Modulatory actions of Echinococcus granulosus antigen B on macrophage inflammatory activation.

Cestodes use own lipid-binding proteins to capture and transport hydrophobic ligands, including lipids that they cannot synthesise as fatty acids and cholesterol. In E. granulosus s.l., one of these lipoproteins is antigen B (EgAgB), codified by a multigenic and polymorphic family that gives rise to five gene products (EgAgB8/1-5 subunits) assembled as a 230 kDa macromolecule. EgAgB has a diagnostic value for cystic echinococcosis, but its putative role in the immunobiology of this infection is still poorly understood. Accumulating research suggests that EgAgB has immunomodulatory properties, but previous studies employed denatured antigen preparations that might exert different effects than the native form, thereby limiting data interpretation. This work analysed the modulatory actions on macrophages of native EgAgB (nEgAgB) and the recombinant form of EgAg8/1, which is the most abundant subunit in the larva and was expressed in insect S2 cells (rEgAgB8/1). Both EgAgB preparations were purified to homogeneity by immunoaffinity chromatography using a novel nanobody anti-EgAgB8/1. nEgAgB and rEgAgB8/1 exhibited differences in size and lipid composition. The rEgAgB8/1 generates mildly larger lipoproteins with a less diverse lipid composition than nEgAgB. Assays using human and murine macrophages showed that both nEgAgB and rEgAgB8/1 interfered with in vitro LPS-driven macrophage activation, decreasing cytokine (IL-1ß, IL-6, IL-12p40, IFN-ß) secretion and ·NO generation. Furthermore, nEgAgB and rEgAgB8/1 modulated in vivo LPS-induced cytokine production (IL-6, IL-10) and activation of large (measured as MHC-II level) and small (measured as CD86 and CD40 levels) macrophages in the peritoneum, although rEgAgB8/1 effects were less robust. Overall, this work reinforced the notion that EgAgB is an immunomodulatory component of E. granulosus s.l. Although nEgAgB lipid's effects cannot be ruled out, our data suggest that the EgAgB8/1 subunit contributes to EgAgB´s ability to regulate the inflammatory activation of macrophages.

Thermodynamic Study of Alkylsilane and Alkylsiloxane-Based Ionic Liquids.

The thermodynamic properties of ionic liquids (ILs) bearing alkylsilane and alkylsiloxane chains, as well as their carbon-based analogs, were investigated. Effects such as the replacement of carbon atoms by silicon atoms, the introduction of a siloxane linkage, and the length of the alkylsilane chain were explored. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to study the thermal and phase behavior (glass transition temperature, melting point, enthalpy and entropy of fusion, and thermal stability). Heat capacity was obtained by high-precision drop calorimetry and differential scanning microcalorimetry. The volatility and cohesive energy of these ILs were investigated via the Knudsen effusion method coupled with a quartz crystal microbalance (KEQCM). Gas phase energetics and structure were also studied to obtain the gas phase heat capacity as well as the energy profile associated with the rotation of the IL side chain. The computational study suggested the existence of an intramolecular interaction in the alkylsiloxane-based IL. The obtained glass transition temperatures seem to follow the trend of chain flexibility. An increase of the alkylsilane chain leads to a seemingly linear increase in molar heat capacity. A regular increment of 30 J·K-1·mol-1 in the molar heat capacity was found for the replacement of carbon by silicon in the IL alkyl chain. The alkylsilane series was revealed to be slightly more volatile than its carbon-based analogs. A further increase in volatility was found for the alkylsiloxane-based IL, which is likely related to the decrease of the cohesive energy due to the existence of an intramolecular interaction between the siloxane linkage and the imidazolium headgroup. The use of Si in the IL structure is a suitable way to significantly reduce the IL's viscosity while preserving its large liquid range (low melting point and high thermal stability) and low volatilities.

ECMO for drug-refractory electrical storm without a reversible trigger: a retrospective multicentric observational study.

