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Environmental pollution problem, especially mercury ions (Hg2+) pollution, seriously threatens the organism health. Numerous researches have revealed that even extremely low concentration of Hg2+ can severely damage the organisms. Therefore, it is essential for real-time detection of Hg2+. Fluorescent probe technology with great advantages has become the preferred technique for environmental detection and in vivo analysis of Hg2+. In recent years, lots of contributions have been committed to designing and synthesizing novel fluorescent probes for environmental pollutant Hg2+ analysis. In this feature article, we review the recent advances in fluorescent probes for Hg2+ analysis, focusing on probe response modes, including signal-decreased fluorescent probes, signal-enhanced fluorescent probes, ratiometric fluorescent probes as well as fluorescent probes for Hg2+ and other species analysis. Moreover, the design strategies, performance and applications of fluorescent probes are summarized in detail. Challenges and prospects for fluorescent probe are proposed, orienting new design strategies and applications expanding.

Avian influenza viruses (AIVs) undergo continuous antigenic drifts, causing annual epidemics in poultry and livestock that result in significant mortality and conspicuous socioeconomic losses. To design vaccines and mitigate epidemics, evolutionary characteristics of AIVs are typically studied through longitudinal surveillance and serological assays. However, such in vivo analysis is often reactive and limited due to the complexities and costs of long-term, multinational surveillance. Consequently, in vivo analysis is enhanced using in silico phylodynamic modeling and simulation methods that simultaneously model evolutionary and epidemiological characteristics of AIVs. This study proposes a novel in silico approach that combines two different agent-based simulation methods: epidemiological simulation and phylogeographic annotations to identify high-risk countries, and phylodynamic simulations to elicit their AIVs evolutionary characteristics. The proposed method elicits detailed ecological characteristics of AIVs that can inform design of vaccines and prophylactic strategies.

Molecular imaging is a newly emerging field aimed at advancing our understanding of biology and medicine through the noninvasive in vivo investigation of cellular molecular events involved in normal and pathologic processes. In this field, researchers and/or clinicians are combining modern tools of molecular and cell biology with state of the art technology in order to noninvasively image living subjects. Various imaging modalities such as optics (fluorescence and luminescence), nuclear magnetic resonance imaging, ultrasound, and radiation are being used to visually capture and study molecular and cellular events in living organisms. Among these modalities, nuclear medical molecular imaging uses radionuclides [i.e., positron emission tomography (PET) and single-photon emission computed tomography (SPECT)], and has characteristic properties that allow researchers and/or clinicians to obtain functional images of living subjects with high sensitivity. Translational molecular imaging, a research step between animal experiments and the clinical setting, has been successful when using nuclear medical molecular imaging. This approach leads to better methods for studying biological processes, as well as for diagnosing and managing diseases. In this review, two topics associated with our research on nuclear medical molecular imaging are summarized: (1) the development of a nuclear medical molecular imaging probe that targets cerebral nicotinic acetylcholine receptors (nAChRs), and the translational molecular imaging research conducted using this nAChR imaging probe; and (2) the development of oxygen-dependent degradable nuclear medical molecular imaging probes that target hypoxia-inducible factor-1-active tumor microenvironments.

This article contains supporting information on data collection for the research article entitled “Aircraft noise exposure drives the activation of white blood cells and induces microvascular dysfunction in mice” by Eckrich et al. We found that noise-induced stress triggered microvascular dysfunction via involvement of innate immune-derived reactive oxygen species. In this article, we present the instrumentation of mice with dorsal skinfold chambers for in vivo microscopic imaging of blood flow, interaction of leukocytes with the vascular wall (also by fluorescent labelling of blood cells) and vessel diameter. In addition, we explain the preparation of cerebral arterioles for measurement of vascular reactivity in vitro.•visualization of noise-dependent effects in dorsal skinfold chamber.•in vivo microscopy of noise-dependent activation of white blood cells.•analysis of noise-dependent microvascular dysfunction in dorsal skinfold chamber and cannulated cerebral arterioles., Graphical abstract Image, graphical abstract

Magnetomotive optical coherence tomography (MMOCT) is a functional modification of conventional optical coherence tomography (OCT). It utilizes the nano-scale displacement embedded magnetic nanoparticles (MNPs) and subsequent amplitude and phase changes in OCT interferogram scattered from samples. We report a new robust method for ‘phase-lock-in’ detection of MMOCT signals and subsequent imaging. We validated this method utilizing iron-gold (Fe-Au) composite nanoparticles as an exogenous contrast agent for MMOCT. High contrast and specific background-subtracted images was generated for Fe-Au MNPs targeted samples. MMOCT with MNPs imaging systems was corroborated with tissue phantoms and in-vivo swiss albino mice model with modulating external magnetic field (resonant frequency of 30 Hz). A time-dependent dynamics study of diffusion for MNPs inside the tissue of mice as a function of time and depth is also reported.

