SARS-CoV-2 is responsible for the development of coronavirus disease 2019 (COVID-19) in infected individuals, who can either exhibit mild symptoms or progress toward a life-threatening acute ...respiratory distress syndrome (ARDS). Exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. Here, we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood and lung of COVID-19 patients with different clinical severity in comparison with healthy individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Our results indicate that inflammatory transitional and nonclassical monocytes and CD1c+ conventional dendritic cells preferentially migrate from blood to lungs in patients with severe COVID-19. Thus, this study increases the knowledge of specific myeloid subsets involved in the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies for fighting SARS-CoV-2 infection.
The impact of the newly discovered severe acute respiratory syndrome coronavirus 2 causing coronavirus disease‐19 (COVID‐19) in hemodialysis patients remains poorly characterized. Some hemodialysis ...techniques reduce systemic inflammation but their impact on COVID‐19 has not been addressed. The aim of this prospective study was to evaluate factors associated with mortality in COVID‐19 hemodialysis patients, including the impact of reducing interleukin‐6 using a cytokine adsorbent filter. This is a prospective single‐center study including 16 hemodialysis patients with COVID‐19. All were dialyzed using a polymethyl methacrylate (PMMA) filter. Interleukin‐6 levels were obtained before and after the first admission hemodialysis session and at 1 week. Baseline comorbidities, laboratory values, chest X‐ray, and treatments were recorded and compared between survivors and non‐survivors. Out of 16 patients (13 males, mean age 72 ± 15 years), 4 (25%) died. Factors associated with mortality were dialysis vintage (P = 0.01), chest X‐ray infiltrates (P = 0.032), serum C‐reactive protein (P = 0.05), and lactate dehydrogenase (P = 0.02) at 1 week, oxygen therapy requirement (P = 0.02) and anticoagulation (P < 0.01). At admission, non‐survivors had higher predialysis and postdialysis interleukin‐6 levels (P = 0.02 for both) and did not present the reduction of interleukin‐6 levels during the dialysis session with PMMA filter that was observed in survivors (survivors vs. non‐survivors: 25.0 17.5–53.2% vs. −2.8 −109.4–12.8% reduction, P = 0.04). A positive balance of interleukin‐6 during the admission dialysis was associated with mortality (P = 0.008). In conclusion, in hemodialysis COVID‐19 patients, a positive interleukin‐6 balance during the admission hemodialysis session was associated with higher mortality.
Animal models of alcohol (ethanol) self‐administration are crucial to dissect the neurobiological mechanisms underlying alcohol dependence, yet only a few of these induce pharmacologically relevant ...levels of alcohol consumption and rarely the alcohol self‐administration co‐occurs with other addictive behaviours. The present study aims to validate a novel model of voluntary ethanol consumption in male Wistar rats, in which ethanol access follows a binge eating experience. Over 10 sessions, Wistar rats were exposed to binge or control eating (i.e., the ingestion of 11.66 and 0.97 kcal/3 min, respectively, derived from a highly palatable food), immediately followed by two‐bottle choice intake tests (2%, 6%, 10% or 14% w/w ethanol vs. water). Rats exposed to binge eating drank significantly more 6% or 10% (w/w) ethanol than control peers, reaching up to 6.3 gEtOH/kg. Rats stimulated with 2%, 6%, 10% or 14% ethanol after binge eating, but not those given those ethanol concentrations after control eating, exhibited significant within‐group increases in ethanol drinking. This ethanol consumption was not altered by quinine adulteration (up to 0.1 g/L), and it was blocked by naltrexone (10 mg/kg), administered immediately before binge eating. Blood ethanol levels significantly correlated with ethanol consumption; and the more ethanol consumed, the greater the distance travelled in an open field test conducted after the two‐bottle choice test. Altogether, this self‐administration model seems a valid and robust alternative with remarkable potential for research on different stages of the alcohol addiction and, particularly, to assess interactions between alcohol consumption and others addictive‐like behaviours.
