GM-CSF receptor expression determines opposing innate memory phenotypes at different stages of myelopoiesis.

Inflammatory responses must be tightly coordinated with the activation of emergency myelopoiesis to produce potent myeloid cells that fight infection without causing excessive host damage. Here, we show that GM-CSF programs myeloid committed progenitors to produce trained macrophages (increased cytokine response), but programs the upstream non-committed LKS+ progenitors to produce tolerized macrophages (decreased cytokine response). In myeloid progenitors, GM-CSF strongly activates STAT5, ERK and Akt-mTOR signaling pathways, which are essential to establish a training program, whereas in LKS+ progenitors GM-CSF induces NF-κB translocation to the nucleus to establish a tolerization program. These differences arise from higher GM-CSF receptor expression in myeloid progenitors compared to LKS+ cells. We demonstrate that ß-catenin regulation of NF-κB nuclear translocation is central in this process. Glycogen synthase kinase 3 (GSK3) inactivation by strong ERK and PI3K-Akt signaling increases cytoplasmic ß-catenin levels to block NF-κB nuclear translocation in myeloid progenitors. In contrast, when ERK and PI3K-Akt signaling are weak, active GSK3 causes a decrease in ß-catenin, allowing NF-κB nuclear translocation in LKS+ progenitors. Finally, GM-CSF-induced LKS+ tolerization takes place in several murine models of trained immunity and in human CD34+ CD38- progenitors. Our study reveals that in addition to activating myelopoiesis, GM-CSF also programs early and immediate myeloid progenitors to produce opposing immune memory phenotypes. We propose that the inflammatory response from immediate myeloid progenitors may be balanced by the tolerized phenotype of early progenitors, thus providing a mechanism for appropriate resolution of inflammation and protection against a prolonged cytokine storm.

Implementation of sonopartogram: multicenter feasibility study.

OBJECTIVES: Well-established clinical practice to assess progress in labor involves routine abdominal palpation and vaginal examination (VE). However, VE is subjective, poorly reproducible and painful for women. In this study, our aim is to evaluate the feasibility of systematically integrating transabdominal and transperineal ultrasound assessment of fetal position, psAOP, HPD and SCD to monitor labor progress in women undergoing induction of labor (IOL). We also aim at determining if ultrasound can reduce women's pain during examinations. METHODS: Women were recruited as they presented for IOL in three maternity units. Ultrasound assessments were performed in 100 women between 37+0 and 41+6 weeks' gestation. A baseline combined transabdominal and transperineal scan was performed, including the assessment of fetal biometry, umbilical artery and middle cerebral artery Dopplers, amniotic fluid index (AFI), fetal spine and occiput positions, psAOP, HPD, SCD, and cervical length. Intrapartum scans were performed instead of VEs according to protocol. Participants were asked to indicate their level of pain by verbally giving a pain score from 0 - 10 (with 0 representing no pain) during assessment. The repeated measures data were analyzed by mixed effect models to identify the significant factors that affected the relationship between psAOP, HPD, SCD and mode of delivery. RESULTS: 223 intrapartum ultrasound scans with a median of 2 scans per participant (interquartile range (IQR) = 1 - 3), and 151 VEs were performed with a median of 1 per participant (IQR = 0 - 2). There were no adverse fetal or maternal outcomes. After excluding those with epidural anesthesia during examination, median pain score for intrapartum scan was 0 (IQR = 0 - 1) and 3 for VE (IQR = 0 - 6). Cesarean delivery and epidural anesthesia were significantly associated with slower rate of change in psAOP, HPD and SCD. Maternal height, parity and neonatal birth weight did not affect ultrasound measurements of labor progress. CONCLUSIONS: Comprehensive transabdominal and transperineal ultrasound assessment can be successfully used to assess progress in labor and can reduce the level of pain experienced during examination. Ultrasound assessment may be able to replace some transabdominal and VE examinations during labor. This article is protected by copyright. All rights reserved.

Prevalence and management of urinary incontinece after pelvic organ prolapse surgery (sacrocolpopexy). A literature review.

