11 research outputs found

    LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy

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    Long non‐coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here, we investigated the role of a novel vascular endothelial‐associated lncRNA (VEAL2) in regulating endothelial permeability. Precise editing of veal2 loci in zebrafish (veal2 (gib005Δ8/+)) induced cranial hemorrhage. In vitro and in vivo studies revealed that veal2 competes with diacylglycerol for interaction with protein kinase C beta‐b (Prkcbb) and regulates its kinase activity. Using PRKCB2 as bait, we identified functional ortholog of veal2 in humans from HUVECs and named it as VEAL2. Overexpression and knockdown of VEAL2 affected tubulogenesis and permeability in HUVECs. VEAL2 was differentially expressed in choroid tissue in eye and blood from patients with diabetic retinopathy, a disease where PRKCB2 is known to be hyperactivated. Further, VEAL2 could rescue the effects of PRKCB2‐mediated turnover of endothelial junctional proteins thus reducing hyperpermeability in hyperglycemic HUVEC model of diabetic retinopathy. Based on evidence from zebrafish and hyperglycemic HUVEC models and diabetic retinopathy patients, we report a hitherto unknown VEAL2 lncRNA‐mediated regulation of PRKCB2, for modulating junctional dynamics and maintenance of endothelial permeability

    Design of a recognition system for special Malaysian car plates using stroke analysis

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    Car-plate recognition systems are used commercially, both in the overseas and locally. In Malaysia, however, the usage of car-plate recognition systems is restricted to the ordinary car-plates. This means that the system is unable to detect car-plates assigned for taxis, as well as special types of car-plates. These special types of car-plates use special words to designate special occasions such as SUKOM, Putrajaya, Tiara, etc., instead of using the normal alphabets. Therefore, this system is aimed for implementation of a recognition system for Special Malaysian car plates using the recognition technique of Stroke Analysis. The system consists of several modules. The system is an offline system where the images gathered are first preprocessed using image processing techniques. Next, the image is converted into a binary image. After that, the boundary of the car plate characters is extracted. Then the image is passed through a stroke analysis system, i.e. the main module of the system. Here, the strokes for the characters are extracted and matched to a listed sequence. Finally, the system displays the output in ASCII format

    Primary Definitive Treatment versus Ureteric Stenting in the Management of Acute Ureteric Colic: A Cost-Effectiveness Analysis

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    Objectives: To analyze the differences in cost-effectiveness between primary ureteroscopy and ureteric stenting in patients with ureteric calculi in the emergency setting. Patients and Methods: Patients requiring emergency intervention for a ureteric calculus at a tertiary centre were analysed between January and December 2019. The total secondary care cost included the cost of the procedure, inpatient hospital bed days, emergency department (A&E) reattendances, ancillary procedures and any secondary definitive procedure. Results: A total of 244 patients were included. Patients underwent ureteric stenting (62.3%) or primary treatment (37.7%), including primary ureteroscopy (URS) (34%) and shock wave lithotripsy (SWL) (3.6%). The total secondary care cost was more significant in the ureteric stenting group (GBP 4485.42 vs. GBP 3536.83; p = 0.65), though not statistically significant. While mean procedural costs for primary treatment were significantly higher (GBP 2605.27 vs. GBP 1729.00; p p p = 0.02) and a significantly greater cost per patient related to revisits to A&E (GBP 61.05 vs. GBP 20.87; p < 0.001). Conclusion: Primary definitive treatment for patients with acute ureteric colic, although associated with higher procedural costs than ureteric stenting, infers a significant reduction in additional expenses, notably related to fewer A&E attendances. This is particularly relevant in the COVID-19 era, where it is crucial to avoid unnecessary attendances to A&E and reduce the backlog of delayed definitive procedures. Primary treatment should be considered concordance with clinical judgement and factors such as patient preference, equipment availability and operator experience