This study validated a novel model of voluntary ethanol consumption in male Wistar rats, in which ethanol access follows a binge eating experience. Rats stimulated with 2%, 6%, 10% or 14% ethanol immediately after binge eating, but not those given those ethanol concentrations after control eating, exhibited significant within‐group increases in ethanol drinking. This ethanol consumption was not altered by quinine adulteration (up to 0.1 g/L), and it was blocked by naltrexone (10 mg/kg), administered immediately before binge eating.
The objective of this work was on the one hand to assess the antibacterial activity of amines anchored to the external surface of mesoporous silica particles against Listeria monocytogenes in ...comparison with the same dose of free amines as well. It was also our aim to elucidate the mechanism of action of the new antimicrobial device. The suitability of silica nanoparticles to anchor, concentrate and improve the antimicrobial power of polyamines against L. monocytogenes has been demonstrated in a saline solution and in a food matrix. Moreover, through microscope observations it has been possible to determine that the attractive binding forces between the positive amine corona on the surface of nanoparticles and the negatively charged bacteria membrane provoke a disruption of the cell membrane. The surface concentration of amines on the surface of the nanoparticles is so effective that immobilized‐amines were 100 times more effective in killing L. monocytogenes bacteria than the same amount of free polyamines. This novel approach for the creation of antimicrobial nanodevices opens the possibility to put in value the antimicrobial power of natural molecules that have been discarded because of its low antimicrobial power.
Practical Application
Consumers demand for high‐quality products, free from chemical preservatives, with an extended shelf‐life. In this study, a really powerful antimicrobial agent based on a nanomaterial functionalized with a non‐antimicrobial organic molecule was developed as a proof of concept. Following this approach it could be possible to develop a new generation of natural and removable antimicrobials based on their anchoring to functional surfaces for food, agricultural or medical purposes.
Summary
The diagnostic criteria for follicular lymphoma (FL) transformation vary among the largest series, which commonly exclude histologically‐documented transformation (HT) mandatorily. The aims ...of this retrospective observational multicentre study by the Spanish Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea, which recruited 1734 patients (800 males/934 females; median age 59 years), diagnosed with FL grades 1–3A, were, (i) the cumulative incidence of HT (CI‐HT); (ii) risk factors associated with HT; and (iii) the role of treatment and response on survival following transformation (SFT). With a median follow‐up of 6·2 years, 106 patients developed HT. Ten‐year CI‐HT was 8%. Considering these 106 patients who developed HT, median time to transformation was 2·5 years. High‐risk FL International Prognostic Index Hazard ratio (HR) 2·6, 95% confidence interval (CI): 1·5–4·5 and non‐response to first‐line therapy (HR 2·9, 95% CI: 1·3–6·8) were associated with HT. Seventy out of the 106 patients died (5‐year SFT, 26%). Response to HT first‐line therapy (HR 5·3, 95% CI: 2·4–12·0), autologous stem cell transplantation (HR 3·9, 95% CI: 1·5–10·1), and revised International Prognostic Index (HR 2·2, 95% CI: 1·1–4·2) were significantly associated with SFT. Response to treatment and HT were the variables most significantly associated with survival in the rituximab era. Better therapies are needed to improve response. Inclusion of HT in clinical trials with new agents is mandatory.
We describe herein a Toll‐like receptor 3 (TLR3) targeting delivery system based on mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic–polycytidylic acid ...(poly(I:C)) for controlled cargo delivery in SK‐BR‐3 breast carcinoma cells. Our results show that poly(I:C)‐conjugated nanoparticles efficiently targeted breast cancer cells due to dsRNA–TLR3 interaction. Such interaction also triggered apoptotic pathways in SK‐BR‐3, significantly decreasing cells viability. Poly(I:C) cytotoxic effect in breast carcinoma cells was enhanced by loading nanoparticles′ mesopores with the anthracyclinic antibiotic doxorubicin, a commonly used chemotherapeutic agent.
