妊娠早期胎儿颈部透明层厚度与胎儿预后的前瞻性队列研究

目的探讨妊娠早期胎儿颈部透明层(NT)厚度与胎儿预后的关系。方法收集2015年12月至2018年12月于南京大学医学院附属鼓楼医院行妊娠早期胎儿NT厚度测量的单胎孕妇,共4958例建立前瞻性研究队列,进行妊娠早期胎儿结构超声筛查、妊娠早期血清学筛查、妊娠中期超声筛查及对新生儿出生后28 d的体格检查。根据妊娠早期超声筛查的结果,分为胎儿NT增厚(≥3.0 mm)者167例与NT厚度正常者4791例;将胎儿NT增厚的孕妇,分为胎儿单纯NT增厚者86例与NT增厚合并结构异常者81例。分析不同NT厚度胎儿的预后,并重点对单纯NT增厚与NT增厚合并结构异常胎儿的妊娠结局进行分析。妊娠早期超声筛查发现胎儿结构异常或血清学筛查结果为高风险的孕妇,经绒毛穿刺取样术行染色体微阵列分析(CMA)检测以明确产前诊断。结果(1)胎儿NT厚度正常孕妇的妊娠结局:共4791例孕妇,包括胎儿NT厚度正常且无结构异常者4726例,其中妊娠中期及产后新诊断结构异常83例,4688例活产;胎儿NT厚度正常但结构异常的孕妇65例,其中61例孕妇终止妊娠,4例活产。(2)胎儿单纯NT增厚孕妇的妊娠结局:86例孕妇中,66例(76.7%,66/86)行CMA检测,3例胎儿诊断为21三体综合征;除7例孕妇选择终止妊娠外,余79例行妊娠中期超声检查、新生儿出生后28 d体格检查、新生儿电话随访至6~21个月均未发现发育异常。(3)胎儿NT增厚合并结构异常孕妇的妊娠结局:81例孕妇中,73例(90.1%,73/81)行CMA检测,其中32例的胎儿为染色体非整倍体异常。70例选择终止妊娠,2例妊娠中期自然流产,9例活产。(4)NT增厚是否合并结构异常胎儿的产前诊断结果及预后比较:单纯NT增厚的胎儿染色体非整倍体的发生率为3.5%(3/86),合并结构异常者为39.5%(32/81),两者比较,差异有统计学意义(χ2=32.7,P<0.01);胎儿单纯NT增厚孕妇的健康新生儿存活率为91.9%(79/86),合并结构异常者为9.9%(8/81),两者比较,差异有统计学意义(χ2=112.3,P<0.01)。结论妊娠早期,超声筛查胎儿NT及结构,能提高出生缺陷的产前筛查率。单纯NT增厚胎儿的染色体非整倍体的发生率较低,新生儿健康存活率较高。     

2012 – The year when BAOMS and its officers prevented closure of all UK shortened medical and dental courses

In Spring 2011 the Department of Health (DH) received a request to review European Union Directive 2005/36 EU – the directive relating to the recognition of professional qualifications. The Department of Health lawyer raised concerns that the existing shortened dental courses may be in breach of EU law. There were three shortened dental courses in the UK: 4 year graduate entry courses in Liverpool/Peninsula and 3-year Dental Programme for Medical Graduates (DPMG) in Kings, London. During the summer the General Dental Council (GDC) was made aware of these concerns. In autumn 2011 the Chief Dental Officer for England with the GDC, told the Dental Deans’ Council (DDC) that shortened dental courses were illegal. On 12th Jan 2012 students on the DPMG were told that they would have to complete a full 5-year dental degree. The GDC said that this interpretation of EU law would also impact on shortened medical courses. In view of the potentially enormous impact that this would have on OMFS training, BAOMS engaged all the resources it could and by assembling legal opinions including written contributions from Sir David Edward, whose opinion was being misinterpreted by the GDC and DH, and by sharing these resources with all the stakeholders, BAOMS was able to preserve shortened dental and medical courses. Now that the UK has left the European Union, negotiations around mutual recognition of qualifications may mean this issue will resurface. We should remain vigilant.     