AIMS: Drug-refractory electrical storm (ES) is a life-threatening medical emergency. We describe the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in drug-refractory ES without a reversible trigger, for which specific guideline recommendations are still lacking. METHODS AND RESULTS: Retrospective observational study in four Iberian centres on the indications, treatment, complications, and outcome of drug-refractory ES not associated with acute coronary syndromes, decompensated heart failure, drug toxicity, electrolyte disturbances, endocrine emergencies, concomitant acute illness with fever, or poor compliance with anti-arrhythmic drugs, requiring VA-ECMO for circulatory support. Thirty-four (6%) out of 552 patients with VA-ECMO for cardiogenic shock were included [71% men; 57 (44-62) years], 65% underwent cardiopulmonary resuscitation before VA-ECMO implantation, and 26% during cannulation. Left ventricular unloading during VA-ECMO was used in 8 (24%) patients: 3 (9%) with intraaortic balloon pump, 3 (9%) with LV vent, and 2 (6%) with Impella. Thirty (88%) had structural heart disease and 8 (24%) had an implantable cardioverter-defibrillator. The drug-refractory ES was mostly due to monomorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) (59%), isolated monomorphic VT (26%), polymorphic VT (9%), or VF (6%). Thirty-one (91%) required deep sedation, 44% overdrive pacing, 36% catheter ablation, and 26% acute autonomic modulation. The main complications were nosocomial infection (47%), bleeding (24%), and limb ischaemia (21%). Eighteen (53%) were weaned from VA-ECMO, and 29% had heart transplantation. Twenty-seven (79%) survived to hospital discharge (48 (33-82) days). Non-survivors were older [62 (58-67) vs. 54 (43-58); P < 0.01] and had a higher first rhythm disorder-to-ECMO interval [0 (0-2) vs. 2 (1-11) days; P = 0.02]. Seven (20%) had rehospitalization during follow-up [29 (12-48) months], with ES recurrence in 6%. CONCLUSIONS: VA-ECMO bridged drug-refractory ES without a reversible trigger with a high success rate. This required prolonged hospital stays and coordination between the ECMO centre, the electrophysiology laboratory, and the heart transplant programme.

Factors influencing the positivity of diagnostic tests for congenital syphilis.

OBJECTIVE: The objective of this study was to analyze the factors that influence the positivity of treponemal and non-treponemal tests in cases of congenital syphilis. METHODS: This cross-sectional and correlational study was carried out from the analysis of the database of Disease and Notification Information System (SINAN, in Portuguese) using the data obtained through the Epidemiological Surveillance Group 29, with 639 notifications of congenital syphilis between 2007 and 2018. The data were analyzed by a descriptive and inferential analysis from logistic regression with a significance level of 5% (p≤0.05). RESULTS: The positivity of the treponemal test was higher by 4.5 times in infants living in rural areas and 19.6 times among those whose mothers obtained the diagnosis of syphilis after birth. The treponemal test showed positivity 3.2 times higher for the variable "having been diagnosed between 2007 and 2015" and 5.5 times higher for the variable "having been diagnosed with maternal syphilis in the postpartum period." CONCLUSION: This study shows that testing during prenatal care is essential for early diagnosis and prevention of syphilis complications.

Neurodegeneration and glial morphological changes are both prevented by TRPM2 inhibition during the progression of a Parkinson's disease mouse model.

Parkinson's disease (PD) is a neurodegenerative disease characterized by dopaminergic neuron death and neuroinflammation. Emerging evidence points to the involvement of the transient receptor potential melastatin 2 (TRPM2) channel in neuron death and glial activation in several neurodegenerative diseases. However, the involvement of TRPM2 in PD and specifically its relation to the neuroinflammation aspect of the disease remains poorly understood. Here, we hypothesized that AG490, a TRPM2 inhibitor, can be used as a treatment in a mouse model of PD. Mice underwent stereotaxic surgery for 6-hydroxydopamine (6-OHDA) administration in the right striatum. Motor behavioral tests (apomorphine, cylinder, and rotarod) were performed on day 3 post-injection to confirm the PD model induction. AG490 was then daily injected i.p. between days 3 to 6 after surgery. On day 6, motor behavior was assessed again. Substantia nigra (SNc) and striatum (CPu) were collected for immunohistochemistry, immunoblotting, and RT-qPCR analysis on day 7. Our results revealed that AG490 post-treatment reduced motor behavior impairment and nigrostriatal neurodegeneration. In addition, the compound prevented TRPM2 upregulation and changes of the Akt/GSK-3ß/caspase-3 signaling pathway. The TRPM2 inhibition also avoids the glial morphology changes observed in the PD group. Remarkably, the morphometrical analysis revealed that the ameboid-shaped microglia, found in 6-OHDA-injected animals, were no longer present in the AG490-treated group. These results indicate that AG490 treatment can reduce dopaminergic neuronal death and suppress neuroinflammation in a PD mouse model. Inhibition of TRPM2 by AG490 could then represent a potential therapeutical strategy to be evaluated for PD treatment.