Muller cells (MC) represent a key element for the metabolic and functional regulation of the vertebrate retina. The aim of the present study was to test the feasibility of a new method for the in-vivo detection and quantification of extrafoveal MC in human retina. We developed a new approach to isolate and analyse extrafoveal MC in vivo, starting from structural optical coherence tomography data. Our pilot investigation was based on the optical properties of MC, which are known to not interfere with the light reaching the outer retinal structures. We reconstructed MC in the macular region of 18 healthy subjects and the quantitative analyses revealed ~42,000/9 mm2 cells detected. Furthermore, we included 2 patients affected by peripheral intraocular melanoma, with macular sparing, needing surgical enucleation. We used these two eyes to perform a qualitative comparison between our reconstructions and histological findings. Our study represents the first pilot investigation dedicated on the non-invasive isolation and quantification of MC, in-vivo, in human retina. Although we are aware that our study has several limitations, first of all related with the proper detection of foveal MC, because of the peculiar z-shape morphology, this approach may open new opportunities for the non-invasive in vivo analysis of MC, providing also potential useful perspectives in retinal diseases.

SUMMARY Malignant gliomas are the most common and aggressive primary brain tumor in adults, and high mitotic rates are associated with their malignancy. Gliomas were modeled in mice using the Sleeping Beauty system to encode genetic lesions recapitulating the human disease. The presented workflow allows the study of the proliferation of glioma cells in vivo, enabling the identification of different phases of the cell cycle, with the advantage that 5-ethynyl-2′-deoxyuridine staining does not involve denaturation steps and samples do not require histological processing. For complete details on the use and execution of this protocol, please refer to Núñez et al. (2019)., Graphical Abstract An optimized protocol to analyze in vivo cell cycle progression in genetically engineered gliomas that are modeled in mice using the Sleeping Beauty method. EdU incorporation and histone 3-serine-10 phosphorylation are analyzed by flow cytometry, enabling the assessment of cells undergoing S or M phase, respectively.

In clinic, we observe that women of African descent have higher incidence rates of breast cancer (BC). These women are disproportionately diagnosed with the most aggressive subtype of BC, triple-negative BC, compared to women belonging to any other ancestry groups. To investigate factors driving this disparity, our work focuses on the tumor microenvironment (TME), specifically through the lens of an atypical chemokine receptor. The Duffy Antigen Receptor for Chemokines (DARC) is a nonsignaling, atypical chemokine receptor that binds two structural classes of chemokines. DARC modulates chemokine availability in circulation and participates in chemokine transport in tissues, to recruit immune cells back to sites of inflammation. DARC additionally serves as a portal of entry for the malaria-causing parasite Plasmodium vivax. In Sub-Saharan Africa, where malaria is endemic, a regulatory variant arose removing DARC expression from red blood cells (RBCs). This mutation, known as the Duffy-Null allele, was highly beneficial in this population, and quickly rose to fixation. Despite being called Duffy-Null, these individuals retain DARC expression in other cell types, only lacking expression on RBCs. Knowing that the Duffy-Null allele is prevalent in this population of women, we aim to investigate how DARC tumor expression and Duffy-Null status impacts the TME in silico through analysis of The Cancer Genome Atlas (TCGA) data, and in vivo through establishment of mouse models that depict Duffy-Null status in the BC TME. Using TCGA data, we see that DARC tumor gene expression is significantly lower among African-Americans compared to Whites. Using the CIBERSORT online platform, we quantified tumor-associated leukocyte (TAL) abundance in the TME. Overall, we found that tumors with high DARC expression have significantly higher total TAL abundance (p < 0.0001), and that DARC expression and TAL abundance are positively and significantly correlated (R = 0.545, p < 0.0001). Specifically, DARC expression influenced levels of B cell, T cell, monocyte and macrophage population in the TME. In our mouse models, we have utilized the C3(1)Tag BC transgenic mouse model, alongside a DARC knock-out mouse. To better recapitulate the Duffy-Null phenotype in our mouse model, our approach is to generate a BC/Duffy-Null bone marrow derived (BMD) chimera, where a DARC+/-; C3(1)Tag+/0 recipient will receive bone marrow from a DARC -/- donor. The resulting chimera mice will retain DARC expression in all cells, aside from bone marrow-derived cells from the null donor. In the C3(1)Tag line, disease onset is at approximately 12 weeks, at which time we will assess changes in disease progression in our chimeras compared to controls by collecting total number of tumors, tumor location, tumor size and weight, and hematoxylin and eosin staining of tumor sections, and immune cell infiltration quantification. Citation Format: Rachel Martini, Brittany Jenkins, Clayton Yates, Lisa Newman, Nancy Manley, Melissa Davis. In silico and in vivo analysis of the Duffy Antigen Receptor for Chemokines (DARC) in the breast tumor microenvironment [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B058.

