Self-gated free-running 5D whole-heart MRI using blind source separation for automated cardiac motion extraction.

PURPOSE: To compare two blind source separation (BSS) techniques to principal component analysis and the electrocardiogram for the identification of cardiac triggers in self-gated free-running 5D whole-heart MRI. To ascertain the precision and robustness of the techniques, they were compared in three different noise and contrast regimes. METHODS: The repeated superior-inferior (SI) projections of a 3D radial trajectory were used to extract the physiological signals in three cardiac MRI cohorts: (1) 9 healthy volunteers without contrast agent injection at 1.5T, (2) 30 ferumoxytol-injected congenital heart disease patients at 1.5T, and (3) 12 gadobutrol-injected patients with suspected coronary artery disease at 3T. Self-gated cardiac triggers were extracted with the three algorithms (principal component analysis [PCA], second-order blind identification [SOBI], and independent component analysis [ICA]) and the difference with the electrocardiogram triggers was calculated. PCA and SOBI triggers were retained for image reconstruction. The image sharpness was ascertained on whole-heart 5D images obtained with PCA and SOBI and compared among the three cohorts. RESULTS: SOBI resulted in smaller trigger differences in Cohorts 1 and 3 compared to PCA (p < 0.01) and in all cohorts compared to ICA (p < 0.04). In Cohorts 1 and 3, the sharpness increased significantly in the reconstructed images when using SOBI instead of PCA (p < 0.03), but not in Cohort 2 (p = 0.4). CONCLUSION: We have shown that SOBI results in more precisely extracted self-gated triggers than PCA and ICA. The validation across three diverse cohorts demonstrates the robustness of the method against acquisition variability.

Redox Reactivity of Nonsymbiotic Phytoglobins towards Nitrite.

Nonsymbiotic phytoglobins (nsHbs) are a diverse superfamily of hemoproteins grouped into three different classes (1, 2, and 3) based on their sequences. Class 1 Hb are expressed under hypoxia, osmotic stress, and/or nitric oxide exposure, while class 2 Hb are induced by cold stress and cytokinins. Both are mainly six-coordinated. The deoxygenated forms of the class 1 and 2 nsHbs from A. thaliana (AtHb1 and AtHb2) are able to reduce nitrite to nitric oxide via a mechanism analogous to other known globins. NsHbs provide a viable pH-dependent pathway for NO generation during severe hypoxia via nitrite reductase-like activity with higher rate constants compared to mammalian globins. These high kinetic parameters, along with the relatively high concentrations of nitrite present during hypoxia, suggest that plant hemoglobins could indeed serve as anaerobic nitrite reductases in vivo. The third class of nsHb, also known as truncated hemoglobins, have a compact 2/2 structure and are pentacoordinated, and their exact physiological role remains mostly unknown. To date, no reports are available on the nitrite reductase activity of the truncated AtHb3. In the present work, three representative nsHbs of the plant model Arabidopsis thaliana are presented, and their nitrite reductase-like activity and involvement in nitrosative stress is discussed. The reaction kinetics and mechanism of nitrite reduction by nsHbs (deoxy and oxy form) at different pHs were studied by means of UV-Vis spectrophotometry, along with EPR spectroscopy. The reduction of nitrite requires an electron supply, and it is favored in acidic conditions. This reaction is critically affected by molecular oxygen, since oxyAtHb will catalyze nitric oxide deoxygenation. The process displays unique autocatalytic kinetics with metAtHb and nitrate as end-products for AtHb1 and AtHb2 but not for the truncated one, in contrast with mammalian globins.

Rewarded Extinction Increases Amygdalar Connectivity and Stabilizes Long-Term Memory Traces in the vmPFC.

