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The ability to produce force rapidly has the potential to directly influence sprinting performance through changes in stride length and stride frequency. This ability is commonly referred to as the rate of force development (RFD). For this reason, many elite sprinters follow a combined program consisting of resistance training and sprint training. The purpose of this study was to investigate the strength, endocrine and body composition adaptations that occur during distinct phases of a block periodized training cycle in a 400 m Olympic level sprinter. The athlete is an elite level 400 m male sprinter (age 31 years, body mass 74 kg, years of training 15 and Personal Best (PB) 45.65 s). This athlete completed four distinct training phases of a block periodized training program (16 weeks) with five testing sessions consisting of testosteronecortisol (T/C) profiles, body composition, vertical jump, and maximum strength testing. Large fluctuations in T/C were found following high volume training and the taper. Minor changes in body mass were observed with an abrupt decrease following the taper which coincided with a small increase in fat mass percentage. Jump height (5.7%), concentric impulse (9.4%), eccentric impulse (3.4%) and power ratio (18.7%) all increased substantially from T1 to T5. Relative strength increased 6.04% from T1 to T5. Lastly, our results demonstrate the effectiveness of a competitive taper in increasing physiological markers for performance as well as dynamic performance variables. Block periodization training was effective in raising the physical capabilities of an Olympic level 400 m runner which have been shown to directly transfer to sprinting performance.Carbonic anhydrase IX (CAIX) is a hypoxia-induced protein that is highly expressed in numerous human cancers. However, the molecular mechanisms involved in CAIX and human cervical cancer metastasis remain poorly understood. In this study, CAIX overexpression in SiHa cells increased cell migration and epithelial-to-mesenchymal transition (EMT). Silencing CAIX in the Caski cell line decreased the motility of cells and EMT. Furthermore, the RNA-sequencing analysis identified a target gene, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB4), which is influenced by CAIX overexpression and knockdown. A positive correlation was found between CAIX expression and PFKFB4 levels in the cervical cancer of the TCGA database. Mechanistically, CAIX overexpression activated the phosphorylation of extracellular signal-regulated kinases (ERKs) to induce EMT and promote cell migration. In clinical results, human cervical cancer patients with CAIXhigh/PFKFB4high expression in the late stage had higher rates of lymph node metastasis and the shortest survival time. Our study found that CAIX overexpression increases PFKFB4 expression and EMT, promoting cervical cancer cell migration. CAIX could contribute to cervical cancer cell metastasis and its inhibition could be a cervical cancer treatment strategy.Fibrinolysis is an important process in hemostasis responsible for dissolving the clot during wound healing. Plasmin is a central enzyme in this process via its capacity to cleave fibrin. The kinetics of plasmin generation (PG) and inhibition during fibrinolysis have been poorly understood until the recent development of assays to quantify these metrics. The assessment of plasmin kinetics allows for the identification of fibrinolytic dysfunction and better understanding of the relationships between abnormal fibrin dissolution and disease pathogenesis. Additionally, direct measurement of the inhibition of PG by antifibrinolytic medications, such as tranexamic acid, can be a useful tool to assess the risks and effectiveness of antifibrinolytic therapy in hemorrhagic diseases. This review provides an overview of available PG assays to directly measure the kinetics of plasmin formation and inhibition in human and mouse plasmas and focuses on their applications in defining the role of plasmin in diseases, including angioedema, hemophilia, rare bleeding disorders, COVID-19, or diet-induced obesity. Moreover, this review introduces the PG assay as a promising clinical and research method to monitor antifibrinolytic medications and screen for genetic or acquired fibrinolytic disorders.Conditionally activated ("caged") oligonucleotides provide useful spatiotemporal control for studying dynamic biological processes, e.g., regulating in vivo gene expression or probing specific oligonucleotide targets. This review summarizes recent advances in caging strategies, which involve different stimuli in the activation step. Oligo cyclization is a particularly attractive caging strategy, which simplifies the probe design and affords oligo stabilization. Our laboratory developed an efficient synthesis for circular caged oligos, and a circular caged antisense DNA oligo was successfully applied in gene regulation. A second technology is Transcriptome In Vivo Analysis (TIVA), where caged oligos enable mRNA isolation from single cells in living tissue. Resveratrol We highlight our development of TIVA probes with improved caging stability. Finally, we illustrate the first protease-activated oligo probe, which was designed for caspase-3. This expands the toolkit for investigating the transcriptome under a specific physiologic condition (e.g., apoptosis), particularly in specimens where light activation is impractical.The proportion of patients over the age of 90 years continues to grow, and the anticipated demand for total joint arthroplasty (TJA) in this population is expected to rise concomitantly. As the country shifts to alternative reimbursement models, data regarding hospital expenses is needed for accurate risk-adjusted stratification. The aim of this study was to compare total in-hospital costs following primary TJA in octogenarians and nonagenarians, and to determine the primary drivers of cost. This was a retrospective analysis from a single institution in the U.S. We used time-drive activity-based costing (TDABC) to capture granular total hospital costs for each patient. 889 TJA's were included in the study, with 841 octogenarians and 48 nonagenarians. Nonagenarians were more likely to undergo total hip arthroplasty (THA) (70.8% vs. 42.4%; p less then 0.0001), had higher ASA classification (2.6 vs. 2.4; p = 0.049), and were more often privately insured (35.4% vs. 27.8%; p = 0.0001) as compared to octogenarians.
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