Introduction: Axial spondyloarthritis (axSpA) is characterized by damage to the axial skeleton and entheses, and is often associated with extra-articular manifestations, in the presence of the human leukocyte antigen (HLA) B27. The aim of our study is to assess the performance of rheumatologists in interpreting the inflammatory and structural damage to sacroiliac joints, in comparison to radiologists. Material and Methods: The present study included a total of 34 patients diagnosed with axSpA, according to the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA, examined from January 2021 to November 2021 in the Departments of Rheumatology and Radiology and Medical Imaging of the University of Medicine and Pharmacy of Craiova. All patients underwent physical examination, laboratory tests, and magnetic resonance imaging (MRI) of the sacroiliac joints. The images were interpreted by a senior radiologist (SR), a junior radiologist (JR), a senior rheumatologist (SRh), and a junior rheumatologist (JRh), who were blinded to the clinical and paraclinical data. Results: The overall κ was 0.7 for the JR (substantial agreement), 0.707 for the SRh (substantial agreement), and 0.601 for the JRh (moderate agreement), in comparison with the SR. Regarding the overall inflammatory changes, the SRh and JR were proven to have substantial agreement (κ = 0.708 and 0.742, respectively) with the SR, while the JRh was proven to have moderate agreement (κ = 0.607). The structural damage observed by the JR showed substantial agreement (κ = 0.676) with the SR, while the SRh and JRh had substantial and moderate agreement (κ = 0.705 and 0.596, respectively) with the SR. Conclusions: Our study showed substantial agreement between the senior radiologist, senior rheumatologist, and junior radiologist, and moderate agreement with the junior rheumatologist. Full article

In this study, three different musculoskeletal modeling approaches were compared to each other. The objective was to show the possibilities in the case of a simple mechanical model of the wrist, using a simple multi-body-simulation (MBS) model, and using a more complex and patient-specific adaptable wrist joint MBS model. Musculoskeletal modeling could be a useful alternative, which can be practiced as a non-invasive approach to investigate body motion and internal loads in a wide range of conditions. The goal of this study was the introduction of computer-based modelling of the physiological wrist with (MBS-) models focused on the muscle and joint forces acting on the wrist. Full article

β-Amyloid (Aβ) is a hallmark peptide of Alzheimer’s disease (AD). Herein, we explored the mechanism underlying the cytotoxicity of this peptide. Double treatment with oligomeric 42-amino-acid Aβ (Aβ42) species, which are more cytotoxic than other conformers such as monomers and fibrils, resulted in increased cytotoxicity. Under this treatment condition, an increase in intracellular localization of the peptide was observed, which indicated that the peptide administered extracellularly entered the cells. The cell-permeable peptide TAT-tagged Aβ42 (tAβ42), which was newly prepared for the study and found to be highly cell-permeable and soluble, induced Aβ-specific lamin protein cleavage, caspase-3/7-like DEVDase activation, and high cytotoxicity (5–10-fold higher than that induced by the wild-type oligomeric preparations). Oligomeric species enrichment and double treatment were not necessary for enhancing the cytotoxicity and intracellular location of the fusion peptide. Taiwaniaflavone, an inhibitor of the cytotoxicity of wild-type Aβ42 and tAβ42, strongly blocked the internalization of the peptides into the cells. These data imply a strong relationship between the cytotoxicity and intracellular location of the Aβ peptide. Based on these results, we suggest that agents that can reduce the cell permeability of Aβ42 are potential AD therapeutics. Full article

Duchenne muscular dystrophy (DMD) is an X-linked disease, caused by a mutant dystrophin gene, leading to muscle membrane instability, followed by muscle inflammation, infiltration of pro-inflammatory macrophages and fibrosis. The calcium-activated potassium channel type 3.1 (K_Ca3.1) plays key roles in controlling both macrophage phenotype and fibroblast proliferation, two critical contributors to muscle damage. In this work, we demonstrate that pharmacological blockade of the channel in the mdx mouse model during the early degenerative phase favors the acquisition of an anti-inflammatory phenotype by tissue macrophages and reduces collagen deposition in muscles, with a concomitant reduction of muscle damage. As already observed with other treatments, no improvement in muscle performance was observed in vivo. In conclusion, this work supports the idea that K_Ca3.1 channels play a contributing role in controlling damage-causing cells in DMD. A more complete understanding of their function could lead to the identification of novel therapeutic approaches. Full article