INTRODUCTION: Stress urinary incontinence (SUI) is frequently associated with pelvic organ prolapse (POP) and may occur after its surgical treatment. AIM: To determine the incidence, risk factors and management of SUI during and after POP surgery through a review of the available literature. MATERIALS AND METHOD: Narrative literature review on the incidence and management of SUI after POP surgery after search of relevant manuscripts indexed in PubMed, EMBASE and Scielo published in Spanish and English between 2013 and 2023. RESULTS: Occult SUI is defined as visible urine leakage when prolapse is reduced in patients without SUI symptoms. De novo SUI develops after prolapse surgery without having previously existed. In continent patients, the number needed to treat (NNT) to prevent one case of de novo SUI is estimated to be 9 patients and about 17 to avoid repeat incontinence surgery. In patients with occult UI, the NNT to avoid repeat incontinence surgery is around 7. Patients with POP and concomitant SUI are the group most likely to benefit from combined surgery with a more favorable NNT (NNT 2). CONCLUSION: Quality studies on combined surgery for treatment SUI and POP repair are lacking. Continent patients with prolapse should be warned of the risk of de novo SUI, although concomitant incontinence treatment is not currently recommended. Incontinence surgery should be considered on an individual basis in patients with prolapse and SUI.

Comparison of different methods of screening for preterm pre-eclampsia: cohort study.

OBJECTIVE: To compare the predictive performance for pre-eclampsia (PE) of three different first-trimester mathematical models of screening, which combine maternal risk factors with mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF), and two risk scoring systems, based on NICE and ACOG recommendations. METHODS: This was a prospective cohort study performed in eight fetal-medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with singleton pregnancies and non-malformed live fetuses attending their routine ultrasound examination at 11+0 to 13+6 weeks' gestation were invited to participate in the study. Maternal characteristics and medical history were recorded and measurements of MAP, UtA-PI, serum PlGF and pregnancy associated plasma protein-A (PAPP-A) were converted into multiples of the median (MoM). Risks for term, preterm-PE (< 37 weeks' gestation) and early-PE (< 34 weeks' gestation) were calculated according to the FMF competing risks model, the Crovetto et al., logistic regression model, and Serra et al., Gaussian model. Patient classification based on NICE and ACOG guidelines was also performed. We estimated detection rates (DR) with their 95% confidence intervals (CIs) at a fixed 10% screen positive rate (SPR), as well as the area under the receiver operating characteristic curve (AUROC) for preterm-PE, early-PE, and all PE for the three mathematical models. For the scoring systems, we calculated DR and SPR. Risk calibration was also assessed. RESULTS: The study population comprised of 10,110 singleton pregnancies, including 32 (0.3%) that developed early-PE, 72 (0.7%) that developed preterm-PE and 230 (2.3%) of any PE. At fixed 10% SPR, the FMF, Crovetto et al., and Serra et al., detected 82.7% (95% CI, 69.6 to 95.8%), 73.8% (95% CI, 58.7 to 88.9%), and 79.8% (95% CI, 66.1 to 93.5%) of early-PE; 72.7% (95% CI, 62.9 to 82.6%), 69.2% (95% CI, 58.8 to 79.6%), and 74.1% (95% CI, 64.2 to 83.9%) of preterm-PE and 55.1% (95% CI, 48.8 to 61.4%), 47.1% (95% CI, 40.6 to 53.5%), and 53.9% (95% CI, 47.4 to 60.4%) of all PE, respectively. The best correlation between predicted and observed cases was achieved by the FMF model, with an AUROC of 0.911 (95% CI, 0.879 to 0.943), a slope of 0.983 (95% CI, 0.846-1.120) and an intercept of 0.154 (95% CI, -0.091 to 0.397). The NICE criteria identified 46.7% (95% CI, 35.3 to 58.0%) of preterm-PE at 11% SPR and ACOG criteria identified 65.9% (95% CI, 55.4 to 76.4%) of preterm-PE at 33.8% SPR. CONCLUSIONS: The best performance of screening for preterm-PE is achieved by mathematical models that combine maternal factors with MAP, UtA-PI and PlGF, as compared to risk-scoring systems like NICE or ACOG criteria. While all three algorithms show similar results in terms of overall prediction, the FMF model showed the best performance at the individual level. This article is protected by copyright. All rights reserved.

