DAMPs (danger-associated molecular patterns) are self-molecules of the organism that appear after damage. The endothelium plays several roles in organ rejection, such as presenting alloantigens to T ...cells and contributing to the development of inflammation and thrombosis. This study aimed to assess whether DAMPs present in the organ preservation solution (OPS) after cold ischemic storage (CIS) contribute to exacerbating the endothelial response to an inflammatory challenge and whether defibrotide treatment could counteract this effect. The activation of cultured human umbilical vein endothelial cells (HUVECs) was analyzed after challenging with end-ischemic OPS (eiOPS) obtained after CIS. Additionally, transwell assays were performed to study the ability of eiOPS to attract lymphocytes across the endothelium. The study revealed that eiOPS upregulated the expression of MCP-1 and IL-6 in HUVECs. Moreover, eiOPS increased the membrane expression of ICAM-1and HLA-DR, which facilitated leukocyte migration toward a chemokine gradient. Furthermore, eiOPS demonstrated its chemoattractant ability. This activation was mediated by free mitochondria. Defibrotide was found to partially inhibit the eiOPS-mediated activation. Moreover, the eiOPS-mediated activation of endothelial cells (ECs) correlated with early allograft dysfunction in liver transplant patients. Our finding provide support for the hypothesis that mitochondria released during cold ischemia could trigger EC activation, leading to complications in graft outcomes. Therefore, the analysis and quantification of free mitochondria in the eiOPS samples obtained after CIS could provide a predictive value for monitoring the progression of transplantation. Moreover, defibrotide emerges as a promising therapeutic agent to mitigate the damage induced by ischemia in donated organs.
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•“Danger signals”, including mitochondria, are released during the cold storage of donated organs before transplantation.•Released mitochondria activate endothelium, which is associated with inflammation, thrombosis, and graft rejection.•Defibrotide is an anti-thrombotic, pro-fibrinolytic, and anti-inflammatory biodrug that inhibits endothelial cell activation.•Defibrotide may represent a promising therapy to partially mitigate the damage caused by the cold storage of donated organs.
This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE.
RELESSER (Spanish Society of Rheumatology Lupus Registry) is a ...nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity.
Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex odds ratio (95% CI), 1.72 (1.07, 2.72), RP 1.63 (1.29, 2.05), interstitial lung disease 3.35 (1.84, 6.01), Jaccoud arthropathy 1.92 (1.40, 2.63), anti-Ro/SSA and/or anti-La/SSB autoantibodies 2.03 (1.55, 2.67), anti-RNP antibodies 1.48 (1.16, 1.90), MTX 1.67 (1.26, 2.18) and antimalarial drugs 0.50 (0.38, 0.67).
Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies.
Type 2 diabetes has been linked to greater cognitive decline, but other glycemic parameters such as prediabetes, diabetes control and treatment, and HOMA-IR and HbA
diabetes-related biomarkers have ...shown inconsistent results. Furthermore, there is limited research assessing these relationships in short-term studies. Thus, we aimed to examine 2-year associations between baseline diabetes/glycemic status and changes in cognitive function in older participants at high risk of cardiovascular disease.
We conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. At baseline, participants were categorized by diabetes status (no-diabetes, prediabetes, and <5 or ≥5-year diabetes duration), and also by diabetes control. Furthermore, insulin resistance (HOMA-IR) and glycated hemoglobin (HbA
) levels were measured, and antidiabetic medications were recorded. Linear and logistic regression models, adjusted by potential confounders, were fitted to assess associations between glycemic status and changes in cognitive function.
Prediabetes status was unrelated to cognitive decline. However, compared to participants without diabetes, those with ≥5-year diabetes duration had greater reductions in GCF (β=-0.11 (95%CI -0.16;-0.06), as well as in processing speed and executive function measurements. Inverse associations were observed between baseline HOMA-IR and changes in GCF β=-0.0094 (95%CI -0.0164;-0.0023), but also between HbA
levels and changes in GCF β=-0.0085 (95%CI -0.0115, -0.0055), the Mini-Mental State Examination, and other executive function tests. Poor diabetes control was inversely associated with phonologic fluency. The use of insulin treatment was inversely related to cognitive function as measured by the GCF β=-0.31 (95%CI -0.44, -0.18), and other cognitive tests.
Insulin resistance, diabetes status, longer diabetes duration, poor glycemic control, and insulin treatment were associated with worsening cognitive function changes in the short term in a population at high cardiovascular risk.
http://www.isrctn.com/ISRCTN89898870, identifier ISRCTN: 89898870.