Exploring altered bovine sperm trajectories by sperm tracking in unconfined conditions.

Mammalian sperm motility is getting more relevant due to rising infertility rates worldwide, generating the need to improve conventional analysis and diagnostic approaches. Nowadays, computer assisted sperm analysis (CASA) technologies represent a popular alternative to manual examination which is generally performed by observing sperm motility in very confined geometries. However, under physiological conditions, sperm describe three-dimensional motility patterns which are not well reconstructed by the limited depth of standard acquisition chambers. Therefore, affordable and more versatile alternatives are needed. Here, a motility analysis in unconfined conditions is proposed. In details, the analysis is characterized by a significant longer duration -with respect to conventional systems- with the aim to observe eventually altered motility patterns. Brightfield acquisition in rectangular glass capillaries captured frozen-thawed bovine spermatozoa which were analyzed by means of a self-written tracking routine and classified in sub-populations, based on their curvilinear velocity. To test the versatility of our approach, cypermethrin -a commonly used pesticides- known to be responsible for changes in sperm motility was employed, assessing its effect at three different time-steps. Experimental results showed that such drug induces an increase in sperm velocity and progressiveness as well as circular pattern formation, likely independent of wall interactions. Moreover, this resulted in a redistribution of sperm with the rapid class declining in number with time, but still showing an overall velocity increase. The flexibility of the approach permits parameter modifications with the experimental needs, allowing us to conduct a comprehensive examination of sperm motility. This adaptability facilitated data acquisition which can be computed at different frame rates, extended time periods, and within deeper observation chambers. The suggested approach for sperm analysis exhibits potential as a valuable augmentation to current diagnostic instruments.

Clinical virtual simulation: predictors of user acceptance in nursing education.

BACKGROUND: Using virtual patients integrated in simulators expands students' training opportunities in healthcare. However, little is known about the usability perceived by students and the factors/determinants that predict the acceptance and use of clinical virtual simulation in nursing education. OBJECTIVES: To identify the factors/determinants that predict the acceptance and use of clinical virtual simulation in learning in nursing education. METHODS: Observational, cross-sectional, analytical study of the use of clinical virtual simulation in nursing to answer the research question: What factors/determinants predict the acceptance and use of a clinical virtual simulator in nursing education? We used a non-probabilistic sampling, more specifically a convenience sample of nursing degree students. The data were collected through a questionnaire adapted from the Technology Acceptance Model 3. In technology and education, the Technology Acceptance Model is a theoretical model that predicts the acceptance of the use of technology by users. RESULTS: The sample comprised 619 nursing students, who revealed mean values of perceived usefulness (M = 5.34; SD = 1.19), ease of use (M = 4.74; SD = 1.07), and intention to use the CVS (M = 5.21; SD = 1.18), in a Likert scale of seven points (1-the worst and 7 the best possible opinion). This study validated the use of Technology Acceptance Model 3 adapted and tested the related hypotheses, showing that the model explains 62% of perceived utility, 32% of ease of use, and 54% of intention to use the clinical virtual simulation in nursing by nursing students. The adequacy of the model was tested by analysis of the direct effects of the relationships between the internal constructs (PU-BI, ß = 0.11, p = 0.012; PEOU-BI, ß = -0.11, p = 0.002) and the direct relations between some of the constructs internal to the Technology Acceptance Model 3 and the external determinants Relevance for learning and Enjoyability. In the proposed model, the external constructs that best predicted perceived usefulness, ease of use, and behaviour intention to use the clinical virtual simulation in nursing were Relevance for learning and Enjoyability. CONCLUSIONS: These study results allowed us to identify relevance for learning and enjoyability as the main factors/determinants that predict the acceptance and use of clinical virtual simulation in learning in nursing.

