A common ABCC2 promoter polymorphism is not a determinant of the risk of spina bifida

BACKGROUND: There is compelling evidence that the risk of spina bifida, a malformation of the caudal neural tube, is associated with maternal and/or embryonic disturbances in folate/homocysteine metabolism. Hence, functional variants of genes that influence folate/homocysteine metabolism constitute a biologically plausible group of candidate risk factors for spina bifida and other neural tube defects. One such candidate is ABCC2, the gene encoding ABCC2, (a.k.a. canalicular multispecific organic anion transporter [cMOAT], multidrug resistance related protein 2 [MRP2]), a member of the ABC transporter family that effluxes natural folates and anti-folate drugs such as methotrexate. METHODS: The association between the risk of spina bifida and both the maternal and embryonic ABCC2 C(-24)T genotype was evaluated by using the transmission disequilibrium test and log-linear modeling. RESULTS: These analyses provided no evidence that the risk of spina bifida was significantly related to either the maternal or embryonic ABCC2 C(-24)T genotype. CONCLUSIONS: The results of the present analyses suggest that the C(-24)T variant of the ABCC2 gene is not a major determinant of spina bifida risk.     

Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: a report from the National Down Syndrome Project

BACKGROUND: Maternal folic acid supplementation has been associated with a reduced risk for neural tube defects and may be associated with a reduced risk for congenital heart defects and other birth defects. Individuals with Down syndrome are at high risk for congenital heart defects and have been shown to have abnormal folate metabolism. METHODS: As part of the population‐based case‐control National Down Syndrome Project, 1011 mothers of infants with Down syndrome reported their use of supplements containing folic acid. These data were used to determine whether a lack of periconceptional maternal folic acid supplementation is associated with congenital heart defects in Down syndrome. We used logistic regression to test the relationship between maternal folic acid supplementation and the frequency of specific heart defects correcting for maternal race or ethnicity, proband sex, maternal use of alcohol and cigarettes, and maternal age at conception. RESULTS: Lack of maternal folic acid supplementation was more frequent among infants with Down syndrome and atrioventricular septal defects (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.08–2.63; p = 0.011) or atrial septal defects (OR, 1.69; 95% CI, 1.11–2.58; p = 0.007) than among infants with Down syndrome and no heart defect. Preliminary evidence suggests that the patterns of association differ by race or ethnicity and sex of the proband. There was no statistically significant association with ventricular septal defects (OR, 1.26; 95% CI, 0.85–1.87; p = 0.124). CONCLUSIONS: Our results suggest that lack of maternal folic acid supplementation is associated with septal defects in infants with Down syndrome. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.     

First-principle study of the native defects in GaAs saturable absorbers

The change of atom configuration in GaAs, caused by intrinsic point defects (Ga and As vacancies, Ga and As antisites, Ga and As interstitials), is first calculated by a plane wave pseudo-potential method with the generalised gradient approximation in the frame of density functional theory, and the most stable structure is obtained. Then, the formation energy of each kind of the native defect is calculated, by which the possibilities of the six kinds of point defects to be formed during crystal growth are analysed. The defect energy levels corresponding to each kind of the native point defect and their electron occupancy are analysed from the aspect of density of states. Finally, the elastic constants of GaAs saturable absorbers with native point defects are calculated, and the impacts on the elastic properties brought by native point defects are studied. The values of defect energy levels obtained will be helpful in ascertaining the mechanism of the EL2 deep level in the GaAs saturable absorber, and the analysis of the elastic properties of a GaAs crystal with native point defects will be helpful in guiding the application of the GaAs crystal as a saturable absorber in passively Q-switched lasers.     

Measurements of birth defect prevalence: Which is most useful as a comparator group for pharmaceutical pregnancy registries?