    A genome-wide map of circular RNAs in adult zebrafish

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    Circular RNAs are a new addition to the growing list of diverse species of RNAs that are formed by covalent linked 3' and 5' end forming a closed loop structure. Circular RNAs are characteristically resistant to exonuclease treatment and are relatively stable to linear transcripts. Circular RNAs are formed by alternate splicing mechanism but do not follow the canonical order of exons. Backsplice junctions are unique to circRNAs.  CircRNAs are shown to possess potential to act as miRNA sponges and control transcription of mRNAs. CircRNAs are also reported as biomarkers for the disease like Alzheimer's, Parkinson's and cancer. A huge number of circRNA transcripts have been identified in model organisms including C.elegans, mouse, Drosophila as well as human. But there are no circular RNAs reported in zebrafish that is a very good model to study developmental stages, cardiovascular and blood-related disorders. In order to use zebrafish as a model organism and study the role of circRNAs in disease, we have used in-house generated RNA-sequencing data for five tissues including blood, brain, muscle, gills and heart. We discarded the reads mapped contiguously and full length over reference genome and identified back-splice junctions for putative circRNA transcripts. We identified a total of 3428 circRNA junctions out of which 78% were tissue specific. We validated 22 selected candidates for 5 tissues based on literature significance. We quantitatively analysed 5 tissue-enriched candidates using Real-time PCR. We also observed that major proportion of circRNAs is originating from protein coding loci. These circRNAs could be used to further study their role in hematopoietic and cardiovascular diseases

    Emergency Primary Ureteroscopy for Acute Ureteric Colic&mdash;From Guidelines to Practice

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    Objective: To review the factors that may influence the ability to achieve the present guidelines&rsquo; recommendations in a well-resourced tertiary centre. According to current National Institute for Health and Care Excellence (NICE) guidelines, definitive treatment (primary ureteroscopy (URS) or shock wave lithotripsy (ESWL)) should be offered to patients with symptomatic renal colic that are unlikely to pass the stone within 48 h of diagnosis. Methods: Retrospective review of all patients presenting to the emergency department between January and December 2019 with a ureteric or renal stone diagnosis. The rate of emergency intervention, risk factors for intervention and outcomes were compared between patients who were treated by primary definitive surgery vs. primary symptom relief by urethral stenting alone. Results: A total of 244 patients required surgical management for symptomatic ureteric colic without symptoms of urinary infection. Of those, 92 patients (37.7%) underwent definitive treatment by either primary URS (82 patients) or ESWL (9 patients). The mean time for the procedure was 25.5 h (range: 1&ndash;118). Patients who underwent primary definitive treatment were likelier to have smaller and distally located stones than the primary stenting group. Primary ureteroscopy was more likely to be performed in a supervised setting than emergency stenting. Conclusions: Although definitive treatment carries high success rates, in a high-volume tertiary referral centre, it may not be feasible to offer it to all patients, with emergency stenting providing a safe and quick interim measure. Factors determining the ability to provide definitive treatment are stone location, stone size and resident supervision in theatre

    Asymptomatic reinfection in two healthcare workers from India with genetically distinct SARS-CoV-2

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    Reinfection of SARS-CoV-2 is an apparently rare entity and only a few cases have been reported from across the world with the genetic characterization of the virus, differentiating reinfection from persistent virus shedding. These cases, therefore, provide unique insights into the long term protective immunity to SARS-CoV-2. The earlier reports suggest that patients were symptomatic in either one or both the episodes of infection. Here we report a unique case of asymptomatic SARS-CoV-2 reinfection in two healthcare workers from India identified in routine surveillance. Genome sequencing of the virus suggests that genetically distinct SARS-CoV-2 caused the infections. Our analysis demonstrates that asymptomatic reinfection could potentially be an under-reported entity with implications in long term surveillance of SARS-CoV-2 infections. This report also highlights the need for genomic surveillance of healthcare workers who are potentially not only at higher risk for primary infections but also for reinfections
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