Registration of FA and T1-Weighted MRI Data of Healthy Human Brain Based on Template Matching and Normalized Cross-Correlation

In this work, we propose a new approach for three-dimensional registration of MR fractional anisotropy images with T1-weighted anatomy images of human brain. From the clinical point of view, this accurate coregistration allows precise detection of nerve fibers that is essential in neuroscience. A template matching algorithm combined with normalized cross-correlation was used for this registration task. To show the suitability of the proposed method, it was compared with the normalized mutual information-based B-spline registration provided by the Elastix software library, considered a reference method. We also propose a general framework for the evaluation of robustness and reliability of both registration methods. Both registration methods were tested by four evaluation criteria on a dataset consisting of 74 healthy subjects. The template matching algorithm has shown more reliable results than the reference method in registration of the MR fractional anisotropy and T1 anatomy image data. Significant differences were observed in the regions splenium of corpus callosum and genu of corpus callosum, considered very important areas of brain connectivity. We demonstrate that, in this registration task, the currently used mutual information-based parametric registration can be replaced by more accurate local template matching utilizing the normalized cross-correlation similarity measure.     

A systematic screening of total antioxidants in dietary plants

A predominantly plant-based diet reduces the risk for development of several chronic diseases. It is often assumed that antioxidants contribute to this protection, but results from intervention trials with single antioxidants administered as supplements quite consistently do not support any benefit. Because dietary plants contain several hundred different antioxidants, it would be useful to know the total concentration of electron-donating antioxidants (i.e., reductants) in individual items. Such data might be useful in the identification of the most beneficial dietary plants. We have assessed systematically total antioxidants in a variety of dietary plants used worldwide, including various fruits, berries, vegetables, cereals, nuts and pulses. When possible, we analyzed three or more samples of dietary plants from three different geographic regions in the world. Total antioxidants was assessed by the reduction of Fe(3+) to Fe(2+) (i.e., the FRAP assay), which occurred rapidly with all reductants with half-reaction reduction potentials above that of Fe(3+)/Fe(2+). The values, therefore, expressed the corresponding concentration of electron-donating antioxidants. Our results demonstrated that there is more than a 1000-fold difference among total antioxidants in various dietary plants. Plants that contain most antioxidants included members of several families, such as Rosaceae (dog rose, sour cherry, blackberry, strawberry, raspberry), Empetraceae (crowberry), Ericaceae (blueberry), Grossulariaceae (black currant), Juglandaceae (walnut), Asteraceae (sunflower seed), Punicaceae (pomegranate) and Zingiberaceae (ginger). In a Norwegian diet, fruits, berries and cereals contributed 43.6%, 27.1% and 11.7%, respectively, of the total intake of plant antioxidants. Vegetables contributed only 8.9%. The systematic analysis presented here will facilitate research into the nutritional role of the combined effect of antioxidants in dietary plants.     

High mortality rates in conservatively managed patients with acute coronary syndrome

OBJECTIVES: The revised diagnostic criteria for the acute coronary syndrome (ACS) have created the need for accurate and representative data on treatment and outcome for the three categories of ACS. DESIGN: Consecutive patients admitted with a suspected ACS (n = 755) from February 1, 2003 to January 31, 2004 was registered and categorised into five diagnostic groups: 1) ST-elevation myocardial infarction (STEMI) (n = 126), 2) Non-ST-elevation myocardial infarction (NSTEMI) (n = 185), 3) Unstable angina pectoris (UAP) (n = 55), 4) Coronary heart disease (CHD) without ACS (n = 164) and 5) Non-coronary chest pain (n = 225). RESULTS: All-cause one-year mortality rates were 20%, 32%, 7%, 10% and 3%, in patients with STEMI, NSTEMI, UAP, CHD without ACS and non-coronary chest pain, respectively. In patients with STEMI, 61% received immediate reperfusion therapy (ratio thrombolysis: primary PCI = 18:1). Only 3% of those with NSTEMI had PCI within two days. CONCLUSION: In this conservatively managed population of consecutive patients with ACS, the one-year mortality rate is significantly higher than seen in most registries and clinical trials.     

Activation of phosphatidylinositol 3-kinase is important for erythropoietin-induced erythropoiesis from CD34(+) hematopoietic progenitor cells

OBJECTIVE: Several transducing molecules, including JAK2, STAT5, MAP kinases, phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma1, and PKC are activated by interaction between erythropoietin (EPO) and the EPO receptor. The aim of this was to examine the relative involvement of PI3K in the development of glycophorin A (GPA)(+) erythroid cells from normal hematopoietic progenitor cells. MATERIALS AND METHODS: CD34(+) hematopoietic progenitor cells or subpopulations obtained by FACS sorting were cultured in serum-free medium containing EPO with or without inhibitors for PI3K, p38, MEK, or PKC for various time periods before phenotypic analysis or detection of apoptosis by flow cytometry, cell cycle analysis, high-resolution tracking of cell division, Western blot analysis, or Akt kinase assay were performed. RESULTS: The PI3K inhibitor LY294002 completely counteracted the EPO-induced proliferation of CD34(+) progenitor cells and CD34(+)CD71(+)CD45RA(-) erythroid progenitors. LY294002 also highly suppressed the expanded erythropoiesis induced by the combined action of EPO and stem cell factor. The profound inhibitory effect of LY294002 on proliferation was caused by its induction of cell cycle arrest in the G(0)/G(1) phase of the cell cycle. Some cells acquired GPA expression before they went through cell division. This was completely blocked by LY294002, implying an inhibitory effect on maturation. In addition, LY294002 completely blocked the viability-enhancing effect of EPO in CD34(+)CD71(+)CD45RA(-) erythroid progenitors. LY294002 and various inhibitors of PKC completely suppressed the EPO-induced increase in the activity of Akt kinase, a direct downstream target of PI3K. CONCLUSIONS: Our results point to an important role for PI3K in mediating EPO-induced survival, proliferation, and possibly maturation of early erythroid progenitors.     

