Insufficient evidence for a role of SERPINF1 in otosclerosis

Otosclerosis is a common form of hearing loss (HL) due to abnormal remodeling of the otic capsule. The genetic causes of otosclerosis remain largely unidentified. Only mutations in a single gene, SERPINF1, were previously published in patients with familial otosclerosis. To unravel the contribution of genetic variation in this gene to otosclerosis, this gene was re-sequenced in a large population of otosclerosis patients and controls. Resequencing of the 5′ and 3′ UTRs, coding regions, and exon–intron boundaries of SERPINF1 was performed in 1604 unrelated otosclerosis patients and 1538 unscreened controls, and in 62 large otosclerosis families. Our study showed no enrichment of rare variants, stratified by type, in SERPINF1 in patients versus controls. Furthermore, the c.392C > A (p.Ala131Asp) variant, previously reported as pathogenic, was identified in three patients and four controls, not replicating its pathogenic nature. We could also not find evidence for a pathogenic role in otosclerosis for 5′ UTR variants in the SERPINF1-012 transcript (ENST00000573763), described as the major transcript in human stapes. Furthermore, no rare variants were identified in the otosclerosis families. This study does not support a pathogenic role for variants in SERPINF1 as a cause of otosclerosis. Therefore, the etiology of the disease remains largely unknown and will undoubtedly be the focus of future studies

Photoreduction of Perfluorooctanoic Acid (PFOA) in Isopropanol Aqueous Solution

全氟辛酸 (perfluorooctanoic acid, PFOA) 是全氟化物 (perfluorinated compounds, PFCs) 的一種，自1950年代被合成出來後，廣泛使用在聚合物、塗料等工業製程中。由於具有持久性有機汙染物的性質，近年來PFOA在環境中的流佈途徑、及生態毒理機制已被廣泛的研究與重視。因此，本研究嘗試利用光 (紫外線) 還原反應的處理方式，探討在水溶液為無氧狀態下，初始pH值、電子提供者 (異丙醇) 濃度與觸媒 (二氧化鈦) 添加量對PFOA降解的影響。 研究結果顯示，在不添加二氧化鈦觸媒的情況下，不論pH值變化與添加異丙醇濃度為何，PFOA在24小時反應時間的去除率都約在20% 左右，但氟離子產率則隨初始pH值與異丙醇濃度的增加而上升。根據質譜儀的分析結果，未添加異丙醇時PFOA紫外線反應之降解產物以短鏈全氟羧酸為主，而含異丙醇環境下之降解機制則明顯不同，其中m/z=235[C4F9O]-為可能的中間產物。推測未添加異丙醇時，PFOA以直接光解方式氧化成短鏈全氟羧酸，而在含異丙醇的環境下，短鏈全氟羧酸進一步產生自由基連鎖還原反應，因此產生更多的氟離子，尤其在鹼性環境下則有利於還原性更強的自由基產生。 在添加觸媒的光還原反應PFOA研究結果上，0.5 g/L 的二氧化鈦添加量有最佳的PFOA降解效果，然而在鹼性環境下PFOA降解不明顯，推測原因為二氧化鈦與PFOA在鹼性條件下均帶負電，在電性相斥的現象下，二氧化鈦無法發揮作用；在酸性溶液之不同異丙醇濃度環境下，PFOA在24小時反應時間的去除率在57至73% 之間，與未添加二氧化鈦觸媒的條件比較，已明顯提高甚多去除率。根據質譜儀的分析結果，未添加異丙醇時降解產物以短鏈全氟羧酸為主，而含異丙醇環境下之降解機制亦明顯不同，還原產物m/z=395[C7F14HCOO]-為可能的中間產物。推測未添加異丙醇時，PFOA與二氧化鈦產生的電洞產生氧化反應，生成短鏈全氟羧酸；在含異丙醇環境下，異丙醇與電洞反應產生自由基，進一步還原PFOA。綜合上述各反應條件，結果顯示添加0.5 g/L二氧化鈦、2 wt %異丙醇與初始pH3的反應條件下，PFOA有最佳的降解效果，24小時反應時間有73%的降解率。Perfluorinated compounds (PFCs) were used as an industrial raw material since 1950s, Perfluorooctanoic acid (PFOA) was one of these PFCs. PFOA has properties of persistant organic pollutants (POPs) and the characteristics of environmental fate and bio-toxicology had investigated widely in recent years. Based on above, this study invesgated the photo-reduction (UV) of PFOA under various pH, electron donor (isopropanol, IPA) concentration and amount of catalyst (titanium dioxide, TiO2) in anaerobic aqueous solution. The experimental result showed that decomposition rate of PFOA was about 20% after 24 hours reaction time in all conditions of no titanium dioxide added. Moreover, higher pH value and isopropanol concentraton implied higher fluoride ion yield in aqueous solution. According to the MASS analysis, the formation of short chain perfluorocarboxylic acids (PFCAs) were main byproduct under no IPA condition, and the reaction mechanism was significantly different with IPA aqueous solution. Especially, the intermediate compound of m/z=235 [C4F9O]- was inferred in IPA aqueous solution. In no IPA condition, direct photolysis was suggested the reaction mechanism to form shorter chain PFCAs. However, the byproduct of shorter chain PFCAs would induce into radical chain reaction and yield more fluoride ion in IPA aqueous solution, especially in alkaline condition. In catalytic photo-reduction PFOA, the result exhibited that the 0.5 g/L of titanium dioxide (optimum dose) presented significantly higher PFOA removal rate than no TiO2 condition. The PFOA removal rate could be ranged from 57% to 73% during 24 hours reaction time under various IPA concentrations in acidic condition. However, in alkaline condition PFOA did not display same high removal rate. The reason could refer that electrical repulsion between TiO2 and PFOA caused by same negative surface charges in alkaline condition. Formation of short chain PFCAs were main byproduct under no IPA condition, and the reaction mechanism was also significantly different with IPA aqueous solution. The intermediate compound of m/z=235 [C7F14HCOO]- of reduced PFOA was inferred in IPA aqueous solution. PFOA react with electron hole which generated by UV/TiO2 to produce shoter chain PFCAs under no IPA added. In IPA aqueous solution, IPA reacts with electron hole to incur radical chain reaction and reduced PFOA. Summarizing, the highest PFOA removal efficiency of 73% during 24 hours reaction time was under the condition of 0.5 g/L TiO2, 2 wt% IPA and pH 3 in aqueous solution

