Functional characterization of CEP250 variant identified in nonsyndromic retinitis pigmentosa

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C‐Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.     

Population pharmacokinetics of theophylline in adult Chinese patients with asthma and chronic obstructive pulmonary disease

Background Theophylline has a narrow therapeutic range and large interindividual variability in blood levels, so a thorough understanding of its pharmacokinetic characteristics is essential. Population pharmacokinetic (PPK) approaches could achieve it and many PPK studies of theophylline have been reported in infants. However, none was conducted in Chinese adults and none has explored the effect of CYP1A2 genotypes on the PPK characteristics of theophylline in adults. Objective To evaluate the PPK characteristics of theophylline and to assess the possible influence of covariates, including CYP1A2 genotypes, on theophylline clearance in Chinese adult patients. Setting The study is conducted at the department of respiration in Zhujiang Hospital, Guangzhou, China. Methods Theophylline concentrations were obtained from eligible patients and were measured by high performance liquid chromatography. The polymorphisms of ??3860G?>?A, ??163C?>?A, C5347T (CYP1A2*1B) and G-3113A were genotyped using a direct sequencing method. Then, CYP1A2 genotypes, age, fat-free mass (FFM) and other covariates were used to develop a PPK model by NONMEM software. Bootstrap analysis was used to asses the accuracy and prediction of the PPK model. Main outcome measure The concentration and clearance of theophylline. Results A total of 134 theophylline concentrations from 95 patients were obtained. The final model was as follows: CL/F(L/h)?=?4.530?×?(FFM/56.1)^0.75 ×?0.713^CYP1A2*1B, the inter-individual variability in clearance/bioavailability (CL/F) was 44.0%, and the residual variability was 9.8%. The final model was proved to be reliable by bootstrap analysis. Conclusion Theophylline clearance was significantly associated with FFM and CYP1A2*1B genotypes in Chinese adult patients.     

Effect of Dibutyl Phthalate on the Tolerance and Lipid Accumulation in the Green Microalgae <Emphasis Type="Italic">Chlorella vulgaris</Emphasis>

Offshore oil exploration creates threats to coastal ecosystems, including increasing urbanization and associated effluent releases. Genotoxicity biomarkers in mussels were determined across a gradient of coastal zone influences of offshore petroleum exploration in southeastern Brazil. Coastal ecosystems such as estuaries, beaches and islands were seasonally monitored for genotoxicity evaluation using the brown mussel Perna perna. The greatest DNA damage (5.2%?±?1.9% tail DNA and 1.5‰? ±?0.8‰ MN) were observed in urban estuaries, while Santana Archipelago showed levels of genotoxicity near zero and is considered a reference site. Mussels from urban and pristine beaches showed intermediate damage levels, but were also influenced by urbanization. Thus, mussel genotoxicity biomarkers greatly indicated the proposed oil exploration and urbanization scenarios that consequently are genetically affecting coastal organisms.     

Assessing the quality of life in infants with deformational plagiocephaly

This was a parent-reported outcome study on the impact of helmet therapy on the quality of life of infants with deformational plagiocephaly and their caregivers. Using survey-based analysis, we compared the quality of life in infants with deformational plagiocephaly with a cohort of their healthy peers. In addition, we compared infant quality of life before and after helmet therapy to evaluate the impact of this mainstay therapy for deformational plagiocephaly.Our results demonstrated that infants with plagiocephaly and their caregivers had a significantly decreased quality of life compared with healthy controls. This reframes our understanding of deformational plagiocephaly and emphasizes the need for therapeutic intervention in these individuals. A common therapeutic option — helmet remolding therapy — was shown to have no negative impact on quality of life, underscoring this as an appropriate therapeutic option. These data will allow us to counsel our future parents more effectively regarding the impact of deformational plagiocephaly and helmet therapy.     

Genotypic diversity of Streptococcus mutans in 3- to 4-year-old Chinese nursery children suggests horizontal transmission

OBJECTIVE: The aims of this study were to investigate the colonisation of Streptococcus mutans and to determine the possibility of horizontal transmission in Chinese nursery children. DESIGN: Fifty-six children aged between 3 and 4 years old from a nursery were included in this study. Twenty-four children were from the day and night nursery class, the others were from the day nursery class. Dental plaque samples were collected with sterile toothpicks and cultured on S. mutans-selective tryptone-yeast-cystine agar supplemented with 0.2U/ml bacitracin and 15% sucrose. The typical isolates of S. mutans were identified by classical microbiological methods and genotyped by arbitrarily primed PCR (AP-PCR) and restriction fragment length polymorphism analysis. RESULTS: S. mutans was isolated from 41 of the 56 children. The prevalence of S. mutans was higher in the children from day nursery class, compared with the children from day and night nursery class (P<0.05). A total of 140 S. mutans isolates from 41 children were analysed by AP-PCR, and 88 different amplitypes were identified. Of 41 children with S. mutans isolates, 82.9% carried two or more genotypes. Two genotypes of S. mutans were repeatedly isolated among 13 children in the day and night nursery class, and one genotype was isolated from two children in the day nursery class. CONCLUSION: The presence of matching genotypes of S. mutans among children attending the same nursery suggests the possibility of horizontal transmission.     