Evidence-making hepatitis C cure: Towards a science that knows more carefully

There has been some controversy concerning the curative potential of new treatments for hepatitis C. This follows a systematic review of the Cochrane Collaboration questioning the clinical benefits of direct-acting antivirals (DAAs). This controversy has been debated as a matter of methods regarding how best to evidence treatment in an evidence-based medicine (EBM) approach. Drawing from science and technology studies (STS), we offer an alternative perspective. We propose a different way of thinking with evidence; one which treats ‘evidencing as performative’. Using the Cochrane review and its linked published responses as a resource for this analysis, we consider how hepatitis C cure is differently made-up through the knowledge-making practices performing it. We show how matters of apparent fact in evidence-based science are enacted as matters of clinical, social and ethico-political concern. We notice hepatitis C cure as a fluid object in negotiation. We highlight the limits of current debate to advocate a more critical and careful practice-based approach to knowing hepatitis C cure. This calls upon public health researchers to reflect on the performative work of their evidencing. We propose a ‘more-than’ EBM approach which treats ‘evidence-based’ science as an ‘evidence-making intervention’. We consider the implications of such an approach for the evidencing of public health interventions and for treating hepatitis C in the DAA era of ‘viral elimination’.     

Synthesis and docking studies of N-(5-(alkylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamide analogues as potential alkaline phosphatase inhibitors

A series of N-(5-(alkylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamides 6a–i were synthesized as alkaline phosphatase inhibitors. The intermediate 5-substituted 1,3,4-oxadiazole-2-thione 4 was synthesized starting with hippuric acid. Hippuric acid in the first step was converted into corresponding methyl ester 2 which upon reaction with hydrazine hydrate furnished the formation of hydrazide 3 . The hippuric acid hydrazide was then cyclized into 5-substituted 1,3,4-oxadiazole-2-thione 4 . The intermediate 4 was then reacted with alkyl or aryl halides 5a–5i to afford the title compounds N-(5-(methylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamides 6a–i . The bioassay results showed that compounds 6a–i exhibited good to excellent alkaline phosphatase inhibitory activity. The most potent activity was exhibited by the compound 6i having IC₅₀ value 0.420 μM, whereas IC₅₀ value of standard (KH₂PO₄) was 2.80 μM. Molecular docking studies was performed against alkaline phosphatase enzyme (PDBID 1EW2) to check binding affinity of the synthesized compounds 6a–i against target protein. The docking results showed that three compounds 6c , 6e , and 6i have maximum binding interactions with binding energy values of −8 kcal/mol. The compound 6i displayed the interactions of oxadiazole ring nitrogen with amino acid His265 having a binding distance 2.13 Ǻ. It was concluded from our results that synthesized compounds, especially compound 6i may serve as lead structure to design more potent inhibitors of human alkaline phosphatase.     

Laser‐based radiocarbon detection in the laboratory: How soon?

Research over the past 25 years and the use of accelerator mass spectrometry (AMS) have demonstrated benefits of single‐atom counting of ¹⁴C compared with scintillation monitoring of ¹⁴C radioactive decay for a multitude of applications in drug development studies. These include pharmacokinetics and metabolism studies, microdosing studies, and quantification of DNA adducts. In the last decade, the possibility of single‐atom counting using lasers has been demonstrated, providing the possibility of simplified laboratory‐based systems, which can equal or excel AMS sensitivity and provide scintillation system convenience without high levels of radioactivity. To achieve the required sensitivity, optical storage cavities have been used to enhance the laser interaction of the low densities of radiocarbon present. Two types of laser technologies have been used‐cavity ring‐down spectroscopy (CRDS) and intracavity opto‐galvanic spectroscopy (ICOGS). Problems to be overcome to achieve routine use have included separation of the ¹⁴C signal from backgrounds, achievement of acceptable precision and accuracy, reduction of measurement times for small samples, and improvement in the ease of use for the operator. Both technologies have achieved impressive results to date using samples of order 1 mg with CRDS and 10 μg with ICOGS. Commercial development is the next step.