Neurobiological evidence in rodents indicates that threat extinction incorporates reward neurocircuitry. Consequently, incorporating reward associations with an extinction memory may be an effective strategy to persistently attenuate threat responses. Moreover, while there is considerable research on the short-term effects of extinction strategies in humans, the long-term effects of extinction are rarely considered. In a within-subjects fMRI study with both female and male participants, we compared counterconditioning (CC; a form of rewarded-extinction) to standard extinction at recent (24 h) and remote (approximately one month) retrieval tests. Relative to standard extinction, rewarded extinction diminished 24-h relapse of arousal and threat expectancy, and reduced activity in brain regions associated with the appraisal and expression of threat (e.g., thalamus, insula, periaqueductal gray). The retrieval of reward-associated extinction memory was accompanied by functional connectivity between the amygdala and the ventral striatum, whereas the retrieval of standard-extinction memories was associated with connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC). One month later, the retrieval of both standard-extinction and rewarded-extinction was associated with amygdala-vmPFC connectivity. However, only rewarded extinction created a stable memory trace in the vmPFC, identified through overlapping multivariate patterns of fMRI activity from extinction to 24-h and one-month retrieval. These findings provide new evidence that reward may generate a more stable and enduring memory trace of attenuated threat in humans.SIGNIFICANCE STATEMENT Prevalent treatments for pathologic fear and anxiety are based on the principles of Pavlovian extinction. Unfortunately, extinction forms weak memories that only temporarily inhibit the retrieval of threat associations. Thus, to increase the translational relevance of extinction research, it is critical to investigate whether extinction can be augmented to form a more enduring memory, especially after long intervals. Here, we used a multiday fMRI paradigm in humans to compare the short-term and long-term neurobehavioral effects of aversive-to-appetitive counterconditioning (CC), a form of augmented extinction. Our results provide novel evidence that including an appetitive stimulus during extinction can reduce short-term threat relapse and stabilize the memory trace of extinction in the ventromedial prefrontal cortex (vmPFC), for at least one month after learning.

The Impact of Fatty Infiltration on MRI Segmentation of Lower Limb Muscles in Neuromuscular Diseases: A Comparative Study of Deep Learning Approaches.

BACKGROUND: Deep learning methods have been shown to be useful for segmentation of lower limb muscle MRIs of healthy subjects but, have not been sufficiently evaluated on neuromuscular disease (NDM) patients. PURPOSE: Evaluate the influence of fat infiltration on convolutional neural network (CNN) segmentation of MRIs from NMD patients. STUDY TYPE: Retrospective study. SUBJECTS: Data were collected from a hospital database of 67 patients with NMDs and 14 controls (age: 53 ± 17 years, sex: 48 M, 33 F). Ten individual muscles were segmented from the thigh and six from the calf (20 slices, 200 cm section). FIELD STRENGTH/SEQUENCE: A 1.5 T. Sequences: 2D T1 -weighted fast spin echo. Fat fraction (FF): three-point Dixon 3D GRE, magnetization transfer ratio (MTR): 3D MT-prepared GRE, T2: 2D multispin-echo sequence. ASSESSMENT: U-Net 2D, U-Net 3D, TransUNet, and HRNet were trained to segment thigh and leg muscles (101/11 and 95/11 training/validation images, 10-fold cross-validation). Automatic and manual segmentations were compared based on geometric criteria (Dice coefficient [DSC], outlier rate, absence rate) and reliability of measured MRI quantities (FF, MTR, T2, volume). STATISTICAL TESTS: Bland-Altman plots were chosen to describe agreement between manual vs. automatic estimated FF, MTR, T2 and volume. Comparisons were made between muscle populations with an FF greater than 20% (G20+) and lower than 20% (G20-). RESULTS: The CNNs achieved equivalent results, yet only HRNet recognized every muscle in the database, with a DSC of 0.91 ± 0.08, and measurement biases reaching -0.32% ± 0.92% for FF, 0.19 ± 0.77 for MTR, -0.55 ± 1.95 msec for T2, and - 0.38 ± 3.67 cm3 for volume. The performances of HRNet, between G20- and G20+ decreased significantly. DATA CONCLUSION: HRNet was the most appropriate network, as it did not omit any muscle. The accuracy obtained shows that CNNs could provide fully automated methods for studying NMDs. However, the accuracy of the methods may be degraded on the most infiltrated muscles (>20%). EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 1.

