LNA aptamer based multi-modal, Fe3O4-saturated lactoferrin (Fe3O4-bLf) nanocarriers for triple positive (EpCAM, CD133, CD44) colon tumor targeting and NIR, MRI and CT imaging

This is the first ever attempt to combine anti-cancer therapeutic effects of emerging anticancer biodrug bovine lactoferrin (bLf), and multimodal imaging efficacy of Fe3O4 nanoparticles (NPs) together, as a saturated Fe3O4-bLf. For cancer stem cell specific uptake of nanocapsules/nanocarriers (NCs), Fe3O4-bLf was encapsulated in alginate enclosed chitosan coated calcium phosphate (AEC-CP) NCs targeted (Tar) with locked nucleic acid (LNA) modified aptamers against epithelial cell adhesion molecule (EpCAM) and nucleolin markers. The nanoformulation was fed orally to mice injected with triple positive (EpCAM, CD133, CD44) sorted colon cancer stem cells in the xenograft cancer stem cell mice model. The complete regression of tumor was observed in 70% of mice fed on non-targeted (NT) NCs, with 30% mice showing tumor recurrence after 30 days, while only 10% mice fed with Tar NCs showed tumor recurrence indicating a significantly higher survival rate. From tumor tissue analyses of 35 apoptotic markers, 55 angiogenesis markers, 40 cytokines, 15 stem cell markers and gene expression studies of important signaling molecules, it was revealed that the anti-cancer mechanism of Fe3O4-bLf was intervened through TRAIL, Fas, Fas-associated protein with death domain (FADD) mediated phosphorylation of p53, to induce activation of second mitochondria-derived activator of caspases (SMAC)/DIABLO (inhibiting survivin) and mitochondrial depolarization leading to release of cytochrome C. Induction of apoptosis was observed by inhibition of the Akt pathway and activation of cytokines released from monocytes/macrophages and dendritic cells (interleukin (IL) 27, keratinocyte chemoattractant (KC)). On the other hand, the recurrence of tumor in AEC-CP-Fe3O4-bLf NCs fed mice mainly occurred due to activation of alternative pathways such as mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK) and Wnt signaling leading to an increase in expression of survivin, survivin splice variant (survivin 2B) and other anti-apoptotic proteins Bad, Bcl-2 and XIAP. Apart from the promising anti-cancer efficacy and the exceptional tumor targeting ability observed by multimodal imaging using near-infrared (NIR) imaging, magnetic resonance imaging (MRI) and computerized tomographic (CT) techniques, these NCs also maintained the immunomodulatory benefits of bLf as they were able to increase the RBC, hemoglobin, iron calcium and zinc levels in mice.

Estimation of changes in volume of individual lower-limb muscles using magnetic resonance imaging (during bed-rest)

Muscle size in the lower limb is commonly assessed in neuromuscular research as it correlates with muscle function and some approaches have been assessed for their ability to provide valid estimates of muscle volume. Work to date has not examined the ability of different measurement approaches (such as cross-sectional area (CSA) measures on magnetic resonance (MR) imaging) to accurately track changes in muscle volume as a result of an intervention, such as exercise, injury or disuse. Here we assess whether (a) the percentage change in muscle CSA in 17 lower-limb muscles during 56 days bed-rest, as assessed by five different algorithms, lies within 0.5% of the muscle volume change and (b) the variability of the outcome measure is comparable to that of muscle volume. We find that an approach selecting the MR image with the highest muscle CSA and then a series of CSA measures, the number of which depended upon the muscle considered, immediately distal and proximal, provided an acceptable estimate of the muscle volume change. In the vastii, peroneal, sartorius and anterior tibial muscle groups, accurate results can be attained by increasing the spacing between CSA measures, thus reducing the total number of MR images and hence the measurement time. In the two heads of biceps femoris, semimembranosus and gracilis, it is not possible to reduce the number of CSA measures and the entire muscle volume must be evaluated. Using these approaches one can reduce the number of CSA measures required to estimate changes in muscle volume by ~60%. These findings help to attain more efficient means to track muscle volume changes in interventional studies.