Gelatinase A (MMP-2) in developing tooth tissues and amelogenin hydrolysis

Matrix metalloproteinases (MMPs) are thought to play important roles during enamel and dentin biomineralization. Previously, membrane type-1 matrix metalloproteinase (MT1-MMP) was localized to the plasma membranes of ameloblasts and odontoblasts of the developing tooth. The best-characterized function of MT1-MMP is to initiate the activation of gelatinase A (MMP-2). Thus, we hypothesized that gelatinase A may also be expressed by developing tooth tissues. A full-length porcine gelatinase A mRNA was isolated by RT-PCR homology cloning of an enamel-organ-specific cDNA library. Northern blot and in situ hybridization analyses demonstrated gelatinase A expression in developing tooth tissues. Immunohistochemical analysis localized gelatinase A close to the plasma membrane of these tissues. Furthermore, recombinant gelatinase A was demonstrated to cleave recombinant amelogenin into several fragments of differing molecular masses. Thus, gelatinase A is expressed by developing tooth tissues along with its activator MT1-MMP and may, therefore, play an important role during tooth development.     

阳极氧化处理后的新型钛合金表面成骨细胞OPG、RANKL基因表达研究

目的:新型钛合金Ti-24Nb-4Zr-7.9Sn(TNZS)经过阳极氧化(anodic oxidation,AD)技术处理后,分析其表面的人成骨样MG63细胞骨保护素(osteoprotegerin,OPG)、细胞核因子-κB受体活化因子配体(RANKL)基因表达水平.方法:将人成骨样MG63细胞接种于Ti-6Al-4V、TNZS、AD-TNZS表面,采用半定量RT-PCR法检测OPG、RANKL mRNA的表达量.结果:人成骨样MG63细胞在AD-TNZS表面的OPGm RNA表达量有所提高,而RANKL mRNA的表达量3组材料间无明显差异.结论:阳极氧化处理的TNZS钛合金可能通过影响骨保护素、细胞核因子-κB受体活化因子配体调节成骨细胞、破骨细胞的平衡,从而促进种植体植入后的骨重建.     

牙槽突裂骨移植稳定性的研究进展

牙槽突裂自体骨移植术是目前常用的修复唇腭裂患者牙槽突骨缺损的手术方法，但术后常存在植入骨再吸收现象。植骨时机、植入骨骨源、裂隙的结构、牙周健康状况和术后并发症等多种因素对手术成功率均有影响，通过加入生长因子和牵引成骨等方法，可增加移植骨的稳定性。作者就有关影响植入骨稳定性的因素及增加移植骨稳定性方法的研究进展作一综述。     

咀嚼肌表面电极肌电图重复性检验和参考值的建立

目的:对成年人咀嚼肌表面电极采集的肌电信号加以分析,研究下颌在6种不同运动状态下咀嚼肌肌电信号的可重复性,并取得正常参考值。方法:30名22-44岁受试者进行咀嚼肌表面电极肌电图检查,记录下颌姿势位、牙尖交错位和扣齿运动时双侧咬肌、颞肌前束和二腹肌前腹的肌电活动,每个受试者在3个不同时段各测试一次。结果:3次测试的咀嚼肌峰值电位之间无统计学差异(P>0.05)。下颌姿势位时,右侧咬肌峰值电位95%正常参考值为0-0.1,左侧为0-0.13,右侧颞肌前束为0-0.67,左侧颞肌前束为0-0.1,右侧二腹肌前腹为0-0.13,左侧二腹肌前腹为0-0.1;牙尖交错位时,右侧咬肌峰值电位95%正常参考值为0.33-2.53,左侧为0.47-2.5,右侧颞肌前束为0.23-2.23,左侧颞肌前束为0.2-3.67,右侧二腹肌前腹为0.13-1.07,左侧二腹肌前腹为0.1-0.87;扣齿运动时右侧咬肌峰值电位95%正常参考值为0.5-2.5,左侧为0.73-2.3,右侧颞肌前束为0.4-3.47,左侧颞肌前束为0.3-3.63,右侧二腹肌前腹为0.2-1.07,左侧二腹肌前腹为0.13-0.97。结论:表面电极采集的双侧咬肌、颞肌前束和二腹肌前腹的肌电活动具有一定的可重复性。