Beyond weakness: Exploring intramuscular fat and quadriceps atrophy in ACLR recovery.

Muscle weakness following anterior cruciate ligament reconstruction (ACLR) increases the risk of posttraumatic osteoarthritis (OA). However, focusing solely on muscle weakness overlooks other aspects like muscle composition, which could hinder strength recovery. Intramuscular fat is a non-contractile element linked to joint degeneration in idiopathic OA, but its role post-ACLR has not been thoroughly investigated. To bridge this gap, we aimed to characterize quadriceps volume and intramuscular fat in participants with ACLR (male/female = 15/9, age = 22.8 ± 3.6 years, body mass index [BMI] = 23.2 ± 1.9, time since surgery = 3.3 ± 0.9 years) and in controls (male/female = 14/10, age = 22.0 ± 3.1 years, BMI = 23.3 ± 2.6) while also exploring the associations between intramuscular fat and muscle volume with isometric strength. Linear mixed effects models assessed (I) muscle volume, (II) intramuscular fat, and (III) strength between limbs (ACLR vs. contralateral vs. control). Regression analyses were run to determine if intramuscular fat or volume were associated with quadriceps strength. The ACLR limb was 8%-11% smaller than the contralateral limb (p < 0.05). No between-limb differences in intramuscular fat were observed (p 0.091-0.997). Muscle volume but not intramuscular fat was associated with strength in the ACLR and control limbs (p < 0.001-0.002). We demonstrate that intramuscular fat does not appear to be an additional source of quadriceps dysfunction following ACLR and that muscle size only explains some of the variance in muscle strength.

Reducing Carbon Dioxide Laser-Induced Postinflammatory Hyperpigmentation with Prophylactic Photobiomodulation: A Case Study.

Objective: This study aimed to investigate the effectiveness of prophylactic photobiomodulation (PBM) in reducing postinflammatory hyperpigmentation (PIH) induced by carbon dioxide (CO2) laser resurfacing in a patient with periorbital syringomas. Background: PIH is a common condition characterized by abnormal skin pigmentation after an inflammatory process occurring in up to 20-30% of patients undergoing CO2 laser resurfacing. Methods: The patient was treated with PBM using a pulsed home-use device at 630 nm before and after CO2 laser treatment. The patient was asked to treat the right periorbital area before and after the CO2 laser treatment, which was continued once a day for 2 consecutive weeks. Results: At 12 weeks, PIH was significantly reduced on the treated side compared with the contralateral untreated side (leading to persistent erythema at 6 months). Conclusions: This is the first report of prophylactic treatment of CO2 laser-induced dyschromia using PBM.

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.

Removal and degradation of sodium diclofenac via radical-based mechanisms using S. sclerotiorum laccase.

The recently isolated Sclerotinia sclerotiorum laccase was used for the degradation of sodium diclofenac, a nonsteroidal anti-inflammatory drug widely found in the aquatic environment. The Michaelis-Menten parameters, half-life of diclofenac at different pH values in presence of this enzyme and potential inhibitors were evaluated. Diclofenac-based radicals formed in presence of laccase were spin-trapped and detected using EPR spectroscopy. Almost complete diclofenac degradation (> 96%) occurred after a 30-h treatment via radical-based generated oligomers and their rapid precipitation, thus ensuring an unprecedented green formula suitable not only for degradation but also for straightforward removal of the degradation products. High performance liquid chromatography coupled with atmospheric pressure chemical ionization-ion trap mass spectrometry (HPLC-APCI-MS) analyses of the degradation products of diclofenac in aqueous dosage revealed the presence of at least seven products while HR Orbitrap MS analysis showed that the enzymatic treatment produced high molecular weight metabolites through a radical oligomerization mechanism of diclofenac. The enzymatically formed products precipitated and its constituting components were also characterized using UV-vis spectroscopy, infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA).

Effect of knee joint angle on vastus medialis and vastus lateralis rigidity during isometric submaximal voluntary knee extensions.