Ultra-high field magnetic resonance imaging of the quadriceps tendon enthesis in healthy subjects.

PURPOSE: Although enthesitis is a hallmark of several rheumatologic conditions, current imaging methods are still unable to characterize entheses changes because of the corresponding short transverse relaxation times (T2). A growing number of MR studies have used Ultra-High Field (UHF) MRI in order to assess low-T2 tissues e.g., tendon but never in humans. The purpose of the present study was to assess in vivo the enthesis of the quadriceps tendon in healthy subjects using UHF MRI. METHODS: Eleven healthy subjects volunteered in an osteoarthritis imaging study. The inclusion criteria were: no knee trauma, Lequesne index = 0, less than 3 h of sport activities per week, and Kellgren and Lawrence grade = 0. 3D MR images were acquired at 7 T using GRE sequences and a T2* mapping. Regions of interest i.e., trabecular bone, subchondral bone, enthesis, and tendon body were identified, and T2* values were quantified and compared. RESULTS: Quadriceps tendon enthesis was visible as a hyper-intense signal. The largest and the lowest T2* values were quantified in the subchondral bone region and the tendon body respectively. T2* value within subchondral bone was significantly higher than T2* value within the enthesis. T2* in subchondral bone region was significantly higher than the whole tendon body T2*. CONCLUSION: A T2* gradient was observed along the axis from the enthesis toward the tendon body. It illustrates different water biophysical properties. These results provide normative values which could be used in the field of inflammatory rheumatologic diseases and mechanical disorders affecting the tendon.

Gadolinium Accumulation and Toxicity on In Vitro Grown Stevia rebaudiana: A Case-Study on Gadobutrol.

Gadolinium-based contrast agents are molecular complexes which are extensively used for diagnostic purposes. Apart from their tremendous contribution to disease diagnostics, there are several issues related to their use. They are extremely stable complexes and potential contaminants of surface and ground waters, an issue which is documented worldwide. The irrigation of fields with contaminated surface waters or their fertilization with sludge from wastewater treatment plants can lead to the introduction of Gd into the human food supply chain. Thus, this study focused on the potential toxicity of Gd on plants. For this purpose, we have studied the molecular effects of gadobutrol (a well-known MRI contrast agent) exposure on in vitro-grown Stevia rebaudiana. The effects of gadobutrol on plant morphology, on relevant plant metabolites such as chlorophylls, carotenoids, ascorbic acids (HPLC), minerals (ICP-OES), and on the generation of free radical species (MDA assay and EPR) were assessed. Exposures of 0.01, 0.05, 0.1, 1, and 3 mM gadobutrol were used. We found a correlation between the gadobutrol dose and the plant growth and concentration of metabolites. Above the 0.1. mM dose of gadobutrol, the toxic effects of Gd+3 ions became significant.

Emotional learning retroactively enhances item memory but distorts source attribution.

An adaptive memory system should prioritize information surrounding a powerful learning event that may prove useful for predicting future meaningful events. The behavioral tagging hypothesis provides a mechanistic framework to interpret how weak experiences persist as durable memories through temporal association with a strong experience. Memories are composed of multiple elements, and different mnemonic aspects of the same experience may be uniquely affected by mechanisms that retroactively modulate a weakly encoded memory. Here, we investigated how emotional learning affects item and source memory for related events encoded close in time. Participants encoded trial-unique category exemplars before, during, and after Pavlovian fear conditioning. Selective retroactive enhancements in 24-h item memory were accompanied by a bias to misattribute items to the temporal context of fear conditioning. The strength of this source memory bias correlated with participants' retroactive item memory enhancement, and source misattribution to the emotional context predicted whether items were remembered overall. In the framework of behavioral tagging: Memory attribution was biased to the temporal context of the stronger event that provided the putative source of memory stabilization for the weaker event. We additionally found that fear conditioning selectively and retroactively enhanced stimulus typicality ratings for related items, and that stimulus typicality also predicted overall item memory. Collectively, these results provide new evidence that items related to emotional learning are misattributed to the temporal context of the emotional event and judged to be more representative of their semantic category. Both processes may facilitate memory retrieval for related events encoded close in time.