Increased grey matter volumes in the temporal lobe and its relationship with cognitive functioning in euthymic patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is characterized by episodic mood dysregulation, although a significant portion of patients suffer persistent cognitive impairment during euthymia. Previous magnetic resonance imaging (MRI) research suggests BD patients may have accelerated brain aging, observed as lower grey matter volumes. How these neurostructural alterations are related to the cognitive profile of BD is unclear. METHODS: We aim to explore this relationship in euthymic BD patients with multimodal structural neuroimaging. A sample of 27 euthymic BD patients and 24 healthy controls (HC) underwent structural grey matter MRI and diffusion-weighted imaging (DWI). BD patient's cognition was also assessed. FreeSurfer algorithms were used to obtain estimations of regional grey matter volumes. White matter pathways were reconstructed using TRACULA, and four diffusion metrics were extracted. ANCOVA models were performed to compare BD patients and HC values of regional grey matter volume and diffusion metrics. Global brain measures were also compared. Bivariate Pearson correlations were explored between significant brain results and five cognitive domains. RESULTS: Euthymic BD patients showed higher ventricular volume (F(1, 46) = 6.04; p = 0.018) and regional grey matter volumes in the left fusiform (F(1, 46) = 15.03; pFDR = 0.015) and bilateral parahippocampal gyri compared to HC (L: F(1, 46) = 12.79, pFDR = 0.025/ R: F(1, 46) = 15.25, pFDR = 0.015). Higher grey matter volumes were correlated with greater executive function (r = 0.53, p = 0.008). LIMITATIONS: We evaluated a modest sample size with concurrent pharmacological treatment. CONCLUSIONS: Higher medial temporal volumes in euthymic BD patients may be a potential signature of brain resilience and cognitive adaptation to a putative illness neuroprogression. This knowledge should be integrated into further efforts to implement imaging into BD clinical management.

Emollients in dermatological creams: Early evaluation for tailoring formulation and therapeutic performance.

The targeted choice of the emollient of a cream determines its physicochemical properties and clinical effectiveness. This work researched the effects of emollient properties on the final characteristics and potential performance of oil-in-water dermatological creams. Seven emollients with different chemical characteristics and structures (alkane, triglyceride, ether, silicone, vegetable oils, and mineral oil) were tested in a model formulation. Early stability, pH, droplet size distribution, rheology, tackiness, adhesivity, spreadability, tribology, and release profile of a lipophilic substance model (in Franz cells, through a synthetic membrane, for six hours) were assessed. The creams had acid epicutaneous pH and a "shear-thinning" "solid-like" viscoelastic behavior. Among the seven emollients' properties, polarity, density, and viscosity were the most influential. Droplet parameters were the most impacted, pH and release were moderately affected, and the textural properties were lowly to moderately impacted. The emollient substitution in the model formulation affected the experimental parameters differently, allowing formulation optimization and tailoring its potential therapeutic performance regarding drug release, coadjutant effects, and dwell time on the skin. By looking at the creams' characteristics, it was possible to select the best-suited emollients for releasing a lipophilic drug, applying on painful skin, and formulation in wash-off products or leave-on protective barrier creams.

[Translated article] Cost of Treating Cutaneous T-Cell Lymphoma in Spain: Analysis of MICADOS Study Data by Disease Stage.

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

Cost of Treating Cutaneous T-Cell Lymphoma in Spain: Analysis of MICADOS Study Data by Disease Stage. / Evaluación de los costes asociados a la enfermedad de pacientes con linfoma cutáneo de células T en España: análisis en función del estadio clínico (estudio MICADOS).

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

Validation of machine-learning model for first-trimester prediction of pre-eclampsia using cohort from PREVAL study.