Messenger of death: A new drug‐delivery system based in mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic–polycytidylic acid (poly(I:C)) for targeting breast carcinoma cells is reported (see figure).
SARS‐CoV‐2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID‐19. We investigated whether the specific immune responses in the ...peripheral blood of 276 patients were associated with the severity and progression of COVID‐19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56–CD16+ NK‐cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID‐19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic intervention.
The pathogenesis of SARS‐CoV‐2 involves both cellular and humoral immunity. The proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh), and CD56‐CD16+ NK‐cells is increased in COVID‐19 patients. However, levels of IgG, and complement proteins are diminished in severe patients, suggesting immunoglobulins and complement consumption.
•Monocyte distribution width is a cellular biomarker which is higher in sicker patients after traumatic injury.•A high monocyte distribution width in trauma reflects a higher risk of multiple organ ...dysfunction and mortality.•The first value of this cellular biomarker, detected on admission of trauma patients, can predict the occurrence of complications during ICU stay.
Traumatic injury elicits an inflammatory response such as the one occurring during systemic infection. Monocyte distribution width (MDW) has been found to distinguish sepsis in a pool of patients with suspected infection. We hypothesized that an elevated MDW in trauma patients would be associated with the development of multiple organ dysfunction syndrome (MODS) and an increased mortality.
Observational study in a dedicated trauma Intensive Care Unit (ICU) in Madrid during 2019–2020. Patients were classified according to their first MDW value on admission, as greater or lesser than 21 U. Clinical data was obtained and univariate and multivariate analysis were realized, as well as a test performance analysis.
354 patients were studied, with a median age of 46 years, 78% male. Half presented with severe trauma ISS > 15, mostly with a blunt mechanism of injury. A MDW ≥ 21 U on admission was found in 17% of cases. These patients were more likely to present with hemodynamic instability and MODS. They had a higher length of stay (3.8 vs 2 days) and higher mortality (21 vs 5%) compared to the low MDW group. These findings remained statistically significant in the multivariate analysis, with an OR 4.6 (IC 95% 1.7–12) for MODS and 3.1 (IC 95% 1.2–8.3) for mortality.
In trauma patients, a MDW ≥ 21 U on admission was independently associated with a greater risk of MODS, a higher mortality and a higher length of stay. This biomarker could be useful in predicting severity in the initial evaluation of trauma patients.
The double vulnerability of women with disabilities places them at the center of this research paper. Intersectionality is key in research on gender-based violence. This study analyzes the ...perspective of the victims and non-victims themselves on this issue, through a comparative analysis between women with and without disabilities, at two levels of analysis: quantitative, through the adaptation of various scales (Assessment Screen-Disability/AAS-D, and the Woman Abuse Screening Tool/WAST), and qualitative, with semi-structured interviews (open scripts and different themes), and focus groups with experts from the associative network. The results obtained indicate that the most frequent type of violence is physical, followed by psychological and sexual, mainly perpetrated by partners. The higher their level of education, the more they defend themselves; receiving public aid can be a risk factor for domestic and sexual violence, and belonging to the associative movement and having paid work outside the home act as preventive measures. In conclusion, it is necessary to establish strategic protection measures and effective detection and intervention systems to make victims visible and care for them.
The evaluation of biorrational products to control the two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is of primary importance in the agriculture sector. In this study, we ...evaluated the effects of commercial botanical acaricides (BAs) on T. urticae and its predatory mite Amblyseius swirskii Athias-Henriot (Acari: Phytoseiidae). In the laboratory, T. urticae was exposed to acaricide-immersed leaves and A. swirskii to acaricide-coated glass vials. In the greenhouse, potted eggplants infested with mites were sprayed with different BAs. In the laboratory, Zea mays oil-based and Glycine max oil-based BAs caused more than 95% and 80% mortality of adults after 48 h of application and caused also 100% mortality of eggs. Residual exposure of A. swirskii adults to the BAs caused 45-60% mortality. In the greenhouse, these BAs caused more than 50% decrease in the population of T. urticae for 21 d.
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