Supervised segmentation framework for evaluation of diffusion tensor imaging indices in skeletal muscle.

Diffusion tensor imaging (DTI) is becoming a relevant diagnostic tool to understand muscle disease and map muscle recovery processes following physical activity or after injury. Segmenting all the individual leg muscles, necessary for quantification, is still a time-consuming manual process. The purpose of this study was to evaluate the impact of a supervised semi-automatic segmentation pipeline on the quantification of DTI indices in individual upper leg muscles. Longitudinally acquired MRI datasets (baseline, post-marathon and follow-up) of the upper legs of 11 subjects were used in this study. MR datasets consisted of a DTI and Dixon acquisition. Semi-automatic segmentations for the upper leg muscles were performed using a transversal propagation approach developed by Ogier et al on the out-of-phase Dixon images at baseline. These segmentations were longitudinally propagated for the post-marathon and follow-up time points. Manual segmentations were performed on the water image of the Dixon for each of the time points. Dice similarity coefficients (DSCs) were calculated to compare the manual and semi-automatic segmentations. Bland-Altman and regression analyses were performed, to evaluate the impact of the two segmentation methods on mean diffusivity (MD), fractional anisotropy (FA) and the third eigenvalue (λ3 ). The average DSC for all analyzed muscles over all time points was 0.92 ± 0.01, ranging between 0.48 and 0.99. Bland-Altman analysis showed that the 95% limits of agreement for MD, FA and λ3 ranged between 0.5% and 3.0% for the transversal propagation and between 0.7% and 3.0% for the longitudinal propagations. Similarly, regression analysis showed good correlation for MD, FA and λ3 (r = 0.99, p < 60; 0.0001). In conclusion, the supervised semi-automatic segmentation framework successfully quantified DTI indices in the upper-leg muscles compared with manual segmentation while only requiring manual input of 30% of the slices, resulting in a threefold reduction in segmentation time.

Chromatographic Determination of Total Selenium in Biofortified Allium sp. following Piazselenol Formation and Micro-Solid-Phase Extraction.

Herein, a method based on selective piazselenol formation is applied for total selenium determination in biofortified Allium species. Piazselenol is formed by reacting Se(IV) with an aromatic diamine, namely 4-nitro-1,2-phenylenediamine, in acidic medium. Samples were digested in a nitric acid/hydrogen peroxide open system, followed by selenate reduction in hydrochloric acid. Reaction conditions were optimized in terms of pH, temperature, reaction time, and other auxiliary reagents for interference removal, namely, EDTA and hydroxylamine. For the extraction of the selectively formed 4-nitro-piazselenol, micro-solid-phase extraction (µSPE) was applied, and the analysis and detection of the corresponding complex was performed by HPLC coupled with DAD. An external standard calibration curve was developed (R2 = 0.9994) with good sensitivity, and was used to calculate the total selenium content from several Allium plants material, with good intermediate precision (RSD% < 16%). The accuracy of the method was evaluated using both, a comparison with an accepted reference method from our previously published data, as well as three certified reference material with recoveries between 84-126%. The limit of detection was determined to be 0.35 µg/g (in solids) and 1.1 µg/L (in solution), while the limit of quantification was 1.07 µg/g and 3.4 µg/L (in solution). Using the proposed method, selenium content can be quickly and accurately determined in several types of samples. In addition, this study present experimental conditions for overcoming the interferences that might be encountered in selenium determination using piazselenol.

The Phytochemical Analysis of Vinca L. Species Leaf Extracts Is Correlated with the Antioxidant, Antibacterial, and Antitumor Effects.

