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Yosra Bouyacoub Mariem Ouederni Marwa Sayeb Aschraf Chedli Mariem Chargui 《Ophthalmic genetics》2013,34(4):329-337
ABSTRACTPurpose: We report the clinical features and the mutational analysis in a large Tunisian family with granular corneal dystrophy type I (GCD1).Patients and Methods: Thirty-three members of the Tunisian family underwent a complete ophthalmologic examination. DNA extraction and direct Sanger sequencing of the exons 4 and 12 of transforming growth factor β Induced (TGFBI) gene was performed for 42 members. For the molecular modeling of TGFBI protein, we used pGenTHREADER method to identify templates, 3D-EXPRESSO program to align sequences, MODELLER to get a homology model for the FAS1 (fasciclin-like) domains and finally NOMAD-ref web server for the energy minimization.Results: The diagnosis of GCD1 was clinically and genetically confirmed. Sequencing of exon 4 of TGFBI gene revealed the p.[R124S] mutation at heterozygous and homozygous states in patients with different clinical severities. Visual acuity was severely affected in the homozygous patients leading to a first penetrating keratoplasty. Recurrence occurred rapidly, began in the seat of the corneal stitches and remained superficial up to 40 years after the graft. For heterozygous cases, visual acuity ranged from 6/10 to 10/10. Corneal opacities were deeper and predominating in the stromal center. According to bioinformatic analysis, this mutation likely perturbs the protein physicochemical properties and reduces its solubility without structural modification.Conclusions: Our study describes for the first time phenotype-genotype correlation in a large Tunisian family with GCDI and illustrates for the first time clinical and histopathological presentation of homozygous p.[R124S] mutation. These results help to understand pathophysiology of the disease. 相似文献
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Peter Ferenci Stefan Bourgeois Peter Buggisch Suzanne Norris Manuela Curescu Dominique Larrey Fiona Marra Henning Kleine Patrick Dorr Mariem Charafeddine Eric Crown Mark Bondin David Back Robert Flisiak 《Journal of viral hepatitis》2019,26(6):685-696
Ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) regimens show high efficacy and good tolerability in clinical trials for chronic hepatitis C virus (HCV) genotypes (GT) 1 or 4. To evaluate whether these results translate to clinical practice, data were pooled from observational studies across 13 countries. Treatment‐naïve or ‐experienced patients, with or without cirrhosis, received OBV/PTV/r ± DSV ± RBV according to approved local labels and clinical practice. Sustained virologic response at post‐treatment Week 12 (SVR12), adverse events (AEs) and comedication management were assessed for patients initiating treatment before 1 June 2017. The safety population included 3850 patients who received ≥1 dose of study drug. The core population (N = 3808) further excluded patients with unknown GT or cirrhosis status, or who received off‐label treatment. Patients had HCV GT1a (n = 732; 19%), GT1b (n = 2619; 69%) or GT4 (n = 457; 12%). In 3546 patients with sufficient follow‐up data at post‐treatment Week 12, the SVR12 rate was 96% (n/N = 3401/3546 [95% CI 95.2‐96.5]). In patients with or without cirrhosis, SVR12 was comparable (96%). In patients with HCV GT1a, GT1b or GT4, SVR12 rates were 93%, 97% and 94%. In GT1b‐infected patients with planned treatment for 8 weeks, SVR12 was 96%. In patients with ≥1 comorbidity (67%), SVR12 was 95%. 58% of patients received ≥1 comedication, and there was minimal impact on SVR12 rates using comedications for peptic ulcers and gastro‐esophageal reflux disease, statins, antipsychotics or antiepileptics. Most comedications were maintained during treatment although 58% of patients changed their statin medication. AEs and serious AEs occurred in 26% and 3% of patients. Post‐baseline Grade 3‐4 laboratory abnormalities were rare (<3%), and discontinuation rates were low (<4%). Real‐world evidence confirms the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with HCV GT1 or GT4, regardless of common comorbidities or comedications, and is consistent with clinical trial results. Adverse safety outcomes may be limited by underreporting in the real‐world setting. 相似文献