Physiological and pathological processes in the central nervous system (CNS) are basically encoded by neuromodulators, neurotransmitters and other kinds of neurochemicals among neurons. However, the chemical complexity of the cerebral environment largely necessitates a capability of the method to measure neurochemicals accurately. Over the past decade, we have been dedicating to develop strategies to in vivo detecting neurochemcial selectively and accurately. In order to differentiate the neurochemicals of interest from others in the CNS, we develop a new kind of microelectrode for in vivo monitoring of H2O2, which is prepared by, first, electrodeposition of Prussian blue (PB) onto carbon nanotube (CNT) assembled carbon fiber microelectrodes (CFEs) and then overcoating of the CFEs with a thin membrane of polydopamine (PDA) through self-polymerization. On the other hand, towards the goal of minimizing the protein adsorption on the brain-implanted microelectrodes, we found that pre-treatment of carbon fiber microelectrode (CFEs) with bovine serum albumin (BSA) can minimize further adsorption of proteins when the electrodes are implanted into the rat brain. We demonstrate that electrode precalibration in aCSF containing BSA is valid and effective for in vivo measurements. However, this also causes significant sensitivity drop of CFEs to neurochemicals, including DA. To in vivo tracking of neurochemical dynamics without decrease of electrode performance, we report an ultrathin cell-membrane-mimic film of ethylenedioxythiophene tailored with zwitterionic phosphorylcholine (EDOT- PC) electropolymerized onto the surface of a carbon fiber microelectrode (CFE), which not only resists protein adsorption but also maintains the sensitivity and time response for in vivo monitoring of dopamine (DA). As a consequence, the as- prepared PEDOT-PC/CFEs could be used as a new reliable platform for tracking DA in vivo and would help understand the physiological and pathological functions of DA

The static magnetic field (SMF) in human exposure has become a health risk concern, especially with respect to prolonged exposure. The International Commission on Non-Ionizing Radiation Protection (ICNIRP) has been considering cell or animal models to be adopted to estimate the possible human health impacts after such exposure. The medaka fish is a good animal model for human-related health assessment studies, this paper examines both the embryo development and behavioral responses in medaka fish in vivo to long-term SMF exposure at the mT level. SMF exposure was examined for the complete developmental period of embryos until hatched, the embryos were monitored and recorded every 24 h for different morphological abnormalities in their developmental stages. The behavioral response of adult fish was also examined by analyzing their swimming velocities and positioning as compared with that of the control group. It was observed that there were no impacts on embryo development under prolonged exposure up to about 100 mT while the swimming behavior of the adult fish under exposure was different to the control group&mdash, the swimming movement of the treated group was more static, with an average velocity of 24.6% less as observed over a 24-h duration.

Analysis of enzyme activities and metabolites in the rhizosphere requires suitable growth systems. Here, we describe the use of plastic syringes as a test system for measuring extracellular root enzyme activities of a single seedling under sterile conditions. Syringes have been originally used to analyze hydrolysis of rhizobial nodulation signals (Nod factors) by host legumes such as Medicago truncatula. The developed method offers now the opportunity to use syringes for other purposes. Syringe systems can be used to determine any enzyme activity in the rhizosphere, providing that the substrates and products in the growth medium are water-soluble, nontoxic, and detectable. Moreover, syringes can be employed to collect root exudates from a single seedling.