The Cardiometabolic Impact of Rebaudioside A Exposure during the Reproductive Stage.

The consumption of non-sugar sweeteners (NSS) has increased during pregnancy. The European Food Safety Agency suggested that steviol glycosides, such as Rebaudioside A (RebA), the major sweetener component of stevia, are safe for humans up to a dose of 4 mg/kg body weight/day. However, the World Health Organization recommended in 2023 the restraint of using NSS, including stevia, at any life stage, highlighting the need to study NSS safety in early periods of development. We aimed to study the mitochondrial and cardiometabolic effects of long-term RebA consumption during the reproductive stage of the life cycle. Female rats were exposed to RebA (4 mg steviol equivalents/kg body weight/day) in the drinking water from 4 weeks before mating until weaning. Morphometry, food and water consumption, glucose and lipid homeostasis, heart structure, function, and mitochondrial function were assessed. RebA showed an atrophic effect in the heart, decreasing cardiomyocyte cross-sectional area and myocardial fibrosis without repercussions on cardiac function. Mitochondrial and myofilamentary functions were not altered. Glucose tolerance and insulin sensitivity were not affected, but fasting glycemia and total plasma cholesterol decreased. This work suggests that this RebA dose is safe for female consumption during the reproductive stage, from a cardiometabolic perspective. However, studies on the effects of RebA exposure on the offspring are mandatory.

Optimization of Platelet-Rich Plasma Preparation for Regenerative Medicine: Comparison of Different Anticoagulants and Resuspension Media.

Platelet-rich plasma (PRP) has emerged as a promising therapy in regenerative medicine. However, the lack of standardization in PRP preparation protocols presents a challenge in achieving reproducible and accurate results. This study aimed to optimize the PRP preparation protocol by investigating the impact of two different anticoagulants, sodium citrate (SC) and ethylenediaminetetraacetic acid (EDTA), and resuspension media, plasma versus sodium chloride (NaCl). Platelet recovery rates were calculated and compared between groups, in addition to platelet activity and vascular endothelial growth factor (VEGF) released into plasma after PRP activation. The platelet recovery rate was higher with EDTA in comparison to SC (51.04% vs. 29.85%, p = 0.005). Platelet activity was also higher, with a higher expression of two platelet antibodies, platelet surface P-Selectin (CD62p) and PAC-1, in the EDTA group. The concentration of VEGF was higher with SC in comparison to EDTA (628.73 vs. 265.44 pg/mL, p = 0.013). Platelet recovery rates and VEGF levels were higher in PRP resuspended in plasma when compared to NaCl (61.60% vs. 48.61%, p = 0.011 and 363.32 vs. 159.83 pg/mL, p = 0.005, respectively). Our study reinforces the superiority of EDTA (as anticoagulant) and plasma (for resuspension) in obtaining a higher platelet recovery and preserving platelet functionality during PRP preparation.

Colonisation of hospital surfaces from low- and middle-income countries by extended spectrum ß-lactamase- and carbapenemase-producing bacteria.

Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum ß-lactamases (blaCTX-M-15) and carbapenemases (blaNDM, blaOXA-48-like and blaKPC), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae, Enterobacter hormaechei, Acinetobacter baumannii, Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines.

Comparison of home-based rehabilitation and a centre-based exercise in terms of functional capacity, muscle oxygenation and quality of life in people with peripheral arterial disease: a protocol for a randomised controlled trial.

