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Chronic kidney disease (CKD) results in calcitriol deficiency and altered vitamin D metabolism. The objective of this study was to assess the 24-hydroxylation-mediated metabolism of 25(OH)D3 and 1,25(OH)2D3 in a cross-sectional analysis of participants with a range of kidney function assessed by precise measured GFR (mGFR) (N = 143) and in rats with the induction and progression of experimental kidney disease. Vitamin D metabolites were assessed with LC-MS/MS. Circulating measures of 24-hydroxylation of 25(OH)D3 (24,25(OH)2D325(OH)D3) precisely decreased according to mGFR in humans and progressively in rats with developing CKD. In contrast, the 1,24,25(OH)3D3 1,25(OH)2D3 vitamin D metabolite ratio increased in humans as the mGFR decreased and in rats with the induction and progression of CKD. Human participants taking cholecalciferol had higher circulating 1,24,25(OH)3D3, despite no increase of 1,25(OH)2D3. This first report of circulating 1,24,25(OH)3D3 in the setting of CKD provides novel insight into the uniquely altered vitamin D metabolism in this setting. A better understanding of the uniquely dysfunctional catabolic vitamin D profile in CKD may guide more effective treatment strategies. The potential that 24-hydroxylated products have biological activity of is an important area of future research.Transdiagnostic psychotherapeutic approaches are increasingly used in neurorehabilitation to address psychological distress. Animal-assistance is thought to increase efficacy. The present study evaluates a psychotherapeutic mindfulness- and self-compassion-based group intervention (MSCBI) with and without animal-assistance for patients with acquired brain injury. Patients (N = 31) were randomly assigned to the 6-week intervention with (n = 14) or without animal-assistance (n = 17). Primary outcome was psychological distress at post- and follow-up treatment, secondary outcomes were changes within-session of patients' emotional states, adherence to treatment and attrition. Psychological distress significantly decreased in both groups from pre- to follow-up treatment with no difference between groups. Patients in the animal-assisted MSCBI group reported significantly higher increases in feeling secure, accepted, comforted, grateful, motivated and at ease during the sessions compared to patients in the MSCBI group without animal-assistance. Adherence to sessions was significantly higher in the animal-assisted MSCBI group. Attrition did not significantly differ between groups. Our results show that both MSCBIs with and without animal-assistance are feasible and effective in reducing psychological distress in patients with acquired brain injury. The significant changes within-sessions mainly in relationship-based emotional states and the higher treatment adherence suggest additional effects of animal-assistance. selleck products Animal-assistance might increase acceptability and patients' commitment to psychotherapy.Although central retinal artery occlusion (CRAO) has its own defining pathomechanism and clinical characteristics, morphologic feature of the optic nerve head (ONH) during its later stage is not diagnostic, which makes it difficult to differentiate CRAO from other optic neuropathies. This cross-sectional study was performed to investigate the differences in the topographic morphology of the ONH in eyes with normal-tension glaucoma (NTG) and CRAO. Thirty-one eyes with NTG; 31 eyes with CRAO; and 31 healthy fellow eyes of the subjects with CRAO were included. ONH morphology was evaluated by measuring horizontal rim width (HRW), minimal rim width in the selected horizontal image (MRW), and lamina cribrosa curvature index (LCCI) in horizontal B-scan images obtained using enhanced depth-imaging optical coherence tomography. HRW was smaller and LCCI was larger in NTG eyes than in both CRAO and healthy fellow eyes (both P  less then  0.001), while both were comparable between CRAO and healthy fellow eyes. MRW differed significantly among the three groups, being smallest in NTG eyes followed by CRAO and healthy fellow eyes (P  less then  0.001). NTG and CRAO eyes with a similar degree of RNFL loss differed in ONH morphology, indicating that mechanisms of ONH damage differ between these two conditions.The stability and safety of products will be reduced if product structures are vulnerable to failures of key components. Existing methods for improving product structural robustness mainly focus on some key components, but they cannot provide designers with universal and explicit structure optimization strategies. From the viewpoint of product structural networks, the motif is the fundamental meta-structure, and it is efficient to analyse product structural properties. Motivated by this, strategies to improve product structural robustness are explored by considering relationships between typical motifs and product structural robustness. First, product structural networks are constructed by collecting the structural information of a series of product generations. Second, typical (anti-) motifs are identified based on an enumeration algorithm, and the robustness is measured considering the largest connected cluster. Then, relationships between the frequency of different motifs and product structural robustness are obtained through principal component regression. The results of a case study on the smartphone show that anti-motifs are negative for product structural robustness. Motifs with loop structures are positive for product structural robustness. Accordingly, relevant strategies to improve product structural robustness in product development are developed.Hot rolling and annealing are critical intermediate steps for controlling microstructures and thickness variations when fabricating uranium alloyed with 10% molybdenum (U-10Mo), which is highly relevant to worldwide nuclear non-proliferation efforts. This work proposes a