This study looks at the effects of potassium nitrate (KNO3) and sodium nitroprusside (SNP), a nitric oxide (NO)-donor, on the development, antioxidant defences and on the abscisic acid (ABA) and ...gibberellin (GA) levels in pea seedlings. Results show that 10 mM KNO3 and 50 μM SNP stimulate seedling fresh weight (FW), although this effect is not reverted by the action of 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), a NO-scavenger.
The KNO3 treatment increased peroxidase (POX) and ascorbate oxidase (AOX) activities. SNP, on the other hand, reduced monodehydroascorbate reductase (MDHAR) activity and produced a significant increase in superoxide dismutase (SOD), POX and AOX activities. The “KNO3 plus cPTIO” treatment increased ascorbate peroxidase (APX), MDHAR, glutathione reductase (GR) and SOD activities, but POX activity decreased in relation to the KNO3 treatment. The “SNP plus cPTIO” treatment increased APX and MDHAR activities, whereas a huge decrease in POX activity occurred. Both the KNO3 and the SNP treatments increased reduced ascorbate (ASC) concentrations, which reached control values in the presence of cPTIO. All treatments increased the dehydroascorbate (DHA) level in pea seedlings, leading to a decrease in the redox state of ascorbate. In the “KNO3 plus cPTIO” treatment, an increase in the redox state of ascorbate was observed. Glutathione contents, however, were higher in the presence of SNP than in the presence of KNO3. In addition, KNO3 produced an accumulation of oxidised glutathione (GSSG), especially in the presence of cPTIO, leading to a decrease in the redox state of glutathione. The effect of SNP on reduced glutathione (GSH) levels was reverted by cPTIO, suggesting that NO has a direct effect on GSH biosynthesis or turnover.
Both the KNO3 and SNP treatments produced an increase in GA4 and a decrease in ABA concentrations, and this effect was reverted in the presence of the NO-scavenger. Globally, the results suggest a relationship between antioxidant metabolism and the ABA/GA balance during early seedling growth in pea. The results also suggest a role for KNO3 and NO in the modulation of GA4 and ABA levels and antioxidant metabolism in pea seedlings. Furthermore, this effect correlated with an increase in the biomass of the pea seedlings.
To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD).
This was an observational, multicentre study of RA-ILD patients treated with at least one dose ...of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect.
We studied 263 RA-ILD patients 150 women/113 men; mean (s.d.) age 64.6 (10) years. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2).
ABA may be an effective and safe treatment for patients with RA-ILD.
Total fruit consumption is important for cardiovascular disease prevention, but also the variety and form in which is consumed. The aim of the study was to assess the associations between total ...fruit, subgroups of fruits based on their color and fruit juices consumption with different cardiometabolic parameters.
A total of 6633 elderly participants (aged 55–75 years) with metabolic syndrome from the PREDIMED-Plus study were included in this analysis. Fruit and fruit juice consumption was assessed using a food frequency questionnaire. Linear regression models were fitted to evaluate the association between exposure variables (total fruit, subgroups based on the color, and fruit juices) and different cardiometabolic risk factors. Individuals in the highest category of total fruit consumption (≥3 servings/d) had lower waist circumference (WC) (β = −1.04 cm; 95%CI:-1.81, −0.26), fasting glucose levels (β = −2.41 mg/dL; 95%CI(-4.19, −0.63) and LDL-cholesterol (β = −4.11 mg/dL; 95%CI:-6.93, −1.36), but, unexpectedly, higher systolic blood pressure (BP) (β = 1.84 mmHg; 95%CI: 0.37, 3.30) and diastolic BP (β = 1.69 mmHg; 95%CI:0.83, 2.56) when compared to those in the lowest category of consumption (<1 servings/d). Participants consuming ≥1 serving/day of total fruit juice had lower WC (β = −0.92 cm; 95%CI:-1.56, −0.27) and glucose levels (β = −1.59 mg/dL; 95%CI:-2.95, −0.23) than those consuming <1 serving/month. The associations with cardiometabolic risk factors differed according to the color of fruits.
Fruit consumption is associated with several cardiometabolic risk factors in Mediterranean elders with metabolic syndrome. The associations regarding BP levels could be attributed, at least partially, to reverse causality bias inherent to the cross-sectional design of the study.