Real-time ultrasound measures of lumbar erector spinae and multifidus: reliability and comparison to magnetic resonance imaging

In this work we examine the reliability and validity (in comparison to magnetic resonance imaging; MRI) of real-time ultrasound measures of lumbar erector spinae thickness. We also consider the between-day reliability of the lumbar multifidus muscle area as measured via ultrasound. 23 male subjects aged 21-45 years were measured three times over the course of nine days by one operator. The first (L1) through to the fifth (L5) lumbar vertebral levels were measured on the left and right sides. MRI was performed on the same day as first ultrasound scanning. For between-day intra-rater reliability, intra-class correlation co-efficients (ICCs), standard error of the measurement, minimal detectable difference and co-efficients of variation (CVs) were calculated along with their 95% confidence intervals and Bland-Altman analysis was performed. On Bland-Altman analysis, erector spinae thickness and multifidus area ultrasound measures 'agreed' with equivalent MR measures, though the correlation between MR and ultrasound measures was typically poor to moderate. For both ultrasound measures, the ICCs ranged from 'moderate' to 'excellent' at individual vertebral levels, although multifidus area (CV ranged from 8 to 15%) was less reliable than erector spinae thickness (CV ranged from 6 to 10%). 'Agreement' on Bland-Altmann analysis was present between days for all ultrasound measures. Averaging between sides and between vertebral levels improved reliability. Average erector spinae thickness showed a CV of 5.5% (ICC 0.77) and average multifidus area 6.2% (ICC 0.80).

Zinc doped ferrite magnetic resonance imaging contrast agent for atherosclerosis

 This project focuses on the development of zinc doped ferrite nanoparticle based MRI contrast agents with enhanced contrast and site-specific targeting for atherosclerosis diagnosis. The engineered nanocomplexes developed were validated through MRI scans using rat models with potential for multimodal imaging and effective therapy.

A fluorescent histone deacetylase (HDAC) inhibitor for cellular imaging

Fluorescence microscopy studies using 4-morpholinoscriptaid (4MS) demonstrated rapid cellular uptake of this scriptaid analogue into the cytoplasm but no nuclear penetration. As 4MS and scriptaid have the same in vitro activity against HDACs and KASUMI-1 cells; 4MS exemplifies a rational approach to subtly modify ‘profluorogenic’ substrates for intracellular studies.

Linking the serotonin transporter gene, family environments, hippocampal volume and depression onset: a prospective imaging gene × environment analysis

A single imaging gene-environment (IGxE) framework that is able to simultaneously model genetic, neurobiological, and environmental influences on psychopathology outcomes is needed to improve understanding of how complex interrelationships between allelic variation, differences in neuroanatomy or neuroactivity, and environmental experience affect risk for psychiatric disorder. In a longitudinal study of adolescent development we demonstrate the utility of such an IGxE framework by testing whether variation in parental behavior at age 12 altered the strength of an imaging genetics pathway, involving an indirect association between allelic variation in the serotonin transporter gene to variation in hippocampal volume and consequent onset of major depressive disorder by age 18. Results were consistent with the presence of an indirect effect of the serotonin transporter S-allele on depression onset via smaller left and right hippocampal volumes that was significant only in family environments involving either higher levels of parental aggression or lower levels of positive parenting. The previously reported finding of S-allele carriers' increased risk of depression in adverse environments may, therefore, be partly because of the effects of these environments on a neurobiological pathway from the serotonin transporter gene to depression onset that proceeds through variation in hippocampal volume. 

Elemental imaging of leaves from the metal hyperaccumulating plant Noccaea caerulescens shows different spatial distribution of Ni, Zn and Cd