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Fred Poordad RuiSarmento E. Castro Armen Asatryan Humberto Aguilar Patrice Cacoub Douglas Dieterich Rui Tato Marinho Armando Carvalho Asma Siddique Yiran Bonnie Hu Mariem Charafeddine Mark Bondin Nader Khan Daniel E. Cohen Franco Felizarta 《Journal of viral hepatitis》2020,27(5):497-504
The 3‐DAA regimen consisting of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) has shown high sustained virologic response rates (~95%) in phase 3 clinical trials including >2300 HCV genotype 1–infected patients. Real‐world evidence studies have confirmed the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with chronic HCV genotype 1 infection and are consistent with clinical trial results. TOPAZ‐I and TOPAZ‐II are ongoing phase 3b trials, assessing safety, efficacy and long‐term progression of liver disease and clinical outcomes for up to 5 years post‐treatment in patients treated with OBV/PTV/r + DSV ± RBV. High rates of sustained virologic response (SVR) were achieved regardless of presence or absence of cirrhosis.In this report, we assessed the long‐term progression of liver disease and incidence of clinical outcomes up to 3 years of post‐treatment follow‐up in patients with chronic HCV GT1 infection who were treated with (OBV/PTV/r + DSV) ± RBV in the TOPAZ‐I and TOPAZ‐II studies. Improvements were observed in liver disease markers including FIB‐4, METAVIR and Child‐Pugh scores as well as platelet counts. Clinical outcomes related to long‐term progression of liver disease such as liver decompensation were infrequent (<1%). Hepatocellular carcinoma (HCC) occurred in 1.4% of cirrhotic patients. 相似文献
75.
Ben Dhia Rihab Aissi Mouna Mhiri Mariem Frih Ayed Mahbouba 《Journal of neurovirology》2021,27(5):787-790
Journal of NeuroVirology - Neurological cytomegalovirus (CMV) infections especially extensive longitudinal myelitis are extremely rare in immunocompetent adults. However, we hereby report a case of... 相似文献
76.
Khadija Mzoughi Ihsen Zairi Mariem Jabeur Sondos Kraiem 《Clinical and experimental hypertension (New York, N.Y. : 1993)》2013,35(8):793-796
ABSTRACTHeart rate variability (HRV) is an independent indicator of increased mortality in patients with myocardial infarction and congestive heart failure. The effects of fasting on the HRV are not known in hypertensive patients. Therefore, studying the effects of Ramadan fasting on hypertensive patients’ HRV seems reasonable to address.We conducted a prospective study including 20 hypertensive patients with sinus rhythm. HRV was determined twice by ambulatory 24-hour Holter recordings at fasting during and after Ramadan.Subjects mean age was 55 ± 11.8 years. Sex-ratio was 1.5. When two groups compared, statistically significant differences were found in terms of SDNN (113 ± 71 vs 140 ± 38, p = 0.001), SDANN (109.7 ± 45 vs 134.8 ± 48.3, p = 0.008), T power (2368.7 ± 121.3 vs 3660.5 ± 170.9, p = 0.03) and LF (552.2 ± 31.3 vs 903.7 ± 48.9, p < 0.0001) values.HRV parameters were found to be decreased in Ramadan. Thus, Ramadan fasting enhances the activity of the sympathetic system in hypertensive patients. 相似文献
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This research investigates the effectiveness of bio-sourced flax fiber-reinforced polymer in comparison with a traditional system based on carbon fiber-reinforced epoxy polymer in order to confine recycled aggregate concretes. The experimental investigation was conducted on two series of concrete including three mixtures with 30%, 50%, and 100% of recycled aggregates and a reference concrete made with natural aggregates. The concrete mixtures were intended for a frost environment where an air-entraining agent was added to the mixture of the second series to achieve 4% air content. The first part of the present work is experimental and aimed to characterize the compressive performance of confined materials. The results indicated that bio-sourced composites are efficient in strengthening recycled aggregates concrete, especially the air-entrained one. It was also found that the compressive strength and the strain enhancement obtained from FRP confinement are little affected by the replacement ratio. The second part was dedicated to the analytical modeling of mechanical properties and stress–strain curves under compression. With the most adequate ultimate strength and strain prediction relationships, the full behavior of FRP-confined concrete can be predicted using the model developed by Ghorbel et al. to account for the presence of recycled aggregates in concrete mixtures. 相似文献
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