流式细胞术检测急性髓系白血病微小残留病的现状与进展

流式细胞术(FCM)检测微小残留病(MRD)具有很高的灵敏度和覆盖率,已经成为急性髓系白血病(AML)重要的疗效监测、预后评估和指导治疗方法选择的生物标记。然而,FCM检测AML患者MRD仍有许多问题亟待解决。本文介绍了FCM检测AML MRD的现状以及存在的问题,提出相应的解决方案与注意事项,并展望了新技术带来的新希望。     

Laboratory validation of a lateral flow device for the detection of CyHV-3 antigens in gill swabs

Cyprinid herpesvirus-3 (CyHV-3) induces the highly contagious koi herpesvirus disease (KHVD) and may result in significant economic losses to the ornamental and food-producing carp industry. Suspicion of KHVD is triggered by clinical signs and confirmed using laboratory techniques. The latter are labour- and time-consuming, require specialised equipment and trained personnel. For rapid, on-site detection of CyHV-3, a lateral flow device (LFD) was developed using two monoclonal antibodies directed towards the viral glycoprotein ORF65. The LFD was highly specific with analytical and diagnostic specificities of 100%. Analytical sensitivity ranged between 1.25 × 10² and 2.40 × 10⁴ plaque forming units per ml for isolates originating from geographically distinct regions. In experimentally infected carp, CyHV-3 was detected as early as 4–5 days post infection. Diagnostic sensitivities of 52.6% and 72.2% relative to PCR were recorded, depending on the viral isolate used. When onset of mortality was taken as reference, diagnostic sensitivities increased to 67.0% and 93.3%. The diagnostic sensitivity for freshly found-dead animals was 100%, irrespective of the virus isolate used. Given the high specificity and ease-of-use for on-site detection of CyHV-3, the LFD was regarded fit for purpose as a first-line diagnostic tool for the identification of acute CyHV-3 infections in KHVD affected (koi) carp.     

Influence of knowledge,training and experience of observers on the reliability of anthropometric measurements in children

Objective : To elucidate the impact of the observer's level of technical knowledge, training and experience with measuring height and triceps skinfold thickness on the reliability of these measurements in children. Despite of instructions and encouraging careful measurements, these factors may significantly affect measurements and lead to interpretation difficulties, especially of short term growth data. Subjects and methods : A cross-sectional study was designed in which 18 children, aged 2-7 years, were measured in duplo by 12 observers with different backgrounds and levels of experience, protocol knowledge and protocol training. The main outcome measures, precision and accuracy, were expressed as technical error of measurement (TEM) and average bias (AB) in comparison with an expert anthropometrist. Results : As expected, the best educated and most experienced observers scored the best precision and accuracy. By ranking analysis and multiple regressions we learned that precision and accuracy in measuring height and triceps skinfold thickness are mainly predicted by allround knowledge of the measurement protocol (p< 0.05) and the years of experience (p< 0.05). A practical training course of only a few hours does not seem to improve reliability significantly. Conclusion : To get a more reliable insight in growth of a child it is important to be aware of the influence on measurement outcome values of protocol knowledge and years of experience. Growth studies should use detailed anthropometric standardization protocols and train people to acquire better insight into these protocols.     

Wireless Capsule Endoscopy Video Reduction Based on Camera Motion Estimation

Wireless capsule endoscopy (WCE) is a novel technology aiming for investigating the diseases and abnormalities in small intestine. The major drawback of WCE examination is that it takes a long time to examine the whole WCE video. In this paper, we present a new reduction scheme for WCE video to reduce the examination time. To achieve this task, a WCE video motion model is proposed. Under this motion model, the WCE imaging motion is estimated in two stages (the coarse level and the fine level). In the coarse level, the WCE camera motion is estimated with a combination of Bee Algorithm and Mutual Information. In the fine level, the local gastrointestinal tract motion is estimated with SIFT flow. Based on the result of WCE imaging motion estimation, the reduction scheme preserves key images in WCE video with scene changes. From experimental results, we notice that the proposed motion model is suitable for the motion estimation in successive WCE images. Through the comparison with APRS and FCM-NMF scheme, our scheme can produce an acceptable reduction sequence for browsing and examination.     

