Recent studies suggest that immune-modulating single-nucleotide polymorphisms (SNPs) influence the risk of developing cancer-related infections. Here, we evaluated whether 36 SNPs within 14 ...immune-related genes are associated with the risk of invasive aspergillosis (IA) and whether genotyping of these variants might improve disease risk prediction. We conducted a case-control association study of 781 immunocompromised patients, 149 of whom were diagnosed with IA. Association analysis showed that the IL4Rrs2107356 and IL8rs2227307 SNPs (using dbSNP numbering) were associated with an increased risk of IA (IL4Rrs2107356 odds ratio OR, 1.92; 95% confidence interval CI, 1.20 to 3.09; IL8rs2227307 OR, 1.73; 95% CI, 1.06 to 2.81), whereas the IL12Brs3212227 and IFNγrs2069705 variants were significantly associated with a decreased risk of developing the infection (IL12Brs3212227 OR, 0.60; 95% CI, 0.38 to 0.96; IFNγrs2069705 OR, 0.63; 95% CI, 0.41 to 0.97). An allogeneic hematopoietic stem cell transplantation (allo-HSCT)-stratified analysis revealed that the effect observed for the IL4Rrs2107356 and IFNγrs2069705 SNPs was stronger in allo-HSCT (IL4Rrs2107356 OR, 5.63; 95% CI, 1.20 to 3.09; IFNγrs2069705 OR, 0.24; 95% CI, 0.10 to 0.59) than in non-HSCT patients, suggesting that the presence of these SNPs renders patients more vulnerable to infection, especially under severe and prolonged immunosuppressive conditions. Importantly, in vitro studies revealed that carriers of the IFNγrs2069705C allele showed a significantly increased macrophage-mediated neutralization of fungal conidia (P = 0.0003) and, under stimulation conditions, produced higher levels of gamma interferon (IFNγ) mRNA (P = 0.049) and IFNγ and tumor necrosis factor alpha (TNF-α) cytokines (P value for 96 h of treatment with lipopolysaccharide PLPS-96 h, 0.057; P value for 96 h of treatment with phytohemagglutinin PPHA-96 h, 0.036; PLPS+PHA-96 h = 0.030; PPHA-72 h = 0.045; PLPS+PHA-72 h = 0.018; PLPS-96 h = 0.058; PLPS+PHA-96 h = 0.0058). Finally, we also observed that the addition of SNPs significantly associated with IA to a model including clinical variables led to a substantial improvement in the discriminatory ability to predict disease (area under the concentration-time curve AUC of 0.659 versus AUC of 0.564; P-2 log likehood ratio test = 5.2 · 10(-4) and P50.000 permutation test = 9.34 · 10(-5)). These findings suggest that the IFNγrs2069705 SNP influences the risk of IA and that predictive models built with IFNγ, IL8, IL12p70, and VEGFA variants can used to predict disease risk and to implement risk-adapted prophylaxis or diagnostic strategies.
Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic ...factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the
and
genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the
,
, and
alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (
value from the meta-analysis
= 9.8 · 10
,
= 1.5 · 10
, and
=7.9 · 10
, respectively). Haplotype analysis also confirmed the association of the
haplotype with
CGG with an increased risk of IA (
= 4.0 · 10
). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the
allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the
and
or
alleles had deregulated immune responses to
conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the
allele with lower levels of
mRNA in whole peripheral blood (
= 2.46 · 10
) and primary monocytes (
= 4.31 · 10
), highlight the role of the
and
loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.
Background. The benefit of the combination of serum galactomannan (GM) assay and polymerase chain reaction (PCR)–based detection of serum Aspergillus DNA for the early diagnosis and therapy of ...invasive aspergillosis (IA) in high-risk hematological patients remains unclear. Methods. We performed an open-label, controlled, parallel-group randomized trial in 13 Spanish centers. Adult patients with acute myeloid leukemia and myelodysplastic syndrome on induction therapy or allogeneic hematopoietic stem cell transplant recipients were randomized (1:1 ratio) to 1 of 2 arms: "GM-PCR group" (the results of serial serum GM and PCR assays were provided to treating physicians) and "GM group" (only the results of serum GM were informed). Positivity in either assay prompted thoracic computed tomography scan and initiation of antifungal therapy. No antimold prophylaxis was permitted. Results. Overall, 219 patients underwent randomization (105 in the GM-PCR group and 114 in the GM group). The cumulative incidence of "proven" or "probable" IA (primary study outcome) was lower in the GM-PCR group (4.2% vs 13.1%; odds ratio, 0.29 95% confidence interval, .09–.91). The median interval from the start of monitoring to the diagnosis of IA was lower in the GM-PCR group (13 vs 20 days; P = .022), as well as the use of empirical antifungal therapy (16.7% vs 29.0%; P = .038). Patients in the GM-PCR group had higher proven or probable IA–free survival (P = .027). Conclusions. A combined monitoring strategy based on serum GM and Aspergillus DNA was associated with an earlier diagnosis and a lower incidence of IA in high-risk hematological patients.