The use of shear wave elastography during voluntary contraction has enabled the non-invasive assessment of load sharing strategies between agonist muscles. However, the change in joint angle and voluntary contraction intensity can modify contribution between muscles. The aim of this study was to investigate the effect of knee joint angle on the local mechanical properties of the vastus medialis (VM) and the vastus lateralis (VL) during isometric submaximal voluntary contractions from shear wave elastography mapping. The VM and VL Young's modulus at rest and during constant isometric submaximal voluntary contractions (i.e., 25%, 50% and 75% of maximal voluntary contraction [MVC]) were assessed for two knee angles (50° and 100° | knee fully extended = 0°) in twelve participants. No significant difference was found in the VM Young's modulus among all torque levels and knee angles (p > 0.05). VL Young's modulus was significantly higher at 25% MVC for a knee angle of 100° than at 75% MVC for the same knee angle and was greater at 25% MVC for a knee angle of 100° than for 50° (p < 0.05). In contrast to the VM, the contribution of the VL to the knee joint torque production during isometric voluntary contraction appears to depend on the muscle length and the relative knee extension torque level.

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.

Four-dimensional reconstruction and characterization of bladder deformations.

BACKGROUND AND OBJECTIVE: Pelvic floor disorders are prevalent diseases and patient care remains difficult as the dynamics of the pelvic floor remains poorly understood. So far, only 2D dynamic observations of straining exercises at excretion are available in the clinics and 3D mechanical defects of pelvic organs are not well studied. In this context, we propose a complete methodology for the 3D representation of non-reversible bladder deformations during exercises, combined with a 3D representation of the location of the highest strain areas on the organ surface. METHODS: Novel image segmentation and registration approaches have been combined with three geometrical configurations of up-to-date rapid dynamic multi-slice MRI acquisitions for the reconstruction of real-time dynamic bladder volumes. RESULTS: For the first time, we proposed real-time 3D deformation fields of the bladder under strain from in-bore forced breathing exercises. The potential of our method was assessed on eight control subjects undergoing forced breathing exercises. We obtained average volume deviations of the reconstructed dynamic volume of bladders around 2.5% and high registration accuracy with mean distance values of 0.4 ± 0.3 mm and Hausdorff distance values of 2.2 ± 1.1 mm. CONCLUSIONS: The proposed framework provides proper 3D+t spatial tracking of non-reversible bladder deformations. This has immediate applicability in clinical settings for a better understanding of pelvic organ prolapse pathophysiology. This work can be extended to patients with cavity filling or excretion problems to better characterize the severity of pelvic floor pathologies or to be used for preoperative surgical planning.

Novel simultaneous determination of alliin and allicin in Allium sp. using digital subtraction HPTLC.

Allicin is a major thiosulfinate found in garlic and other Allium sp. and it is responsible for their pungent aroma. It is formed during the tissue lysis of garlic, by the initial action of alliinase upon alliin, the major cysteine sulfoxide. Simultaneous detection of these two analytes is usually performed using HPLC. Contrary to the most important phytoconstituents in other samples, allicin is scarcely detected using the simple HPTLC technique, due to challenges caused by its unique structure, despite its simplicity and high needs in the analytical monitoring of the Allium sp. In this work, a cost-effective, simple, sensitive and accurate method was developed for the determination of allicin together with alliin, using HPTLC. Allicin is quickly pre-derivatised with cysteine in excess to the stable S-allylmercaptocysteine that is then simultaneously detected with alliin, using ninhydrin reagent. The method was validated in terms of accuracy (recoveries of 90-120 %), precision (RSD% of 4-12 %), selectivity, robustness, peak purity and limit of detection (LOD = 0.05 µg/band for allicin and LOD = 0.10 µg/band for alliin). The method was successfully applied using real Allium sp. samples and the results were in good agreement with HPLC data.

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.

Selective Attachment of Polyethylene Glycol to Hemerythrin for Potential Use in Blood Substitutes.

Due to its ability to reversibly bind O2, alongside a relatively low redox reactivity and a limited cytotoxicity, the oxygen-carrying protein hemerythrin has been considered as an alternative to hemoglobin in preparing blood substitutes. In order to increase the hydrodynamic volume and lower antigenicity, two site-directed variants, H82C and K92C, were engineered that contained a single cysteine residue on the surface of each hemerythrin octamer for the specific attachment of polyethylene glycol (PEG). A sulfhydryl-reactive PEGylation reagent with a 51.9 Å spacer arm was used for selective cysteine derivatization. The mutants were characterized by UV-vis spectroscopy, size-exclusion chromatography, oxygen affinity, and autooxidation rate measurements. The H82C variant showed altered oligomeric behavior compared to the wild-type and was unstable in the met form. The PEGylated K92C variant is reasonably stable, displays an oxygen affinity similar to that of the wild-type, and shows an increased rate of autoxidation; the latter disadvantage may be counteracted by further chemical modifications.

Low-Intensity Visible and Near-Infrared Light-Induced Cell Signaling Pathways in the Skin: A Comprehensive Review.

