fibronectin, tenascin-C), and proteoglycans (fibromodulin, and decorin). A two-way repeated-measures (time-leg) ANOVA was used to compare changes in muscle connective protein synthesis rates during immobilization and recovery.
RESULTS
During immobilization, muscle connective protein synthesis rates were lower in the immobilized (1.07 ± 0.30%·d -1 ) compared with the nonimmobilized (1.48 ± 0.44%·d -1 ; P < 0.01) leg. When compared with the immobilization period, connective protein synthesis rates in the immobilized leg increased during subsequent recovery (1.48 ± 0.64%·d -1 ; P < 0.01). After recovery, skeletal muscle collagen I, collagen III, fibronectin, fibromodulin, and decorin mRNA expression increased when compared with the postimmobilization time point (all P < 0.001).
CONCLUSIONS
One week of leg immobilization lowers muscle connective protein synthesis rates. Muscle connective protein synthesis rates increase during subsequent ambulant recovery, which is accompanied by increased mRNA expression of key extracellular matrix proteins.
Topics: Male; Humans; Young Adult; Leg; Fibronectins; Fibromodulin; Decorin; Muscle, Skeletal; Extracellular Matrix Proteins; Collagen; Collagen Type I; RNA, Messenger
PubMed: 37994085
DOI: 10.1249/MSS.0000000000003342 -
Inorganic Chemistry Dec 2023Due to notable thermochemical stability, polyphosphamides are often regarded as flame retardants, while molecular phosphamides can serve as versatile Lewis base to...
Due to notable thermochemical stability, polyphosphamides are often regarded as flame retardants, while molecular phosphamides can serve as versatile Lewis base to catalyze diverse organic transformations. Being chemically analogous to phosphine oxide, phosphamide can also be considered as a mediator for the phosphine-mediated reaction. Herein, an amorphous polymeric material consisting of phosphamide (-NH-P(O)) in the repeating unit () has been prepared via condensation of tris(2-aminoethyl)amine (TREN) and phenyl phosphinic dichloride (PPDC). The is isolated as a metal-free and pure organic material which is made of a strong covalent bond and the phosphamide unit is deployed in the organic framework. The presence of phosphamide in the repeating unit of the isolated amorphous material can be confirmed by P CPMAS NMR, FTIR, and Raman studies. The core-level N 2p and P 2p X-ray photoelectron spectra are in accordance with the presence of tertiary amine nitrogen attached to carbon and secondary amine nitrogen attached to phosphorus. Elemental analyses have depicted approximately 19.7% of phosphorus content in the material, which is being utilized to study the catalytic Appel reaction with 76% conversion of alcohol to a corresponding halide and TON of 462. Quasi in situ Raman study has identified that amino phosphine formed via in situ reduction of the phosphamide unit of the catalyzes the halogenation of primary and secondary alcohols with wide substrate scope and functional group tolerance. Kinetic studies have established a first-order dependence with respect to alcohol, while deuterium labeling experiments emphasize that the deprotonation of alcohol is the rate-limiting step. High thermal stability of the material, scope of easy catalyst recyclability, and a cumulative TON of 1386 have led the as an emerging pure organic material to be explored further for other phosphine-mediated organocatalysis.
PubMed: 37982144
DOI: 10.1021/acs.inorgchem.3c02989 -
The Journal of Biological Chemistry Jan 2024Neuronal nitric oxide synthase (nNOS) is a homodimeric cytochrome P450-like enzyme that catalyzes the conversion of L-arginine to nitric oxide in the presence of NADPH...
Neuronal nitric oxide synthase (nNOS) is a homodimeric cytochrome P450-like enzyme that catalyzes the conversion of L-arginine to nitric oxide in the presence of NADPH and molecular oxygen. The binding of calmodulin (CaM) to a linker region between the FAD/FMN-containing reductase domain, and the heme-containing oxygenase domain is needed for electron transfer reactions, reduction of the heme, and NO synthesis. Due to the dynamic nature of the reductase domain and low resolution of available full-length structures, the exact conformation of the CaM-bound active complex during heme reduction is still unresolved. Interestingly, hydrogen-deuterium exchange and mass spectrometry studies revealed interactions of the FMN domain and CaM with the oxygenase domain for iNOS, but not nNOS. This finding prompted us to utilize covalent crosslinking and mass spectrometry to clarify interactions of CaM with nNOS. Specifically, MS-cleavable bifunctional crosslinker disuccinimidyl dibutyric urea was used to identify thirteen unique crosslinks between CaM and nNOS as well as 61 crosslinks within the nNOS. The crosslinks provided evidence for CaM interaction with the oxygenase and reductase domain residues as well as interactions of the FMN domain with the oxygenase dimer. Cryo-EM studies, which gave a high-resolution model of the oxygenase domain, along with crosslink-guided docking provided a model of nNOS that brings the FMN within 15 Å of the heme in support for a more compact conformation than previously observed. These studies also point to the utility of covalent crosslinking and mass spectrometry in capturing transient dynamic conformations that may not be captured by hydrogen-deuterium exchange and mass spectrometry experiments.
Topics: Calmodulin; Heme; Mass Spectrometry; Nitric Oxide Synthase Type I; Oxygenases; Cross-Linking Reagents; Calcium; Models, Molecular; Protein Structure, Quaternary; Protein Binding; Cryoelectron Microscopy
PubMed: 37979917
DOI: 10.1016/j.jbc.2023.105464 -
Proteomics Nov 2023This pilot experiment examines if a loss in muscle proteostasis occurs in people with obesity and whether endurance exercise positively influences either the abundance...
This pilot experiment examines if a loss in muscle proteostasis occurs in people with obesity and whether endurance exercise positively influences either the abundance profile or turnover rate of proteins in this population. Men with (n = 3) or without (n = 4) obesity were recruited and underwent a 14-d measurement protocol of daily deuterium oxide (D O) consumption and serial biopsies of vastus lateralis muscle. Men with obesity then completed 10-weeks of high-intensity interval training (HIIT), encompassing 3 sessions per week of cycle ergometer exercise with 1 min intervals at 100% maximum aerobic power interspersed by 1 min recovery periods. The number of intervals per session progressed from 4 to 8, and during weeks 8-10 the 14-d measurement protocol was repeated. Proteomic analysis detected 352 differences (p < 0.05, false discovery rate < 5%) in protein abundance and 19 (p < 0.05) differences in protein turnover, including components of the ubiquitin-proteasome system. HIIT altered the abundance of 53 proteins and increased the turnover rate of 22 proteins (p < 0.05) and tended to benefit proteostasis by increasing muscle protein turnover rates. Obesity and insulin resistance are associated with compromised muscle proteostasis, which may be partially restored by endurance exercise.
PubMed: 37963832
DOI: 10.1002/pmic.202300395