Hearing in children with congenital cytomegalovirus infection: results of a longitudinal study

Objectives: To evaluate hearing outcome, to characterize the nature of symptomatic and asymptomatic congenital cytomegalovirus (cCMV) infection and associated hearing loss, and to compare results with data from previous studies. Study design: A prospective multicenter registry was set up in 2007. Six centers participated in the development of a standardized protocol for diagnosis, treatment, and follow-up. Data were gathered in an online registry. Children (n = 379) with a documented cCMV infection and at least 2 separate audiologic evaluations were included. Audiometric results from a multicenter cohort study of children with cCMV infection with longitudinal observation were examined. Results: Results from 123 children with a symptomatic and 256 children with an asymptomatic cCMV infection were analyzed. In the group with symptomatic cCMV, 63% had hearing loss, compared with 8% in the group with asymptomatic cCMV. Delayed-onset hearing loss occurred in 10.6% of symptomatic cCMV and in 7.8% of asymptomatic cCMV. In the group with symptomatic cCMV, 29.3% of children used some kind of hearing amplification; 1.6% in the group with asymptomatic cCMV used hearing amplification. Conclusions: Symptomatic and asymptomatic cCMV infections are a major cause of hearing loss in childhood. Reliable estimates of the long-term outcome of cCMV infection are mandatory to increase vigilance, especially among pregnant women and to draw attention to preventive measures, vaccine development, and prenatal and postnatal therapy. Universal screening of newborns for cCMV infection should be initiated and combined with longitudinal audiometric follow-up

Hearing in Children with Congenital Cytomegalovirus Infection: Results of a Longitudinal Study

Objectives: To evaluate hearing outcome, to characterize the nature of symptomatic and asymptomatic congenital cytomegalovirus (cCMV) infection and associated hearing loss, and to compare results with data from previous studies. Study design: A prospective multicenter registry was set up in 2007. Six centers participated in the development of a standardized protocol for diagnosis, treatment, and follow-up. Data were gathered in an online registry. Children (n = 379) with a documented cCMV infection and at least 2 separate audiologic evaluations were included. Audiometric results from a multicenter cohort study of children with cCMV infection with longitudinal observation were examined. Results: Results from 123 children with a symptomatic and 256 children with an asymptomatic cCMV infection were analyzed. In the group with symptomatic cCMV, 63% had hearing loss, compared with 8% in the group with asymptomatic cCMV. Delayed-onset hearing loss occurred in 10.6% of symptomatic cCMV and in 7.8% of asymptomatic cCMV. In the group with symptomatic cCMV, 29.3% of children used some kind of hearing amplification; 1.6% in the group with asymptomatic cCMV used hearing amplification. Conclusions: Symptomatic and asymptomatic cCMV infections are a major cause of hearing loss in childhood. Reliable estimates of the long-term outcome of cCMV infection are mandatory to increase vigilance, especially among pregnant women and to draw attention to preventive measures, vaccine development, and prenatal and postnatal therapy. Universal screening of newborns for cCMV infection should be initiated and combined with longitudinal audiometric follow-up