Open clusters have long been used to study the chemodynamical evolution of the Galactic disc. This requires a homogeneously analysed sample covering a wide range of ages and distances. In this paper, ...we present the Open Clusters Chemical Abundances from Spanish Observatories (OCCASO) second data release. This comprises a sample of high-resolution (R > 65 000) and high signal-to-noise spectra of 115 red clump stars in 18 open clusters. We derive atmospheric parameters (Teff, log g, ξ), and Fe/H abundances using two analysis techniques: equivalent widths and spectral synthesis. A detailed comparison and a critical review of the results of the two methods are made. Both methods are carefully tested between them, with the Gaia FGK benchmark stars, and with an extensive sample of literature values. We perform a membership study using radial velocities and the resulting abundances. Finally, we compare our results with a chemodynamical model of the Milky Way thin disc concluding that the oldest open clusters are consistent with the models only when dynamical effects are taken into account.
Venous-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment for acute cardiogenic shock in patients who also have acute lung injury predisposes development of a serious complication ...called “north-south syndrome” (NSS) which causes cerebral hypoxia. NSS is poorly characterized and hemodynamic studies have focused on cerebral perfusion ignoring the heart. We hypothesized in NSS the heart would be more likely to receive hypoxemic blood than the brain due to the proximity of the coronary arteries to the aortic annulus. To test this, we conducted a computational fluid dynamics simulation of blood flow in a human supported by VA-ECMO. Simulations quantified the fraction of blood at each aortic branching vessel originating from residual native cardiac output versus VA-ECMO. As residual cardiac function was increased, simulations demonstrated myocardial hypoxia would develop prior to cerebral hypoxia. These results illustrate the conditions where NSS will develop and the relative cardiac function that will lead to organ-specific hypoxia.
Graphical Abstract
Illustration of the impact of north-south syndrome on organ-specific oxygen delivery. Patients on VA-ECMO have two sources of blood flow, one from the VA-ECMO circuit and one from the residual cardiac function. When there is no residual cardiac function, all organs are perfused with oxygenated blood. As myocardial recovery progresses, blood supply from the two sources will begin to mix resulting in non-homogeneous mixing and differential oxygenation based upon the anatomical site of branching vessels.
Patients with post-coronavirus disease 2019 (COVID-19) conditions typically experience cognitive problems. Some studies have linked COVID-19 severity with long-term cognitive damage, while others did ...not observe such associations. This discrepancy can be attributed to methodological and sample variations. We aimed to clarify the relationship between COVID-19 severity and long-term cognitive outcomes and determine whether the initial symptomatology can predict long-term cognitive problems. Cognitive evaluations were performed on 109 healthy controls and 319 post-COVID individuals categorized into three groups according to the WHO clinical progression scale: severe-critical (
n
= 77), moderate-hospitalized (
n
= 73), and outpatients (
n
= 169). Principal component analysis was used to identify factors associated with symptoms in the acute-phase and cognitive domains. Analyses of variance and regression linear models were used to study intergroup differences and the relationship between initial symptomatology and long-term cognitive problems. The severe-critical group performed significantly worse than the control group in general cognition (Montreal Cognitive Assessment), executive function (Digit symbol, Trail Making Test B, phonetic fluency), and social cognition (Reading the Mind in the Eyes test). Five components of symptoms emerged from the principal component analysis: the “Neurologic/Pain/Dermatologic” “Digestive/Headache”, “Respiratory/Fever/Fatigue/Psychiatric” and “Smell/ Taste” components were predictors of Montreal Cognitive Assessment scores; the “Neurologic/Pain/Dermatologic” component predicted attention and working memory; the “Neurologic/Pain/Dermatologic” and “Respiratory/Fever/Fatigue/Psychiatric” components predicted verbal memory, and the “Respiratory/Fever/Fatigue/Psychiatric,” “Neurologic/Pain/Dermatologic,” and “Digestive/Headache” components predicted executive function. Patients with severe COVID-19 exhibited persistent deficits in executive function. Several initial symptoms were predictors of long-term sequelae, indicating the role of systemic inflammation and neuroinflammation in the acute-phase symptoms of COVID-19.”
Study Registration
:
www.ClinicalTrials.gov
, identifier NCT05307549 and NCT05307575.