Bacteria can bind on clothes, but the impacts of textiles leachables on cutaneous bacteria remain unknown. Here, we studied for the first time the effects of cotton and flax obtained through classical and soft ecological agriculture on the representatives S. aureus and S. epidermidis bacteria of the cutaneous microbiota. Crude flax showed an inhibitory potential on S. epidermidis bacterial lawns whereas cotton had no effect. Textile fiber leachables were produced in bacterial culture media, and these extracts were tested on S. aureus and S. epidermidis. Bacterial growth was not impacted, but investigation by the crystal violet technique and confocal microscopy showed that all extracts affected biofilm formation by the two staphylococci species. An influence of cotton and flax culture conditions was clearly observed. Flax extracts had strong inhibitory impacts and induced the formation of mushroom-like defense structures by S. aureus. Conversely, production of biosurfactant by bacteria and their surface properties were not modified. Resistance to antibiotics also remained unchanged. All textile extracts, and particularly soft organic flax, showed strong inhibitory effects on S. aureus and S. epidermidis cytotoxicity on HaCaT keratinocytes. Analysis of flax leachables showed the presence of benzyl alcohol that could partly explain the effects of flax extracts. Full article

Water present on the surface of early Mars (>3.0 Ga) may have been habitable. Characterising analogue environments and investigating the aspects of their microbiome best suited for growth under simulated martian chemical conditions is key to understanding potential habitability. Experiments were conducted to investigate the viability of microbes from a Mars analogue environment, Colour Peak Springs (Axel Heiberg Island, Canadian High Arctic), under simulated martian chemistries. The fluid was designed to emulate waters thought to be typical of the late Noachian, in combination with regolith simulant material based on two distinct martian geologies. These experiments were performed with a microbial community from Colour Peak Springs sediment. The impact on the microbes was assessed by cell counting and 16S rRNA gene amplicon sequencing. Changes in fluid chemistries were tested using ICP-OES. Both chemistries were shown to be habitable, with growth in both chemistries. Microbial communities exhibited distinct growth dynamics and taxonomic composition, comprised of sulfur-cycling bacteria, represented by either sulfate-reducing or sulfur-oxidising bacteria, and additional heterotrophic halophiles. Our data support the identification of Colour Peak Springs as an analogue for former martian environments, with a specific subsection of the biota able to survive under more accurate proxies for martian chemistries. Full article

Impact delivery of prebiotic compounds to the early Earth from an impacting comet is considered to be one of the possible ways by which prebiotic molecules arrived on the Earth. Given the ubiquity of impact features observed on all planetary bodies, bolide impacts may be a common source of organics on other planetary bodies both in our own and other solar systems. Biomolecules such as amino acids have been detected on comets and are known to be synthesized due to impact-induced shock processing. Here we report the results of a set of hypervelocity impact experiments where we shocked icy mixtures of amino acids mimicking the icy surface of planetary bodies with high-speed projectiles using a two-stage light gas gun and analyzed the ejecta material after impact. Electron microscopic observations of the ejecta have shown the presence of macroscale structures with long polypeptide chains revealed from LCMS analysis. These results suggest a pathway in which impact on cometary ices containing building blocks of life can lead to the synthesis of material architectures that could have played a role in the emergence of life on the Earth and which may be applied to other planetary bodies as well. Full article

Membrane-free stem cell extract (MFSCE) of human adipose tissues possesses various biological activities. However, the effects of MFSCE on blood–brain barrier dysfunction and brain damage are unknown. In this study, we determined the role of MFSCE in an ischemic stroke mouse model. Mice were treated with MFSCE once daily for 4 days and 1 h before ischemic damage. Experimental ischemia was induced by photothrombosis. Pretreatment with MFSCE reduced infarct volume and edema and improved neurological, as well as motor functions. Evans blue leakage and water content in the brain tissue were reduced by MFSCE pretreatment relative to those in the vehicle group. MFSCE increased the expression of the tight junction proteins zonula occludens 1 and claudin-5, as well as vascular endothelial-cadherin, but decreased that of matrix metalloproteinase 9. Notably, MFSCE treatment decreased cell death and the level of NOD-like receptor protein 3 inflammasome, consistent with the downregulated expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 in the ischemic brain. These effects might have occurred via the suppression of the expression of Toll-like receptor 4 and activation of nuclear factor-κB. The results highlighted the potential of MFSCE treatment as a novel and preventive strategy for patients at a high risk of ischemic stroke. Full article