•Total fruit consumption is inversely associated with cardiometabolic risk factors.•At least 1 serving/day of fruit juice is associated with low waist circumference.•At least 1 serving/day of fruit juice is associated with low glucose levels.•Cardiometabolic risk factors differed according to the color of fruits.
To describe characteristics and prognosis of patients with suboptimal immunological response to combined antiretroviral therapy (CART). Using data from a multicenter cohort study, we selected ...patients who initiated CART and showed suboptimal CD4-T cell response (defined as <50 cells/L increase) after 1 year of therapy, despite sustained virological suppression. Characteristics of those patients were compared with subjects who showed optimal immunological response. Of 650 patients with virological suppression, 108 (16.6%) showed suboptimal CD4-T cell response. Independent predictors of suboptimal response were previous injection drug use (OR, 1.85; 95% CI, 1.12-2.98) and age at CART initiation (OR, 1.04 per year increase; 95%CI, 1.01-1.06). Hepatitis C virus coinfection was not associated with impaired immunological response. As compared with patients with optimal immunological response, those with suboptimal response had a higher mortality rate (3.22 versus 0.71 per 100 person-years; p=.001), but a similar rate of new AIDS-defining events. In patients with sustained virological suppression with CART, previous injection drug use, but not hepatitis C virus coinfection, and older age at initiation of therapy were associated with suboptimal CD4 T-cell responses. Patients with suboptimal response had a higher mortality over time, mainly due to diseases other than AIDS-defining events.
The prevalence of hyperuricemia has increased substantially in recent decades. It has been suggested that it is an independent risk factor for weight gain, hypertension, hypertriglyceridemia, ...metabolic syndrome (MetS), and cardiovascular disease. Results from epidemiological studies conducted in different study populations have suggested that high consumption of dairy products is associated with a lower risk of developing hyperuricemia. However, this association is still unclear. The aim of the present study is to explore the association of the consumption of total dairy products and their subtypes with the risk of hyperuricemia in an elderly Mediterranean population with MetS.
Baseline cross-sectional analyses were conducted on 6329 men/women (mean age 65 years) with overweight/obesity and MetS from the PREDIMED-Plus cohort. Dairy consumption was assessed using a food frequency questionnaire. Multivariable-adjusted Cox regressions were fitted to analyze the association of quartiles of consumption of total dairy products and their subtypes with the prevalence of hyperuricemia. Participants in the upper quartile of the consumption of total dairy products (multiadjusted prevalence ratio (PR) = 0.84; 95% CI: 0.75–0.94; P-trend 0.02), low-fat dairy products (PR = 0.79; 95% CI: 0.70–0.89; P-trend <0.001), total milk (PR = 0.81; 95% CI: 0.73–0.90; P-trend<0.001), low-fat milk (PR = 0.80; 95% CI: 0.72–0.89; P-trend<0.001, respectively), low-fat yogurt (PR = 0.89; 95% CI: 0.80–0.98; P-trend 0.051), and cheese (PR = 0.86; 95% CI: 0.77–0.96; P-trend 0.003) presented a lower prevalence of hyperuricemia. Whole-fat dairy, fermented dairy, and yogurt consumption were not associated with hyperuricemia.
High consumption of total dairy products, total milk, low-fat dairy products, low-fat milk, low-fat yogurt, and cheese is associated with a lower risk of hyperuricemia.
•Total dairy product consumption is associated with a lower prevalence risk of hyperuricemia.•Milk, low-fat yogurt, and cheese consumption is associated with a lower prevalence risk of hyperuricemia.•Consumption of whole-fat dairy products and the different subtypes is not associated with hyperuricemia.
rock engraving made by Neanderthals in Gibraltar Rodríguez-Vidal, Joaquín; d'Errico, Francesco; Pacheco, Francisco Giles ...
Proceedings of the National Academy of Sciences - PNAS,
09/2014, Letnik:
111, Številka:
37
Journal Article
Recenzirano
Odprti dostop
Significance The production of purposely made painted or engraved designs on cave walls is recognized as a major cognitive step in human evolution, considered exclusive to modern humans. Here we ...present the first known example of an abstract pattern engraved by Neanderthals, from Gorham’s Cave in Gibraltar. It consists of a deeply impressed cross-hatching carved into the bedrock of the cave older than 39 cal kyr. The engraving was made before the accumulation of Mousterian layer IV. Most of the lines composing the design were made by repeatedly and carefully passing a pointed lithic tool into the grooves, excluding the possibility of an unintentional or utilitarian origin. This discovery demonstrates the Neanderthals’ capacity for abstract thought and expression.
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