Noninvasive Stem Cell Labeling Using USPIO Technique and their Detection with MRI

Background: To date, several imaging techniques to track stem cells are used such as positron emission tomography (PET), single photon emission computed tomography (SPECT), Bioluminescence imaging (BLI), fluorescence imaging, CT scan and magnetic resonance imaging (MRI). Although, overall sensitivity of MRI compared to SPECT and Bioluminescence techniques are lower, but due to high spatial resolution (~100 mm), long term three-dimensional imaging capability, in vivo quick access to images in three different sections, and noninvasiveness it is being used as the method of choice. Methods: The present study is the search results for authors and sources of information in the field of molecular and cellular imaging to examine the problems and perspectives about stem cells labeling with Ultrasmall Super Paramagnetic Iron Oxide (USPIO) and their tracking by MRI. Results: With the advancement of technology, including quantum physics, chemistry, and computer software, MRI with an excellent spatial resolution and contrast, is surpasses other imaging modalities in the analysis of anatomical and pathological features and images of all body tissues. From the other side, advances in the astronomical science, chemistry and nanotechnology, high biocompatibility and cytotoxicity of nanoparticles, and due to analysis in the metabolic pathways of iron made the procedure easier; however, there are still several fundamental questions in understanding the mechanism of biological molecules in the living cells including: 1- How to detect not only the location but also the performance of the labeled cells? Probably combination of USPIO nanoparticles with other reporter genes as contrast agents for MRI and PET can simultaneously be used to overcome these limitations 2) How to trace stem cells from pre-clinical models to translate to humans? Up to now, due to issues of bioethics, little studies have been done in this area. 3) Whether the transplanted stem cells that have reached the target tissue, will remain or migrate? Despite the fact that cell proliferation and exocytosis are two main factors for long term protection of USPIO nanoparticles inside cells, their signals cannot be received for a long time. 4) What mechanisms cause stem cells reaching the target tissue to react with their environment? And 5) what is the number of transplanted cells in live tissue, and what is their half-life? Conclusion: This study showed that USPIO nanoparticles can enter the cell with a clear dose without any adverse biological effects and could be detected by SWI and T2* techniques under MRI (1.5 Tesla) scanner for almost one month. MRI as a secure mean can illustrate with optimal resolution the spatial-resolution and three-dimensional positions of the stem cells. Keywords: Ultrasmall Super Paramagnetic Iron Oxide (USPIO), labeled stem cell, in vivo tracking, MRI

Prognostic value of mean platelet volume in patients undergoing elective percutaneous coronary intervention

Objective: We sought to determine the role of mean platelet volume (MPV) for predicting long-term outcomes of elective percutaneous coronary intervention (PCI). Methods: On the basis of retrospective cohort study, we collected characteristics of 680 patients undergoing elective PCI from October 2005 to August 2010. The patients who had preoperative MPV were assessed for developing major adverse cardiac events (MACE) during 1-year follow- up. They were categorized into two groups including MPV <9.6 fL (n=89) and MPV �9.6 fL (n=92). Data were analyzed using t-test, chi-square test, Pearson correlation, receiver operating characteristic (ROC) curve and logistic regression. Results: One-hundred eighty one patients (26.6) met inclusion criteria. The MACE was observed in 29 patients (16); and its rate in low- and high-MPV groups was 11.2 and 20.7, respectively (p=0.084). MPV was significantly higher in the patients with left ventricular ejection fraction (LVEF) <40 compared with that of �40 (p<0.001). There were a significant and negative correlation between MPV and platelet count (r=-0.305, p<0.001), and significant and positive correlations between MPV and platelet distribution width (PDW) and platelet large cell ratio (P-LCR) (r=0.615, p<0.001 and r=0.913, p<0.001; respectively). The best MPV cut-off point was 9.25 fL; the sensitivity and specificity were 79 and 38, respectively. Elevated MPV was the best predictor of MACE at 1-year follow-up (OR=11.359, 95 CI 2.481-51.994, p=0.002). Conclusion: The results indicate that preoperative MPV is an independent predictor of the MACE at 1-year follow-up in the patients undergoing elective PCI. Moreover, it may be useful for risk stratification in such cases. © 2015 by Turkish Society of Cardiology