machine-learning surrogate model combined with sensitivity analysis to identify and predict U-10Mo microstructure development during thermomechanical processing. Over 200 simulations were collected using physics-based microstructure models covering a wide range of thermomechanical processing routes and initial alloy grain features. Based on the sensitivity analysis, we determined that an increase in rolling reduction percentage at each processing pass has the strongest effect in reducing the grain size. Multi-pass rolling and annealing can significantly improve recrystallization regardless of the reduction percentage. With a volume fraction below 2%, uranium carbide particles were found to have marginal effects on the average grain size and distribution. The proposed stratified stacking ensemble surrogate predicts the U-10Mo grain size with a mean square error four times smaller than a standard single deep neural network. At the same time, with a significant speedup (1000×) compared to the physics-based model, the machine learning surrogate shows good potential for U-10Mo fabrication process optimization.Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a pneumonia-like disease with a pattern of acute respiratory symptoms, currently remains a significant public health concern causing tremendous human suffering. Although several approved vaccines exist, vaccine hesitancy, limited vaccine availability, high rate of viral mutation, and the absence of approved drugs account for the persistence of SARS-CoV-2 infections. The investigation of possibly repurposing of phytochemical compounds as therapeutic alternatives has gained momentum due to their reported affordability and minimal toxicity. This study investigated anti-viral phytochemical compounds from ethanolic leaf extracts of Spondias mombin L as potential inhibitor candidates against SARS-CoV-2. We identified Geraniin and 2-O-Caffeoyl-(+)-allohydroxycitric acid as potential SARS-CoV-2 inhibitor candidates targeting the SARS-CoV-2 RNA-dependent polymerase receptor-binding domain (RBD) of SARS-CoV-2 viral S-protein and the 3C-like main protease (3CLpro). Geraniin exhibited binding free energy (ΔGbind) of - 25.87 kcal/mol and - 21.74 kcal/mol towards SARS-CoV-2 RNA-dependent polymerase and receptor-binding domain (RBD) of SARS-CoV-2 viral S-protein respectively, whereas 2-O-Caffeoyl-(+)-allohydroxycitric acid exhibited a ΔGbind of - 32 kcal/mol towards 3CLpro. Molecular Dynamics simulations indicated a possible interference to the functioning of SARS-CoV-2 targets by the two identified inhibitors. However, further in vitro and in vivo evaluation of these potential SARS-CoV-2 therapeutic inhibitor candidates is needed.It is widely accepted that nonverbal communication is crucial for learning, but the exact functions of interpersonal coordination between instructors and learners remain unclear. Specifically, it is unknown what role instructional approaches play in the coupling of physical motion between instructors and learners, and crucially, how such instruction-mediated Body-to-Body Coupling (BtBC) might affect learning. We used a video-based, computer-vision Motion Energy Analysis (MEA) to quantify BtBC between learners and instructors who used two different instructional approaches to teach psychological concepts. BtBC was significantly greater when the instructor employed a scaffolding approach than when an explanation approach was used. The importance of the instructional approach was further underscored by the fact that an increase in motion in the instructor was associated with boosted BtBC, but only during scaffolding; no such relationship between the instructor movements and BtBC was found during explanation interactions. Finally, leveraging machine learning approaches (i.e., support vector and logistic regression models), we demonstrated that both learning outcome and instructional approaches could be decoded based on BtBC. Collectively, these results show that the real-time interaction of teaching and learning bodies is important for learning and that the instructional approach matters, with possible implications for both in-person and online learning.The mRNA vaccine platform has offered the greatest potential in fighting the COVID-19 pandemic owing to rapid development, effectiveness, and scalability to meet the global demand. There are many other mRNA vaccines currently being developed against different emerging viral diseases. As with the current COVID-19 vaccines, these mRNA-based vaccine candidates are being developed for parenteral administration via injections. However, most of the emerging viruses colonize the mucosal surfaces prior to systemic infection making it very crucial to target mucosal immunity. Although parenterally administered vaccines would induce a robust systemic immunity, they often provoke a weak mucosal immunity which may not be effective in preventing mucosal infection. In contrast, mucosal administration potentially offers the dual benefit of inducing potent mucosal and systemic immunity which would be more effective in offering protection against mucosal viral infection. There are however many challenges posed by the mucosal environment which impede successful mucosal vaccination. The development of an effective delivery system remains a major challenge to the successful exploitation of mucosal mRNA vaccination. Nonetheless, a number of delivery vehicles have been experimentally harnessed with different degrees of success in the mucosal delivery of mRNA vaccines. In this review, we provide a comprehensive overview of mRNA vaccines and summarise their application in the fight against emerging viral diseases with particular emphasis on COVID-19 mRNA platforms. Furthermore, we discuss the prospects and challenges of mucosal administration of mRNA-based vaccines, and we explore the existing experimental studies on mucosal mRNA vaccine delivery.

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