The phytochemical analysis of Vinca minor, V. herbacea, V. major, and V. major var. variegata leaf extracts showed species-dependent antioxidant, antibacterial, and cytotoxic effects correlated with the identified phytoconstituents. Vincamine was present in V. minor, V. major, and V. major var. variegata, while V. minor had the richest alkaloid content, followed by V. herbacea. V. major var. variegata was richest in flavonoids and the highest total phenolic content was found in V. herbacea which also had elevated levels of rutin. Consequently, V. herbacea had the highest antioxidant activity followed by V. major var. variegata. Whereas, the lowest one was of V. major. The V. minor extract showed the most efficient inhibitory effect against both Staphylococcusaureus and E. coli. On the other hand, V. herbacea had a good anti-bacterial potential only against S. aureus, which was most affected at morphological levels, as indicated by scanning electron microscopy. The Vinca extracts acted in a dose-depended manner against HaCaT keratinocytes and A375 melanoma cells and moreover, with effects on the ultrastructure, nitric oxide concentration, and lactate dehydrogenase release. Therefore, the Vinca species could be exploited further for the development of alternative treatments in bacterial infections or as anticancer adjuvants.

A novel segmentation framework dedicated to the follow-up of fat infiltration in individual muscles of patients with neuromuscular disorders.

PURPOSE: To propose a novel segmentation framework that is dedicated to the follow-up of fat infiltration in individual muscles of patients with neuromuscular disorders. METHODS: We designed a semi-automatic segmentation pipeline of individual leg muscles in MR images based on automatic propagation through nonlinear registrations of initial delineation in a minimal number of MR slices. This approach has been validated for the segmentation of individual muscles from MRI data sets, acquired over a 10-month period, from thighs and legs in 10 patients with muscular dystrophy. The robustness of the framework was evaluated using conventional metrics related to muscle volume and clinical metrics related to fat infiltration. RESULTS: High accuracy of the semi-automatic segmentation (mean Dice similarity coefficient higher than 0.89) was reported. The provided method has excellent reliability regarding the reproducibility of the fat fraction estimation, with an average intraclass correlation coefficient score of 0.99. Furthermore, the present segmentation framework was determined to be more reliable than the intra-expert performance, which had an average intraclass correlation coefficient of 0.93. CONCLUSION: The proposed framework of segmentation can successfully provide an effective and reliable tool for accurate follow-up of any MRI biomarkers in neuromuscular disorders. This method could assist the quantitative assessment of muscular changes occurring in such diseases.

Deep learning-based fully automatic segmentation of wrist cartilage in MR images.

The study objective was to investigate the performance of a dedicated convolutional neural network (CNN) optimized for wrist cartilage segmentation from 2D MR images. CNN utilized a planar architecture and patch-based (PB) training approach that ensured optimal performance in the presence of a limited amount of training data. The CNN was trained and validated in 20 multi-slice MRI datasets acquired with two different coils in 11 subjects (healthy volunteers and patients). The validation included a comparison with the alternative state-of-the-art CNN methods for the segmentation of joints from MR images and the ground-truth manual segmentation. When trained on the limited training data, the CNN outperformed significantly image-based and PB-U-Net networks. Our PB-CNN also demonstrated a good agreement with manual segmentation (Sørensen-Dice similarity coefficient [DSC] = 0.81) in the representative (central coronal) slices with a large amount of cartilage tissue. Reduced performance of the network for slices with a very limited amount of cartilage tissue suggests the need for fully 3D convolutional networks to provide uniform performance across the joint. The study also assessed inter- and intra-observer variability of the manual wrist cartilage segmentation (DSC = 0.78-0.88 and 0.9, respectively). The proposed deep learning-based segmentation of the wrist cartilage from MRI could facilitate research of novel imaging markers of wrist osteoarthritis to characterize its progression and response to therapy.

In vivo characterization of skeletal muscle function in nebulin-deficient mice.

