Synthesis and Application of Negatively Charged PNA Analogues

Negatively charged DNA mimics containing phosphonate analogues of peptide nucleic acids were designed, and their physicochemical and biological properties were evaluated in the comparison with natural oligonucleotides, classical peptide nucleic acids, and morpholino phosphorodiamidate oligonucleotide analogues. The results obtained revealed a high potential of phosphonate-containing PNA derivatives for a number of biological applications, such as diagnostic, nucleic acids analysis, and inhibition of gene expression.     

Minimal Erythema Dose (MED) Testing

Ultraviolet radiation (UV) therapy is sometimes used as a treatment for various common skin conditions, including psoriasis, acne, and eczema. The dosage of UV light is prescribed according to an individual''s skin sensitivity. Thus, to establish the proper dosage of UV light to administer to a patient, the patient is sometimes screened to determine a minimal erythema dose (MED), which is the amount of UV radiation that will produce minimal erythema (sunburn or redness caused by engorgement of capillaries) of an individual''s skin within a few hours following exposure. This article describes how to conduct minimal erythema dose (MED) testing. There is currently no easy way to determine an appropriate UV dose for clinical or research purposes without conducting formal MED testing, requiring observation hours after testing, or informal trial and error testing with the risks of under- or over-dosing. However, some alternative methods are discussed.     

The relationship between the presence of ADHD and certain candidate gene polymorphisms in a Turkish sample

Due to the high heritability of attention-deficit hyperactivity disorder (ADHD), parents of children with ADHD appear to represent a good sample group for investigating the genetics of the disorder. The aim of this study was to investigate the association between ADHD and six polymorphisms in five candidate genes [5-HT2A (rs6311), NET1 (rs2242447), COMT (rs4818), NTF3 (rs6332), SNAP-25 (rs3746544) and (rs1051312)]. We included 228 parents of children diagnosed with ADHD and 109 healthy parents as the control group. The polymorphisms were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays and analyzed using the chi-square test and the multinomial logit model. SNAP-25 (rs3746544) polymorphism was associated with loading for ADHD, while 5-HT2A (rs6311) and NET1 (rs2242447) polymorphisms were associated with ADHD. On the other hand, there was no significant association between the SNAP-25 (rs1051312), NTF3 (rs6332), or COMT (rs4818) gene polymorphisms and ADHD.     

Differences Between Men and Women in Ambulatory Blood Pressure Thresholds for Diagnosis of Hypertension Based on Cardiovascular Outcomes

Previous studies have reported sex differences in the pathophysiology of hypertension and responses to blood pressure (BP)-lowering medications. Moreover, men exhibit typically higher BP than women, the differences being greater for systolic (SBP) than diastolic (DBP) BP. These differences become apparent during adolescence and remain significant at least until 55–60 yrs of age. Despite such significant sex-related differences in BP regulation, the current recommended ambulatory BP monitoring (ABPM) thresholds for diagnosis of hypertension do not differentiate between men and women. We aimed to derive separate male and female diagnostic thresholds for the awake and asleep SBP and DBP means based upon cardiovascular disease (CVD) outcome. We prospectively studied 3344 subjects (1718 men/1626 women), 52.6?±?14.5 yrs of age, during a median follow-up of 5.6 yrs. Those with hypertension at baseline were randomized to ingest all their prescribed hypertension medications upon awakening or the entire daily dose of ≥1 of them at bedtime. At baseline, BP was measured at 20-min intervals from 07:00 to 23:00?h and at 30-min intervals at night for 48?h, and physical activity was simultaneously monitored every minute by wrist actigraphy to accurately derive the awake and asleep BP means. Identical assessment was scheduled annually and more frequently (quarterly) if treatment adjustment was required. Cox regression analysis was used to derive outcome-based reference thresholds for ABPM in men and women. Men exhibited greater event rates than women of CVD death, myocardial infarction, angina pectoris, coronary revascularization, and heart failure; however, event rates of non-CVD death and cerebrovascular events were comparable. The relationship between progressively higher ambulatory BP and CVD risk increased more rapidly in women than men for awake SBP/DBP means ≥125/75?mm Hg and asleep means ≥110/70?mm Hg. The derived outcome-based reference thresholds for men were 135/85?mm Hg for the awake and 120/70?mm Hg for the asleep SBP/DBP means. In terms of CVD outcome, the equivalent cutoff threshold values for women were 125/80?mm Hg for the awake and 110/65?mm Hg for the asleep SBP/DBP means. Outcome-based reference thresholds for the diagnosis of hypertension were 10/5?mm Hg lower for ambulatory SBP/DBP in women than men. This marked sex difference indicates the need for revision of current guidelines that propose diagnostic thresholds for ambulatory BP without differentiation between men and women. (Author correspondence: rhermida@uvigo.es)     