Elemental imaging using laser ablation inductively coupled plasma mass spectrometry was performed on whole leaves of the hyperaccumulating plant Noccaea caerulescens after treatments with either Ni, Zn or Cd. These detailed elemental images reveal differences in the spatial distribution of these three elements across the leaf and provide new insights in the metal ion homeostasis within hyperaccumulating plants. In the Zn treated plants, Zn accumulated in the leaf tip while Mn was co-localised with Zn suggesting similar storage mechanisms for these two metals. These data show a Zn concentration difference of up to 13-fold higher in the distal part of the leaf. Also, there was no correlation between the S and Zn concentrations providing further evidence against S-binding ligands. In contrast, Ni was more evenly distributed while a more heterogeneous distribution of Cd was present with some high levels on leaf edges, suggesting that different storage and transport mechanisms are used for the hyperaccumulation of these two metals. These results show the importance of correct sampling when carrying out subcellular localisation studies as the hyperaccumulated elements are not necessarily homogenously distributed over the entire leaf area. The results also have great implications for biotechnological applications of N. caerulescens showing that it may be possible to use the mechanisms employed by N. caerulescens to increase the Zn concentration in nutrient poor crops without increasing the risk of accumulating other toxic elements such as Ni and Cd.

Locally sparsified compressive sensing in magnetic resonance imaging

Magnetic Resonance Imaging (MRI) is a widely used technique for acquiring images of human organs/tissues. Due to its complex imaging process, it consumes a lot of time to produce a high quality image. Compressive Sensing (CS) has been used by researchers for rapid MRI. It uses a global sparsity constraint with variable density random sampling and L1 minimisation. This work intends to speed up the imaging process by exploiting the non-uniform sparsity in the MR images. Locally Sparsified CS suggests that the image can be even better sparsified by applying local sparsity constraints. The image produced by local CS can further reduce the sample set. This paper establishes the basis for a methodology to exploit non-uniform nature of sparsity and to make the MRI process time efficient by using local sparsity constraints.

Quantitative secondary electron imaging for work function extraction at atomic level and layer identification of graphene

Two-dimensional (2D) materials usually have a layer-dependent work function, which require fast and accurate detection for the evaluation of their device performance. A detection technique with high throughput and high spatial resolution has not yet been explored. Using a scanning electron microscope, we have developed and implemented a quantitative analytical technique which allows effective extraction of the work function of graphene. This technique uses the secondary electron contrast and has nanometre-resolved layer information. The measurement of few-layer graphene flakes shows the variation of work function between graphene layers with a precision of less than 10 meV. It is expected that this technique will prove extremely useful for researchers in a broad range of fields due to its revolutionary throughput and accuracy.

Surface-enhanced Raman scattering and micro-Raman imaging of Langmuir-Blodgett films of rhodium phthalocyanine

Rhodium phthalocyanine (RhPc) was synthesized and ultra thin Langmuir-Blodgett (LB) films of RhPc were successfully fabricated. The LB film characterization was carried out using both UV-vis absorption spectra and Raman scattering. The Raman spectroscopy was carried out using 633 and 780 nm laser lines. LB films were deposited onto Ag nanoparticles to achieve the surface-enhanced pre-resonance Raman scattering (pre-SERRS) and surface-enhanced Raman scattering (SERS) for both laser lines, respectively, which allowed the characterization of the RhPc ultra thin films. The morphology of the LB RhPc neat film is extracted from micro-Raman imaging. (C) 2003 Elsevier B.V. All rights reserved.

Case study: a 3D resistivity and induced polarization imaging from downstream a waste disposal site in Brazil

A contaminated site from a downstream municipal solid waste disposal site in Brazil was investigated by using a 3D resistivity and induced polarization (IP) imaging technique. This investigation purpose was to detect and delineate contamination plume produced by wastes. The area was selected based on previous geophysical investigations, and chemical analyses carried out in the site, indicating the presence of a contamination plume in the area. Resistivity model has successfully imaged waste presence (rho < 20 Omega m), water table depth, and groundwater flow direction. A conductive anomaly (rho < 20 Omega m) outside wastes placement was interpreted as a contamination plume. Chargeability model was also able to imaging waste presence (m > 31 mV/V), water table depth, and groundwater flow direction. A higher chargeability zone (m > 31 mV/V) outside wastes placement and following conductive anomaly was interpreted as a contamination plume. Normalized chargeability (MN = m/rho) confirmed polarizable zone, which could be an effect of a salinity increase (contamination plume), and the clay presence in the environment.

