Dysregulation and fibrosis of the extracellular matrix (ECM) in skeletal muscle is a consequence of injury. Current ECM assessment necessitates muscle biopsies to evaluate alterations to the muscle ECM, which is often not practical in humans. The goal of this study was to evaluate the potential of a magnetic resonance imaging sequence that quantifies T1ρ relaxation time to predict ECM collagen composition and organization. T1ρ imaging was performed and muscle biopsies obtained from the involved and non-involved vastus lateralis muscle on 27 subjects who had an anterior cruciate ligament (ACL) tear. T1ρ times were quantified via mono exponential decay curve fitted to a series of T1ρ-weighted images. Several ECM indices, including collagen content and organization, were obtained using immunohistochemistry and histochemistry in addition

Vitamin D is an essential nutrient for the maintenance of skeletal muscle and bone health. The vitamin D receptor (VDR) is present in muscle, as is CYP27B1, the enzyme that hydroxylates 25(OH)D to its active form, 1,25(OH)D. Furthermore, mounting evidence suggests that vitamin D may play an important role during muscle damage and regeneration. Muscle damage is characterized by compromised muscle fiber architecture, disruption of contractile protein integrity, and mitochondrial dysfunction. Muscle regeneration is a complex process that involves restoration of mitochondrial function and activation of satellite cells (SC), the resident skeletal muscle stem cells. VDR expression is strongly upregulated following injury, particularly in central nuclei and SCs in animal models of muscle injury. Mechanistic studies provide some insight into the possible role of vitamin D activity in injured muscle. In vitro and in vivo rodent studies show that vitamin D mitigates reactive oxygen species (R...

Meal timing affects metabolic responses to diet, but participant compliance in time-restricted feeding and other diet studies is challenging to monitor and is a major concern for research rigor and reproducibility. To facilitate automated validation of participant self-reports of meal timing, the present study focuses on the creation of a meal detection algorithm using continuous glucose monitoring (CGM), physiological monitors and machine learning. While most CGM-related studies focus on participants who are diabetic, this study is the first to apply machine learning to meal detection using CGM in metabolically healthy adults. Furthermore, the results demonstrate a high area under the receiver operating characteristic curve (AUC-ROC) and precision-recall curve (AUC-PR). A cold-start simulation using a random forest algorithm yields .891 and .803 for AUC-ROC and AUC-PR respectively on 110minutes data, and a non-cold start simulation using a gradient boosted tree model yields over .996 (AUC-ROC) and .964 (AUC-PR). Here it is demonstrated that CGM and physiological monitoring data is a viable tool for practitioners and scientists to objectively validate self-reports of meal consumption in healthy participants.