OBJECTIVE: Effective first-trimester screening for pre-eclampsia (PE) can be achieved using a competing-risks model that combines risk factors from the maternal history with multiples of the median (MoM) values of biomarkers. A new model using artificial intelligence through machine-learning methods has been shown to achieve similar screening performance without the need for conversion of raw data of biomarkers into MoM. This study aimed to investigate whether this model can be used across populations without specific adaptations. METHODS: Previously, a machine-learning model derived with the use of a fully connected neural network for first-trimester prediction of early (< 34 weeks), preterm (< 37 weeks) and all PE was developed and tested in a cohort of pregnant women in the UK. The model was based on maternal risk factors and mean arterial blood pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A). In this study, the model was applied to a dataset of 10 110 singleton pregnancies examined in Spain who participated in the first-trimester PE validation (PREVAL) study, in which first-trimester screening for PE was carried out using the Fetal Medicine Foundation (FMF) competing-risks model. The performance of screening was assessed by examining the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% screen-positive rate (SPR). These indices were compared with those derived from the application of the FMF competing-risks model. The performance of screening was poor if no adjustment was made for the analyzer used to measure PlGF, which was different in the UK and Spain. Therefore, adjustment for the analyzer used was performed using simple linear regression. RESULTS: The DRs at 10% SPR for early, preterm and all PE with the machine-learning model were 84.4% (95% CI, 67.2-94.7%), 77.8% (95% CI, 66.4-86.7%) and 55.7% (95% CI, 49.0-62.2%), respectively, with the corresponding AUCs of 0.920 (95% CI, 0.864-0.975), 0.913 (95% CI, 0.882-0.944) and 0.846 (95% CI, 0.820-0.872). This performance was achieved with the use of three of the biomarkers (MAP, UtA-PI and PlGF); inclusion of PAPP-A did not provide significant improvement in DR. The machine-learning model had similar performance to that achieved by the FMF competing-risks model (DR at 10% SPR, 82.7% (95% CI, 69.6-95.8%) for early PE, 72.7% (95% CI, 62.9-82.6%) for preterm PE and 55.1% (95% CI, 48.8-61.4%) for all PE) without requiring specific adaptations to the population. CONCLUSIONS: A machine-learning model for first-trimester prediction of PE based on a neural network provides effective screening for PE that can be applied in different populations. However, before doing so, it is essential to make adjustments for the analyzer used for biochemical testing. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Detecting emerald green in 19thC book bindings using vis-NIR spectroscopy.

Detection and identification of heavy metal-based pigments in 19th-century bookbindings is crucial to avoid human user exposure to toxic substances. Vibrant green bookbindings with arsenical emerald green are particularly problematic due to their friability. A pilot study at St Andrews University tested 800 green bookbindings for arsenic presence using visible near-infrared spectrometry, a technique not previously applied to the detection of heavy metals in bindings. The ASD TerraSpec Halo portable spectrometer that is normally used in geology to identify minerals in rocks, is used here to collect hyperspectral reflectance data between 350 and 2500 nm. Raman spectroscopy and Scanning Electron Microscopy with Energy Dispersive X-ray Spectroscopy (SEM-EDS) are used here to validate hyperspectral test results. The study finds that bookbindings containing emerald green have a distinctive pattern in the visible part of the spectrum that is distinguishable from other green pigments. This finding opens up the possibility for all collecting institutions to test bindings for this toxic compound in a non-destructive, cost-effective and efficient manner.

Lessons Learned from Catalysis to Qubits: General Strategies to Build Accessible and Accurate First-Principles Models of Point Defects.

Defects and dopants play critical roles in defining the properties of a material. Achieving a mechanistic understanding of how such properties arise is challenging with current experimental methods, and computational approaches suffer from significant modeling limitations that frequently require a posteriori fitting. Consequently, the pace of dopant discovery as a means of tuning material properties for a particular application has been slow. However, recent advances in computation have enabled researchers to move away from semiempirical schemes to reposition density functional theory as a predictive tool and improve the accessibility of highly accurate first-principles methods to all researchers. This Perspective discusses some of these recent achievements that provide more accurate first-principles geometric, thermodynamic, optical, and electronic properties simultaneously. Advancements related to supercells, basis sets, functionals, and optimization protocols, as well as suggestions for evaluating the quality of a computational model through comparison to experimental data, are discussed. Moreover, recent computational results in the fields of energy materials, heterogeneous catalysis, and quantum informatics are reviewed along with an evaluation of current frontiers and opportunities in the field of computational materials chemistry.

The association of circulating endocannabinoids with neuroimaging and blood biomarkers of neuro-injury.

