Assessment of haemophilic arthropathy through balance analysis: a promising tool

This is an Author's Accepted Manuscript of an article published in Xavier García-Massó, Yiyao Ye-Lin, Javier Garcia-Casado, Felipe Querol & Luis-Millan Gonzalez (2019) Assessment of haemophilic arthropathy through balance analysis: a promising tool, Computer Methods in Biomechanics and Biomedical Engineering, 22:4, 418-425, DOI: 10.1080/10255842.2018.1561877, available online at: http://doi.org/10.1080/10255842.2018.1561877.[EN] The purpose of this study was to develop a tool able to distinguish between subjects who have haemophilic arthropathy in lower limbs and those who do not by analyzing the centre of pressure displacement. The second objective was to assess the possible different responses of haemophiliacs and healthy subjects by creating a classifier that could distinguish between both groups. Fiftyfour haemophilic patients (28 with and 26 without arthropathy) and 23 healthy subjects took part voluntarily in the study. A force plate was used to measure postural stability. A total of 276 centre of pressure displacement parameters were calculated under different conditions: unipedal/bipedal balance with eyes open/closed. These parameters were used to design a Quadratic Discriminant Analysis classifier. The arthropathy versus non-arthropathy classifier had an overall accuracy of 97.5% when only 10 features were used in its design. Similarly, the haemophiliac versus nonhaemophiliac classifier had an overall accuracy of 97.2% when only 7 features were used. In conclusion, an objective haemophilic arthropathy in lower limbs evaluation system was developed by analyzing centre of pressure displacement signals. The haemophiliac vs. non-haemophiliac classifier designed was also able to corroborate the existing differences in postural control between haemophilic patients (with and without arthropathy) and healthy subjects.García-Massó, X.; Ye Lin, Y.; Garcia-Casado, J.; Querol -Fuentes, F.; Gonzalez, L. (2019). 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Protein C activation peptide inhibits the expression of ICAM-1, VCAM-1, and interleukin-8 induced by TNF-a in human dermal microvascular endothelial cells

Activated protein C (APC) is generated from the cleavage of protein C by thrombin coupled to thrombomodulinand, subsequently, is released as protein C activation peptide (papC). The aim of this study was toevaluate the effect of papC on human dermal microvascular endothelial cells (HMEC-1), activated with 5 ng//mL TNF-a. Flow cytometry showed that papC inhibited the expression of VCAM-1 and ICAM-1, after activationwith TNF-a. Similarly, RT-PCR analysis revealed that 2 and 4 pM papC inhibited the expression of VCAM-1and IL-8 mRNA in TNF-a-treated HMEC-1. In addition, the expression of endothelial nitric oxide synthase(eNOS) increased in HMEC-1 treated with papC, compared to those without treatment. Furthermore, Jurkatcell adhesion to HMEC-1 induced by TNF-a was significantly inhibited after the addition of papC, compared toHMEC-1 without papC (p = 0.03). Finally, a control peptide analog to papC showed no effect on the expressionof ICAM and VCAM on the surface of HMEC-1. In conclusion, our results suggest that papC exerts antiinflammatoryeffects on endothelial cells.Activated protein C (APC) is generated from the cleavage of protein C by thrombin coupled to thrombomodulinand, subsequently, is released as protein C activation peptide (papC). The aim of this study was toevaluate the effect of papC on human dermal microvascular endothelial cells (HMEC-1), activated with 5 ng//mL TNF-a. Flow cytometry showed that papC inhibited the expression of VCAM-1 and ICAM-1, after activationwith TNF-a. Similarly, RT-PCR analysis revealed that 2 and 4 pM papC inhibited the expression of VCAM-1and IL-8 mRNA in TNF-a-treated HMEC-1. In addition, the expression of endothelial nitric oxide synthase(eNOS) increased in HMEC-1 treated with papC, compared to those without treatment. Furthermore, Jurkatcell adhesion to HMEC-1 induced by TNF-a was significantly inhibited after the addition of papC, compared toHMEC-1 without papC (p = 0.03). Finally, a control peptide analog to papC showed no effect on the expressionof ICAM and VCAM on the surface of HMEC-1. In conclusion, our results suggest that papC exerts antiinflammatoryeffects on endothelial cells