Aim. To evaluate the conditioning capabilities of the DAR™ Hygrobac™ S, a Heat and Moisture Exchanger (HME), using a new device to measure the temperature (T) and the absolute humidity (AH) of the ventilated gases in vivo during mechanical ventilation in Intensive Care Unit (ICU) patients. Materials and Methods. In 49 mechanically ventilated ICU patients, we evaluated T and AH, indicating the HME efficacy, during the inspiratory phase upstream and downstream the HME and the ratio of inspired AH to expired AH and the difference between expired T and inspired T indicated the HME efficiency. Efficacy and efficiency were assessed at three time points: at baseline (t0, HME positioning time), at 12 hours (t1), and at 24 hours (t2) using a dedicated, ad hoc built wireless device. Differences over time were evaluated using one-way ANOVA for repeated measures, whereas differences between in vivo and laboratory values (declared by the manufacturer according to UNI® EN ISO 9360 international standard) were evaluated using one-sample Student t-test. Results. 49 HMEs were analysed in vivo during mechanical ventilation. T and AH means (SD) of the inspired gas (the efficacy) were 31.5°C (1.54) and 32.3 mg/l (2.60) at t0, 31.1°C (1.34) and 31.7 mg/l (2.26) at t1, and 31°C (1.29) and 31.4 mg/l (2.27) at t2. Both efficiency parameters were constant over time (inspired AH/expired AH=89%, p=0.24; and expired T–inspired T = 2.2°C, p=0.81). Compared with laboratory values, in vivo T and AH indicating efficacy were significantly lower (p Conclusions. HME performances can be accurately assessed for prolonged periods in vivo during routine mechanical ventilation in ICU patients. Temperature and absolute humidity of ventilated gases in vivo were maintained within the expected range and remained stable over time. HME efficacy and efficiency in vivo significantly differed from laboratory values.

Stereotaxic systems and automatic tissue segmentation routines enable neuronavigation as well as reproducible processing of neuroimage datasets. Such systems have been developed for humans, non-human-primates, sheep, and rodents, but not for dogs. Although dogs share important neurofunctional and -anatomical features with humans, and in spite of their importance in translational neuroscience, little is known about the variability of the canine brain morphology and, possibly related, function. Moreover, we lack templates, tissue probability maps (TPM), and stereotaxic brain labels for implementation in standard software utilities such as Statistical Parametric Mapping (SPM). Hence, objective and reproducible, image-based investigations are currently impeded in dogs. We have created a detailed stereotaxic reference frame for dogs including TPM and tissue labels, enabling inter-individual and cross-study neuroimage analysis. T2w datasets were acquired from 16 neurologically inconspicuous dogs of different breeds by 3T MRI. The datasets were averaged after initial preprocessing using linear and nonlinear registration algorithms as implemented in SPM8. TPM for gray (GM) and white matter (WM) as well as cerebrospinal fluid (CSF) were created. Different cortical, subcortical, medullary, and CSF regions were manually labeled to create a spatial binary atlas being aligned with the template. A proof-of-concept for automatic determination of morphological and volumetrical characteristics was performed using additional canine datasets (n = 64) including a subgroup of laboratory beagles (n = 24). Overall, 21 brain regions were labeled using the segmented tissue classes of the brain template. The proof-of-concept trial revealed excellent suitability of the created tools for image processing and subsequent analysis. There was high intra-breed variability in frontal lobe and hippocampus volumes, and noticeable inter-breed corpus callosum volume variation. The T2w brain template provides important, breed-averaged canine brain anatomy features in a spatial standard coordinate system. TPM allows automatic tissue segmentation using SPM and enables unbiased automatic image processing or morphological characterization in different canine breeds. The reported volumetric and morphometric results may serve as a starting point for further research aimed at in vivo analysis of canine brain anatomy and function.

Background The increasing use of gold nanoparticles (AuNPs) in the field of neuroscience instilled hope for their rapid translation to the clinical practice. AuNPs can be engineered to carry therapeutics or diagnostics in the diseased brain, possibly providing greater cell specificity and low toxicity. Although there is a general enthusiasm for these tools, we are in early stages of their development. Overall, their brain penetrance, stability and cell specificity are critical issues that must be addressed to drive AuNPs to the clinic. Results We studied the kinetic, distribution and stability of PEG-coated AuNPs in mice receiving a single injection into the cisterna magna of the 4th ventricle. AuNPs were conjugated with the fluorescent tag Cy5.5 (Cy5.5-AuNPs) to track their in vivo distribution. Fluorescence levels from such particles were detected in mice for weeks. In situ analysis of brains by immunofluorescence and electron microscopy revealed that Cy5.5-AuNPs penetrated the brain parenchyma, spreading in the CNS parenchyma beneath the 4th ventricle. Cy5.5-AuNPs were preferentially found in neurons, although a subset of resting microglia also entrapped these particles. Conclusions Our results suggest that the ICM route for delivering gold particles allows the targeting of neurons. This approach might be pursued to carry therapeutics or diagnostics inside a diseased brain with a surgical procedure that is largely used in gene therapy approaches. Furthermore, this approach could be used for radiotherapy, enhancing the agent’s efficacy to kill brain cancer cells. Electronic supplementary material The online version of this article (10.1186/s12951-019-0481-3) contains supplementary material, which is available to authorized users.