Application of allogeneic fibroblast cells in cellular therapy of recessive dystrophic epidermolysis bullosa

Context: Connective tissue cells include fibroblasts, chondrocytes, adipocyte, and osteocytes. These cells are specialized for the secretion of collagenous extracellular matrix and are responsible for the architectural framework of the human body. Evidence Acquisition: Connective tissue cells play a central role in supporting as well as repairing tissues and organs. Fibroblast cell therapy could be used for the treatment of burn wounds, scars, diabetic foot ulcers, acne scars and skin aging. This review focused on biology of fibroblasts and their role in cell therapy of recessive dystrophic epidermolysis bullosa (RDEB). Results: Fibroblasts are known to play a pivotal role in skin structure and integrity, and dermal fibroblasts are believed to promote skin regeneration and rejuvenation via collagen production. Conclusions: Fibroblasts can be used in transplantations to ameliorate an immune system response, in order to reduce antigen production. Human fibroblasts suppress ongoing mixed lymphocyte reactions (MLRs) between lymphocyte cells from two individuals, and supernatant materials from fibroblast cultures suppress MLRs. © 2015, Skin and Stem Cell Journal

Realtime Video Classification Using Dense HOF/HOG

ABSTRACT The current state-of-the-art in Video Classification is based on Bag-of-Words using local visual descriptors. Most commonly these are Histogram of Oriented Gradient (HOG) and Histogram of Optical Flow (HOF) descriptors. While such system is very powerful for classification, it is also computationally expensive. This paper addresses the problem of computational efficiency. Specifically: (1) We propose several speed-ups for densely sampled HOG and HOF descriptors and release Matlab code. (2) We investigate the trade-off between accuracy and computational efficiency of descriptors in terms of frame sampling rate and type of Optical Flow method. (3) We investigate the trade-off between accuracy and computational efficiency for the video representation, using either a k-means or hierarchical k-means based visual vocabulary, a Random Forest based vocabulary or the Fisher kernel

The value of standards for health datasets in artificial intelligence-based applications

Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative)

Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: a cross-sectional study

Background: White matter hyperintensities (WMH) in subjects across the Alzheimer’s disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathology—not just arterial hypertension—impacts WMH, which in turn adversely influences cognition. Here we seek to determine the effect of both hypertension and Aβ positivity on WMH, and their impact on cognition. Methods: We analysed data from subjects with a low vascular profile and normal cognition (NC), subjective cognitive decline (SCD), and amnestic mild cognitive impairment (MCI) enrolled in the ongoing observational multicentre DZNE Longitudinal Cognitive Impairment and Dementia Study (n = 375, median age 70.0 [IQR 66.0, 74.4] years; 178 female; NC/SCD/MCI 127/162/86). All subjects underwent a rich neuropsychological assessment. We focused on baseline memory and executive function—derived from multiple neuropsychological tests using confirmatory factor analysis—, baseline preclinical Alzheimer’s cognitive composite 5 (PACC5) scores, and changes in PACC5 scores over the course of three years (ΔPACC5). Results: Subjects with hypertension or Aβ positivity presented the largest WMH volumes (pFDR < 0.05), with spatial overlap in the frontal (hypertension: 0.42 ± 0.17; Aβ: 0.46 ± 0.18), occipital (hypertension: 0.50 ± 0.16; Aβ: 0.50 ± 0.16), parietal lobes (hypertension: 0.57 ± 0.18; Aβ: 0.56 ± 0.20), corona radiata (hypertension: 0.45 ± 0.17; Aβ: 0.40 ± 0.13), optic radiation (hypertension: 0.39 ± 0.18; Aβ: 0.74 ± 0.19), and splenium of the corpus callosum (hypertension: 0.36 ± 0.12; Aβ: 0.28 ± 0.12). Elevated global and regional WMH volumes coincided with worse cognitive performance at baseline and over 3 years (pFDR < 0.05). Aβ positivity was negatively associated with cognitive performance (direct effect—memory: − 0.33 ± 0.08, pFDR < 0.001; executive: − 0.21 ± 0.08, pFDR < 0.001; PACC5: − 0.29 ± 0.09, pFDR = 0.006; ΔPACC5: − 0.34 ± 0.04, pFDR < 0.05). Splenial WMH mediated the relationship between hypertension and cognitive performance (indirect-only effect—memory: − 0.05 ± 0.02, pFDR = 0.029; executive: − 0.04 ± 0.02, pFDR = 0.067; PACC5: − 0.05 ± 0.02, pFDR = 0.030; ΔPACC5: − 0.09 ± 0.03, pFDR = 0.043) and WMH in the optic radiation partially mediated that between Aβ positivity and memory (indirect effect—memory: − 0.05 ± 0.02, pFDR = 0.029). Conclusions: Posterior white matter is susceptible to hypertension and Aβ accumulation. Posterior WMH mediate the association between these pathologies and cognitive dysfunction, making them a promising target to tackle the downstream damage related to the potentially interacting and potentiating effects of the two pathologies. Trial registration: German Clinical Trials Register (DRKS00007966, 04/05/2015)

Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

peer reviewed[en] BACKGROUND AND OBJECTIVES: To determine the relevance of minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) with regard to CSF levels of Alzheimer disease (AD) biomarkers, cognitive decline, and clinical progression to mild cognitive impairment (MCI). METHODS: This study included patients with clinical SCD and SCD-free, healthy control (HC) participants with available baseline CSF and/or longitudinal cognitive data from the observational DZNE Longitudinal Cognitive Impairment and Dementia study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery. We compared SCD patients with MNPD and those without MNPD with regard to CSF amyloid-β (Aβ)42/Aβ40, phosphorylated tau (p-tau181), total tau and Aβ42/p-tau181 levels, longitudinal cognitive composite trajectories, and risk of clinical progression to incident MCI (follow-up M ± SD: 40.6 ± 23.7 months). In addition, we explored group differences between SCD and HC in those without MNPD. RESULTS: In our sample (N = 672, mean age: 70.7 ± 5.9 years, 50% female), SCD patients with MNPD (n = 55, 12.5% of SCD group) showed significantly more abnormal CSF biomarker levels, increased cognitive decline, and a higher risk of progression to incident MCI (HR: 4.07, 95% CI 2.46-6.74) compared with SCD patients without MNPD (n = 384). MNPD had a positive predictive value of 57.0% (95% CI 38.5-75.4) and a negative predictive value of 86.0% (95% CI 81.9-90.1) for the progression of SCD to MCI within 3 years. SCD patients without MNPD showed increased cognitive decline and a higher risk of incident MCI compared with HC participants without MNPD (n = 215; HR: 4.09, 95% CI 2.07-8.09), while AD biomarker levels did not differ significantly between these groups. DISCUSSION: Our results suggest that MNPD are a risk factor for AD-related clinical progression in cognitively normal patients seeking medical counseling because of SCD. As such, the assessment of MNPD could be useful for individual clinical prediction and for AD risk stratification in clinical trials. However, SCD remains a risk factor for future cognitive decline even in the absence of MNPD

Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

Background and ObjectivesTo determine the relevance of minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) with regard to CSF levels of Alzheimer disease (AD) biomarkers, cognitive decline, and clinical progression to mild cognitive impairment (MCI).MethodsThis study included patients with clinical SCD and SCD-free, healthy control (HC) participants with available baseline CSF and/or longitudinal cognitive data from the observational DZNE Longitudinal Cognitive Impairment and Dementia study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery. We compared SCD patients with MNPD and those without MNPD with regard to CSF amyloid-beta (A beta)42/A beta 40, phosphorylated tau (p-tau181), total tau and A beta 42/p-tau181 levels, longitudinal cognitive composite trajectories, and risk of clinical progression to incident MCI (follow-up M +/- SD: 40.6 +/- 23.7 months). In addition, we explored group differences between SCD and HC in those without MNPD.ResultsIn our sample (N = 672, mean age: 70.7 +/- 5.9 years, 50% female), SCD patients with MNPD (n = 55, 12.5% of SCD group) showed significantly more abnormal CSF biomarker levels, increased cognitive decline, and a higher risk of progression to incident MCI (HR: 4.07, 95% CI 2.46-6.74) compared with SCD patients without MNPD (n = 384). MNPD had a positive predictive value of 57.0% (95% CI 38.5-75.4) and a negative predictive value of 86.0% (95% CI 81.9-90.1) for the progression of SCD to MCI within 3 years. SCD patients without MNPD showed increased cognitive decline and a higher risk of incident MCI compared with HC participants without MNPD (n = 215;HR: 4.09, 95% CI 2.07-8.09), while AD biomarker levels did not differ significantly between these groups.DiscussionOur results suggest that MNPD are a risk factor for AD-related clinical progression in cognitively normal patients seeking medical counseling because of SCD. As such, the assessment of MNPD could be useful for individual clinical prediction and for AD risk stratification in clinical trials. However, SCD remains a risk factor for future cognitive decline even in the absence of MNPD

Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: a cross-sectional study

Background White matter hyperintensities (WMH) in subjects across the Alzheimer’s disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathology—not just arterial hypertension—impacts WMH, which in turn adversely influences cognition. Here we seek to determine the effect of both hypertension and Aβ positivity on WMH, and their impact on cognition. Methods We analysed data from subjects with a low vascular profile and normal cognition (NC), subjective cognitive decline (SCD), and amnestic mild cognitive impairment (MCI) enrolled in the ongoing observational multicentre DZNE Longitudinal Cognitive Impairment and Dementia Study (n = 375, median age 70.0 [IQR 66.0, 74.4] years; 178 female; NC/SCD/MCI 127/162/86). All subjects underwent a rich neuropsychological assessment. We focused on baseline memory and executive function—derived from multiple neuropsychological tests using confirmatory factor analysis—, baseline preclinical Alzheimer’s cognitive composite 5 (PACC5) scores, and changes in PACC5 scores over the course of three years (ΔPACC5). Results Subjects with hypertension or Aβ positivity presented the largest WMH volumes (pFDR < 0.05), with spatial overlap in the frontal (hypertension: 0.42 ± 0.17; Aβ: 0.46 ± 0.18), occipital (hypertension: 0.50 ± 0.16; Aβ: 0.50 ± 0.16), parietal lobes (hypertension: 0.57 ± 0.18; Aβ: 0.56 ± 0.20), corona radiata (hypertension: 0.45 ± 0.17; Aβ: 0.40 ± 0.13), optic radiation (hypertension: 0.39 ± 0.18; Aβ: 0.74 ± 0.19), and splenium of the corpus callosum (hypertension: 0.36 ± 0.12; Aβ: 0.28 ± 0.12). Elevated global and regional WMH volumes coincided with worse cognitive performance at baseline and over 3 years (pFDR < 0.05). Aβ positivity was negatively associated with cognitive performance (direct effect—memory: − 0.33 ± 0.08, pFDR < 0.001; executive: − 0.21 ± 0.08, pFDR < 0.001; PACC5: − 0.29 ± 0.09, pFDR = 0.006; ΔPACC5: − 0.34 ± 0.04, pFDR < 0.05). Splenial WMH mediated the relationship between hypertension and cognitive performance (indirect-only effect—memory: − 0.05 ± 0.02, pFDR = 0.029; executive: − 0.04 ± 0.02, pFDR = 0.067; PACC5: − 0.05 ± 0.02, pFDR = 0.030; ΔPACC5: − 0.09 ± 0.03, pFDR = 0.043) and WMH in the optic radiation partially mediated that between Aβ positivity and memory (indirect effect—memory: − 0.05 ± 0.02, pFDR = 0.029). Conclusions Posterior white matter is susceptible to hypertension and Aβ accumulation. Posterior WMH mediate the association between these pathologies and cognitive dysfunction, making them a promising target to tackle the downstream damage related to the potentially interacting and potentiating effects of the two pathologies. Trial registration German Clinical Trials Register (DRKS00007966, 04/05/2015)