Multi-test analysis and model-based estimation of the prevalence of Taenia saginata cysticercus infection in naturally infected dairy cows in the absence of a ‘gold standard’ reference test

The diagnostic values of seven serological tests (ELISAs) and of the obligatory European Union-approved routine visual meat inspection for the detection of Taenia saginata cysticercosis were investigated. A total of 793 slaughtered dairy cows were selected in three European Union approved abattoirs in Switzerland, an endemic area (apparent prevalence by enhanced meat inspection up to 4.5%) with typically low parasite burdens. ELISAs based on a somatic larval antigen, isoelectric focused somatic larval antigen, larval excretory/secretory antigens, peptide HP6-2, peptide Ts45S-10, pooled peptide solution and a monoclonal antibody antigen capture assay were initially screened. As there is no perfect diagnostic ‘gold standard’ reference test, the obligatory meat inspection and four selected serological tests were further analysed using Bayesian inference to estimate the “true” prevalence and the diagnostic test sensitivities and specificities. The ELISA for specific antibody detection based on excretory/secretory antigens showed highest sensitivity and specificity with 81.6% (95% credible interval: 70–92) and 96.3% (95% credible interval: 94–99), respectively. The Bayesian model estimated the specificity of the ELISA, based on the synthetic peptide Ts45S-10 as 55.2% (95% credible interval: 46–65) and sensitivity as 84.7% (95% credible interval: 82–88). The sensitivity of the ELISA based on mAbs, detecting circulating antigen, was 14.3% (95% credible interval: 9–23) with a specificity of 93.7% (95% credible interval: 92–96). The diagnostic sensitivity of the obligatory standard European Union meat inspection procedure for the detection of T. saginata cysticercus infection at the abattoir was estimated to be 15.6% (95% credible interval: 10–23). Based on these data, the modelled prevalence of cysticercosis in dairy cows presented at abattoirs in Switzerland was estimated to be 16.5% (95% credible interval: 13–21). These cattle also had a high prevalence of infection with Dicrocoelium dendriticum (60.8%) and Fasciola hepatica (13.5%).     

自动乳腺全容积扫描联合乳腺钼靶摄影在乳腺疾病诊断中的价值

目的：探讨自动乳腺全容积扫描（automated breast volume scanner,ABVS）联合乳腺钼靶摄影在乳腺疾病诊断中的价值。方法：观察随访130例就诊我科的乳腺疾病患者,进行ABVS、传统超声和乳腺钼靶检查。结果：130例患者中ABVS的疾病单独诊断准确率为91．5％（119／130）,传统乳腺超声的单独诊断准确率为84．6％（110／130）,乳腺钼靶的单独诊断准确率为86．9％（113／130）,而ABVS联合乳腺钼靶应用的诊断准确率为95．4％（124／130）,明显优于两者单独应用,差异具有统计学意义（P〈0．05）。结论：ABVS是一种全新的乳腺检查方法,较传统乳腺超声、乳腺钼靶具有较高的疾病诊断准确率,而ABVS联合乳腺钼靶可以显著提高诊断的准确率,值得在临床推广。     