Background. Compared with open surgery, minimally invasive surgery is limited by reduced sensation of tissue properties. A laparoscopic grasper with integrated haptic feedback technology that improves the ability to sense tissue properties might provide a solution. The force reflecting operation instrument (FROI) is a new laparoscopic grasper, designed to provide information about the interaction forces between the instrument and tissue through resistance in the handle. This pilot study aimed to assess the functionality of the FROI compared with a conventional grasper in an in vivo setting. Methods. In this randomized trial, we used a standard laparoscopic surgical setup to perform laparoscopic surgery in pigs. In all, 11 surgeons performed colorectal, gynecological, or urological procedures, once with the FROI and once with a conventional grasper. Participants were asked to complete the NASA Task Load Index Rating Scale and rate 5 specific features for both graspers. To capture opinions on the overall functionality of the FROI, participants were asked to answer 8 open questions. Results. The surgeons reported that the use of the FROI significantly improved tissue consistency perception, arterial pulse detection, and force control compared with the conventional grasper. No significant differences were found in surgeons’ muscular strain or operative time. The most emphasized topics in the open questions were improved soft-tissue handling and importance for complex procedures. Conclusion. Through this first in vivo analysis of the functionality of the FROI, a multispecialty group of laparoscopic surgeons confirmed the added value of haptic feedback technology in a live surgical setting.

Objective Subchondral bone plays an important role in the pathological mechanisms of knee osteoarthritis (OA). High-resolution peripheral quantitative computed tomography (HR-pQCT) is an imaging modality allowing noninvasive microstructural analysis of human bone, and the second generation enables scanning of the knee. The purpose of this study was to perform in vivo analysis of subchondral trabecular bone in patients with medial knee OA, to elucidate features of bone microstructure in medial knee OA, and to investigate relationships between bone microstructure and both stage of disease and lower limb alignment. Methods Subjects were 20 women, including both patients with medial knee OA (Kellgren-Lawrence (KL) grade 2, n = 5, KL grade 3, n = 7, and KL grade 4, n = 4; mean age: 63.0 years; body mass index (BMI): 23.8 kg/m2) and volunteers without knee OA (KL grade 1, n = 4, mean age: 66.0 years; BMI: 23.8 kg/m2). The proximal tibia (20-mm length) was scanned by second-generation HR-pQCT at a voxel size of 60.7 μm. A subchondral trabecular bone volume of 5 mm length was extracted from the medial and lateral plateaus. They were then divided into 4 regions: anterior, central, medial or lateral, and posterior. Finally, subchondral bone microstructure parameters were analyzed and compared, between each plateau and region. Relationships between microstructural parameters and disease stage (KL grade, minimum joint space width), and between those parameters and lower limb alignment (femorotibial angle: FTA, mechanical axis deviation: MAD) were also investigated. Results In the medial plateau, volumetric bone mineral density (vBMD), bone volume fraction (BV/TV), and trabecular thickness were significantly higher and structure model index (SMI) was significantly lower than in the lateral plateau, particularly in the anterior, central, and medial regions (p Conclusions Higher bone volume, trabecular thickness, and a more plate-like structure were observed in the medial tibial plateau than in the lateral. Subchondral bone microstructure at the anterior region in the medial plateau showed strong relationships with KL grade and lower limb alignment. These results indicate that subchondral bone microstructure in this region may provide representative indices, particularly in medial knee OA. Although this study involved a specifically Asian cohort with a lower BMI distribution than other ethnic groups, the technique presented may be useful in studying the pathogenesis of OA or evaluating treatment effects.

Hyperspectral imaging has shown great potential for optical skin analysis by providing noninvasive, pixel-by-pixel surface measurements from which, applying an optical model, information such as melanin concentration and total blood volume fraction can be mapped. Such applications have been successfully performed on small flat skin areas, but existing methods are not suited to large areas such as an organ or a face, due to the difficulty of ensuring homogeneous illumination on complex three-dimensional (3-D) objects, which leads to errors in the maps. We investigate two methods to account for these irradiance variations on a face. The first one relies on a radiometric correction of the irradiance, using 3-D information on the face’s shape acquired by combining the hyperspectral camera with a 3-D scanner; the second relies on an optimization metric used in the map computation, which is invariant to irradiance. We discuss the advantages and drawbacks of the two methods, after having presented in detail the whole acquisition setup, which has been designed to provide high-resolution images with a short acquisition time, as required for live surface measurements of complex 3-D objects such as the face.