Pharmaceutical pregnancy registries document birth defects and other complications reported in pregnancies exposed to specific medications or diseases. A baseline estimate of birth defect prevalence is necessary for comparison. To identify potential teratogenic signals, the pregnancy registry must have a comparator that most closely matches the exposed population and data collection methodology, which are characteristics that vary among the multiplicity of birth defect surveillance systems. The system that yields the most accurate prevalence data may be different from that most closely matching the pregnancy registry methods. State public health programs have highly accurate and precise statistics, but their populations are broader than those of a pharmaceutical pregnancy registry. Large collaborative databases may have a more useful covered population, but there are secondary problems related to data precision. Health care databases enroll large numbers of patients and have good information about exposures and health problems, but the data can be difficult to access and lack useful detail. Exposure‐related databases are closer in population definition and collection methods, though the presence of different diseases and exposures can be problematic. Internal comparators are likely to be most useful in formal statistical analysis, but added cost and management burden and may require significantly increased registry enrollment. There is no ideal comparator, and this must be taken into account when planning a single‐exposure or single‐disease pregnancy registry. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

修复与重建大面积胸壁缺损的临床研究进展

造成胸壁缺损的原因很多,但大面积胸壁缺损是胸外科不可忽视的一个重要问题,过大的胸壁缺损可导致患者气胸、胸壁软化、反常呼吸及纵膈摆动等,影响患者呼吸循环功能,必须修复重建。关于胸壁缺损的修复与重建手术技术已发展得较为成熟,对于术后影响较大的因素主要是对于不同胸壁缺损区域的选择手术方法及使用的修补材料的性质。本文就大面积胸壁缺损特点、原因、修复重建材料及技术应用的临床研究进展进行综述。     

Frequency of the SCID gene among Arabian horses in the USA

Severe combined immunodeficiency disease (SCID) of horses is an autosomal, recessive hereditary disease occurring among Arabian horses. The genetic defect responsible for this disease was recently identified as a 5-basepair deletion in the gene encoding DNA-protein kinase catalytic subunit (DNA-PKcs). Horses with one copy of the gene appear normal, while horses with two copies of the gene manifest the disease. The present report describes a PCR-based test for detection of the gene defect and the results from testing 250 randomly selected Arabian horses. The frequency of SCID gene carriers was 8·4% (21/250). Based on the gene frequency reported here, the authors would expect 0·18% (1 out of 567) of Arabian foals to be affected with SCID based on a random breeding population.     

关节镜制备膝关节软骨缺损的动物模型

目的:经微创手术制备膝关节软骨缺损动物模型,减少因手术创伤造成对实验结果的影响。方法:关节镜下对9只山羊(9膝)进行关节面钻孔术,造成软骨缺损模型,对其缺损位置进行准确定位。结果:9只山羊(9膝)均在关节镜下顺利进行了关节软骨缺损模型的建立,并进行了缺损部位的定位。结论:对比开放性手术,经关节镜制备关节缺损模型是一种对实验干预最少的微创方法,有助于减少手术本身造成的实验误差。     

腓肠神经营养血管皮瓣修复跟骨骨折术后皮肤软组织缺损的临床研究

摘要 目的：探讨负压引流技术结合腓肠神经营养皮瓣在跟骨骨折钢板内固定术后皮肤软组织缺损的临床效果。方法：回顾性分析我院骨科2012年5月-2020年5月共31例跟骨骨折术后钢板外露,皮肤软组织缺损住院病人。纳入患者均使用负压引流技术结合腓肠神经营养皮瓣修复技术。创面给予彻底清创后行封闭负压吸引引流术,待创面新鲜后以腓肠神经营养皮瓣修复创面。对术后皮瓣成活情况;Maryland功能评分以及BMRC感觉功能评分进行综合评估。结果：术后2周时,28例皮瓣顺利成活,供区与受区伤口愈合良好,干燥、无渗出。3例术后出现皮瓣肿胀,皮瓣颜色发暗,伤口渗出较多,皮瓣边缘坏死,窦道形成等,给予切开引流、加强换药、敏感抗生素控制感染等治疗后,皮瓣成活。术后随访6-24个月皮瓣外观及功能恢复良好,无创面再坏死,裂开,感染等情况出现。其中2例再次入院行皮瓣整形术。术后6个月时,Maryland功能评分：优：17例;良：11例;优良率为：90.3%。BMRC感觉功能评分：S3-S4：20例;S2：8例;S1：3例。结论：腓肠神经营养皮瓣联合封闭负压吸引技术在跟骨骨折钢板内固定术后皮肤软组织缺损的治疗中能够缩短治疗时间,操作简单,疗效确切,可获得良好的修复效果。     

