Nedergaardhalberg5612

e., CEP290, C5ORF, TCTN1, CC2D2A, RPGRP1L, TCTN3, AHI1, INPP5E, TCTN2, NPHP1, and TMEM237. For the first time, we identified a ciliopathy gene, CCDC28B, as a causal gene in Joubert syndrome in one family. CEP290 accounted for 37.8% cases of pure Joubert syndrome, Joubert syndrome with retinal and renal disease, and Meckel-Gruber syndrome. The p.G1890∗ allele in CEP290 is highly recurrent. Of the six families with Joubert syndrome who had a prenatal diagnosis, one fetus was normal, two were carriers, and three were affected. CONCLUSIONS This is the largest study of Joubert syndrome from India. Although a high degree of locus and allelic heterogeneity was observed, CEP290 variants were the most common among these patients. BACKGROUND Diffuse white matter abnormality (diffuse excessive high signal intensity) is the most common finding on structural brain magnetic resonance imaging (MRI) at term-equivalent age in very preterm infants. Yet, there remains a large gap in our understanding of the etiology of diffuse white matter abnormality. Our objective was to evaluate perinatal and neonatal inflammation-associated antecedents of diffuse white matter abnormality on MRI. METHODS We prospectively enrolled 110 very preterm infants born at ≤31 weeks gestational age and collected data on multiple perinatal/neonatal exposures, especially inflammation initiating-illnesses. We performed structural MRI at term-equivalent age and quantified the volume of diffuse white matter abnormality objectively. Multivariable regression was used to identify clinical antecedents of diffuse white matter abnormality. RESULTS The mean (S.D.) birth gestational age of the final study sample of 98 very preterm infants was 28.3 (2.5) weeks. Multiple inflammation initiating-illnesses were associated with diffuse white matter abnormality in univariate analyses. In multivariable linear regression analyses controlling for gestational age, severe retinopathy of prematurity (P  less then  0.001) and bronchopulmonary dysplasia (P = 0.006) were independent risk factors, whereas maternal treatment with 17-hydroxyprogesterone (P  less then  0.001) was protective of later development of objectively quantified diffuse white matter abnormality. CONCLUSIONS We identified several perinatal and neonatal antecedent clinical factors associated with diffuse white matter abnormality. Although we found some support for inflammation as a common underlying mechanism, larger studies are needed to validate inflammation as a potential common pathway to the development of diffuse white matter abnormality in very preterm infants. IL-5 is the most potent activator of eosinophils and is produced by Th2 cells and ILC2s. A role for IL-5 in eosinophil extracellular trap cell death, i.e., a proinflammatory cell death, has also been reported. Clozapine N-oxide nmr Mepolizumab and benralizumab are humanized mAbs that target IL-5 and the IL-5 receptor α, respectively, and their therapeutic efficacy for severe asthma has been established. Although consistent differences in the efficacies of those drugs have not been proven, benralizumab extensively depleted eosinophils via Ab-dependent cell-mediated cytotoxicity. Blood eosinophil count, but not FeNO or IgE, is the best-established predictive biomarker of the efficacy of anti-IL-5 treatment. Regarding the choice of biologics, the balance between blood eosinophil count and FeNO, indication of comorbidities, longitudinal safety, and interval of injection should be considered. Mepolizumab was also effective in maintaining the remission of refractory eosinophilic granulomatous polyangiitis. Moreover, mepolizumab decreased the proportion of patients who required surgery and lowered the nasal polyp score in patients with chronic rhinosinusitis with nasal polyps; a further extensive trial is currently under way. In a phase II benralizumab study performed in Japan, no significant effect on nasal polyp score at week 12 was observed, suggesting a requirement for longer treatment. In this review, the role of IL-5 in eosinophil biology and the current status of anti-IL-5 therapy are discussed. The longitudinal safety of anti-IL-5 therapy has been increasingly established, and this strategy will be continuously indicated for eosinophilic diseases as a specific treatment for eosinophilic inflammation. The management of severe aortic regurgitation (AR) in patients with reduced left ventricular function and extreme left ventricular dilatation presents a therapeutic dilemma. This study aims to assess risk factors of aortic valve replacement (AVR) for these particular population based on its performances. Two hundred twelve severe AR patients accompanied by left ventricular ejection fraction (LVEF) 70 mm) due to poor postoperative early- and long-term outcomes. Patients with hypertension who develop atrial premature complexes (APCs) are at a particularly high risk for atrial fibrillation (AF). We sought to identify medications and modifiable risk factors that could reduce the risk of AF imposed by presence of APCs in such a high risk group. This analysis included 4,331 participants with treated hypertension from the Reasons for Geographic and Racial Differences in Stroke study who were free of AF and cardiovascular disease at the time of enrollment (2003-2007). APCs were detected in 8.2% (n = 356) of the participants at baseline. During a median follow-up of 9.4 years, 9.9% (n = 429) of the participants developed AF. Participants with APCs, compared with those without, were more than twice as likely to develop AF (Odds ratio [95% confidence interval] 2.36[1.75, 3.19]). This association was significantly weaker in statin users than nonusers (Odds ratio [95% confidence interval]1.42[0.81,2.48] vs 3.01[2.11,4.32], respectively; interaction p-value = 0.02), and in angiotensin-II receptor blocker users than nonusers (Odds ratio [95% confidence interval]1.31[0.66,2.61] vs 2.78[1.99,3.89], respectively; interaction p-value = 0.05). Borderline weaker associations between APCs and AF were also observed in alpha-blocker users than nonusers, nondiabetics than diabetics, and in those with systolic blood pressure level 130 to 139 mm Hg compared with those with other systolic blood pressure levels. No significant effect modifications were observed by use of other medications or by presence of other cardiovascular risk factors. In conclusion, the significant AF risk associated with APCs in patients with hypertension could potentially be reduced by treatment with angiotensin-II receptor blockers and statins along with lowering blood pressure and management of diabetes.