HIV-associated cerebrovascular events remain highly prevalent even in the current era of antiretroviral therapy (ART). We hypothesize that low-level HIV replication and associated inflammation endure despite antiretroviral treatment and affect ischemic stroke severity and outcomes. Using the EcoHIV infection model and the middle cerebral artery occlusion as the ischemic stroke model in mice, we present in vivo analysis of the relationship between HIV and stroke outcome. EcoHIV infection increases infarct size and negatively impacts tissue and functional recovery. Ischemic stroke also results in an increase in EcoHIV presence in the affected regions, suggesting post-stroke reactivation that magnifies pro-inflammatory status. Importantly, ART with a high CNS penetration effectiveness (CPE) is more beneficial than low CPE treatment in limiting tissue injury and accelerating post-stroke recovery. These results provide potential insight for treatment of HIV-infected patients that are at risk of developing cerebrovascular disease, such as ischemic stroke.

Purpose To investigate the prevalence of isthmi and middle mesial (MM) canals in the mesial roots of mandibular first molars (MFM) in a Mongoloid subpopulation and to evaluate their association with demographic and anatomic characteristics. Methods Cone-beam computed tomography (CBCT) images of 496 patients with 823 MFMs were selected and analyzed. The following data were collected: patient age and gender, side, presence and distribution of MM canal and isthmus, distance between mesiobuccal (MB) and mesiolingual (ML) orifices, and MB–ML root canal system (RCS) morphology. Logistic regression was used to determine the association between demographic and anatomic characteristics and the presence of isthmi in the apical third. Results The overall prevalence of isthmus and an MM canal in MFM was 64.6% and 10.8%, respectively. The highest prevalence of isthmi and MM canals was found in patients of ≤ 20 and of 41–60 years, respectively (p

Photobiomodulation (PBM) has been studied mainly for its effects on the repair, regeneration, and healing of tissue due to its direct and indirect actions on cell proliferation. However, it is necessary to consider the way in which laser acts, that is, whether it affects the rates of spontaneous mutation and mitotic recombination of cells.This study investigated the genotoxic potential of PBM (904 nm) based on an in vivo bioassay that concomitantly evaluates mitotic recombination and point and chromosomal mutations.Strains of Drosophila melanogaster that carry specific marker genes were used to detect the induction of mutation and somatic recombination when exposed to different fluences (3, 5, 10, and 20 J/cmThe doses 5, 10, and 20 J/cmBesides recombination events, the quantitative and qualitative analysis of mutant hairs revealed the occurrence of mutagenic events, both punctual and chromosomal. In addition, the results point to a dose-dependent response.

This study presents the toxicological effects of iron nanoparticles (NP Fe2O3) using in vitro and in vivo tests. Initially nanoparticles were characterized physic-chemically followed by evaluation of cell viability using different cell lines. Allium cepa test and comet assay (cell lines and Danio rerio) were used for evaluation of genotoxicity. Oxidative stress analyses were performed using D. rerio exposed to NP-Fe2O3, and the enzymatic activity of the enzymes catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were evaluated. The results showed that initially nanoparticles had 65.55 nm, 0.24 of polydispersity of and 11.4 mV of zeta potential. Regarding cell viability, it was observed that this did not reach the IC50 up to the concentration 1 x 1010 NP mL-1. The in vitro comet assay showed that in concentrations 1.96 x108 and 109 NPs mL-1 these presented toxicity, for Allium cepa evaluation in concentrations 19.6 and 39.0 x109 NPs mL-1 presented significant damages when compared to the control. Oxidative stress showed that the liver was the most affected organ when compared to the control. Although studies show that iron nanoparticles do not lead to changes, further studies are needed to make sure they do not lead to environmental changes.