Cardiovascular assessment of patients with Ullrich-Turner's Syndrome on Doppler echocardiography and magnetic resonance imaging

OBJECTIVE: To assess the cardiovascular features of Ullrich-Turner's syndrome using echocardiography and magnetic resonance imaging, and to correlate them with the phenotype and karyotype of the patients. The diagnostic concordance between the 2 methods was also assessed. METHODS: Fifteen patients with the syndrome were assessed by echocardiography and magnetic resonance imaging (cardiac chambers, valves, and aorta). Their ages ranged from 10 to 28 (mean of 16.7) years. The karyotype was analyzed in 11 or 25 metaphases of peripheral blood lymphocytes, or both. RESULTS: The most common phenotypic changes were short stature and spontaneous absence of puberal development (100%); 1 patient had a cardiac murmur. The karyotypes detected were as follows: 45,X (n=7), mosaics (n=5), and deletions (n=3). No echocardiographic changes were observed. In regard to magnetic resonance imaging, coarctation and dilation of the aorta were found in 1 patient, and isolated dilation of the aorta was found in 4 patients. CONCLUSION: The frequencies of coarctation and dilation of the aorta detected on magnetic resonance imaging were similar to those reported in the literature (5.5% to 20%, and 6.3% to 29%, respectively). This confirmed the adjuvant role of magnetic resonance imaging to Doppler echocardiography for diagnosing cardiovascular alterations in patients with Ullrich-Turner's syndrome.

Magnetic resonance imaging in the diagnosis of type 1 dermoid sinus in two Rhodesian ridgeback dogs

Two cases of type 1 dermoid sinus in Rhodesian ridgebacks are described, with emphasis on the use of magnetic resonance imaging (MRI) in the diagnosis and delineation of the lesions. Magnetic resonance imaging was useful in identifying fluid-filled structures, fibrous capsules, and sinus tracts, but was not able to identify the termination of the tracts.

Hydatidiform Mole in Ectopic Pregnancy Clinical, Imaging, Pathological and Immunohistochemical Characteristics

OBJECTIVE: To determine the clinical, pathological, immunohistochemical and imaging characteristics of hydatidiform mole in ectopic pregnancy (HMEP) in all the cases admitted to the Department of Obstetrics and Gynecology, University Hospital of Caracas (HUC), Central University of Venezuela.STUDY DESIGN: Retrospective and comparative study, based on clinical records review of 2 groups: 10 cases with a diagnosis of HMEP and 20 cases with intrauterine hydatidiform mole (IUHM) admitted to the Obstetrics and Gynecology Department of HUC from 1996 to 2010. Clinical, pathological, immunohistochemical and imaging features were analyzed.RESULTS: The prevalence of HMEP in this study was 0.14:1,000 pregnancies; in this group the mean age was 28.8 years, and the mean gestational age at admission was 8.6 weeks. Both groups (HMEP and IUHM) were comparable in these last variables. Abdominal pain and genital bleeding were the most common clinical symptoms in the HMEP group, while it was vaginal bleeding in the IUHM group. Ultrasound findings were similar to those traditionally described in nonmolar ectopic pregnancy. Histology and immunohistochemistry showed that all cases of HMEP were partial mole.CONCLUSION: Although in this study the prevalence of HMEP was high, the size of the sample limits definitive conclusions. This study concludes that all cases of HMEP are partial mole. (J Reprod Med 2012;57:329-332)

C5 and C6 human dermatomes: a clinical, electromyographical, imaging and surgical findings

There is substantial controversy in literature about human dermatomes. In this work, C5 and C6 superior limb dermatomes were studied. The method consisted of comparing clinical signs and symptoms with conduction studies, electromyographical data, neurosurgical findings, and imaging findings obtained by computerized tomography (CT) or magnetic resonance imaging (MRI), for each patient. Data analysis from superior members in 18 patients suggests that C5 is located in the lateral aspect of the shoulder and arm, and C6 in the lateral aspect of the forearm and 1(st), 2(nd), and 3(rd) fingers. To our knowledge this is the first time that C5 and C6 human dermatomes have been studied by all the following methods together: clinical, electromyographical, CT and MR imaging, and surgical findings.