Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection

The cantilever sensor, which acts as a transducer of reactions between model bacterial cell wall matrix immobilized on its surface and antibiotic drugs in solution, has shown considerable potential in biochemical sensing applications with unprecedented sensitivity and specificity^1-5. The drug-target interactions generate surface stress, causing the cantilever to bend, and the signal can be analyzed optically when it is illuminated by a laser. The change in surface stress measured with nano-scale precision allows disruptions of the biomechanics of model bacterial cell wall targets to be tracked in real time. Despite offering considerable advantages, multiple cantilever sensor arrays have never been applied in quantifying drug-target binding interactions.Here, we report on the use of silicon multiple cantilever arrays coated with alkanethiol self-assembled monolayers mimicking bacterial cell wall matrix to quantitatively study antibiotic binding interactions. To understand the impact of vancomycin on the mechanics of bacterial cell wall structures^1,6,7. We developed a new model¹ which proposes that cantilever bending can be described by two independent factors; i) namely a chemical factor, which is given by a classical Langmuir adsorption isotherm, from which we calculate the thermodynamic equilibrium dissociation constant (K_d) and ii) a geometrical factor, essentially a measure of how bacterial peptide receptors are distributed on the cantilever surface. The surface distribution of peptide receptors (p) is used to investigate the dependence of geometry and ligand loading. It is shown that a threshold value of p ~10% is critical to sensing applications. Below which there is no detectable bending signal while above this value, the bending signal increases almost linearly, revealing that stress is a product of a local chemical binding factor and a geometrical factor combined by the mechanical connectivity of reacted regions and provides a new paradigm for design of powerful agents to combat superbug infections.     

Towards the definition of Institutional diagnostic reference levels in paediatric interventional cardiology procedures in Greece

This study aimed to evaluate paediatric radiation doses in a dedicated cardiology hospital, with the objective of characterising patterns in dose variation. The ultimate purpose was to define Local (Institutional) Diagnostic Reference Levels (LDRLs) for different types of paediatric cardiac interventional procedures (IC), according to patient age. From a total of 710 cases performed during three consecutive years, by operators with more than 15 years of experience, the age was noted in only 477 IC procedures. The median values obtained for Fluoroscopy Time (FT), Number of Frames (N) and Kerma Area Product (P_KA) by age range were 5.8 min, 1322 and 2.0 Gy.cm² for <1 y; 6.5 min, 1403 and 3.0 Gy.cm² for 1 to <5 y; 5.9 min, 950 and 7.0 Gy.cm² for 5 to <10 y; 5.7 min, 940 and 14.0 Gy.cm² for 10 to <16 y, respectively. A large range of patient dose data is observed, depending greatly on procedure type and patient age. In all age groups the range of median FT, N and P_KA values was 3.1–15.8 min, 579–1779 and 1.0–20.8 Gy.cm² respectively. Consequently, the definition of LDRLs presents challenges mainly due to the multiple clinical and technical factors affecting the outcome. On the other hand the lack of paediatric IC DRLs makes the identification of good practices more difficult. A consensus is needed on IC procedures nomenclature and grouping in order to allow a common assessment and comparison of doses.     

Clinical aspects of radiolabeled aptamers in diagnostic nuclear medicine: A new class of targeted radiopharmaceuticals

Targeted radiopharmaceuticals offer the possibility of improved imaging with reduced side effects. Up to now, a variety of biological receptors such as aptamers have been successfully radiolabeled and applied to diagnostic imaging of cancers. The concept of using radio-labeled aptamers for binding to their targets has stimulated an immense body of research in diagnostic nuclear medicine. These biological recognition elements are single-stranded oligonucleotides that interact with their target molecules with high affinity and specificity in unique three-dimensional structures. Because of their high affinity and specificity, the receptor-binding aptamers labeled with gamma emitters such as ^99mTc, ⁶⁴Cu, ¹¹¹In, ¹⁸F and ⁶⁷Ga can facilitate the visualization of receptor-expressing tissues noninvasively. Compared to the antibody-based radiopharmaceuticals, the radiolabeled aptamers provide a number of advantages for clinical diagnostics including high stability, low cost, and ease of production and modification, low immunogenicity and, especially, superior tissue penetration because of their smaller size. In this review, we present recent progresses and challenges in aptamer-based diagnostic radiopharmaceuticals and highlight some representative applications of aptamers in nuclear medicine.     

Difference of two dependent sensitivities and specificities: Comparison of various approaches

In diagnostic studies, a new diagnostic test is often compared with a standard test and both tests are applied on the same patients, called paired design. The true disease state is in general given by the so‐called gold standard (most reliable method for classification), which has to be known for all patients. The benefit of the new diagnostic test can be evaluated by sensitivity and specificity, which are in fact proportions. This means, for the comparison of two diagnostic tests, confidence intervals for the difference of the dependent estimated sensitivities and specificities are calculated. In the literature, many comparisons of different approaches can be found, but none explicitly for diagnostic studies. For this reason we compare 13 approaches for a set of scenarios that represent data of diagnostic studies (e.g., with sensitivity and specificity ?0.8). With simulation studies, we show that the nonparametric interval with normal approximation can be recommended for the difference of two dependent sensitivities or specificities without restriction, the Wald interval with the limitation of slightly anti‐conservative results for small sample sizes, and the nonparametric intervals with t‐approximation, and the Tango interval with the limitation of conservative results for high correlations.     