Quantifying the Interface Defect for the Stability Origin of Perovskite Solar Cells

The stability issue that is obstructing commercialization of the perovskite solar cell is widely recognized, and tremendous effort has been dedicated to solving this issue. However, beyond the apparent thermal and moisture stability, more intrinsic semiconductor mechanisms regarding defect behavior have yet to be explored and understood. Herein, defects are quantified; especially interface defects, within the cell to reveal their impact on device performance and especially stability. Both the bulk and interface defects are distinguished and traced in situ using an expanded admittance model when the cell degrades in its efficiency under illumination or voltage. The electric field‐induced interface, rather than bulk defects, is found to have a direct correlation to stability. Releasing the interface strain using a fullerene derivative is an effective way to suppress interface defect formation and improve stability. Overall, this work provides a quantitative approach to probing the semiconductor mechanism behind the stability issue, and the inherent correlation discovered here among the electric field, interface strain, interface defects, and cell stability has important implications for ongoing device stability engineering.     

Characterization of the Skeletal Fusion with Sterility (sks) Mouse Showing Axial Skeleton Abnormalities Caused by Defects of Embryonic Skeletal Development

The development of the axial skeleton is a complex process, consisting of segmentation and differentiation of somites and ossification of the vertebrae. The autosomal recessive skeletal fusion with sterility (sks) mutation of the mouse causes skeletal malformations due to fusion of the vertebrae and ribs, but the underlying defects of vertebral formation during embryonic development have not yet been elucidated. For the present study, we examined the skeletal phenotypes of sks/sks mice during embryonic development and the chromosomal localization of the sks locus. Multiple defects of the axial skeleton, including fusion of vertebrae and fusion and bifurcation of ribs, were observed in adult and neonatal sks/sks mice. In addition, we also found polydactyly and delayed skull ossification in the sks/sks mice. Morphological defects, including disorganized vertebral arches and fusions and bifurcations of the axial skeletal elements, were observed during embryonic development at embryonic day 12.5 (E12.5) and E14.5. However, no morphological abnormality was observed at E11.5, indicating that defects of the axial skeleton are caused by malformation of the cartilaginous vertebra and ribs at an early developmental stage after formation and segmentation of the somites. By linkage analysis, the sks locus was mapped to an 8-Mb region of chromosome 4 between D4Mit331 and D4Mit199. Since no gene has already been identified as a cause of malformation of the vertebra and ribs in this region, the gene responsible for sks is suggested to be a novel gene essential for the cartilaginous vertebra and ribs.     

Articular surface defects in the third metatarsal and third cuneiform: Nonosseous tarsal coalition

Frequencies of articular surface defects on the third metatarsal and third cuneiform, seen as pits of varying sizes on the plantar one third of the tarsometatarsal articular face, were investigated in skeletal populations from North America and Japan, as well as in gibbon, orangutan, chimpanzee, and gorilla skeletons. The apes did not exhibit the defects, although the number of observed specimens of each type was small. The newly presented human frequencies corresponded well with those from other published sources. The defects appeared both unilaterally and bilaterally, with no apparent sex or side biases. Statistical tests between the various populations found that, in general, geographically close populations had more similar frequencies of the defect. Possible etiologies for the defect were investigated, including biomechanical influences, degenerative arthritis, infection, trauma, and a developmental condition known as tarsal coalition, which proved to be the best explanation. Tarsal coalition results from the failure of a joint space to form properly during fetal growth. It can occur between any two adjacent bones of the foot. Several clinically important coalitions, whose presence interferes with normal walking, are known. However, coalition between the third metatarsal and third cuneiform has not been reported in the clinical literature, suggesting that the defect causes little or no foot dysfunction. Tarsal coalition is thought to have a strong genetic component, suggesting that the pit defect may be useful as a skeletal nonmetric trait, as others have stated. Am J Phys Anthropol 109:53–65, 1999. © 1999 Wiley-Liss, Inc.     

