Single Production of Kojic Acid by Aspergillus flavus and the Revision of Flufuran

Timor Island is very hot and dry due to the high intensity of sunlight experienced throughout the year. The endophytic fungi Aspergillus flavus had been isolated from medicinal plants such as Catharanthus roseus, Annona squamosa and Curcuma xanthorisa. The endophytic fungi A. flavus from each plant was cultivated on solid rice media and then analyzed for its capability for producing kojic acid. The production of kojic acid was analyzed by HPLC; the highest amount of kojic acid was observed from the endophytic fungi A. flavus, isolated from the stem of Catharanthus roseus, followed by A. flavus from Annona squamosa and Curcuma xanthorisa. Simple VLC fractionation of the extract of A. flavus from C.roseus led to the isolation of around 11.1 g of pure kojic acid. The structure of kojic acid (1) was confirmed by NMR and MS spectroscopic data. A comparison of the NMR data with the literature supported the revision of the natural product flufuran to kojic acid. To the best of our knowledge, this is the first report of a strain of endophytic fungi producing only kojic acid without any other toxic metabolites such as alfatoxins. Therefore, this Aspergillus flavus strain can be applied as a potential producer of kojic acid for industrial use

Genetic determinants of haemolysis in sickle cell anaemia

Haemolytic anaemia is variable among patients with sickle cell anaemia and can be estimated by reticulocyte count, lactate dehydrogenase, aspartate aminotransferase and bilirubin levels. Using principal component analysis of these measurements we computed a haemolytic score that we used as a subphenotype in a genome-wide association study. We identified in one cohort and replicated in two additional cohorts the association of a single nucleotide polymorphism in NPRL3 (rs7203560; chr16p13·3) (P = 6·04 × 10-07). This association was validated by targeted genotyping in a fourth independent cohort. The HBA1/HBA2 regulatory elements, hypersensitive sites (HS)-33, HS-40 and HS-48 are located in introns of NPRL3. Rs7203560 was in perfect linkage disequilibrium (LD) with rs9926112 (r2 = 1) and in strong LD with rs7197554 (r2 = 0·75) and rs13336641 (r2 = 0·77); the latter is located between HS-33 and HS-40 sites and next to a CTCF binding site. The minor allele for rs7203560 was associated with the -∝3·7thalassaemia gene deletion. When adjusting for HbF and ∝ thalassaemia, the association of NPRL3 with the haemolytic score was significant (P = 0·00375) and remained significant when examining only cases without gene deletion∝ thalassaemia (P = 0·02463). Perhaps by independently down-regulating expression of the HBA1/HBA2 genes, variants of the HBA1/HBA2 gene regulatory loci, tagged by rs7203560, reduce haemolysis in sickle cell anaemia. © 2013 Blackwell Publishing Ltd

Transradial Versus Transfemoral Access for Woven EndoBridge (WEB) Embolization of Intracranial Aneurysms: A Propensity-Score Matched Multicenter Study (P1-1.Virtual)

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The Woven EndoBridge (WEB) device for the treatment of Intracranial Aneurysms: A Decade of Lessons Learned and Changes in Practice from the WorldwideWEB Consortium (P1-1.Virtual)

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Transradial versus transfemoral access for embolization of intracranial aneurysms with the Woven EndoBridge device: a propensity score–matched study

OBJECTIVE Transradial access (TRA) is commonly utilized in neurointerventional procedures. This study compared the technical and clinical outcomes of the use of TRA versus those of transfemoral access (TFA) for intracranial aneurysm embolization with the Woven EndoBridge (WEB) device. METHODS This is a secondary analysis of the Worldwide WEB Consortium, which comprises multicenter data related to adult patients with intracranial aneurysms who were managed with the WEB device. These aneurysms were categorized into two groups: those who were treated with TRA or TFA. Patient and aneurysm characteristics and technical and clinical outcomes were compared between groups. Propensity score matching (PSM) was used to match groups according to the following baseline characteristics: age, sex, subarachnoid hemorrhage, aneurysm location, bifurcation aneurysm, aneurysm with incorporated branch, neck width, aspect ratio, dome width, and elapsed time since the last follow-up imaging evaluation. RESULTS This study included 682 intracranial aneurysms (median [interquartile range] age 61.3 [53.0–68.0] years), of which 561 were treated with TFA and 121 with TRA. PSM resulted in 65 matched pairs. After PSM, both groups had similar characteristics, angiographic and functional outcomes, and rates of retreatment, thromboembolic and hemorrhagic complications, and death. TFA was associated with longer procedure length (median 96.5 minutes vs 72.0 minutes, p = 0.006) and fluoroscopy time (28.2 minutes vs 24.8 minutes, p = 0.037) as compared with TRA. On the other hand, deployment issues were more common in those treated with TRA, but none resulted in permanent complications. CONCLUSIONS TRA has comparable outcomes, with shorter procedure and fluoroscopy time, to TFA for aneurysm embolization with the WEB device

Comparing treatment outcomes of various intracranial bifurcation aneurysms locations using the Woven EndoBridge (WEB) device