INTRODUCTION: Peripheral arterial disease (PAD) is increasingly prevalent, and supervised physical exercise programmes are recommended as the first-line treatment. However, these programmes are underused. Alternative delivery models may be able to expand treatment coverage. The objective of this study was to compare a home-based exercise programme (HBEP) and a centre-based exercise (CBE) in terms of their effects on functional capacity, peripheral muscle oxygenation and quality of life in individuals with PAD. METHODS AND ANALYSIS: This single-blind, parallel randomised clinical trial will consist of two groups: HBEP and CBE. A qualitative analysis will be carried out to investigate acceptability and satisfaction. The primary outcome will be functional capacity, assessed by the incremental shuttle walk test. Secondary outcomes will include functional capacity, assessed by a treadmill walking test; peripheral muscle oxygenation and quality of life; and self-reported functional impairment, risk factors, morbidity, level of physical activity, adherence, acceptability and satisfaction. The intervention protocols will consist of 12 weeks of intermittent walking until claudication symptoms, three times a week. Participants randomly assigned to the CBE group will participate in supervised face-to-face sessions. The HBEP group will perform exercises at home with remote supervision, monitored by a pedometer and heart rate monitor, and subjective perception of effort during each session will be recorded by participants in a training diary; follow-up will be conducted by telephone calls. Statistical analyses will follow the intention-to-treat principle. Participants allocated to the HBEP group will be interviewed about their experience of remote treatment using a qualitative approach. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the Universidade Federal de Minas Gerais. The results will be disseminated in a peer-reviewed journal and presented at international congresses. This research has the potential to improve the care of people with PAD because if home-based rehabilitation demonstrates effectiveness, it could be considered an alternative or support resource to the usual centre-based treatment models, expanding access, coverage and participation in vascular physiotherapy TRIAL REGISTRATION: https://ensaiosclinicos.gov.br/rg/RBR-97vy9n7 on 14 April 2022.

A Review on Blood Reference Values as a Valuable Marker of Wildlife Welfare in Erinaceus europaeus.

The western-European hedgehog (Erinaceus europaeus), in expanding its range towards human habitats, faces exposure to contaminants and biological agents, potentially leading to diseases associated with hematological and biochemical changes. As bioindicators of environmental pollution and carriers of zoonotic agents, hedgehogs play a crucial role in One Health studies, emphasizing the need for a comprehensive understanding of their clinical-pathological aspects. Exploring the blood reference values in healthy animals of this species is crucial for understanding and improving their well-being, and identifying possible diseases/pathogens that may affect its conservation and/or impact human health. This review is focused on analyzing the data available in the literature for Erinaceus europaeus blood reference intervals. A comprehensive literature review of the studies published in Europe is performed, highlighting their specificities, and emphasizing the need for continuous research in this field. Our final goal is to provide a crucial tool for assessing the health status of the species, and underscoring the significance of research in this specific domain.

Enhanced Antimalarial Activity of Extracts of Artemisia annua L. Achieved with Aqueous Solutions of Salicylate Salts and Ionic Liquids.

Artemisinin, a drug used to treat malaria, can be chemically synthesized or extracted from Artemisia annua L. However, the extraction method for artemisinin from biomass needs to be more sustainable while maintaining or enhancing its bioactivity. This work investigates the use of aqueous solutions of salts and ionic liquids with hydrotropic properties as alternative solvents for artemisinin extraction from Artemisia annua L. Among the investigated solvents, aqueous solutions of cholinium salicylate and sodium salicylate were found to be the most promising. To optimize the extraction process, a response surface method was further applied, in which the extraction time, hydrotrope concentration, and temperature were optimized. The optimized conditions resulted in extraction yields of up to 6.50 and 6.44 mg·g-1, obtained with aqueous solutions of sodium salicylate and cholinium salicylate, respectively. The extracts obtained were tested for their antimalarial activity, showing a higher efficacy against the Plasmodium falciparum strain compared with pure (synthetic) artemisinin or extracts obtained with conventional organic solvents. Characterization of the extracts revealed the presence of artemisinin together with other compounds, such as artemitin, chrysosplenol D, arteannuin B, and arteannuin J. These compounds act synergistically with artemisinin and enhance the antimalarial activity of the obtained extracts. Given the growing concern about artemisinin resistance, the results here obtained pave the way for the development of sustainable and biobased antimalarial drugs.