INTRODUCTION: The conditional nebulin knockout mouse is a new model mimicking nemaline myopathy, a rare disease characterized by muscle weakness and rods within muscle fibers. We investigated the impact of nebulin (NEB) deficiency on muscle function in vivo. METHODS: Conditional nebulin knockout mice and control littermates were studied at 10 to 12 months. Muscle function (force and fatigue) and anatomy (muscles volume and fat content) were measured in vivo. Myosin heavy chain (MHC) composition and nebulin (NEB) protein expression were assessed by protein electrophoresis. RESULTS: Conditional nebulin knockout mice displayed a lower NEB level (-90%) leading to a 40% and 45% reduction in specific maximal force production and muscles volume, respectively. Nebulin deficiency was also associated with higher resistance to fatigue and increased MHC I content. DISCUSSION: Adult nebulin-deficient mice displayed severe muscle atrophy and weakness in vivo related to a low NEB content but an improved fatigue resistance due to a slower contractile phenotype.

Effects of Long-Term Exposure to Low-Power 915 MHz Unmodulated Radiation on Phaseolus vulgaris L.

The morphophysiological response of Phaseolus vulgaris L. to low-power electromagnetic radiation was investigated in order to assess the potential harmful effects of long-term continuous exposure. The plants were grown in two separate electromagnetic field (EMF) shielded rooms, in a controlled, greenhouse-like environment. One batch was continuously irradiated during the growth period (from sowing to maturity) and the other one was used as a reference. An unmodulated signal at 915 MHz (the central frequency between the uplink and downlink of the GSM900 mobile communications band) was used, with a maximum power density of 10 mW/m2 measured near the plants. The plants were analyzed using ultraviolet-visible, statistical, morphometric, and electron microscopy methods. Significant differences were observed regarding the height of the plants, number of inflorescences, and chlorophyll and carotenoid content, all closely connected with the ultrastructural changes observed in the leaves. The irradiated batch grew higher (19% increase in plant height, 20% increase in stem and leaves' dry mass), with 18% fewer inflorescences, and extremely long roots (34% increase in dry mass). The ultrastructure of the irradiated leaves showed irregular cells and a higher content of plastoglobules in the chloroplasts. All results indicate that the irradiated plants suffered significant morphological modifications during their long-term exposure to the specific EM radiation. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.

Muscle alterations induced by electrostimulation are lower at short quadriceps femoris length.

PURPOSE: This study aimed at determining through MRI investigations, force and soreness assessments whether the modulation of muscle length is a relevant strategy for minimising neuromuscular electrical stimulation (NMES)-induced muscle damage in young healthy participants. METHODS: Comparison of 2 NMES sessions (40 isometric electrically-evoked contractions of the knee extensors) was randomly performed on 1 knee flexed at 50° (short muscle length) and the contralateral at 100° (long muscle length) in a single group of healthy participants. Indirect markers of muscle damage including changes in maximal voluntary isometric contraction (MVC) force, muscle volume and transverse relaxation time (T2) were measured before, 2 days (D2), 4 days (D4) and 7 days (D7) after the NMES sessions in each limb of the ten participants. RESULTS: Although stimulation intensity was similar during the NMES session on both limbs, significantly lower force production was recorded at long muscle length (peak at 30 ± 5% MVC force) as compared to short muscle length (peak at 61 ± 12% MVC force). In the following days, MVC force at long muscle length was decreased from D2 to D7, whereas no significant change occurred at short muscle length. Increases in muscle volume and T2 were found at each time point in stimulated muscles at long muscle length, whereas no change was found at short muscle length. CONCLUSION: For the same stimulation intensity, NMES-induced isometric contractions generate higher knee extension force output and result in lower muscle tissues alterations that could be related to a lower intramuscular shear strain when exercise is performed at short muscle length.

Spatial difference can occur between activated and damaged muscle areas following electrically-induced isometric contractions.