Diagnostic quality assessment of compressed SENSE accelerated magnetic resonance images in standard neuroimaging protocol: Choosing the right acceleration

PurposeTo investigate the impact of compressed sensing – sensitivity encoding (CS-SENSE) acceleration factor on the diagnostic quality of magnetic resonance images within standard brain protocol.MethodsThree routine clinical neuroimaging sequences were chosen for this study due to their long acquisition time: T2-weighted turbo spin echo (TSE), fluid - attenuated inversion recovery (FLAIR), and 3D time of flight (TOF). Fully sampled reference scans and multiple prospectively 2x to 5x undersampled CS scans were acquired. Retrospectively, undersampled scans were compared to fully sampled scans and visually assessed for image quality and diagnostic quality by three independent radiologists.ResultsImages obtained with CS-SENSE accelerated acquisition were of diagnostically acceptable quality at up to 3x acceleration for T2 TSE (average qualitative score 3.53 on a 4-point scale, with the acquisition time reduction of 64%), up to 2x for FLAIR (average qualitative score 3.27, with the acquisition time reduction of 43%) and 4x acceleration for 3D TOF sequence (average qualitative score 3.13, with the acquisition time reduction of 73%). There were no substantial differences between the readers’ diagnostic quality scores (p > 0.05).ConclusionsCS-SENSE accelerated T2 TSE, FLAIR, and 3D TOF sequences of the brain show image quality similar to that of conventional acquisitions with reduced acquisition time. CS-SENSE can moderately reduce scan time, providing many benefits without losing the image quality.     

血清铜蓝蛋白联合透明质酸检测在肝纤维化患者诊断中的应用

目的探讨血清铜蓝蛋白(CP)联合透明质酸(HA)检测在肝纤维化患者诊断中的应用前景。方法选取2015年1月至2018年12月本院收治的疑似肝纤维化患者226例为研究对象,对患者的CP、HA水平进行联合检测,根据各项指标检测水平对患者做出诊断,并与金标准诊断方法肝穿刺活检结果进行对比。对CP、HA单独检测和联合检测的诊断结果进行统计对比,并对各组检查方法的灵敏度、特异度、假阳性率、假阴性率、准确度等进行统计对比,比较不同检查方法在不同肝纤维化分级患者中的诊断正确率。结果 226例患者中金标准诊断201例(88.94%)为肝纤维化,CP单独检测检出154例(68.14%),HA单独检测检出143例(63.27%),CP+HA联合检测检出195例(86.28%)。经Kappa一致性检验分析CP+HA联合检测与金标准结果有高度一致性,CP、HA单独检测与金标准结果为中等一致性。CP+HA联合检测的灵敏度、特异度、准确度均高于CP、HA单独检测,方法间比较差异有统计学意义(χ~2=11.602、55.959、78.047,P=0.003、0.039、0.002)。在不同分级肝纤维化患者中,CP+HA联合检测在Ⅰ级、Ⅱ级纤维化检出率高于CP、HA单独检测,方法间比较差异有统计学意义(χ~2=9.432、8.324,P=0.007、0.010)。结论 CP联合HA检测在肝纤维化患者诊断中应用情况良好,有较高的诊断正确率,且对症状程度较轻的肝纤维化患者有较高的检出率,可作为肝纤维化诊断检查的主要手段加以推广应用。     

Interpreting coral reef monitoring data: A guide for improved management decisions

Coral reef monitoring programmes exist in all regions of the world, recording reef attributes such as coral cover, fish biomass and macroalgal cover. Given the cost of such monitoring programs, and the degraded state of many of the world’s reefs, understanding how reef monitoring data can be used to shape management decisions for coral reefs is a high priority. However, there is no general guide to understanding the ecological implications of the data in a format that can trigger a management response. We attempt to provide such a guide for interpreting the temporal trends in 41 coral reef monitoring attributes, recorded by seven of the largest reef monitoring programmes. We show that only a small subset of these attributes is required to identify the stressors that have impacted a reef (i.e. provide a diagnosis), as well as to estimate the likely recovery potential (prognosis). Two of the most useful indicators, turf algal canopy height and coral colony growth rate are not commonly measured, and we strongly recommend their inclusion in reef monitoring. The diagnosis and prognosis system that we have developed may help guide management actions and provides a foundation for further development as biological and ecological insights continue to grow.     

经阴道超声与宫腔镜对子宫内膜病变患者的诊断价值比较研究

目的:探讨经阴道超声与宫腔镜检查诊断子宫内膜病变的临床价值,为临床诊断子宫内膜病变提供理论依据。方法:选取2011年3月-2014年3月间我院收治的158例疑似子宫内膜病变患者,分别采用经阴道超声和宫腔镜进行检查,并以病理诊断结果为"金标准",比较两种检查方法的诊断价值。结果:病理检查结果中,143例患者被确诊为子宫内膜病变,其中子宫内膜增生23例(16.08%),子宫内膜息肉31例(21.68%),子宫粘膜下肌瘤24例(16.78%),子宫内膜癌19例(13.29%),慢性非特异性子宫内膜炎46例(32.17%)。宫腔镜对子宫内膜病变诊断的准确率为94.41%,高于阴道超声的81.12%,差异有统计学意义(P0.05),其中阴道超声和宫腔镜对子宫粘膜下肌瘤、子宫内膜癌诊断的准确率比较差异无统计学意义(P0.05),阴道超声对子宫内膜增生、子宫内膜息肉及慢性非特异性子宫内膜炎的诊断准确率均较宫腔镜降低,差异有统计学意义(P0.05)。阴道超声对子宫内膜病变诊断的特异度较宫腔镜更低(P0.05),但两者灵敏度、AUC比较差异无统计学意义(P0.05)。结论:经阴道超声诊断子宫内膜病变简单、有效,而宫腔镜诊断子宫内膜病变具有准确率以及特异度较高的特点。