The response to in vitro tissue culture of five important Mexican malting barley cultivars namely 'Armida', 'Esmeralda', 'Adabella', 'Esperanza' and 'Alina', was evaluated. Callus induction and plant ...regeneration were evaluated in shoot apices and immature barley embryos harvested eight, 12, 16, 20 and 24 days after pollination. These explants were cultured on 22 media formulations that included Murashige and Skoog (MS) and Chu (N6) media amended with two carbon sources and different concentrations of 2, 4-Dichlorophenoxyacetic acid (2, 4-D), 3, 6-dichtoro-2-methoxybenzoic acid (Dicamba), 6-benzyladenine (BA), casein hydrolyzate and L-proline. No regenerable callus lines could be recovered from the experiments using shoot apices as the starting material. Conversely, immature embryos harvested at 12 to 16 days after pollination (1.0 to 1.5 mm long) and cultured on formulations containing the basal MS medium supplemented with 2 mg L super(-1) of 2, 4-D or Dicamba resulted in the production of nodular and friable embryogenic calli with regenerative capacity in all barley cultivars. A medium containing MS, Dicamba and maltose generated the highest percentage of embryogenic calli formation (2.1 in 'Adabella' vs. 23.4 in 'Alina' cultivar) with the maximal regenerative potential (7.2 in 'Armida' vs. 9.1 recovered plants per gram FW callus in 'Esperanza' cultivar). Using this medium, 'Esmeralda' embryogenic callus lines have been maintained for more than five years without loss of regenerability or the capacity for producing normal plants.
Invasive fungal infections (IFIs) caused by filamentous fungi still have high rates of mortality, associated with difficulties in early detection of the infection and therapeutic limitations. ...Consequently, a useful approach is to prevent patients at risk of fungal infection from coming into contact with conidia of Aspergillus and other mould species. This document describes the recommendations for preventing IFI caused by filamentous fungi worked out by Spanish experts from different medical and professional fields. The article reviews the incidence of IFI in different risk populations, and questions related to environmental measures for prevention, control of hospital infections, additional procedures for prevention, prevention of IFI outside of hospital facilities and antifungal prophylaxis are also analysed.
Objective
A long‐term decline in health‐related quality of life (HRQoL) has been reported after coronavirus disease 2019 (COVID‐19). Studies with people with persistent symptoms showed inconsistent ...outcomes. Cognition and emotion are important determinants in HRQoL, but few studies have examined their prognostic significance for HRQoL and functionality in post‐COVID patients with persisting symptoms. We aimed to describe QoL, HRQoL, and functioning in individuals post‐COVID with varying COVID‐19 severities and to investigate the predictive value of cognitive and emotional variables for QoL, HRQoL, and functioning.
Methods
In total, 492 participants (398 post‐COVID and 124 healthy controls) underwent a neurobehavioral examination that included assessments of cognition, mood, QoL/HRQoL (WHOQOL‐BREF, EQ‐5D), and functioning (WHODAS‐II). Analysis of covariance and linear regression models were used to study intergroup differences and the relationship between cognitive and emotional variables and QoL and functioning.
Results
The Physical and Psychological dimensions of WHOQoL, EQ‐5D, and WHODAS Cognition, Mobility, Life Activities, and Participation dimensions were significantly lower in post‐COVID groups compared with a control group. Regression models explaining 23.9%–53.9% of variance were obtained for the WHOQoL‐BREF dimensions and EQ‐5D, with depressive symptoms, post‐COVID symptoms, employment status, income, and mental speed processing as main predictors. For the WHODAS, models explaining 17%–60.2% of the variance were obtained. Fatigue, depressive symptoms, mental speed processing, and post‐COVID symptoms were the main predictors.
Interpretation
QoL/HRQoL and functioning after COVID‐19 in individuals with persistent symptoms were lower than in non‐affected persons. Depressive symptoms, fatigue, and slower mental processing speed were predictors of lower QoL/HRQoL and functioning.
The study aimed to assess sleep quality in PCC patients and its predictors by analysing its relationship with emotional, cognitive and functional variables, as well as possible differences based on ...COVID-19 severity. We included 368 individuals with PCC and 123 healthy controls (HCs) from the NAUTILUS Project (NCT05307549 and NCT05307575). We assessed sleep quality (Pittsburgh Sleep Quality Index, PSQI), anxiety (Generalized Anxiety Disorder, GAD-7), depression (Patient Health Questionnaire, PHQ-9), global cognition (Montreal Cognitive Assessment, MoCA), everyday memory failures (Memory Failures of Everyday Questionnaire, MFE-30), fatigue (Chadler Fatigue Questionnaire, CFQ), quality of life (European Quality of Life-5 Dimensions, EQ-5D), and physical activity levels (International Physical Activity Questionnaire, IPAQ). 203 were nonhospitalized, 83 were hospitalized and 82 were admitted to the intensive care unit (ICU). We found statistically significant differences in the PSQI total score between the PCC and HC groups (p < 0.0001), but there were no differences among the PCC groups. In the multiple linear regressions, the PHQ-9 score was a predictor of poor sleep quality for mild PCC patients (p = 0.003); GAD-7 (p = 0.032) and EQ-5D (p = 0.011) scores were predictors of poor sleep quality in the hospitalized PCC group; and GAD-7 (p = 0.045) and IPAQ (p = 0.005) scores were predictors of poor sleep quality in the group of ICU-PCC. These results indicate that worse sleep quality is related to higher levels of depression and anxiety, worse quality of life and less physical activity. Therapeutic strategies should focus on these factors to have a positive impact on the quality of sleep.
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