Endometrial cancer (EC) is the most common form of gynecological cancer. Type 2 diabetes mellitus is associated with an increased risk of EC. Currently, no proteomic studies have investigated the role of diabetes in endometrial cancers from clinical samples. The present study aims to elucidate the molecular link between diabetes and EC using a proteomic approach. Endometrial tissue samples were obtained from age-matched patients (EC Diabetic and EC Non-Diabetic) during surgery. Untargeted proteomic analysis of the endometrial tissues was carried out using a two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF). A total of 53 proteins were identified, with a significant difference in abundance (analysis of variance (ANOVA) test, p ≤ 0.05; fold-change ≥ 1.5) between the two groups, among which 30 were upregulated and 23 downregulated in the EC Diabetic group compared to EC Non-Diabetic. The significantly upregulated proteins included peroxiredoxin-1, vinculin, endoplasmin, annexin A5, calreticulin, and serotransferrin. The significantly downregulated proteins were myosin regulatory light polypeptide 9, Retinol dehydrogenase 12, protein WWC3, intraflagellar transport protein 88 homolog, superoxide dismutase [Cu-Zn], and retinal dehydrogenase 1. The network pathway was related to connective tissue disorder, developmental disorder, and hereditary disorder, with the identified proteins centered around dysregulation of ERK1/2 and F Actin signaling pathways. Cancer-associated protein alterations such as upregulation of peroxiredoxin-1, annexin 5, and iNOS, and downregulation of RDH12, retinaldehyde dehydrogenase 1, SOD1, and MYL 9, were found in the EC tissues of the diabetic group. Differential expression of proteins linked to cancer metastasis, such as the upregulation of vinculin and endoplasmin and downregulation of WWC3 and IFT88, was seen in the patients with diabetes. Calreticulin and alpha-enolase, which might have a role in the interplay between diabetes and EC, need further investigation. Full article

Concepts about motor unit recruitment are important learning contents in exercise physiology and biomechanics classes that are usually taught theoretically. In the last few years, great advances have occurred in the decomposition of surface electromyography, allowing the learning of theoretical contents in an experimental way. In this tutorial paper, we have described the decomposition of surface electromyography methodological aspects and examples to teach motor unit recruitment concepts in exercise physiology and biomechanics practical lessons. This work has the aim to facilitate physiology and biomechanics academics to introduce this technique in practical classes. Full article

Many studies have demonstrated a reduced number and vasculogenic capacity of endothelial colony-forming cells (ECFCs) in diabetic patients. However, whether the vasculogenic capacity of ECFCs is recovered or not when combined with pericyte precursors, mesenchymal stem cells (MSCs), under hyperglycemic conditions has not been studied. Thus, we investigated the role of MSCs in ECFC-mediated vascular formation under high-glucose conditions. The ECFCs and MSCs were treated with normal glucose (5 mM; NG) or high glucose (30 mM; HG) for 7 days. The cell viability, proliferation, migration, and tube formation of ECFCs were reduced in HG compared to NG. Interestingly, the ECFC+MSC combination after HG treatment formed tubular structures similar to NG-treated ECFCs+MSCs. An in vivo study using a diabetic mouse model revealed that the number of perfused vessels formed by HG-treated ECFCs+MSCs in diabetic mice was comparable with that of NG-treated ECFCs+MSCs in normal mice. Electron microscopy revealed that the ECFCs+MSCs formed pericyte-covered perfused blood vessels, while the ECFCs alone did not form perfused vessels when injected into the mice. Taken together, MSCs potentiate the vasculogenic capacity of ECFCs under hyperglycemic conditions, suggesting that the combined delivery of ECFCs+MSCs can be a promising strategy to build a functional microvascular network to repair vascular defects in diabetic ischemic regions. Full article

Environmental factors affect plant metabolites, different climates, cultivation conditions, and biotic stresses and genotypes strongly affect their chemical composition and contents. Our aim is to examine the environmental and genetic interaction effects on tobacco metabolite composition. UPLC-QTOF MS/MS coupled with multivariate data analyses were applied for the metabolomics analysis of three tobacco cultivars from different planting regions in China. Principal component analysis (PCA) revealed that environmental factors have a greater effect on tobacco metabolism compared to genotypes. Twelve biomarkers were screened by orthogonal partial least squares discrimination analysis (OPLS-DA). Univariate analysis indicated that Malate, conjugated chlorogenic acid, chlorogenic acid, quercetin 3-rutinoside-7-glucoside, and unknown compound 5 were only influenced by environmental factors (independent of genotype). Quinate, neochlorogenic acid, and ouabagenin, taxezopidine K1, taxezopidine K2, and taxezopidine K3 in tobacco were influenced by the interaction of environmental factors and the genotype. Our results suggest that metabolomics based on UPLC-QTOF MS/MS could be used to analyze the ecological functions of biomarker metabolites and understand the mechanisms of plant adaption to the environment. Full article