Objective: To describe current knowledge regarding established and putative cell signaling pathways involved in skin photobiomodulation. Background: The skin is the largest and most accessible organ of the body. It is the first line of defense against the external environment, including solar radiation. Among solar rays, visible and infrared non-ionizing photons may reach human skin and trigger a cascade of non-thermal cell signaling pathways called photobiomodulation (PBM). The use of PBM using artificial light sources has been known for more than 50 years, but it has not yet been widely accepted due to uncertainty about the cellular mechanisms of action. However, much knowledge has been gained in this field in recent years, which will be summarized in this review. Methods: An extensive literature review was performed using Medline, Embase, and Google Scholar as research databases to acquire relevant publications in this particular field. Results: A comprehensive description of chromophores, primary and secondary effectors is provided in addition to a visual representation of known and putative cell signaling mechanisms involved in such complex light-skin interactions. Also, a summary of clinical indications of skin PBM, key light parameters, and promising skin applications (local and systemic) are mentioned. Conclusions: In PBM, skin cells are the first to absorb photons, triggering specific cell-signaling pathways through primary and secondary effectors, leading to enhanced cell repair and survival, notably in hypoxic or stressed cells. A better understanding of the mechanisms of action will help us optimize known indications and discover new ones.

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.

Pattern analysis of neuroimaging data reveals novel insights on threat learning and extinction in humans.

Several decades of rodent neurobiology research have identified a network of brain regions that support Pavlovian threat conditioning and extinction, focused predominately on the amygdala, hippocampus, and medial prefrontal cortex (mPFC). Surprisingly, functional magnetic resonance imaging (fMRI) studies have shown inconsistent evidence for these regions while humans undergo threat conditioning and extinction. In this review, we suggest that translational neuroimaging efforts have been hindered by reliance on traditional univariate analysis of fMRI. Whereas univariate analyses average activity across voxels in a given region, multivariate pattern analyses (MVPA) leverage the information present in spatial patterns of activity. MVPA therefore provides a more sensitive analysis tool to translate rodent neurobiology to human neuroimaging. We review human fMRI studies using MVPA that successfully bridge rodent models of amygdala, hippocampus, and mPFC function during Pavlovian learning. We also highlight clinical applications of these information-sensitive multivariate analyses. In sum, we advocate that the field should consider adopting a variety of multivariate approaches to help bridge cutting-edge research on the neuroscience of threat and anxiety.

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 Preperitoneal Space in Hernia Repair.

The preperitoneal spaces relevant for incisional hernia repair and minimally invasive groin hernia repair are described in terms of surgical anatomy. Emphasis is put on the transversalis fascia and the urogenital fascia and its extensions, the vesicoumbilical fascia, and the spermatic sheath of Stoppa procedure. Steps in hernia surgery where these structures are relevant are reviewed.

The Road Toward Reproducibility of Parametric Mapping of the Heart: A Technical Review.

Parametric mapping of the heart has become an essential part of many cardiovascular magnetic resonance imaging exams, and is used for tissue characterization and diagnosis in a broad range of cardiovascular diseases. These pulse sequences are used to quantify the myocardial T1, T2, T 2 * , and T1ρ relaxation times, which are unique surrogate indices of fibrosis, edema and iron deposition that can be used to monitor a disease over time or to compare patients to one another. Parametric mapping is now well-accepted in the clinical setting, but its wider dissemination is hindered by limited inter-center reproducibility and relatively long acquisition times. Recently, several new parametric mapping techniques have appeared that address both of these problems, but substantial hurdles remain for widespread clinical adoption. This review serves both as a primer for newcomers to the field of parametric mapping and as a technical update for those already well at home in it. It aims to establish what is currently needed to improve the reproducibility of parametric mapping of the heart. To this end, we first give an overview of the metrics by which a mapping technique can be assessed, such as bias and variability, as well as the basic physics behind the relaxation times themselves and what their relevance is in the prospect of myocardial tissue characterization. This is followed by a summary of routine mapping techniques and their variations. The problems in reproducibility and the sources of bias and variability of these techniques are reviewed. Subsequently, novel fast, whole-heart, and multi-parametric techniques and their merits are treated in the light of their reproducibility. This includes state of the art segmentation techniques applied to parametric maps, and how artificial intelligence is being harnessed to solve this long-standing conundrum. We finish up by sketching an outlook on the road toward inter-center reproducibility, and what to expect in the future.