BACKGROUND: Preclinical studies highlight the importance of endogenous cannabinoids (endocannabinoids; eCBs) in neurodegeneration. Yet, prior observational studies focused on limited outcome measures and assessed only few eCB compounds while largely ignoring the complexity of the eCB system. We examined the associations of multiple circulating eCBs and eCB-like molecules with early markers of neurodegeneration and neuro-injury and tested for effect modification by sex. METHODS: This exploratory cross-sectional study included a random sample of 237 dementia-free older participants from the Framingham Heart Study Offspring cohort who attended examination cycle 9 (2011-2014), were 65 years or older, and cognitively healthy. Forty-four eCB compounds were quantified in serum, via liquid chromatography high-resolution mass spectrometry. Linear regression models were used to examine the associations of eCB levels with brain MRI measures (i.e., total cerebral brain volume, gray matter volume, hippocampal volume, and white matter hyperintensities volume) and blood biomarkers of Alzheimer's disease and neuro-injury (i.e., total tau, neurofilament light, glial fibrillary acidic protein and Ubiquitin C-terminal hydrolase L1). All models were adjusted for potential confounders and effect modification by sex was examined. RESULTS: Participants mean age was 73.3 ± 6.2 years, and 40% were men. After adjustment for potential confounders and correction for multiple comparisons, no statistically significant associations were observed between eCB levels and the study outcomes. However, we identified multiple sex-specific associations between eCB levels and the various study outcomes. For example, high linoleoyl ethanolamide (LEA) levels were related to decreased hippocampal volume among men and to increased hippocampal volume among women (ß ± SE = - 0.12 ± 0.06, p = 0.034 and ß ± SE = 0.08 ± 0.04, p = 0.026, respectively). CONCLUSIONS: Circulating eCBs may play a role in neuro-injury and may explain sex differences in susceptibility to accelerated brain aging. Particularly, our results highlight the possible involvement of eCBs from the N-acyl amino acids and fatty acid ethanolamide classes and suggest specific novel fatty acid compounds that may be implicated in brain aging. Furthermore, investigation of the eCBs contribution to neurodegenerative disease such as Alzheimer's disease in humans is warranted, especially with prospective study designs and among diverse populations, including premenopausal women.

Food Allergens: When Friends Become Foes-Caveats and Opportunities for Oral Immunotherapy Based on Deactivation Methods.

Food allergies represent a serious health concern and, since the 1990s, they have risen gradually in high-income countries. Unfortunately, the problem is complex because genetic, epigenetic, and environmental factors may be collectively involved. Prevention and diagnoses have not yet evolved into efficacious therapies. Identification and control of allergens present in edible substances hold promise for multi-purpose biomedical approaches, including oral immunotherapy. This review highlights recent studies and methods to modify the otherwise innocuous native proteins in most subjects, and how oral treatments targeting immune responses could help cancel out the potential risks in hypersensitive individuals, especially children. We have focused on some physical methods that can easily be conducted, along with chemo-enzymatic modifications of allergens by means of peptides and phytochemicals in particular. The latter, accessible from naturally-occurring substances, provide an added value to hypoallergenic matrices employing vegetal wastes, a point where food chemistry meets sustainable goals as well.

Effectiveness and safety of brodalumab in the treatment of plaque, scalp and palmoplantar psoriasis: A multicentre retrospective study in a Spanish population.

BACKGROUND AND OBJECTIVE: The data in clinical practice regarding the effectiveness and safety of brodalumab in psoriasis are scarce, especially at scalp and palmoplantar locations. The main objective was the percentage of patients achieving absolute PASI ≤3/ ≤1/ =0 for plaque psoriasis and the percentage of patients achieving an IGA 0-1/IGA 0 for the special locations at Week 52 of treatment. PATIENTS AND METHODS: Observational retrospective multicentre study in 28 Spanish Hospitals that included adult patients with plaque psoriasis treated with brodalumab, from September 2018 until March 2021. RESULTS: A total of 200 patients were included. The mean baseline PASI was 10.97 (±6.28) with a mean basal scalp (n = 58) and palmoplantar (n = 40) IGA of 2.10 (±0.97) and 2.15 (±1.26), respectively. At Week 52, 93.98%/75.90%/68.67% of patients reached an absolute PASI ≤3/ ≤1/ =0 in plaque psoriasis (n = 83), with a percentage of patients achieving scalp (n = 27) and palmoplantar (n = 19) IGA 0-1/IGA 0 of 96.3%/88.9% and 100%/88.9%, respectively. Fifteen per cent of patients reported any adverse events with candidiasis being the most reported (6%), but only 6% of the adverse events required the withdrawal. CONCLUSIONS: Brodalumab demonstrated high PASI and IGA responses and was well tolerated in clinical practice in plaque, scalp and palmoplantar psoriasis.

Controlling product selectivity in oxidative desulfurization using an electrodeposited iron oxide film.

