A detailed understanding of molecular responses to a hypertrophic stimulus in skeletal muscle leads to therapeutic advances aimed at promoting muscle mass. To decode the molecular factors regulating skeletal muscle mass, we utilized a 24-h time course of human muscle biopsies after a bout of resistance exercise. Our findings indicate: (1) the DNA methylome response at 30 min corresponds to upregulated genes at 3 h, (2) a burst of translation- and transcription-initiation factor-coding transcripts occurs between 3 and 8 h, (3) changes to global protein-coding gene expression peaks at 8 h, (4) ribosome-related genes dominate the mRNA landscape between 8 and 24 h, (5) methylation-regulated MYC is a highly influential transcription factor throughout recovery.
View Article and Find Full Text PDFMicroRNA-1 (miR-1) is the most abundant miRNA in adult skeletal muscle. To determine the function of miR-1 in adult skeletal muscle, we generated an inducible, skeletal muscle-specific miR-1 knockout (KO) mouse. Integration of RNA-sequencing (RNA-seq) data from miR-1 KO muscle with Argonaute 2 enhanced crosslinking and immunoprecipitation sequencing (AGO2 eCLIP-seq) from human skeletal muscle identified miR-1 target genes involved with glycolysis and pyruvate metabolism.
View Article and Find Full Text PDFRadiation therapy plays a crucial role in cancer treatment, necessitating precise delivery of radiation to tumors while sparing healthy tissues over multiple days. Computed tomography (CT) is integral for treatment planning, offering electron density data crucial for accurate dose calculations. However, accurately representing patient anatomy is challenging, especially in adaptive radiotherapy, where CT is not acquired daily.
View Article and Find Full Text PDFIn oncology, medical imaging is crucial for diagnosis, treatment planning and therapy execution. Treatment responses can be complex and varied and are known to involve factors of treatment, patient characteristics and tumor microenvironment. Longitudinal image analysis is able to track temporal changes, aiding in disease monitoring, treatment evaluation, and outcome prediction.
View Article and Find Full Text PDFMolecular control of recovery after exercise in muscle is temporally dynamic. A time course of biopsies around resistance exercise (RE) combined with -omics is necessary to better comprehend the molecular contributions of skeletal muscle adaptation in humans. Vastus lateralis biopsies before and 30 minutes, 3-, 8-, and 24-hours after acute RE were collected.
View Article and Find Full Text PDFNeuromodulation
December 2023
Objectives: Commercial intrathecal baclofen treatment (ITBT) infusion pumps are recommended to be refilled within a maximum of 180 days, thus necessitating at least twice-yearly outpatient visits and refill injections. In particular, pumps with 40-mL reservoir volumes would allow much longer refill intervals. We investigated baclofen stability in active implanted ITBT infusion pumps in vivo with refill intervals up to 367 days to study the feasibility of lengthening refill intervals beyond six months.
View Article and Find Full Text PDFMurine exercise models are developed to study the molecular and cellular mechanisms regulating muscle mass. A progressive weighted wheel running model, named 'PoWeR', was previously developed to serve as a more translatable alternative to involuntary resistance-type exercise models in rodents, such as synergist ablation. However, mice still run great distances despite the added resistance as evidenced by a large glycolytic-to-oxidative shift in muscle fibre type.
View Article and Find Full Text PDFSatellite cells are bona fide muscle stem cells that are indispensable for successful post-natal muscle growth and regeneration after severe injury. These cells also participate in adult muscle adaptation in several capacities. MicroRNAs (miRNAs) are post-transcriptional regulators of mRNA that are implicated in several aspects of stem cell function.
View Article and Find Full Text PDFBackground: Novel mRNA-based vaccines have been used to protect against SARS-CoV-2, especially in vulnerable populations who also receive an annual influenza vaccination. The TACTIC study investigated potential immune interference between the mRNA COVID-19 booster vaccine and the quadrivalent influenza vaccine, and determined if concurrent administration would have effects on safety or immunogenicity.
Methods: TACTIC was a single-blind, placebo-controlled randomized clinical trial conducted at the Radboud University Medical Centre, the Netherlands.
Sports Med Health Sci
March 2023
Muscle fibers are multinucleated, and muscle fiber nuclei (myonuclei) are believed to be post-mitotic and are typically situated near the periphery of the myofiber. Due to the unique organization of muscle fibers and their nuclei, the cellular and molecular mechanisms regulating myofiber homeostasis in unstressed and stressed conditions (e.g.
View Article and Find Full Text PDFMicroRNAs (miRs) control stem cell biology and fate. Ubiquitously expressed and conserved miR-16 was the first miR implicated in tumorigenesis. miR-16 is low in muscle during developmental hypertrophy and regeneration.
View Article and Find Full Text PDFPurpose: To investigate the safety and efficacy of nivolumab plus cabozantinib with or without ipilimumab in patients with advanced hepatocellular carcinoma.
Methods: In cohort 6 of the multicohort, open-label, phase I/II CheckMate 040 study, patients who were treatment-naive, sorafenib-intolerant, or had progressed on sorafenib were randomly assigned 1:1 to nivolumab 240 mg once every 2 weeks plus cabozantinib 40 mg once daily (doublet arm); or nivolumab 3 mg/kg every 2 weeks plus cabozantinib 40 mg once daily with ipilimumab 1 mg/kg once every 6 weeks (triplet arm). Primary objectives were safety and tolerability, objective response rate, and duration of response by investigator assessment per RECIST v1.