Characterization of surface motion patterns in highly deformable soft tissue organs from dynamic MRI: An application to assess 4D bladder motion.

BACKGROUND AND OBJECTIVES: Dynamic Magnetic Resonance Imaging (MRI) may capture temporal anatomical changes in soft tissue organs with high-contrast but the obtained sequences usually suffer from limited volume coverage which makes the high-resolution reconstruction of organ shape trajectories a major challenge in temporal studies. Because of the variability of abdominal organ shapes across time and subjects, the objective of the present study is to go towards 3D dense velocity measurements to fully cover the entire surface and to extract meaningful features characterizing the observed organ deformations and enabling clinical action or decision. METHODS: We present a pipeline for characterization of bladder surface dynamics during deep respiratory movements. For a compact shape representation, the reconstructed temporal volumes were first used to establish subject-specific dynamical 4D mesh sequences using the large deformation diffeomorphic metric mapping (LDDMM) framework. Then, we performed a statistical characterization of organ dynamics from mechanical parameters such as mesh elongations and distortions. Since we refer to organs as non-flat surfaces, we have also used the mean curvature change as metric to quantify surface evolution. However, the numerical computation of curvature is strongly dependant on the surface parameterization (i.e. the mesh resolution). To cope with this dependency, we employed a non-parametric method for surface deformation analysis. Independent of parameterization and minimizing the length of the geodesic curves, it stretches smoothly the surface curves towards a sphere by minimizing a Dirichlet energy. An Eulerian PDE approach is used to derive a shape descriptor from the curve-shortening flow. Intercorrelations between individuals' motion patterns are computed using the Laplace-Beltrami Operator (LBO) eigenfunctions for spherical mapping. RESULTS: Application to extracting characterization correlation curves for locally-controlled simulated shape trajectories demonstrates the stability of the proposed shape descriptor. Its usability was shown on MRI acquired for seven healthy participants for which the bladder was highly deformed by maximum of inspiration. As expected, the study showed that deformations occured essentially on the top lateral regions. CONCLUSION: Promising results were obtained, showing the organ in its 3D complexity during deformation due to strain conditions. Smooth genus-0 manifold reconstruction from sparse dynamic MRI data is employed to perform a statistical shape analysis for the determination of bladder deformation.

Neural reinstatement reveals divided organization of fear and extinction memories in the human brain.

Neurobiological research in rodents has revealed that competing experiences of fear and extinction are stored as distinct memory traces in the brain. This divided organization is adaptive for mitigating overgeneralization of fear to related stimuli that are learned to be safe while also maintaining threat associations for unsafe stimuli. The mechanisms involved in organizing these competing memories in the human brain remain unclear. Here, we used a hybrid form of Pavlovian conditioning with an episodic memory component to identify overlapping multivariate patterns of fMRI activity associated with the formation and retrieval of fear versus extinction. In healthy adults, distinct regions of the medial prefrontal cortex (PFC) and hippocampus showed selective reactivation of fear versus extinction memories based on the temporal context in which these memories were encoded. This dissociation was absent in participants with posttraumatic stress disorder (PTSD) symptoms. The divided neural organization of fear and extinction may support flexible retrieval of context-appropriate emotional memories, while their disorganization may promote overgeneralization and increased fear relapse in affective disorders.

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.

Impaired aerobic capacity and premature fatigue preceding muscle weakness in the skeletal muscle Tfam-knockout mouse model.

Mitochondrial diseases are genetic disorders that lead to impaired mitochondrial function, resulting in exercise intolerance and muscle weakness. In patients, muscle fatigue due to defects in mitochondrial oxidative capacities commonly precedes muscle weakness. In mice, deletion of the fast-twitch skeletal muscle-specific Tfam gene (Tfam KO) leads to a deficit in respiratory chain activity, severe muscle weakness and early death. Here, we performed a time-course study of mitochondrial and muscular dysfunctions in 11- and 14-week-old Tfam KO mice, i.e. before and when mice are about to enter the terminal stage, respectively. Although force in the unfatigued state was reduced in Tfam KO mice compared to control littermates (wild type) only at 14 weeks, during repeated submaximal contractions fatigue was faster at both ages. During fatiguing stimulation, total phosphocreatine breakdown was larger in Tfam KO muscle than in wild-type muscle at both ages, whereas phosphocreatine consumption was faster only at 14 weeks. In conclusion, the Tfam KO mouse model represents a reliable model of lethal mitochondrial myopathy in which impaired mitochondrial energy production and premature fatigue occur before muscle weakness and early death.