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The number of cyclists and cycling crashes have increased in the last years around the world. Road Cycling and Mountain Bike are the most frequent practiced styles. The main purpose of this study was to analyze the severity of the injuries related to these two disciplines. Furthermore, we evaluated the frequency and the risk factors associated to these two cycling disciplines within the broad category of cycling. We performed a prospective study including 149 injured Road or Mountain Bike cyclists that we received to our Emergency Trauma Department between the period of November 1st 2020 to October 31st 2021. We analyzed the severity of the injuries by using the Injury Severity Score (ISS). Other associated variables like mechanism of the injury, use of helmet, alcohol or drugs consumption and the experience of the cyclist were also evaluated. Chi-square Test or the Student T-test were performed, as appropriate, to test for differences between the two groups, and correlations were performed to denote associations. We observed significant higher values on the ISS score and less frequency of the injuries in the Road Cycling group compared to the Mountain Bike one (67.1% vs. 32.9% respectively). We also found a relation between the age of the cyclist and the severity of the injury. Older patients suffered more serious lesions. In absolute terms Road Cycling crashes were less frequent than Mountain Bike ones but provided more risk of serious injuries. Older cyclist had more risk to suffer severe lesions.

Background To cope with shortages of equipment during the COVID-19 pandemic, we established a nonprofit end-to-end system to identify, validate, regulate, manufacture, and distribute 3D-printed medical equipment. Here we describe the local and global impact of this system. Methods Together with critical care experts, we identified potentially lacking medical equipment and proposed solutions based on 3D printing. Validation was based on the ISO 13485 quality standard for the manufacturing of customized medical devices. We posted the design files for each device on our website together with their technical and printing specifications and created a supply chain so that hospitals from our region could request them. We analyzed the number/type of items, petitioners, manufacturers, and catalogue views. Results Among 33 devices analyzed, 26 (78·8%) were validated. Of these, 23 (88·5%) were airway consumables and 3 (11·5%) were personal protective equipment. Orders came from 19 (76%) hospitals and 6 (24%) other healthcare institutions. Peak production was reached 10 days after the catalogue was published. A total of 22,135 items were manufactured by 59 companies in 18 sectors; 19,212 items were distributed to requesting sites during the busiest days of the pandemic. Our online catalogue was also viewed by 27,861 individuals from 113 countries. Conclusions 3D printing helped mitigate shortages of medical devices due to problems in the global supply chain.

Purpose Multiple-ligament knee reconstruction techniques often involve the creation of several bone tunnels for various reconstruction grafts. A critical step in this procedure is to avoid short tunnels or convergences among them. Currently, no specific template guide to reproduce these angulations has been reported in the literature, and the success of the technique still depends on the experience of the surgeon. The aim of this study is to analyze the accuracy and reliability of 3D-printed patient-specific instrumentation (PSI) for lateral and medial anatomical knee reconstructions. Methods Ten cadaveric knees were scanned by computed tomography (CT). Using specific computer software, anatomical femoral attachments were identified: (1) on the lateral side the lateral collateral ligament (LCL) and the popliteal tendon (PT) and (2) on the medial side the medial collateral ligament (MCL) and the posterior oblique ligament (POL). Four bone tunnels were planned for each knee, and PSI with different directions were designed as templates to reproduce the planned tunnels during surgery. Twenty 3D-printed PSI were used: ten were tailored to the medial side for reconstructing MCL and POL tunnels, and the other ten were tailored to the lateral side for reconstructing LCL and PT tunnels. Postoperative CT scans were made for each cadaveric knee. The accuracy of the use of 3D-printed PSI was assessed by superimposing post-operative CT images onto pre-operative images and analyzing the deviation of tunnels performed based on the planning, specifically the entry point and the angular deviations. Results The median entry point deviations for the tunnels were as follows: LCL tunnel, 1.88 mm (interquartile range (IQR) 2.2 mm); PT tunnel, 2.93 mm ( IQR 1.17 mm); MCL tunnel, 1.93 mm ( IQR 4.26 mm); and POL tunnel, 2.16 mm ( IQR 2.39). The median angular deviations for the tunnels were as follows: LCL tunnel, 2.42° ( IQR 6.49°); PT tunnel, 4.15° ( IQR 6.68); MCL tunnel, 4.50° ( IQR 6.34°); and POL tunnel, 4.69° ( IQR 3.1°). No statistically significant differences were found in either the entry point or the angular deviation among the different bone tunnels. Conclusion The use of 3D-printed PSI for lateral and medial anatomical knee reconstructions provides accurate and reproducible results and may be a promising tool for use in clinical practice.

Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis. Conversely, lipolysis was decreased and lipogenesis was increased in mice expressing a mutant hyperactive form of CDK4 (CDK4(R24C)). A global kinome analysis of CDK4-deficient mice following insulin stimulation revealed that insulin signaling is impaired in these animals. We determined that insulin activates the CCND3-CDK4 complex, which in turn phosphorylates insulin receptor substrate 2 (IRS2) at serine 388, thereby creating a positive feedback loop that maintains adipocyte insulin signaling. Furthermore, we found that CCND3 expression and IRS2 serine 388 phosphorylation are increased in human obese subjects. Together, our results demonstrate that CDK4 is a major regulator of insulin signaling in WAT.

Abstract The energetic demands of proliferating cells during tumorigenesis require close coordination between the cell cycle and metabolism. While CDK4 is known for its role in cell proliferation, its metabolic function in cancer, particularly in triple-negative breast cancer (TNBC), remains unclear. Our study, using genetic and pharmacological approaches, reveals that CDK4 inactivation only modestly impacts TNBC cell proliferation and tumor formation. Notably, CDK4 depletion or long-term CDK4/6 inhibition confers resistance to apoptosis in TNBC cells. Mechanistically, CDK4 enhances mitochondria-endoplasmic reticulum contact (MERCs) formation, promoting mitochondrial fission and ER-mitochondrial calcium signaling, which are crucial for TNBC metabolic flexibility. Phosphoproteomic analysis identified CDK4’s role in regulating PKA activity at MERCs. In this work, we highlight CDK4’s role in mitochondrial apoptosis inhibition and suggest that targeting MERCs-associated metabolic shifts could enhance TNBC therapy.