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1.
Am Surg ; 90(4): 502-509, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38124318

ABSTRACT

BACKGROUND: This study aimed to quantify the impact of intermittent visual occlusion via stroboscopic goggles on suture accuracy and precision. METHODS: This crossover study recruited and randomized 72 graduate students to train with stroboscopic goggles early or late in structured suture practice. Participants completed assessments of 10 running sutures with 2 training sessions between baseline and follow-up assessments. The procedure was repeated after crossover. Suture photos were analyzed using ImageJ. Total error among all measurements represented accuracy; standard deviation of error represented precision. Intra- and inter-group trends were identified with Wilcoxon rank-sum tests. RESULTS: Both groups significantly improved in accuracy in the sessions immediately following goggle use, but the group that used goggles later in training continued improving in accuracy and precision while the group that trained with stroboscopic goggles early plateaued. CONCLUSIONS: Using stroboscopic goggles showed quantifiable benefit for augmenting suture training with greatest effect after initial skill acquisition is completed.


Subject(s)
Eye Protective Devices , Sutures , Humans , Cross-Over Studies , Neurosurgical Procedures , Statistics, Nonparametric
2.
Nat Commun ; 14(1): 8444, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38114498

ABSTRACT

RNA splicing is an important biological process associated with cancer initiation and progression. However, the contribution of alternative splicing to pancreatic cancer (PDAC) development is not well understood. Here, we identify an enrichment of RNA binding proteins (RBPs) involved in splicing regulation linked to PDAC progression from a forward genetic screen using Sleeping Beauty insertional mutagenesis in a mouse model of pancreatic cancer. We demonstrate downregulation of RBFOX2, an RBP of the FOX family, promotes pancreatic cancer progression and liver metastasis. Specifically, we show RBFOX2 regulates exon splicing events in transcripts encoding proteins involved in cytoskeletal remodeling programs. These exons are differentially spliced in PDAC patients, with enhanced exon skipping in the classical subtype for several RBFOX2 targets. RBFOX2 mediated splicing of ABI1, encoding the Abelson-interactor 1 adapter protein, controls the abundance and localization of ABI1 protein isoforms in pancreatic cancer cells and promotes the relocalization of ABI1 from the cytoplasm to the periphery of migrating cells. Using splice-switching antisense oligonucleotides (AONs) we demonstrate the ABI1 ∆Ex9 isoform enhances cell migration. Together, our data identify a role for RBFOX2 in promoting PDAC progression through alternative splicing regulation.


Subject(s)
Alternative Splicing , Pancreatic Neoplasms , Mice , Animals , Humans , Alternative Splicing/genetics , RNA Splicing Factors/genetics , RNA Splicing Factors/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , RNA Splicing , Protein Isoforms/genetics , Pancreatic Neoplasms/genetics , Repressor Proteins/metabolism , Cytoskeletal Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism
3.
Int J Mol Sci ; 24(4)2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36835484

ABSTRACT

The prominent flavonoids apigenin and chrysin have been demonstrated to have systemic benefits. Our previous work was first to establish the impact of apigenin and chrysin on cellular transcriptome. In the current study, we have revealed the ability of apigenin and chrysin to alter the cellular metabolome based on our untargeted metabolomics. Based on our metabolomics data, both these structurally related flavonoids demonstrate diverging and converging properties. Apigenin demonstrated the potential to possess anti-inflammatory and vasorelaxant properties through the upregulation of intermediate metabolites of alpha-linolenic acid and linoleic acid pathways. Chrysin, on the other hand, exhibited abilities to inhibit protein and pyrimidine synthesis along with downregulation of gluconeogenesis pathways based on the altered metabolites detected. Chrysin-mediated metabolite changes are mostly due to its ability to modulate L-alanine metabolism and the urea cycle. On the other hand, both the flavonoids also demonstrated converging properties. Apigenin and chrysin were able to downregulate metabolites involved in cholesterol biosynthesis and uric acid synthesis, namely 7-dehydrocholesterol and xanthosine, respectively. This work will provide understanding regarding the diverse therapeutic potential of these naturally occurring flavonoids and help us in curbing an array of metabolic complications.


Subject(s)
Apigenin , Flavonoids , Apigenin/pharmacology , Flavonoids/pharmacology , Up-Regulation , Metabolomics
4.
J Pers Med ; 12(11)2022 Nov 03.
Article in English | MEDLINE | ID: mdl-36579545

ABSTRACT

Glucocorticoids are not only endogenous hormones but are also administered exogenously as an anti-inflammatory and immunosuppressant for their long-term beneficial and lifesaving effects. Because of their potent anti-inflammatory property and ability to curb the cytokines, they are administered as lifesaving steroids. This property is not only made use of in the cardiovascular system but also in other major organ systems and networks. There is a fine line between their use as a protective anti-inflammatory and a steroid that could cause overuse-induced complications in major organ systems including the cardiovascular system. Studies conducted in the cardiovascular system demonstrate that glucocorticoids are required for growth and development and also for offering protection against inflammatory signals. Excess or long-term glucocorticoid administration could alter cardiac metabolism and health. The endogenous dysregulated state due to excess endogenous glucocorticoid release from the adrenals as seen with Cushing's syndrome or excess exogenous glucocorticoid administration leading to Cushing's-like condition show a similar impact on the cardiovascular system. This review highlights the importance of maintaining a glucocorticoid balance whether it is endogenous and exogenous in regulating cardiovascular health.

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