许家窑人幼年个体的釉质发育缺陷

上世纪70年代在许家窑-侯家窑地点发现的人类化石对了解东亚中晚更新世过渡时期古人类的形态演化起到了重要作用。除形态特征外,针对许家窑人病理表现也开展过相关研究,其中许家窑人幼年个体前部牙齿上出现的黄色小坑被认为是患有氟斑牙病的证据,且可能代表世界范围内该牙病的最早实例。然而,经电子显微镜和显微断层扫描显示,这些黄色小坑或凹陷是釉质发育不良表现,而不是代表个体患有氟斑牙病后牙齿受咀嚼压力而产生的物理破损。同步辐射扫描显示,许家窑幼年个体前部牙齿釉质密度均匀,没有出现浅层釉质矿化减小的现象,不支持该个体因釉质矿化过程受影响而患有典型氟斑牙的结论。尽管如此,后部牙齿上大量坑状的釉质缺陷和坑状缺陷底部的加重生长线特征不排除是个体氟摄入过量而影响釉质形成的分泌期而导致的。除表面坑状釉质缺陷外,许家窑幼年个体恒齿不同部位的釉质内部出现缺失（空间结构一般为圆球状）。缺失主要集中在浅层区域,沿齿尖-齿颈方向的密集程度变化与釉质发育不良位置具有一定相关性。釉质内部缺失有时互连并与釉质表面垂直。以上特征显示釉质内部缺失是釉质形成过程受影响所致,且影响因素和发生机理可能与釉质发育不良的类似。许家窑幼年个体不同牙齿在外部釉质缺陷和内部釉质缺失密集程度上的差别可能反映的是个体在发育过程中所需应对的外界扰动因素程度不同。未来研究可对包含许家窑人化石的堆积物中以及许家窑人牙齿中的氟含量进行测定,以进一步研究许家窑人个体的生活环境中是否有过量的氟以及许家窑人是否摄入了过量氟元素,从而对许家窑人的牙齿发育缺陷机理有一个进一步的了解。     

Cell-based gene therapy for repair of critical size defects in the rat fibula

More than a decade has passed since the first experiments using adenovirus-transduced cells expressing bone morphogenetic protein 2 were performed for the synthesis of bone. Since this time, the field of bone gene therapy has tackled many issues surrounding safety and efficacy of this type of strategy. We present studies examining the parameters of the timing of bone healing, and remodeling when heterotopic ossification (HO) is used for bone fracture repair using an adenovirus gene therapy approach. We use a rat fibula defect, which surprisingly does not heal even when a simple fracture is introduced. In this model, the bone quickly resorbs most likely due to the non-weight bearing nature of this bone in rodents. Using our gene therapy system robust HO can be introduced at the targeted location of the defect resulting in bone repair. The HO and resultant bone healing appeared to be dose dependent, based on the number of AdBMP2-transduced cells delivered. Interestingly, the HO undergoes substantial remodeling, and assumes the size and shape of the missing segment of bone. However, in some instances we observed some additional bone associated with the repair, signifying that perhaps the forces on the newly forming bone are inadequate to dictate shape. In all cases, the HO appeared to fuse into the adjacent long bone. The data collectively indicates that the use of BMP2 gene therapy strategies may vary depending on the location and nature of the defect. Therefore, additional parameters should be considered when implementing such strategies.     

围产儿出生缺陷分析及干预措施

摘要目的：掌握围产儿出生缺陷的发生情况,探讨引起围产儿出生缺陷的相关因素,为制订及完善出生缺陷预防对策及干预措施提供科学依据。方法：按照全国出生缺陷监测中心制定的监测方案,对2010年10月1日～2011年9月30日在湘潭市县级及以上医疗保健机构住院分娩的围生儿出生缺陷监测资料进行分析。结果：5年出生缺陷的平均发生率为93．30／万,出生缺陷的发生率无明显趋势（x2=0．114,P=0．736）乡村的出生缺陷发生率明显高于城镇（X2=24．638,P〈O．001）,男性围产儿的出生缺陷发生率显著高于女性（XZ=6．693,P=0．010）,出生缺陷的发生率与季节无关（x2=3．852,P=0．278）,出生缺陷的围产儿死亡率大大高于非出生缺陷）L（X2=2904．583,P〈0．001）,先天性心脏病、肢体畸形（并指／趾、多指／趾、肢体短缩、马蹄内翻足）、唇裂及唇腭裂是高发的出生缺陷。结论：减少出生缺陷的发生是一项长期工程,需要采取综合措施,从各个环节入手,以预防为主,加强优生优育健康教育,落实婚前及围产期保健,推行新生儿疾病筛查,可有效降低出生缺陷的发病率,提高出生人口素质。     