KEY POINTS: T2 mapping combined to image registration and statistical parametric mapping analysis is a suitable methodology to accurately localize and compare the extent of both activated and damaged muscle areas. Activated muscle areas following electrically-induced isometric contractions are superficial, but damaged regions are muscle specific and can be related to the muscle morphology and/or the relative spatial position within a muscle group leading to potential intramuscular muscle shear strain. Tissues other than active skeletal muscle fibres can be altered during unaccustomed neuromuscular electrical stimulation-induced isometric contractions. ABSTRACT: Skeletal muscle isometric contractions induced by neuromuscular electrical stimulation (NMES) exercise can generate damage within activated muscles. This study aimed at comparing the localization and the extent of NMES-activated muscle areas and induced damage regions using magnetic resonance imaging. Thirteen healthy subjects performed a single bout of NMES-induced isometric contractions known to induce a decrease in maximal voluntary isometric contraction (MVC) and increase in muscle volume and transverse relaxation time (T2 ). All the parameters were measured before, immediately after (POST), 7 days (D7), 14 days (D14) and 21 days (D21) after the NMES session. Spatial normalization of T2 maps were performed to compare the localization of muscle activation areas and damaged muscle regions from statistical mapping analyses. A significant decrease in MVC was found at POST (-26 ± 9%) and in delayed time at D7 (-20 ± 6%) and D14 (-12 ± 5%). Although muscle activation was statistically detected through T2 increase at POST in superficial parts of the two muscles located beneath the stimulation electrodes (i.e. vastus lateralis and vastus medialis), alterations quantified in a delayed time from increased T2 were mainly located in the deep muscle region of the vastus lateralis (+57 ± 24% of mean T2 ) and superficial area of the vastus medialis (+24 ± 16% of mean T2 ) at D7 and were still observed in whole muscle at D21. The discrepancy between activated and damaged areas in the vastus lateralis implies that tissues other than active skeletal muscle fibres were altered during unaccustomed NMES-induced isomeric contractions.

Remarkable rutin-rich Hypericum capitatum extract exhibits anti-inflammatory effects on turpentine oil-induced inflammation in rats.

BACKGROUND: Natural extracts with beneficial biological activities are nowadays of high interest, in various treatment or prophylaxis. Hypericum capitatum has been known for its curative effects for centuries and its extracts have become of interest due to their distinct activity among other Hypericaceae members. In this study, further light is aimed to be shed on the secondary-metabolites composition of H. capitatum extracts, using chromatographic techniques and Electron paramagnetic resonance profiles in alkaline medium. Considering that no previous works explored the anti-inflammatory activity of H. capitatum, here, an in vivo study is also designed in order to evaluate this property by assessing the impact of one of H. capitatum extracts in ameliorating turpentine oil-induced inflammation on rats and to quantify their blood antioxidants level. METHODS: Chromatographic techniques and Electron paramagnetic resonance spectroscopy were used in order to describe the chemical profile in different parts of the plant. The in vivo study on turpentine-oil induced inflammation in rats included three doses of H. capitatum extract expressed in rutin concentration. Oxidative stress was measured using total oxidative status, total antioxidant capacity, oxidative stress index, 3-nitrotyrosine, nitric oxide, malondialdehyde, superoxide dismutase, catalase and the inflammatory response was evaluated by performing a complete blood cells count and C reactive protein. RESULTS: The extract was remarkably rich in rutin; however, other polyphenolic-like minor components appeared important in explaining the observed biological properties. The tested extract prevents the increase of inflammation-induced white blood cell count, number of neutrophils, and serum nitric oxide, and did so in a dose-dependent manner, similarly to the positive control-diclofenac. In addition, the same extract appeared to be a good alternative to diclofenac to restore total oxidative status, thiobarbituric active reactive species, total proteins and C reactive proteins. Moreover, antioxidant enzymes such as catalase, superoxide dismutase and total serum thiol concentration were significantly increased by the tested extract. CONCLUSIONS: Due to its powerful reservoir rich in rutin, H. capitatum extract depicted its in vivo antioxidant and anti-inflammatory effects indicating it to be a good alternative to conventional drugs for oxidative stress protection.