The impact of comorbid psychiatric disorders on chronic obstructive pulmonary disease (COPD) hospitalizations: a nationwide retrospective study.

AIMS: To characterize the register of a secondary diagnosis of mental illnesses in all chronic obstructive pulmonary disease (COPD) hospitalizations registered in Portugal from 2008 to 2015 and explore their impact on hospitalization outcomes. METHODS: A retrospective observational study was conducted. Hospitalizations of patients with at least 40 years old, discharged between 2008 and 2015 with a primary diagnosis of COPD (ICD-9-CM codes 491.x, 492.x and 496) were retrieved from a national administrative database. Comorbid psychiatric diagnoses were identified and defined by the HCUP Clinical Classification Software (CCS) category codes 650-670 (excluding 662). Length of hospital stay (LoS), admission type, in-hospital mortality, and estimated hospital charges were analyzed according to psychiatric diagnostic categories using sex and age-adjusted models. RESULTS: Of 66,661 COPD hospitalizations, 25,869 (38.8%) were episodes with a registered psychiatric comorbidity. These were more likely to correspond to younger inpatients (OR = 2.16, 95%CI 2.09-2.23; p < 0.001), to stay longer at the hospital (aOR = 1.08, 95%CI 1.05-1.12; p < 0.001), to incur in higher estimated hospital charges (aOR = 1.37, 95%CI 1.33-1.42; p < 0.001) and to be urgently admitted (aOR = 1.33, 95%CI 1.23-1.44; p < 0.001). After adjustment for age, in-hospital mortality was lower for episodes with psychiatric diagnoses (aOR = 0.90; 95%CI 0.84-0.96; p < 0.001), except for organic and neurodegenerative diseases category and developmental disorders, intellectual disabilities and disorders usually diagnosed in infancy, childhood, or adolescence category. DISCUSSION: These findings corroborate the additional burden placed by psychiatric disorders on COPD hospitalizations, highlighting the importance of individualizing care to address these comorbidities and minimize their impact on treatment outcomes.

Serum Biochemistry Parameters of the Endangered Miranda's Donkey Breed: Reference Intervals and the Influence of Gender and Age.

Miranda's donkey is an endangered, autochthone breed from Northern Portugal. Understanding the physiological and pathological conditions of Miranda's donkey is crucial for the conservation of the breed. Our study aimed to establish reference intervals (RIs) for blood biochemistry parameters and to evaluate the influence of gender and age on these parameters. Blood samples from 75 clinically healthy animals were analyzed for 21 blood biochemistry parameters using Respons® 920 and Start® 4-Diagnostica-Stago. RIs were calculated according to the ASVCP guidelines, utilizing Reference Advisor software V. 2.1 and the statistical program SPSS version 29 to analyze the effects of gender and age. Significant gender-related differences (p < 0.05) were observed in cholesterol, chlorine, creatinine (CREA), glucose (GLU), sodium, and triglycerides (with higher values in females) and in aspartate aminotransferase, creatine phosphokinase (CK), gamma-glutamyl transferase, potassium, magnesium (Mg), and urea (with higher values in males). Age-related differences (p < 0.05) were noted for alkaline phosphatase, CK, fibrinogen, GLU, and phosphorus (higher in young animals) and for globulin, Mg, and total protein (higher in adults). The RIs described here are invaluable for assessing and monitoring the health status of individual animals and herds. Our study highlights the importance of considering gender and age in the interpretation of biochemical parameters, providing critical insights for the conservation and management of this endangered breed.

Influenza A virus propagation requires the activation of the unfolded protein response and the accumulation of insoluble protein aggregates.

Influenza A virus (IAV) employs multiple strategies to manipulate cellular mechanisms and support proper virion formation and propagation. In this study, we performed a detailed analysis of the interplay between IAV and the host cells' proteostasis throughout the entire infectious cycle. We reveal that IAV infection activates the inositol requiring enzyme 1 (IRE1) branch of the unfolded protein response, and that this activation is important for an efficient infection. We further observed the accumulation of virus-induced insoluble protein aggregates, containing both viral and host proteins, associated with a dysregulation of the host cell RNA metabolism. Our data indicate that this accumulation is important for IAV propagation and favors the final steps of the infection cycle, more specifically the virion assembly. These findings reveal additional mechanisms by which IAV disrupts host proteostasis and uncovers new cellular targets that can be explored for the development of host-directed antiviral strategies.

