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  • Ovid Technologies (Wolters Kluwer Health)  (2)
  • Medicine  (2)
  • 1
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 125, No. Suppl_1 ( 2019-08-02)
    Abstract: Background: TBX5 mutations cause Holt-Oram syndrome (HOS) characterized by upper limb and cardiac malformations, but can also contribute to early-onset of atrial fibrillation. Focusing on miRNAs involved in TBX5 regulatory circuits with a cardiac relevant role, we identified miR-182-5p, belonging to miR-183 cluster, found upregulated in Tbx5-depleted hearts of mouse and zebrafish embryos. Methods: To functionally analyse the miR-182-5p role in developing heart, miR-182-5p was dysregulated in zebrafish zygotes of Tg(Myl7:EGFP) and Tg(myl7:gCaMP) transgenic lines. To stably deregulate miR-182-5p in zebrafish heart we exploited the Gal4/UAS system to restrict the miR-182 expression into cardiac context. For physiological analyses we performed the mechanogram of cardiac contraction and electrocardiogram recording. To understand miR-182-5p downstream regulation, in silico analyses, followed by ddPCR/real-time quantifications on dissected zebrafish hearts and rescue experiments both in transient and stable miR-182-5p overexpressing zebrafish embryos were performed. Results: Depletion of Tbx5 from cardiomyocytes increased the expression of miR-182 cluster family that is controlled by Kruppel-like factor 4 (KLF4), a transcription factor repressed by Tbx5. Both transient and stable upregulation of miR-182 in zebrafish affect heart morphology, calcium handling and the onset of arrhythmia while its cardiac-specific downregulation decreases cardiac defects in zebrafish HOS hearts. Expression analyses on selected miR-182-5p putative targets revealed that several calcium channel proteins resulted downregulated in miR-182-5p overexpressing hearts. Transgenic zebrafish line stably overexpressing miR-182-5p in the heart manifested arrhythmia overtime with or without cardiac structural defects. Conclusion: We identified miR-182-5p as a potential suitable target to interfere in the circuit between upstream genetic abnormalities and downstream effectors leading to arrhythmia occurrence.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467838-X
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  • 2
    In: Cornea, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 7 ( 2023-07), p. 815-820
    Abstract: The purpose of the study was to compare the clinical outcomes of large 9.0-mm diameter and conventional 8.0-mm big-bubble deep anterior lamellar keratoplasty (DALK). Methods: In this comparative, retrospective interventional case series, medical records of 124 cases of large 9.0-mm diameter DALK from January 2017 to December 2019 and 133 conventional 8.0-mm DALK from January 2014 to December 2016 performed by a single surgeon for the indication of keratoconus were reviewed. Main outcome measures were best spectacle-corrected visual acuity (BSCVA), refractive astigmatism (RA), and postoperative complication rates. Results: Postoperative logarithm of the minimum angle of resolution BSCVA did not significantly differ between 9.0-mm and 8.0-mm DALK at any time points. Although the cumulative percentage of eyes achieving Snellen BSCVA of 20/40 or better was comparable between groups (9.0-mm DALK: 93%, 8.0-mm DALK: 90%, P = 0.571), the cumulative percentage of eyes achieving 20/20 or better (9.0-mm DALK: 44%, 8.0-mm DALK: 26%, P = 0.01) and 20/25 or better (9.0-mm DALK: 74%, 8.0-mm DALK: 59%, P = 0.03) was significantly higher in the 9.0-mm DALK group. RA was significantly lower in the 9.0-mm DALK group compared with the 8.0-mm DALK group during all time points ( P 〈 0.001). The percentage of eyes with RA less than or equal to 4.0 D was significantly lower in the 9.0-mm DALK patients (90%) compared with in 8.0-mm DALK group (72%) ( P = 0.002). Postoperative complication rates were similar between groups. Conclusions: Compared with conventional 8.0-mm DALK, large 9.0-mm DALK can provide superior visual outcomes at higher levels of Snellen BSCVA and significantly lower degrees of astigmatism without an increased risk of immune rejection and graft failure.
    Type of Medium: Online Resource
    ISSN: 0277-3740
    RVK:
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2045943-9
    Location Call Number Limitation Availability
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