Conjugating doxorubicin to polymannose: a new strategy for target specific delivery to lung cancer cells

Abstract

As mannose receptors are known to be over-expressed in cancer cells, we synthesized polymannose-doxorubicin (PM-DOX) conjugates with the objective of targeting the drug to cancer cells. DOX was conjugated to oxidized PM through Schiff’s linkages to obtain PM-DOX conjugates. In order to examine the superior targeting efficacy of PM-DOX conjugate, sodium alginate (SA) was conjugated to DOX by similar chemistry and compared with PM-DOX conjugate. The cytotoxicity of the conjugates was investigated in A549 cell lines using MTT Assay and the cell uptake and retention studies, were performed using flow cytometry and cell imaging. In vitro drug release studies with both PM-DOX and SA-DOX conjugates showed an initial burst release of DOX up to 37–39% at 1?h, followed by a steady release up to 58–62% at 24?h in human plasma while negligible release was observed in phosphate buffered saline. The conjugates exhibited negligible hemolytic potential to human erythrocytes compared to free DOX. The PM-DOX conjugate showed better cytotoxic potential against A549 cells at lower concentration (equivalent to 0.27?μg/mL of DOX) at 72?h compared to free DOX and SA-DOX conjugate. Further, PM-DOX conjugate showed enhanced uptake by the cells in comparison with SA-DOX conjugate thereby confirming the target specificity of PM to the cancer cells.     

Estimating contrast agent motion from ultrasound images using an anisotropic diffusion-based optical flow technique

The purpose of this study was to suggest a novel optical flow method to estimate the motion patterns of contrast agents from an ultrasound image. We first recomposed the original image with relative structural and textural parts. We embedded an anisotropic diffusion model into a slightly non-convex total variation-L1 approximation scheme to provide more reliable estimates. An intermediate bilateral filter was adopted after each computation step to prevent over-smoothing effects. Ultrasound data were acquired during continuous injection of contrast agent into a tissue mimicking phantom. The results showed that our method provided robust performance for estimating contrast agent flow patterns.     

Dynamic CT Myocardial Perfusion Imaging in Patients without Obstructive Coronary Artery Disease: Quantification of Myocardial Blood Flow according to Varied Heart Rate Increments after Stress

ObjectiveThe present study aimed to investigate the association between myocardial blood flow (MBF) quantified by dynamic CT myocardial perfusion imaging (CT-MPI) and the increments in heart rate (HR) after stress in patients without obstructive coronary artery disease.Materials and MethodsWe retrospectively included 204 subjects who underwent both dynamic CT-MPI and coronary CT angiography (CCTA). Patients with more than minimal coronary stenosis (diameter ≥ 25%), history of myocardial infarction/revascularization, cardiomyopathy, and microvascular dysfunction were excluded. Global MBF at stress was measured using hybrid deconvolution and maximum slope model. Furthermore, the HR increments after stress were recorded.ResultsThe median radiation dose of dynamic CT-MPI plus CCTA was 5.5 (4.5–6.8) mSv. The median global MBF of all subjects was 156.4 (139.8–180.4) mL/100 mL/min. In subjects with HR increment between 10 to 19 beats per minute (bpm), the global MBF was significantly lower than that of subjects with increment between 20 to 29 bpm (153.3 mL/100 mL/min vs. 171.3 mL/100 mL/min, p = 0.027). This difference became insignificant when the HR increment further increased to ≥ 30 bpm.ConclusionThe global MBF value was associated with the extent of increase in HR after stress. Significantly higher global MBF was seen in subjects with HR increment of ≥ 20 bpm.     