BackgroundThe Woven EndoBridge (WEB) device has Food and Drug Administration approval for treatment of wide-necked intracranial bifurcation aneurysms. The WEB device has been shown to result in adequate occlusion in bifurcation aneurysms overall, but its usefulness in the individual bifurcation locations has been evaluated separately only in few case series, which were limited by small sample sizes.ObjectiveTo compare angiographic and clinical outcomes after treatment of bifurcation aneurysms at various locations, including anterior communicating artery (AComA), anterior cerebral artery (ACA) bifurcation distal to AComA, basilar tip, internal carotid artery (ICA) bifurcation, and middle cerebral artery (MCA) bifurcation aneurysms using the WEB device.MethodsA retrospective cohort analysis was conducted at 22 academic institutions worldwide to compare treatment outcomes of patients with intracranial bifurcation aneurysms using the WEB device. Data include patient and aneurysm characteristics, procedural details, angiographic and functional outcomes, and complications.ResultsA total of 572 aneurysms were included. MCA (36%), AComA (35.7%), and basilar tip (18.9%) aneurysms were most common. The rate of adequate aneurysm occlusion was significantly higher for basilar tip (91.6%) and ICA bifurcation (96.7%) aneurysms and lower for ACA bifurcation (71.4%) and AComA (80.6%) aneurysms (p=0.04).ConclusionTo our knowledge, this is the most extensive study to date that compares the treatment of different intracranial bifurcation aneurysms using the WEB device. Basilar tip and ICA bifurcation aneurysms showed significantly higher rates of aneurysm occlusion than other locations

Multicenter Study for the Treatment of Sidewall versus Bifurcation Intracranial Aneurysms with Use of Woven EndoBridge (WEB)

Background: The Woven EndoBridge (WEB) device was explicitly designed for wide- neck intracranial bifurcation aneurysms. Small-scale reports have evaluated the off-label use of WEB devices for the treatment of sidewall aneurysms, with promising outcomes. Purpose: To compare the angiographic and clinical outcomes of the WEB device for the treatment of sidewall aneurysms compared with the treatment of bifurcation aneurysms. Materials and Methods: A retrospective review of the WorldWideWEB Consortium, a synthesis of retrospective databases spanning from January 2011 to June 2021 at 22 academic institutions in North America, South America, and Europe, was performed to identify patients with intracranial aneurysms treated with the WEB device. Characteristics and outcomes were compared between bifurcation and sidewall aneurysms. Propensity score matching (PSM) was used to match by age, pretreatment ordinal modified Rankin Scale score, ruptured aneurysms, location of aneurysm, multiple aneurysms, prior treatment, neck, height, dome width, daughter sac, and incorporated branch. Results: A total of 683 intracranial aneurysms were treated using the WEB device in 671 patients (median age, 61 years [IQR, 53-68 years]; male-to-female ratio, 1:2.5). Of those, 572 were bifurcation aneurysms and 111 were sidewall aneurysms. PSM was performed, resulting in 91 bifurcation and sidewall aneurysms pairs. No significant difference was observed in occlusion status at last follow-up, deployment success, or complication rates between the two groups. Conclusion: No significantly different outcomes were observed following the off-label use of the Woven EndoBridge, or WEB, device for treatment of sidewall aneurysms compared with bifurcation aneurysms. The correct characterization of the sidewall aneurysm location, neck angle, and size is crucial for successful treatment and lower retreatment rate. (C) RSNA, 202

Stent-assisted Woven EndoBridge device for the treatment of intracranial aneurysms: an international multicenter study

OBJECTIVE The Woven EndoBridge (WEB) device is an intrasaccular flow disruptor designed for wide-necked bifurcation aneurysms. These aneurysms may require the use of a concomitant stent. The objective of this study was to determine the clinical and radiological outcomes of patients undergoing stent-assisted WEB treatment. In addition, the authors also sought to determine the predictors of a concomitant stent in aneurysms treated with the WEB device. METHODS The data for this study were taken from the WorldWideWEB Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups based on treatment: stent-assisted WEB and WEB device alone. The authors compared clinical and radiological outcomes of both groups. Univariable and multivariable binary logistic regression analyses were performed to determine factors that predispose to stent use. RESULTS The study included 691 intracranial aneurysms (31 with stents and 660 without stents) treated with the WEB device. The adequate occlusion status did not differ between the two groups at the latest follow-up (83.3% vs 85.6%, p = 0.915). Patients who underwent stenting had more thromboembolic (32.3% vs 6.5%, p < 0.001) and procedural (16.1% vs 3.0%, p < 0.001) complications. Aneurysms treated with a concomitant stent had wider necks, greater heights, and lower dome-to-neck ratios. Increasing neck size was the only significant predictor for stent use. CONCLUSIONS This study demonstrates that there is no difference in the degree of aneurysm occlusion between the two groups; however, complications were more frequent in the stent group. In addition, a wider aneurysm neck predisposes to stent assistance in WEB-treated aneurysms