24 research outputs found

    Disrupting Circadian Homeostasis of Sympathetic Signaling Promotes Tumor Development in Mice

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    and why disruption of circadian rhythm may lead to tumorigenesis. oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice. is a clock-controlled physiological function. The central circadian clock paces extracellular mitogenic signals that drive peripheral clock-controlled expression of key cell cycle and tumor suppressor genes to generate a circadian rhythm in cell proliferation. Frequent disruption of circadian rhythm is an important tumor promoting factor

    Discovertebral (Andersson) lesions of the spine in ankylosing spondylitis revisited

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    A well-known complication in patients with ankylosing spondylitis (AS) is the development of localised vertebral or discovertebral lesions of the spine, which was first described by Andersson in 1937. Since then, many different terms are used in literature to refer to these localised lesions of the spine, including the eponym ‘Andersson lesion’ (AL). The use of different terms reflects an ongoing debate on the exact aetiology of the AL. In the current study, we performed an extensive review of the literature in order to align communication on aetiology, diagnosis and management between treating physicians. AL may result from inflammation or (stress-) fractures of the complete ankylosed spine. There is no evidence for an infectious origin. Regardless of the exact aetiology, a final common pathway exists, in which mechanical stresses prevent the lesion from fusion and provoke the development of pseudarthrosis. The diagnosis of AL is established on conventional radiography, but computed tomography and magnetic resonance imaging both provide additional information. There is no indication for a diagnostic biopsy. Surgical instrumentation and fusion is considered the principle management in symptomatic AL that fails to resolve from a conservative treatment. We advise to use the term Andersson lesion for these spinal lesions in patients with AS

    Checkpoint-Dependent and -Independent Roles of Swi3 in Replication Fork Recovery and Sister Chromatid Cohesion in Fission Yeast

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    Multiple genome maintenance processes are coordinated at the replication fork to preserve genomic integrity. How eukaryotic cells accomplish such a coordination is unknown. Swi1 and Swi3 form the replication fork protection complex and are involved in various processes including stabilization of replication forks, activation of the Cds1 checkpoint kinase and establishment of sister chromatid cohesion in fission yeast. However, the mechanisms by which the Swi1–Swi3 complex achieves and coordinates these tasks are not well understood. Here, we describe the identification of separation-of-function mutants of Swi3, aimed at dissecting the molecular pathways that require Swi1–Swi3. Unlike swi3 deletion mutants, the separation-of-function mutants were not sensitive to agents that stall replication forks. However, they were highly sensitive to camptothecin that induces replication fork breakage. In addition, these mutants were defective in replication fork regeneration and sister chromatid cohesion. Interestingly, unlike swi3-deleted cell, the separation-of-functions mutants were proficient in the activation of the replication checkpoint, but their fork regeneration defects were more severe than those of checkpoint mutants including cds1Δ, chk1Δ and rad3Δ. These results suggest that, while Swi3 mediates full activation of the replication checkpoint in response to stalled replication forks, Swi3 activates a checkpoint-independent pathway to facilitate recovery of collapsed replication forks and the establishment of sister chromatid cohesion. Thus, our separation-of-function alleles provide new insight into understanding the multiple roles of Swi1-Swi3 in fork protection during DNA replication, and into understanding how replication forks are maintained in response to different genotoxic agents

    ICAR: endoscopic skull‐base surgery

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    International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

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    Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS
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