Approaches to diagnose DNA mismatch repair gene defects in cancer

The DNA repair pathway mismatch repair (MMR) is responsible for the recognition and correction of DNA biosynthetic errors caused by inaccurate nucleotide incorporation during replication. Faulty MMR leads to failure to address the mispairs or insertion deletion loops (IDLs) left behind by the replicative polymerases and results in increased mutation load at the genome. The realization that defective MMR leads to a hypermutation phenotype and increased risk of tumorigenesis highlights the relevance of this pathway for human disease. The association of MMR defects with increased risk of cancer development was first observed in colorectal cancer patients that carried inactivating germline mutations in MMR genes and the disease was named as hereditary non-polyposis colorectal cancer (HNPCC). Currently, a growing list of cancers is found to be MMR defective and HNPCC has been renamed Lynch syndrome (LS) partly to include the associated risk of developing extra-colonic cancers. In addition, a number of non-hereditary, mostly epigenetic, alterations of MMR genes have been described in sporadic tumors. Besides conferring a strong cancer predisposition, genetic or epigenetic inactivation of MMR genes also renders cells resistant to some chemotherapeutic agents. Therefore, diagnosis of MMR deficiency has important implications for the management of the patients, the surveillance of their relatives in the case of LS and for the choice of treatment. Some of the alterations found in MMR genes have already been well defined and their pathogenicity assessed. Despite this substantial wealth of knowledge, the effects of a large number of alterations remain uncharacterized (variants of uncertain significance, VUSs). The advent of personalized genomics is likely to increase the list of VUSs found in MMR genes and anticipates the need of diagnostic tools for rapid assessment of their pathogenicity. This review describes current tools and future strategies for addressing the relevance of MMR gene alterations in human disease.     

16层螺旋CT三维重建与DR平片检查对外伤性肋骨骨折的诊断价值比较研究

目的:研究16层螺旋电子计算机断层扫描(CT)三维重建与数字化摄影(DR)平片检查对外伤性肋骨骨折的诊断价值,为临床诊治提供参考。方法:将2017年6月至2018年6月期间于本院接受诊治的82例外伤性肋骨骨折患者作为研究对象,所有患者均接受16层螺旋CT三维重建与DR平片检查,观察并记录患者的骨折发生部位,并比较两种诊断方法对外伤性肋骨骨折诊断的准确率、灵敏度、特异性、阳性预测值、阴性预测值以及漏诊情况。结果:82例外伤性肋骨骨折患者经影像学与临床诊断明确发生骨折179处,多发性骨折发生率为62.20%,单发性骨折发生率为37.80%,骨折肋骨段位中4-10段骨折发生率最高为69.83%,骨折肋骨水平阶段中腋肋骨折发生率最高为59.78%。相较于DR平片,16层螺旋CT三维重建诊断外伤性肋骨骨折的准确率、灵敏度、特异性、阳性预测值、阴性预测值更高,漏诊率更低,差异有统计学意义(P0.05)。结论:相较于DR平片检查,应用16层螺旋CT三维重建检查外伤性肋骨骨折能明显提高临床诊断的准确率、灵敏度和特异性,减少漏诊,可为临床诊治提供更可靠的信息,值得临床推广。     

超声对早期糖尿病肾病的诊断价值及肾动脉血流阻力指数与血清hs-CRP、VEGF的关系分析

目的:研究彩色多普勒超声对早期糖尿病肾病的诊断价值及肾动脉血流阻力指数与血清超敏C反应蛋白(hs-CRP)、血管内皮生长因子(VEGF)的关系。方法:选取从2017年2月～2018年2月兰州大学第二医院收治的早期糖尿病肾病患者50例记为病变组,另取同期于该院进行体检的健康人员50例记为对照组。分别对两组人员进行彩色多普勒超声检查,比较肾血流参数。采用酶联免疫吸附法检测两组人员血清hs-CRP、VEGF水平,并作指标间的相关性分析。结果:病变组肾主动脉、肾锥体两侧叶间动脉、肾段动脉的收缩期峰值速度、舒张期最低速度较对照组降低,病变组肾主动脉、肾锥体两侧叶间动脉、肾段动脉的阻力指数较对照组升高(均P0.05)。病变组血清hs-CRP、VEGF水平较对照组升高(均P0.05)。经Pearson相关性分析显示:早期糖尿病肾病患者肾主动脉、肾锥体两侧叶间动脉、肾段动脉的血流阻力指数与血清hs-CRP、VEGF均呈正相关关系(均P0.05)。结论:彩色多普勒超声应用于早期糖尿病肾病的诊断价值较高,且肾动脉血流阻力指数与血清hs-CRP、VEGF密切相关,临床工作中通过联合检测血清hs-CRP、VEGF,从而有助于早期糖尿病肾病的诊断。     

Proteome Analysis of Human Neutrophil Granulocytes From Patients With Monogenic Disease Using Data-independent Acquisition

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Highlights

• •Data-independent acquisition proteomics analysis of naive neutrophils from patients with rare monogenic diseases.
• •Proteomics analysis helps guide targeted genetic diagnostics of patients for which routine clinical diagnostics proved inconclusive.