Made available in DSpace on 2019-10-03T17:31:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-09-01 This study presents the toxicological effects of iron nanoparticles (NP Fe2O3) using in vitro and in vivo tests. Initially nanoparticles were characterized physic-chemically followed by evaluation of cell viability using different cell lines. Allium cepa test and comet assay (cell lines and Danio rerio) were used for evaluation of genotoxicity. Oxidative stress analyses were performed using D. rerio exposed to NP-Fe2O3, and the enzymatic activity of the enzymes catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were evaluated. The results showed that initially nanoparticles had 65.55 nm, 0.24 of polydispersity of and 11.4 mV of zeta potential. Regarding cell viability, it was observed that this did not reach the IC50 up to the concentration 1 x 1010 NP mL-1. The in vitro comet assay showed that in concentrations 1.96 x108 and 109 NPs mL-1 these presented toxicity, for Allium cepa evaluation in concentrations 19.6 and 39.0 x109 NPs mL-1 presented significant damages when compared to the control. Oxidative stress showed that the liver was the most affected organ when compared to the control. Although studies show that iron nanoparticles do not lead to changes, further studies are needed to make sure they do not lead to environmental changes. Universidade Federal de São Carlos Departamento de Biologia Universidade de Sorocaba Departamento de Biotecnologia Universidade Estadual de São Paulo Departamento de Engenharia Ambiental

Background: This study was done to demonstrate the safety and efficacy of a novel fractional 1550 nm laser device with a rolling mechanism (FRAX1550 Ellipse Medical, Horsholm, Denmark).Obje...

Purpose Choroideremia is a currently incurable X‐linked recessive retinal degeneration that leads to blindness. Gene therapy approaches to date target the outer retinal layers. However, the choroideremia (CHM) gene is expressed in all retinal layers, and a previous study on a small cohort of choroideremia patients suggested possible thinning of the retinal nerve fibre layer (RNFL). The purpose of the study was to examine the RNFL in detail using advanced imaging techniques in a larger cohort of choroideremia patients. Methods Spectral domain optical coherence tomography of the peripapillary RNFL acquired with the Heidelberg Spectralis HRA circular scan mode were analysed retrospectively in 41 eyes of 21 choroideremia patients aged 39.6 years (±3.7 SEM). As age‐matched controls, 20 eyes from 10 patients with retinitis pigmentosa and 56 eyes from 28 healthy individuals were also assessed. Automated RNFL segmentation was adjusted manually to precisely delineate the RNFL. The data were also compared against an external normative database. Results Mean peripapillary RNFL thickness in choroideremia was 130 ± 3 μm in the right eye (OD) and 133 ± 3 μm in the left eye (OS). This was 24% and 27% thicker than RNFL thickness in the controls (p < 0.001 for both). Patients with retinitis pigmentosa also showed an increase in RNFL thickness, which was no different to the choroideremia cohort (p > 0.05). Compared with manual analysis, the automated function of the inbuilt software was consistently inaccurate in segmenting the RNFL in choroideremia. Conclusion The RNFL is significantly thicker in choroideremia compared with age‐matched normal controls, which was similar to what was seen in retinitis pigmentosa.

Direct selective sensing of arginine in central nervous systems remains very essential to understanding of the molecular basis of some physiological events. This study presents the first demonstration on a simple yet effective method for arginine sensing with gold nanoparticles (Au-NPs) as the signal readout. The rationale for the method is based on the pH-dependent feature of the interionic interaction between cysteine and arginine. At pH 6.0, cysteine can only interact with arginine through the ion-pair interaction and such interaction can lead to the changes in both the solution color and UV-vis spectrum of the cysteine-protected Au-NPs upon the addition of arginine. These changes are further developed into an analytical strategy for effective sensing of arginine by rationally controlling the pH values of Au-NP dispersions with the ratio of the absorbance at 650 nm (A 650) to that at 520 nm (A 520) (A 650/A 520) as a parameter for analysis. The method is responsive to arginine without the interference from other species in the cerebral system; under the optimized conditions, the A 650/A 520 values are linear with the concentration of arginine within a concentration range from 0.80 to 64 μM, yet remain unchanged with the addition of other kinds of amino acids or the species in the central nervous system into the Au-NPs dispersion containing cysteine. The method demonstrated here is reliable and robust and could thus be used for detection of the increase of arginine in central nervous systems.

We investigated the effectiveness of artificial silk-based nerve graft in nerve recovery and in helping regain motor functionality in rats. The purpose of this study is to test two questions: (1) Can nerve growth after transection be improved using artificial nerve guides? (2) Does nerve recovery have an impact on the walking patterns of the rat during the recovery period? Rats underwent sciatic nerve sectioning followed by reconstructive surgery. In these experiments, the sciatic nerve was substituted with an artificial silk guide that was biofunctionalized with growth factors and tested in vitro, as described previously. Three-dimensional motion capture and histological analyses were performed. After recovery periods of three and six months, the rats’ kinematics were analyzed during an over-ground walking task to evaluate the nerve recovery progress. The functional nerve recovery showed significant differences between the operated and non-operated sides of the rat, but no differences in their wa...