Importance of measurement site on assessment of lesion-specific ischemia and diagnostic performance by coronary computed tomography Angiography-Derived Fractional Flow Reserve

BackgroundValues of fractional flow reserve (FFR_CT) by coronary computed tomography angiography (CTA) decline from the ostium to the terminal vessel, irrespective of stenosis severity. The purpose of this study is to determine if the site of measurement of FFR_CT impacts assessment of ischemia and its diagnostic performance relative to invasive FFR (FFR_INV).Methods1484 patients underwent FFR_CT; 1910 vessels were stratified by stenosis severity (normal; <25%, 25–50%, 50–70%, and >70% stenosis). The rates of positive FFR_CT (≤0.8) were determined by measuring FFR_CT from the terminal vessel and from distal-to-the-lesion. Reclassification rates from positive to negative FFR_CT were calculated. Diagnostic performance of FFR_CT relative to FFR_INV was evaluated in 182 vessels using linear regression, Bland Altman analysis, and receiver operating characteristic (ROC) curves.ResultsPositive FFR_CT was identified in 24.9% of vessels using terminal vessel FFR_CT and 10.1% using FFR_CT distal-to-the-lesion (p ?< ?0.001). FFR_CT obtained distal-to-the-lesion resulted in reclassification of 59.6% of positive terminal FFR_CT to negative FFR_CT. Relative to FFR_INV, there were improvements in specificity (50% to 86%, p ?< ?0.001), diagnostic accuracy (65% to 88%, p ?< ?0.001), positive predictive value (50% to 78%, p ?< ?0.001), and area-under-the-curve (AUC, 0.83 to 0.91, p ?< ?0.001) when FFR_CT was measured distal-to-the-lesion.ConclusionFFR_CT values from the terminal vessel should not be used to assess lesion-specific ischemia due to high rates of false positive results. FFR_CT measured distal-to-the-lesion improves the diagnostic performance of FFR_CT relative to FFR_INV, ensures that FFR_CT values are due to lesion-specific ischemia, and could reduce the rate of unnecessary invasive procedures.     

Effects of mild chronic cerebral hypoperfusion and early amyloid pathology on spatial learning and the cellular innate immune response in mice

Understanding the contribution of cerebrovascular factors in the progression of cognitive decline in Alzheimer's disease (AD) is a key step for the development of preventive therapies. Among these factors, chronic cerebral hypoperfusion is an early component of AD pathogenesis that can predict the progression from mild cognitive impairment to AD. Here, we investigated the effects of a protocol of mild chronic cerebral hypoperfusion in the APPswe/PS1 transgenic mouse model of AD. We observed that the permanent occlusion of the right common carotid artery induced spatial learning impairments in young APPswe/PS1 mice, but not in their wild type littermates. Furthermore, the extent of learning deficits strongly correlated with the number of cortical β-amyloid plaques, with the mobilization of monocytes into the blood and with the number of bone marrow-derived microglia in the brain. These results indicate that a mild reduction of cerebral blood flow can selectively induce cognitive deficits at an early stage of amyloid pathology, eliciting a cellular innate immune response, even without causing neuronal death.     

Impaired glucose tolerance in midlife and longitudinal changes in brain function during aging

We investigated whether individuals with impaired glucose tolerance (IGT) in midlife subsequently show regionally specific longitudinal changes in regional cerebral blood flow (rCBF) relative to those with normal glucose tolerance (NGT). Sixty-four cognitively normal participants in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging underwent serial ¹⁵O-water positron emission tomography scans (age at first scan, 69.6 ± 7.5 years) and oral glucose tolerance tests 12 years earlier (age at first oral glucose tolerance test, 57.2 ± 11.1 years). Using voxel-based analysis, we compared changes in rCBF over an 8-year period between 15 participants with IGT in midlife and 49 with NGT. Significant differences were observed in longitudinal change in rCBF between the IGT and NGT groups. The predominant pattern was greater rCBF decline in the IGT group in the frontal, parietal, and temporal cortices. Some brain regions in the frontal and temporal cortices also showed greater longitudinal increments in rCBF in the IGT group. Our findings suggest that IGT in midlife is associated with subsequent longitudinal changes in brain function during aging even in cognitively normal older individuals.