Linking teratogen information service and birth defects registry databases to improve knowledge of birth defect status

BACKGROUND: Although teratogen information services (TISs) obtain maternal exposure information from their callers, such services often do not know if the pregnancies were affected by a birth defect. This study attempted to improve the completeness of this information for Texas Teratogen Information Service (TTIS) callers by linking their records with the Texas Birth Defects Registry (TBDR) and Texas birth certificates (TBCs). METHODS: A total of 344 expectant mothers called TTIS with expected dates of delivery between 1 January 2000 and 31 December 2001. These pregnancies were linked with TBDR and TBC data. The percentages of pregnancies with known birth defect information both before and after the linkage were compared. RESULTS: The TTIS originally collected birth defect status information for 101 of the 344 callers (29.4%) and 0.6% of all 344 callers or 2.0% of callers with birth defect status information had a pregnancy affected by a birth defect. Linking TTIS records with TBDR and TBC data helped to raise the percentage of callers with birth defect status information from 29.4% to 71.5%. Among those callers, the percentage known to have birth defects increased from 2.0% to 4.1%. The sensitivity of TTIS follow-up calls in identifying birth defects was 50%, and the specificity was 100%. CONCLUSIONS: Linking TTIS caller records with TBDR and TBC data significantly increased both the percentage of pregnancies with birth defect status information and the percentage of pregnancies identified as affected by birth defects. Such linkage may be a good approach by which TISs can increase the completeness of their birth defect status information.     

自固化磷酸钙人工骨修复小儿局部骨缺损的临床应用

目的：研讨自固化磷酸钙人工骨（Calcium Phosphate Cement,CPC)填充修复小儿局部骨缺损的临床意义,方法：选用CPC修复小儿骨缺损18例,年龄最小8个月,最大12岁,平均8岁,骨缺损部位：肱骨9例,胫骨6例,胫骨3例,病因,单纯性骨囊肿8例,骨纤维异常增生症5例,动脉瘤样骨囊肿4例,嗜酸性肉芽肿1例,骨缺损大小,最大7cm,最小2cm,平均5cm,CPC填充方式：单纯粉末7例,粉末＋松质骨粒6例,粉末＋条形骨块5例。CPC初步固化时间,最短15分钟,最长30分钟,平均20分钟,随访时间：13－27个月,平均18．5个月。结果：全组18例应用CPC后未见明显局部和全身不良反应。手术前后血PH值钙磷代谢无异常改变。X线片显示：CPC与宿主骨接触紧密,无脱落,术后3个月出现降解,新生骨形成。结论：CPC安全无毒,使用方便,易塑形,生物相容性好,能在体内降解,可以替代自体骨材料在小儿局部骨缺损应用。     

Using 3D finite element models verified the importance of callus material and microstructure in biomechanics restoration during bone defect repair

Background: There is lack of further observations on the microstructure and material property of callus during bone defect healing and the relationships between callus properties and the mechanical strength. Methods: Femur bone defect model was created in rabbits and harvested CT data to reconstruct finite element models at 1 and 2 months. Three types of assumed finite element models were compared to study the callus properties, which assumed the material elastic property as heterogeneous (R-model), homogenous (H-model) or did not change from 1 to 2 months (U-model). Results: The apparent elastic moduli increased at 2 months (from 355.58 ± 132.67 to 1139.30 ± 967.43 MPa) in R-models. But there was no significant difference in apparent elastic moduli between R-models (355.58 ± 132.67 and 1139.30 ± 967.43 MPa) and H-models (344.79 ± 138.73 and 1001.52 ± 692.12 MPa) in 1 and 2 months. A significant difference of apparent elastic moduli was found between the R-model (1139.30 ± 967.43 MPa) and U-model group (207.15 ± 64.60 MPa) in 2 months. Conclusions: This study showed that the callus structure stability remodeled overtime to achieve a more effective structure, while the material quality of callus tissue is a very important factor for callus strength. At the meantime, this study showed an evidence that the material heterogeneity maybe not as important as it is in bone fracture model.