Skin inflammation may cause allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis. Euphorbia hirta (E. hirta) is a member of the Euphorbiaceae family and is well-known for its anti-asthma effects. E. hirta has traditionally been used to treat respiratory ailments, dysentery, jaundice, and digestive problems. However, its effects on skin inflammation remain unclear. Here, we determined the effects of 70% ethanol extract of E. hirta leaves (ELE) in vitro using human keratinocyte HaCaT cells, which constitute most epidermal skin cells. We determined the inhibitory effects of ELE on the inflammation caused by tumor necrosis factor (TNF)-α/interferon (IFN)-γ in keratinocytes using ELISA, immunoblotting, and qRT-PCR assay. ELE was found to reduce the production and mRNA expression of pro-inflammatory cytokines such as TNF-α or interleukin-6 and the expression of various proteins, including signal transducers, activators of transcription 1/3, and mitogen-activated protein kinase. Expression levels of these proteins were found to be upregulated in the TNF-α/IFN-γ-stimulated condition and downregulated by ELE treatment. These results indicate that ELE protects HaCaT cells against TNF-α/IFN-γ-induced skin inflammation. Full article

Background: The prognostic impact and predictors of NOAF in HF patients are not fully elucidated. This study aims to determine whether new-onset atrial fibrillation (NOAF) affects patient outcome and investigate predictors of atrial fibrillation (AF) in acute heart failure (HF) patients using real-world data. Methods: The factors associated with NOAF in 2894 patients with sinus rhythm (SR) enrolled in the Korean Acute Heart Failure (KorAHF) registry were investigated. Survival was analyzed using AF as a time-dependent covariate. Relevant predictors of NOAF were analyzed using multivariate proportional hazards models. Results: Over 27.4 months, 187 patients developed AF. The median overall survival time was over 48 and 9.9 months for the SR and NOAF groups, respectively. Cox regression analysis with NOAF as a time-dependent covariate showed a higher risk of death among patients with NOAF. Multivariate Cox modeling showed that age, worsening HF, valvular heart disease (VHD), loop diuretics, lower heart rate, larger left atrium (LA) diameter, and elevated creatinine levels were independently associated with NOAF. Risk score indicated the number of independent predictors. The incidence of NOAF was 2.9%, 9.4%, and 21.8% in the low-risk, moderate-risk, and high-risk groups, respectively (p < 0.001). Conditional inference tree analysis identified worsening HF, heart rate, age, LA diameter, and VHD as discriminators. Conclusions: NOAF was associated with decreased survival in acute HF patients with SR. Age, worsening HF, VHD, loop diuretics, lower heart rate, larger LA diameter, and elevated creatinine could independently predict NOAF. This may be useful to risk-stratify HF patients at risk for AF. Full article

Advanced stage heart failure patients can benefit from the unloading effects of an implantable left ventricular assist device. Despite best clinical practice, LVADs are associated with adverse events, such as pump thrombosis (PT). An adaptive algorithm alerting when an individual’s appropriate levels in pump power uptake are exceeded, such as in the case of PT, can improve therapy of patients implanted with a centrifugal LVAD. We retrospectively studied 75 patients implanted with a centrifugal LVAD in a single center. A previously optimized adaptive pump power-tracking algorithm was compared to clinical best practice and clinically available constant threshold algorithms. Algorithm performances were analyzed in a PT group (n = 16 patients with 30 PT events) and a thoroughly selected control group (n = 59 patients, 34.7 patient years of LVAD data). Comparison of the adaptive power-tracking algorithm with the best performing constant threshold algorithm resulted in sensitivity of 83.3% vs. 86.7% and specificity of 98.9% vs. 95.3%, respectively. The power-tracking algorithm produced one false positive detection every 11.6 patient years and early warnings with a median of 3.6 days prior to PT diagnosis. In conclusion, a retrospective single-center validation study with real-world patient data demonstrated advantageous application of a power-tracking algorithm into LVAD systems and clinical practice. Full article