Inpatient populations are at increased risk of hyperglycemia due to factors such as medications, physical inactivity and underlying illness, which increases morbidity and mortality. Unfortunately, clinicians have limited tools available to prospectively identify those at greatest risk. We evaluated the ability of 10 common genetic variants associated with development of type 2 diabetes to predict impaired glucose metabolism. Our research model was a simulated inpatient hospital stay (7 day bed rest protocol, standardized diet, and physical inactivity) in a cohort of healthy older adults (n = 31, 65 ± 8 years) with baseline fasting blood glucose < 100 mg/dL. Participants completed a standard 75 g oral glucose tolerance test (OGTT) at baseline and post-bed rest. Bed rest increased 2-h OGTT blood glucose and insulin independent of genetic variant. In multiple regression modeling, the transcription factor 7-like 2 (TCF7L2) rs7903146 T allele predicted increases in 2-h OGTT blood glucose (p = 0.039). We showed that the TCF7L2 rs7903146 T allele confers risk for loss of glucose tolerance in nondiabetic older adults following 7 days of bed rest. Nondiabetic patients who develop hyperglycemia during hospitalization have increased lengths of stay and mortality risk 1-7. In critically ill patients, mortality increases incrementally with rising blood glucose, and patients reaching values above 300 mg/dL have high mortality rates independent of diabetes diagnosis 3. Likewise, postoperative hyperglycemia increases the risk of post-operative infection by 30% with every 40-point increase from normoglycemia (< 100 mg/dl) 7. Currently, clinicians are unable to identify nondiabetic inpatients at greater risk for developing hyperglycemia, limiting their ability to initiate preventive therapy. Dozens of common genetic variants are associated with increased risk for type 2 diabetes. For example, the odds of developing type 2 diabetes is 1.5 when having the transcription factor 7-like 2 (TCF7L2) rs7903146 T allele (rs7903146 T), which is established across many ethnic groups 8,9. The TCF7L2 rs7903146 T variant is also associated with impaired pancreatic function and elevated glycated hemoglobin in nondiabetic individuals 10,11. Though some genetic variants, including TCF7L2 rs7903146 T , are associated with elevated glycemic indicators in nondiabetic individuals, more evidence is needed to determine how genetic testing of these risk variants may support clinical decision making in the inpatient setting. Inpatient hyperglycemia is multifactorial and mediated by factors like physical inactivity, medications, medical nutrition therapies, and underlying acute illnesses/chronic disease 2,4,5,12. Inpatient bed rest in healthy research subjects models the physical inactivity aspect of a hospital stay while avoiding the confounding influence of variable nutrition therapies and disease-related comorbidities. Therefore, inpatient bed rest is a powerful tool to understand how the interaction of physical inactivity and genetic variation may contribute to a decline in insulin sensitivity and subsequent impaired glucose tolerance independent of the catabolic burden of the clinical milieu. We sought to determine if genetic testing for ten common type 2 diabetes risk variants could predict changes in fasting blood glucose or glucose intolerance during an oral glucose tolerance test (OGTT) challenge in healthy older adults completing a 7 day inpatient bed rest protocol. We selected genetic variants based on their previously reported effect size, effect on beta cell function, or location of the single nucleotide polymorphism (SNP), with preference for those located in exons 9,13,14. Here we report on the ability of MTNR1B (rs10830963), NOTCH2

Objective: We evaluated associations between vitamin D status and skeletal muscle, strength, and bone mineral density (BMD) outcomes after ACL reconstruction (ACLR) in an observational study. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 1 Methods: Serum measures included 25-hydroxyvitamin D (25(OH)D; free and total), vitamin D binding protein (DBP), and 1,25-dihydroxy vitamin D (1,25(OH) 2 D) at baseline, 1 week, 4 months, and 6 months post-ACLR. Vastus lateralis biopsies were collected from the healthy and ACL-injured limb of 21 young, healthy participants (62% female; 17.8 [3.2] yr, BMI: 26.0 [3.5] kg/m 2) during ACLR and the injured limb only at 1 week and 4 month follow ups. RNA and protein were isolated from biopsies and assessed for vitamin D receptor [VDR], and vitamin D-activating enzymes. Quadriceps fiber cross-sectional area (CSA) was determined with immunohistochemistry. BMD of femur and tibia were determined at baseline and 6 months post-ACLR; strength was assessed with an isokinetic dynamometer. Results: 1,25(OH) 2 D decreased from baseline to one week after ACLR (21.6 [7.9] vs. 13.8 [5.5] pg/mL; p<0.0001). VDR and 25-hydroxylase transcript abundance and VDR and DBP proteins were elevated one week after ACLR compared with baseline (FDR<0.05; p<0.05). Participants with an average total 25(OH)D <30 ng/mL showed significant decreases in CSA 1 week and 4 months after ACLR (p<0.01; p=0.041 for time x D status interaction), whereas those with total 25(OH)D ≥ 30ng/mL showed no significant differences (p>0.05 for all comparisons). BMD and strength measures were lower at follow up but did not associate with vitamin D status. Conclusion: ACLR promotes vitamin D pathways in the quadriceps and low status is associated with loss of skeletal muscle both 1 week and 4 months after ACLR.

Inpatient populations are at increased risk of hyperglycemia due to factors such as medications, physical inactivity and underlying illness, which increases morbidity and mortality. Unfortunately, clinicians have limited tools available to prospectively identify those at greatest risk. We evaluated the ability of 10 common genetic variants associated with development of type 2 diabetes to predict impaired glucose metabolism. Our research model is a simulated hospital stay (7 day bed rest protocol, standardized diet, and physical inactivity) and included a cohort of healthy older adults (n = 31, 65 ± 8 years) with baseline fasting blood glucose