Expression of B-Cell Surface Antigens in Subpopulations of Exosomes Released From B-Cell Lymphoma Cells

Purpose

Exosomes are small (30- to 100-nm) vesicles secreted by all cell types in culture and found in most body fluids. A mean of 1 mL of blood serum, derived from healthy donors, contains approximately 10¹² exosomes. Depending on the disease, the number of exosomes can fluctuate. Concentration of exosomes in the bloodstream and all other body fluids is extremely high. Several B-cell surface antigens (CD19, CD20, CD22, CD23, CD24, CD37, CD40, and HLA-DR) and the common leukocyte antigen CD45 are interesting in terms of immunotherapy of hematologic malignant neoplasms. The established standard for exosome isolation is ultracentrifugation. However, this method cannot discriminate between exosome subpopulations and other nanovesicles. The main purpose of this study was to characterize CD81⁺ and CD63⁺ subpopulations of exosomes in terms of these surface markers after release from various types of B-cell lymphoma cell lines using an easy and reliable method of immunomagnetic separation.

Methods

Western blotting, flow cytometry, and electron microscopy were used to compare the total preenriched extracellular vesicle (EV) pool to each fraction of vesicles after specific isolation, using magnetic beads conjugated with antibodies raised against the exosome markers CD63 and CD81.

Findings

Magnetic bead–based isolation is a convenient method to study and compare subpopulations of exosomes released from B-cell lymphoma cells. The data indicated that the specifically isolated vesicles differed from the total preenriched EV pool. CD19, CD20, CD24, CD37, and HLA-DR, but not CD22, CD23, CD40, and CD45, are expressed on exosomes from B-cell lymphoma cell lines with large heterogeneity among the different B-cell lymphoma cell lines. Interestingly, these B-cell lymphoma–derived EVs are able to rescue lymphoma cells from rituximab-induced complement-dependent cytotoxicity.

Implications

Distribution of exosomes that contain CD19, CD20, CD24, CD37, and HLA-DR may intercept immunotherapy directed against these antigens, which is important to be aware of for optimal treatment. The use of an immunomagnetic separation platform enables easy isolation and characterization of exosome subpopulations for further studies of the exosome biology to understand the potential for therapeutic and diagnostic use.     

Reliability,sensitivity, and predictive value of fMRI during multiple object tracking as a marker of cognitive training gain in combination with tDCS in stroke survivors

Computerized cognitive training (CCT) combined with transcranial direct current stimulation (tDCS) has showed some promise in alleviating cognitive impairments in patients with brain disorders, but the robustness and possible mechanisms are unclear. In this prospective double‐blind randomized clinical trial, we investigated the feasibility and effectiveness of combining CCT and tDCS, and tested the predictive value of and training‐related changes in fMRI‐based brain activation during attentive performance (multiple object tracking) obtained at inclusion, before initiating training, and after the three‐weeks intervention in chronic stroke patients (>6 months since hospital admission). Patients were randomized to one of two groups, receiving CCT and either (a) tDCS targeting left dorsolateral prefrontal cortex (1 mA), or (b) sham tDCS, with 40s active stimulation (1 mA) before fade out of the current. Of note, 77 patients were enrolled in the study, 54 completed the cognitive training, and 48 completed all training and MRI sessions. We found significant improvement in performance across all trained tasks, but no additional gain of tDCS. fMRI‐based brain activation showed high reliability, and higher cognitive performance was associated with increased tracking‐related activation in the dorsal attention network and default mode network as well as anterior cingulate after compared to before the intervention. We found no significant associations between cognitive gain and brain activation measured before training or in the difference in activation after intervention. Combined, these results show significant training effects on trained cognitive tasks in stroke survivors, with no clear evidence of additional gain of concurrent tDCS.     

The glia doctrine: Addressing the role of glial cells in healthy brain ageing

Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction.     

Perceiving haptic feedback in virtual reality simulators

Background

To improve patient safety, training of psychomotor laparoscopic skills is often done on virtual reality (VR) simulators outside the operating room. Haptic sensations have been found to influence psychomotor performance in laparoscopy. The emulation of haptic feedback is thus an important aspect of VR simulation. Some VR simulators try to simulate these sensations with handles equipped with haptic feedback. We conducted a survey on how laparoscopic surgeons perceive handles with and without haptic feedback.

Methods

Surgeons with different levels of experience in laparoscopy were asked to test two handles: Xitact IHP with haptic feedback and Xitact ITP without haptic feedback (Mentice AB, Gothenburg, Sweden), connected to the LapSim (Surgical Science AB, Sweden) VR simulator. They performed two tasks on the simulator before answering 12 questions regarding the two handles. The surgeons were not informed about the differences in the handles.

Results

A total of 85 % of the 20 surgeons who participated in the survey claimed that it is important that handles with haptic feedback feel realistic. Ninety percent of the surgeons preferred the handles without haptic feedback. The friction in the handles with haptic feedback was perceived to be as in reality (5 %) or too high (95 %). Regarding the handles without haptic feedback, the friction was perceived as in reality (45 %), too low (50 %), or too high (5 %). A total of 85 % of the surgeons thought that the handle with haptic feedback attempts to simulate the resistance offered by tissue to deformation. Ten percent thought that the handle succeeds in doing so.

Conclusions

The surveyed surgeons believe that haptic feedback is an important feature on VR simulators; however, they preferred the handles without haptic feedback because they perceived the handles with haptic feedback to add additional friction, making them unrealistic and not mechanically transparent.