QCD Corrections to QED Vacuum Polarization

We compute QCD corrections to QED calculations for vacuum polarization in background magnetic fields. Formally, the diagram for virtual $e\bar{e}$ loops is identical to the one for virtual $q\bar{q}$ loops. However due to confinement, or to the growth of $\alpha_s$ as $p^2$ decreases, a direct calculation of the diagram is not allowed. At large $p^2$ we consider the virtual $q\bar{q}$ diagram, in the intermediate region we discuss the role of the contribution of quark condensates \left and at the low-energy limit we consider the $\pi^0$, as well as charged pion $\pi^+\pi^-$ loops. Although these effects seem to be out of the measurement accuracy of photon-photon laboratory experiments they may be relevant for $\gamma$-ray burst propagation. In particular, for emissions from the center of the galaxy (8.5 kpc), we show that the mixing between the neutral pseudo-scalar pion $\pi_0$ and photons renders a deviation from the power-law spectrum in the $TeV$ range. As for scalar quark condensates \left and virtual $q\bar{q}$ loops are relevant only for very high radiation density $\sim 300 MeV/fm^3$ and very strong magnetic fields of order $\sim 10^{14} T$.Comment: 15 pages, 4 figures; Final versio

Pulmonary arterial hypertension in children with congenital heart disease: a deeper look into the role of endothelial progenitor cells and circulating endothelial cells to assess disease severity

Endothelial progenitor cells and circulating endothelial cells have been proposed as useful markers of severity and disease progression in certain vascular diseases, including pulmonary arterial hypertension. Our study focused on evaluating the levels of circulating endothelial progenitor cells and circulating endothelial cells in patients with congenital left-to-right shunts and pulmonary hypertension undergoing definitive repair. Endothelial progenitor cells (identified by simultaneous co-expression of CD45dim, CD34 + and KDR2 + surface antibodies) and circulating endothelial cells (identified by simultaneous co-expression of inherent antibodies CD45-, CD31+, CD146 + and CD105+) were prospectively measured in seventy-four children (including children with Down syndrome), median age six years (2.75–10), with clinically significant left-to-right shunts undergoing transcatheter or surgical repair and compared to thirty healthy controls. Endothelial progenitor cells and, particularly, circulating endothelial cells were significantly higher in children with heart disease and pulmonary arterial hypertension when compared to controls. Endothelial progenitor cells showed significant correlation with pulmonary vascular resistance index when measured both systemically (r = 0.259; p = 0.026) and in the superior vena cava (r = 0.302; p = 0.009). Children with Down syndrome showed a stronger correlation between systemic cellularity and pulmonary vascular resistance index (r = 0.829; p = 0.002). Endothelial progenitor cells were reduced along their transit through the lung, whereas circulating endothelial cells did not suffer any modification across the pulmonary circulation. In children with yet to be repaired left-to-right shunts, endothelial progenitor cells and circulating endothelial cell counts are increased compared to healthy subjects

The hepatocyte growth factor induces an anti-inflammatory and repairing response in the cholestasis-induced colon damage

Aim: Cholestasis remains a partially characterized disease. Evidence has been gained that it is a systemic disease that begins in the liver but significantly impacts other organs and systems such as the kidney, heart, and intestine, among others. One of the primary damage mechanisms is the generation of reactive oxygen species (ROS), which eventually leads to oxidative stress, impacting canalicular morphology and actin cytoskeleton changes that could worsen the problem. These characteristics are also observed in the kidney and intestine. The work focused on addressing the intestine effects of intrahepatic cholestasis induced by α-naphthyl isothiocyanate (ANIT) and the protective response of the hepatocyte growth factor (HGF). Methods: The 10- to 12-week-old CD1 male mice were treated with ANIT and then treated or not with HGF; intestine damage was addressed by histology, immunohistochemistry (IHC) of specific markers, oxidative stress, and apoptosis. Results: Results show changes in the intestine histology, particularly the colon and ileum, induced by the cholestasis. HGF treatment restored the histology presentation and reverted the oxidative damage, clearly indicating a healing response. This observation was supported by an increment in anti-inflammatory macrophages (CD163+) in the HGF treatment. Conclusions: The data prove that HGF induces a protective and repairing response in the intestine under cholestatic challenges

Improved Efficiency of Cardiomyocyte-Like Cell Differentiation from Rat Adipose Tissue-Derived Mesenchymal Stem Cells with a Directed Differentiation Protocol