The zebrafish (Danio rerio) has recently become a powerful animal model for cardiovascular research and drug discovery due to its ease of maintenance, genetic manipulability and ability for high-throughput screening. Recent advances in imaging techniques and generation of transgenic zebrafish have greatly facilitated in vivo analysis of cellular events of cardiovascular development and pathogenesis. More importantly, recent studies have demonstrated the functional similarity of drug metabolism systems between zebrafish and humans, highlighting the clinical relevance of employing zebrafish in identifying lead compounds in Chinese herbal medicine with potential beneficial cardiovascular effects. This paper seeks to summarise the scope of zebrafish models employed in cardiovascular studies and the application of these research models in Chinese herbal medicine to date.

When obtaining a chemical element image through energy dispersive X-ray fluorescence (EDXRF) scanning of a specific sample, it is important to determine the minimum detection time (MDT) required per dot (pixel) and per element in order to identify the minority and the trace elements present in the sample. Starting from the statistical criteria of limit of detection, quantitative estimations can be made regarding the concentration of elements present in the samples, determining the MDT which fits to the limit of detection previously established. Given that with this technique it is possible to implement in vivo applications, in this work, a process was developed for the MDT that is capable of generating the minimum radiation exposure in imaging EDXRF. For this proposal, the MDT is determined for metals, such as Fe, Cu, and Pb, given their great biomedical interest, in a series of equivalent bone and soft tissue phantom samples. Consequently, a criteria for global scanning time per dot was established, hence providing an elemental XRF image according to the As Low As Reasonably Achievable principles, i.e. as low an exposure as reasonably possible for each sample type studied by this sort of devices, in order to obtain appropriate information for each field of application. Copyright © 2015 John Wiley & Sons, Ltd.

Estimating the main axis of rotation (AoR) of a human joint represents an important issue in biomechanics. This study compared three formal methods used to estimate functional AoR, namely a cylindrical fitting method, a mean helical axis transformation, and a symmetrical axis approach. These methods were tested on 106 subjects undergoing navigated total knee arthroplasty. AoR orientation in 3D and in the frontal and coronal planes provided by each method was compared to the transepicondylar axis direction. Although all the methods resulted effective, significant differences were identified among them, relatively to the orientation in 3D and in the frontal plane projection. This was probably due to the presence of secondary rotations during the first degrees of knee flexion.

The experimental objective of this research was to develop and validate a mechanical device that can generate lifelike fluidic pharmacokinetic (PK) profiles for any chemical compound based on preset parameters. The device is intended to “copy” the PK profile of a compound for teaching and research purposes. An in vitro apparatus matching the pharmacokinetically relevant characteristics of a rat was developed in order to generate PK profiles corresponding to the one-compartment and two-compartment models with various routes of administration. The majority of experimental setups were used to generate exponential concentration versus time curves, with one setup used to produce a zero-order elimination profile. The basic design of the device was entirely mechanical, created with pumps and tubing. The change in compound concentration in the circulatory fluid was monitored online. The device successfully generated ten types of realistic pharmacokinetic profiles, with all coefficients of correlation (r 2) between the desired models and experimental results higher than 0.99. Most relative standard deviations (RSDs) for the various concentration time points were less than 1 %, while those for the fitted PK parameters were below 5 %. The results show that the proposed device is highly accurate and precise at generating realistic PK profiles based on preset parameters, and could be used in certain teaching and research projects in the pharmaceutical, analytical, and biomedical sciences. For example, the device would be particularly useful for studying the influence of predefined variable drug concentrations on cell cultures and for calibrating analytical procedures for in vivo analysis.

The live attenuated influenza virus vaccine (LAIV) is preferentially recommended for use in persons 2 through 49 years of age but has not been approved for children under 2 or asthmatics due to safety concerns. Therefore, increasing safety is desirable. Here we describe a murine LAIV with reduced pathogenicity that retains lethality at high doses and further demonstrate that we can enhance safety in vivo through mutations within NS1. This model may permit preliminary safety analysis of improved LAIVs.

Neurotransmitter release at synapses is mediated by the fusion of synaptic vesicles with the plasma membrane. Fusion is mediated by the interaction of three SNARE proteins (soluble NSF-attachment receptor): synaptobrevin in the vesicle membrane and syntaxin and SNAP-25 in the plasma membrane ([

A very first prototype of a Mueller polarimetrie colposcope was used for in vivo analysis of the human uterine cervix. We believe this device of great interest to improve early detection of cervical cancer.