Sulfur-containing compounds must be removed from raw fuel oils before use and recently, there has been an effort to identify and optimize a more energy efficient method of oil processing. One promising route is electrochemical oxidative desulfurization (ODS), and in this work, we investigate an electrodeposited iron oxide film (FeOx(OH)y) as a working electrode to catalyze the oxidation of dibenzothiophene (DBT). The FeOx(OH)y film displays unexpected selectivity for the DBT sulfoxide (DBTO)-departing from the catalytic behavior of gold, which favors the dimerization of DBT. In addition, we observe a morphological change within our FeOx(OH)y film from γ-FeOOH to γ-Fe2O3. This change provides insight to the activity of each structure for ODS as the rate of oxidation increases after the incorporation of γ-Fe2O3. Our experimental observations are corroborated with DFT calculations, which suggest that the adsorption energy of DBT on Au is significantly greater than on the FeOx(OH)y, favoring the formation of dimeric and oligomeric products. Calculations also demonstrate that DBT binds preferably in a monodentate configuration but that oxidation occurs via DBT bound via a bidentate configuration. Monodentate binding on γ-FeOOH is significantly stronger than binding on γ-Fe2O, resulting in easier conversation to bidentate binding on γ-Fe2O3.

Inbreeding Effects on the Performance and Genomic Prediction for Polysomic Tetraploid Potato Offspring Grown at High Nordic Latitudes.

Inbreeding depression (ID) is caused by increased homozygosity in the offspring after selfing. Although the self-compatible, highly heterozygous, tetrasomic polyploid potato (Solanum tuberosum L.) suffers from ID, some argue that the potential genetic gains from using inbred lines in a sexual propagation system of potato are too large to be ignored. The aim of this research was to assess the effects of inbreeding on potato offspring performance under a high latitude and the accuracy of the genomic prediction of breeding values (GEBVs) for further use in selection. Four inbred (S1) and two hybrid (F1) offspring and their parents (S0) were used in the experiment, with a field layout of an augmented design with the four S0 replicated in nine incomplete blocks comprising 100, four-plant plots at Umeå (63°49'30″ N 20°15'50″ E), Sweden. S0 was significantly (p < 0.01) better than both S1 and F1 offspring for tuber weight (total and according to five grading sizes), tuber shape and size uniformity, tuber eye depth and reducing sugars in the tuber flesh, while F1 was significantly (p < 0.01) better than S1 for all tuber weight and uniformity traits. Some F1 hybrid offspring (15-19%) had better total tuber yield than the best-performing parent. The GEBV accuracy ranged from -0.3928 to 0.4436. Overall, tuber shape uniformity had the highest GEBV accuracy, while tuber weight traits exhibited the lowest accuracy. The F1 full sib's GEBV accuracy was higher, on average, than that of S1. Genomic prediction may facilitate eliminating undesired inbred or hybrid offspring for further use in the genetic betterment of potato.

La influencia de la gestión organizativa en el tiempo puerta-aguja del tratamiento fibrinolítico / The influence of organisational management on door-to-needle times for fibrinolytic treatment

Introducción: El tiempo puerta-aguja (TPA) es el principal indicador del proceso del código ictus (CI). Según la guía de 2018 de la American Heart Association/American Stroke Associa-tion, el objetivo TPA debe ser inferior a 45 minutos. Para conseguirlo son necesarios protocolos eficaces y revisados de actuación extrahospitalaria e intrahospitalaria. Método: Analizamos la influencia de cambios organizativos entre 2011 y 2019 en el TPA y en la evolución clínica de los pacientes tratados con fibrinólisis. Utilizamos los datos de nuestro centro monitorizados y custodiados por el Pla Director en l’àmbit de la Malaltia Vascular Cerebral dela Generalitat de Catalunya. Entre otras medidas se han analizado las diferencias entre los a ̃nos y las derivadas de la implantación del modelo Helsinki. Resultados: Se estudiaron 447 pacientes, existiendo diferencias estadísticamente significativas en el TPA entre los diferentes a ̃nos. La activación del CI de forma extrahospitalaria en 315(70,5%) pacientes redujo el TPA una mediana de 14 minutos. Sin embargo, el modelo de regresión lineal sólo evidenció una relación inversamente proporcional entre la adopción del modelo deCI Helsinki (MH) y el TPA (coeficiente beta −0,42; p < 0,001). La eliminación de la figura delneurólogo vascular tras la adopción del MH empeoró el TPA y la mortalidad a los 90 días.Conclusión: El modelo organizativo influye en el TPA, siendo en nuestra muestra la aplicacióndel MH, la existencia de la figura del neurólogo vascular referente y la prenotificación del CIfactores claves para la reducción del TPA y la mejora clínica del paciente.(AU)