Diffusion Properties and 3D Architecture of Human Lower Leg Muscles Assessed with Ultra-High-Field-Strength Diffusion-Tensor MR Imaging and Tractography: Reproducibility and Sensitivity to Sex Difference and Intramuscular Variability.

Purpose To demonstrate the reproducibility of the diffusion properties and three-dimensional structural organization measurements of the lower leg muscles by using diffusion-tensor imaging (DTI) assessed with ultra-high-field-strength (7.0-T) magnetic resonance (MR) imaging and tractography of skeletal muscle fibers. On the basis of robust statistical mapping analyses, this study also aimed at determining the sensitivity of the measurements to sex difference and intramuscular variability. Materials and Methods All examinations were performed with ethical review board approval; written informed consent was obtained from all volunteers. Reproducibility of diffusion tensor indexes assessment including eigenvalues, mean diffusivity, and fractional anisotropy (FA) as well as muscle volume and architecture (ie, fiber length and pennation angle) were characterized in lower leg muscles (n = 8). Intramuscular variability and sex differences were characterized in young healthy men and women (n = 10 in each group). Student t test, statistical parametric mapping, correlation coefficients (Spearman rho and Pearson product-moment) and coefficient of variation (CV) were used for statistical data analysis. Results High reproducibility of measurements (mean CV ± standard deviation, 4.6% ± 3.8) was determined in diffusion properties and architectural parameters. Significant sex differences were detected in FA (4.2% in women for the entire lower leg; P = .001) and muscle volume (21.7% in men for the entire lower leg; P = .008), whereas architecture parameters were almost identical across sex. Additional differences were found independently of sex in diffusion properties and architecture along several muscles of the lower leg. Conclusion The high-spatial-resolution DTI assessed with 7.0-T MR imaging allows a reproducible assessment of structural organization of superficial and deep muscles, giving indirect information on muscle function. ©RSNA, 2018 Online supplemental material is available for this article.

Real-time detection of N-end rule-mediated ubiquitination via fluorescently labeled substrate probes.

The N-end rule pathway has emerged as a major system for regulating protein functions by controlling their turnover in medical, animal and plant sciences as well as agriculture. Although novel functions and enzymes of the pathway have been discovered, the ubiquitination mechanism and substrate specificity of N-end rule pathway E3 ubiquitin ligases have remained elusive. Taking the first discovered bona fide plant N-end rule E3 ligase PROTEOLYSIS1 (PRT1) as a model, we used a novel tool to molecularly characterize polyubiquitination live, in real time. We gained mechanistic insights into PRT1 substrate preference and activation by monitoring live ubiquitination using a fluorescent chemical probe coupled to artificial substrate reporters. Ubiquitination was measured by rapid in-gel fluorescence scanning as well as in real time by fluorescence polarization. The enzymatic activity, substrate specificity, mechanisms and reaction optimization of PRT1-mediated ubiquitination were investigated ad hoc instantaneously and with significantly reduced reagent consumption. We demonstrated that PRT1 is indeed an E3 ligase, which has been hypothesized for over two decades. These results demonstrate that PRT1 has the potential to be involved in polyubiquitination of various substrates and therefore pave the way to understanding recently discovered phenotypes of prt1 mutants.

Detection of blood and DNA traces after thermal exposure.

The analysis of blood traces is often of significant reconstructive and evidence-gathering importance. Perpetrators deliberately set fires to destroy evidence. There is little literature regarding the effect of fire and extreme heat on blood and the detection of blood. Blood and DNA are believed to be no longer traceable after exposure to a temperature of 1000 °C. This study exposed different objects of a standardized procedure to temperatures of 300, 700, and 1000 °C. It documented the influence of heat on blood traces through the use of luminol. DNA analysis confirmed that fewer DNA profiles can be created with increasing temperature. However, even after exposure up to a max. of 1000 °C, it was still possible to produce a complete DNA pattern from approx. 60% of the samples. Consequently, crime scenes that have been destroyed by fire should be evaluated with the same attention to detail as the unburned areas.