Laminar functional magnetic resonance imaging (fMRI) using the gradient echo (GRE) blood oxygenation level dependent (BOLD) contrast is prone to signal changes arising from large unspecific venous vessels. Alternatives based on changes of cerebral blood volume (CBV) become more popular since it is expected that this hemodynamic response is dominant in microvasculature. One approach to sensitize the signal toward changes in CBV, and to simultaneously reduce unwanted extravascular (EV) BOLD blurring, is to selectively reduce gray matter (GM) signal via magnetization transfer (MT).
View Article and Find Full Text PDFIntroduction: Skin revitalizers are used for skin quality improvement purposes. Hyaluronan hybrid cooperative complexes (HCC, Profhilo®, IBSA Pharmaceuticals) are an anti-aging treatment with a large amount of pure hyaluronic acid (HA) based on stable, cooperative, and hybrid complexes. Cohesive polydensified matrix Hyaluronic Acid (CPM-HA20, Belotero Revive®, Merz Pharmaceuticals GmbH) is a slightly cross-linked HA (20 mg/ml) with glycerol (17.
View Article and Find Full Text PDFIntroduction: Alignment goals in total knee replacement (TKR) is a topical subject. This study compares the short-term functional outcomes and patient reported outcome measures (PROMs) of two philosophies for knee arthroplasty alignment: measured resection (MR) and an individualised alignment philosophy, with the tibia mechanically aligned and an instrumented gap balancer (GB) to align the femur in both flexion and extension.
Patients And Methods: 94 knees were enrolled in this randomised controlled trial.
Previously developed rodent resistance-based exercise models, including synergistic ablation, electrical stimulation, weighted-ladder climbing, and most recently, weighted-sled pulling, are highly effective at providing a hypertrophic stimulus to induce skeletal muscle adaptations. While these models have proven invaluable for skeletal muscle research, they are either invasive or involuntary and labor-intensive. Fortunately, many rodent strains voluntarily run long distances when given access to a running wheel.
View Article and Find Full Text PDFLaminar functional magnetic resonance imaging (fMRI) holds the potential to study connectivity at the laminar level in humans. Here we analyze simultaneously recorded electroencephalography (EEG) and high-resolution fMRI data to investigate how EEG power modulations, induced by a task with an attentional component, relate to changes in fMRI laminar connectivity between and within brain regions in visual cortex. Our results indicate that our task-induced decrease in beta power relates to an increase in deep-to-deep layer coupling between regions and to an increase in deep/middle-to-superficial layer connectivity within brain regions.
View Article and Find Full Text PDFBackground: patients with a subarachnoid hemorrhage (SAH) might need a flow diverter (FD) placement for complex acutely ruptured intracranial aneurysms (IAs). We conducted a meta-analysis and developed a prediction model to estimate the favorable clinical outcome after the FD treatment in acutely ruptured IAs.
Methods: a systematic literature search was performed from 2010 to January 2021 in PubMed and Embase databases.
In patients hospitalized for corona virus infectious disease 19 (COVID-19) it is currently unknown whether myocardial function changes after recovery and whether this is related to elevated cardiac biomarkers. In this single center, prospective cohort study we consecutively enrolled hospitalized COVID-19 patients between 1 April and 12 May 2020. All patients underwent transthoracic echocardiography (TTE) evaluation during hospitalization and at a median of 131 days (IQR; 116-136) follow-up.
View Article and Find Full Text PDFFunctional magnetic resonance imaging (fMRI) using blood oxygenation level dependent (BOLD) contrast at a sub-millimeter scale is a promising technique to probe neural activity at the level of cortical layers. While gradient echo (GRE) BOLD sequences exhibit the highest sensitivity, their signal is confounded by unspecific extravascular (EV) and intravascular (IV) effects of large intracortical ascending veins and pial veins leading to a downstream blurring effect of local signal changes. In contrast, spin echo (SE) fMRI promises higher specificity towards signal changes near the microvascular compartment.
View Article and Find Full Text PDFBackground: N-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP), a marker for neurohumoral activation, has been associated with adverse outcome in patients with myocardial infarction. NT-proBNP levels may reflect extensive ischemia and microvascular damage, therefore we investigated the potential association between baseline NT-proBNP level and ST-resolution (STR), a marker of myocardial reperfusion, after primary percutaneous coronary intervention (pPCI).
Methods: we performed a post-hoc analysis of the On-TIME II trial (which randomized ST-elevation myocardial infarction (STEMI) patients to pre-hospital tirofiban administration vs placebo).
Purpose: To improve partial Fourier (PF) imaging reconstruction in time-series or multi-echo acquisitions.
Methods: Many PF methods use a phase estimate to restore Hermitian symmetry before filling missing k-space entries with measured data from the opposite half. This estimate is obtained from the symmetrically sampled, central part of k-space and its low-resolution results in artifacts near high-frequency phase effects (eg, tissue boundaries, vessels), limiting PF undersampling.