Introduction: Door-to-needle time (DNT) has been established as the main indicator in codestroke protocols. According to the 2018 guidelines of the American Heart Association/AmericanStroke Association, DNT should be less than 45 minutes; therefore, effective and revised pre-admission and in-hospital protocols are required. Method: We analysed organisational changes made between 2011 and 2019 and their influenceon DNT and the clinical progression of patients treated with fibrinolysis. We collected datafrom our centre, stored and monitored under the Master Plan for Cerebrovascular Disease ofthe regional government of Catalonia. Among other measures, we analysed the differencesbetween years and differences derived from the implementation of the Helsinki model.Results: The study included 447 patients, and we observed significant differences in DNTbetween different years. Pre-hospital code stroke activation, recorded in 315 cases (70.5%),reduced DNT by a median of 14 minutes. However, the linear regression model only showed aninversely proportional relationship between the adoption of the Helsinki code stroke model andDNT (beta coefficient, —0.42; P < .001). The removal of vascular neurologists after the adoptionof the Helsinki model increased DNT and the 90-day mortality rate. Conclusion: DNT is influenced by the organisational model. In our sample, the application ofthe Helsinki model, the role of the lead vascular neurologist, and notification of code strokeby pre-hospital emergency services are key factors for the reduction of DNT and the clinicalimprovement of the patient.(AU)

Performance of first-trimester combined screening for preterm pre-eclampsia: findings from cohort of 10 110 pregnancies in Spain.

OBJECTIVE: To evaluate the diagnostic accuracy of the Fetal Medicine Foundation (FMF) competing-risks model, incorporating maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and placental growth factor (PlGF) (the 'triple test'), for the prediction at 11-13 weeks' gestation of preterm pre-eclampsia (PE) in a Spanish population. METHODS: This was a prospective cohort study performed in eight fetal medicine units in five different regions of Spain between September 2017 and December 2019. All pregnant women with a singleton pregnancy and a non-malformed live fetus attending a routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation were invited to participate. Maternal demographic characteristics and medical history were recorded and MAP, UtA-PI, serum PlGF and pregnancy-associated plasma protein-A (PAPP-A) were measured following standardized protocols. Treatment with aspirin during pregnancy was also recorded. Raw values of biomarkers were converted into multiples of the median (MoM), and audits were performed periodically to provide regular feedback to operators and laboratories. Patient-specific risks for term and preterm PE were calculated according to the FMF competing-risks model, blinded to pregnancy outcome. The performance of screening for PE, taking into account aspirin use, was assessed by calculating the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed screen-positive rate (SPR). Risk calibration of the model was assessed. RESULTS: The study population comprised 10 110 singleton pregnancies, including 72 (0.7%) that developed preterm PE. In the preterm PE group, compared to those without PE, median MAP MoM and UtA-PI MoM were significantly higher, and median serum PlGF MoM and PAPP-A MoM were significantly lower. In women with PE, the deviation from normal in all biomarkers was inversely related to gestational age at delivery. Screening for preterm PE by a combination of maternal characteristics and medical history with MAP, UtA-PI and PlGF had a DR, at 10% SPR, of 72.7% (95% CI, 62.9-82.6%). An alternative strategy of replacing PlGF with PAPP-A in the triple test was associated with poorer screening performance for preterm PE, giving a DR of 66.5% (95% CI, 55.8-77.2%). The calibration plot showed good agreement between predicted risk and observed incidence of preterm PE, with a slope of 0.983 (95% CI, 0.846-1.120) and an intercept of 0.154 (95% CI, -0.091 to 0.397). CONCLUSIONS: The FMF model is effective in predicting preterm PE in the Spanish population at 11-13 weeks' gestation. This method of screening is feasible to implement in routine clinical practice, but it should be accompanied by a robust audit and monitoring system, in order to maintain high-quality screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.