Cell-based therapy has become a resource for the treatment of cardiovascular diseases; however, there are some conundrums to achieve. In vitro cardiomyocyte generation could be a solution for scaling options in clinical applications. Variability on cardiac differentiation in previously reported studies from adipose tissue-derived mesenchymal stem cells (ASCs) and the lack of measuring of the cardiomyocyte differentiation efficiency motivate the present study. Here, we improved the ASC-derived cardiomyocyte-like cell differentiation efficiency with a directed cardiomyocyte differentiation protocol: BMP-4 + VEGF (days 0-4) followed by a methylcellulose-based medium with cytokines (IL-6 and IL-3) (days 5-21). Cultures treated with the directed cardiomyocyte differentiation protocol showed cardiac-like cells and “rosette-like structures” from day 7. The percentage of cardiac troponin T- (cTnT-) positive cells was evaluated by flow cytometry to assess the cardiomyocyte differentiation efficiency in a quantitative manner. ASCs treated with the directed cardiomyocyte differentiation protocol obtained a differentiation efficiency of up to 44.03% (39.96%±3.78) at day 15 without any enrichment step. Also, at day 21 we observed by immunofluorescence the positive expression of early, late, and cardiac maturation differentiation markers (Gata-4, cTnT, cardiac myosin heavy chain (MyH), and the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCa2)) in cultures treated with the directed cardiomyocyte differentiation protocol. Unlike other protocols, the use of critical factors of embryonic cardiomyogenesis coupled with a methylcellulose-based medium containing previously reported cardiogenic cytokines (IL-6 and IL-3) seems to be favorable for in vitro cardiomyocyte generation. This novel efficient culture protocol makes ASC-derived cardiac differentiation more efficient. Further investigation is needed to identify an ASC-derived cardiomyocyte surface marker for cardiac enrichment

Correlation of Plasmatic Amyloid Beta Peptides (Aβ-40, Aβ-42) with Myocardial Injury and Inflammatory Biomarkers in Acute Coronary Syndrome

Background/Objective: Amyloid beta (β) -40 levels increase with age and inflammation states and appear to be associated with clinical manifestations of acute coronary syndrome (ACS). We investigated the correlation of Aβ peptides with myocardial injury and inflammation biomarkers in patients with or without ST elevation myocardial infarction (STEMI, NSTEMI). Methods: This singe-center, cross-sectional, observational, and correlation study included 65 patients with ACS (n = 34 STEMI, 29 males, age = 58 ± 12 years; n = 31 NSTEMI, 22 males, age = 60 ± 12 years) who were enrolled in the coronary care unit within 12 h after symptom onset from February 2022 to May 2023. Aβ peptide levels and biochemical parameters were assessed. Results: NSTEMI patients had a higher prevalence of hypertension (p = 0.039), diabetes (p = 0.043), smoking (p = 0.003), and prior myocardial infarction (p = 0.010) compared to STEMI patients. We observed a higher level of Aβ-42 in NSTEMI (p = 0.001) but no difference in Aβ-40 levels. We also found a correlation between age and NT-proBNP with both Aβ peptides (Aβ-40, Aβ-42) (p = 0.001, p = 0.002 respectively). Conclusions: Our results show that patients with NSTEMI had a higher prevalence of cardiovascular risk factors (hypertension, diabetes, smoking, and prior myocardial infarction). Considering these results, we propose that Aβ-42 can add value to risk stratification in NSTEMI patients

Type-III interferons and rheumatoid arthritis: Correlation between interferon lambda 1 (interleukin 29) and antimutated citrullinated vimentin antibody levels

<p><i>Aim</i>: To assess serum type III or lambda (λ) interferons (IFN) levels and its clinical and laboratory associations in rheumatoid arthritis (RA). <i>Methods</i>: A cross-sectional study including 43 patients with RA (86% females; age 45.3 ± 10.3 years) and 43 healthy individuals was performed. Clinical data including disease activity, acute-phase reactants, rheumatoid factor and anticyclic citrullinated peptide (anti-CCP) antibodies were collected. Serum IFNλ1, IFNλ2, IFNλ3, CXCL8 and anti-mutated citrullinated vimentin (anti-MCV) antibody levels were measured. <i>Results</i>: Patients with RA had higher IFNλ1 (113.5 ± 118.6 pg/mL versus 55.9 ± 122.3 pg/mL; <i>p</i> <<i> </i>0.0001) and IFNλ2 (245.4 ± 327.7 pg/mL versus 5.1 ± 11.0 pg/mL; <i>p </i>=<i> </i>0.009) levels than controls, but not IFNλ3 levels. Notably, IFNλ1 levels were found to be higher in both patients with active disease (124.9 ± 135.9 pg/mL; <i>p</i> <<i> </i>0.001) and quiescent disease (99.0 ± 93.7 pg/mL; <i>p</i> <<i> </i>0.01), while IFNλ2 levels were higher only in patients with active disease (264.0 ± 356.1 pg/mL; <i>p =</i> 0.02). A noteworthy association between serum IFNλ1 levels and anti-MCV antibody titers (Spearman's rho coefficient 0.36, 95% CI 0.36 to 0.61; <i>p</i> =<i> </i>0.02) was observed. <i>Conclusion:</i> Serum IFNλ1 and IFNλ2 levels are abnormally elevated in patients with RA and the former are linearly associated with circulating anti-MCV antibody levels. These results may place type-III IFN as an attractive new therapeutic target in RA.</p