Maternal serum amino acids and hydroxylated sphingomyelins at pregnancy are associated with anxiety symptoms during pregnancy and throughout the first year after delivery.

BACKGROUND: Studies suggest an interplay between maternal metabolome and mental health. OBJECTIVE: We investigated the association of maternal serum metabolome at pregnancy with anxiety scores during pregnancy and throughout the first year postpartum. METHODS: A prospective cohort of Brazilian women collected 119 serum metabolome at pregnancy (28-38 weeks) and anxiety scores measured by the State-Trait Anxiety Inventory (STAI) at pregnancy (n = 118), 1 (n = 83), 6 (n = 68), and 12 (n = 57) months postpartum. Targeted metabolomics quantified metabolites belonging to amino acids (AA), biogenic amines/amino acid-related compounds, acylcarnitines, lysophosphatidylcholines, diacyl phosphatidylcholines, alkyl:acyl phosphatidylcholines, non-hydroxylated and hydroxylated sphingomyelins [SM(OH)], and hexoses classes. Linear mixed-effect models were used to evaluate the association of metabolites and STAI scores. Hierarchical clustering and principal component analyses were employed to identify clusters and metabolites, which drove their main differences. Multiple comparison-adjusted p-values (q-value) ≤ 0.05 were considered significant. RESULTS: AA (ß = -1.44) and SM(OH) (ß = -1.49) classes showed an association with STAI scores trajectory (q-value = 0.047). Two clusters were identified based on these classes. Women in cluster 2 had decreased AA and SM(OH) concentrations and higher STAI scores (worse symptoms) trajectory (ß = 2.28; p-value = 0.041). Isoleucine, leucine, valine, SM(OH) 22:1, 22:2, and 24:1 drove the main differences between the clusters. LIMITATIONS: The target semiquantitative metabolome analysis and small sample size limited our conclusions. CONCLUSIONS: Our results suggest that AA and SM(OH) during pregnancy play a role in anxiety symptoms throughout the first year postpartum.

BEST-J Score: Validation of a Predicting Model for Delayed Bleeding After Gastric Endoscopic Submucosal Dissection on a European Sample.

BACKGROUND: Delayed bleeding (DB) is a possible adverse event following gastric endoscopic submucosal dissection (ESD). The BEST-J score was created as a risk prediction model for DB following gastric ESD, but is yet to be validated in Western populations. AIMS: We aimed to validate the BEST-J score on a European sample and to perform a subgroup analysis according to histological classification. METHODS: Retrospective study of all consecutive patients undergoing gastric ESD on a European Endoscopic Unit. DB was defined as hemorrhage with clinical symptoms and confirmed by emergency endoscopy from the time of completion to 28 days after ESD. BEST-J score was calculated in each patient and confronted with the outcome (DB). RESULTS: Final sample included 161 patients. From these, 10 (6.2%) presented DB following ESD, with a median time to bleeding of 7 days (IQR 6.8). BEST-J score presented an excellent accuracy predicting DB in our sample, with an AUC = 0.907 (95%CI 0.801-1.000; p < 0.001). Subgroup analysis by histological classification proved that the discriminative power was still excellent for each grade: low-grade dysplasia-AUC = 0.970 (p < 0.001); high-grade dysplasia-AUC = 0.874 (p < 0.001); early gastric cancer-AUC = 0.881 (p < 0.001). The optimal cut-off value to predict DB was a BEST-J score ≥ 3, which matches the cut-off value for high-risk of bleeding in the original investigation. CONCLUSIONS: The BEST-J score still presents excellent accuracy in risk stratification for post-ESD bleeding in European individuals. Thus, this score may help to guide which patients benefit the most from prophylactic therapies following gastric ESD in this setting.