Effect of plasma exchange with albumin replacement on albumin functionality and organ dysfunction in acute-on-chronic liver failure.

Background & Aims: Effective treatments for acute-on-chronic liver failure (ACLF) are a major unmet need. This proof-of-concept pilot study was aimed at evaluating the effects of plasma exchange (PE) with albumin 5% (PE-A5%) on albumin functional capacity and organ dysfunction in patients with ACLF. Methods: Ten adult patients were enrolled in a single-center phase II, prospective, open-label, non-controlled study. Six PE-A5% sessions were performed in 10 days followed by a 1-month follow-up visit. Albumin functional capacity and circulatory function were assessed, as were renal, cerebral, and liver function, and systemic inflammation. The main safety variable was the percentage of PE sessions associated with at least one procedure-related adverse event (AE). Results: Patients with ACLF showed lower albumin binding capacity, lower antioxidant capacity, and lower levels of albumin with preserved structure compared to healthy donors (n = 19). From baseline to day 11, PE-A5% treatment increased albumin levels and improved albumin binding capacity to Sudlow site II (15.3±1.6 mg/ml to 18.9±1.7 mg/ml; p = 0.003), fatty acid-binding capacity (8.2±1.4 µM to 3.1±1.5 µM; p = 0.013) and antioxidant capacity (human mercaptalbumin 9.5±1.5 mg/ml to 14.6±1.6 mg/ml; p = 0.001). Native albumin levels were increased throughout day 1-11 PE-A5% sessions (6.5±1.0 mg/ml to 10.2±1.4 mg/ml; p = 0.035). PE-A5% improved systemic hemodynamics (mean arterial pressure, heart rate, cardiac index), renal function (creatinine level, blood urea nitrogen), cerebral function (hepatic encephalopathy grade), liver parameters (transaminases, bilirubin) and inflammatory parameters (C-reactive protein, leukocyte count). All patients had at least one of the 78 AEs reported, mostly mild (product/procedure-related: 36%). Sixteen serious AEs were reported in eight patients (procedure/product-related: none). Conclusions: PE-A5% was a safe procedure associated with positive effects on albumin functionality, and circulatory, renal, cerebral, and liver function in patients with ACLF. Impact and implications: Acute-on-chronic liver failure (ACLF) is a clinical condition characterized by severe systemic inflammation, organ failure, and high mortality. Plasma exchange removes patient's plasma containing pathogenic substances, replacing it with 5% albumin and fresh frozen plasma (PE-A5%). In this study, cirrhotic patients with ACLF were treated with PE-A5%, which was a safe procedure that increased binding and antioxidant capacity of patients' albumin, while improving circulatory, kidney, brain, and liver functions. These beneficial effects could impact survival in ACLF. ClinicalTrialsgov Identifier: NCT01201720. EudraCT number: 2010-021360-15.

EP2 and EP4 blockade prevents tumor-induced suppressive features in human monocytic myeloid-derived suppressor cells.

Tumors educate their environment to prime the occurrence of suppressive cell subsets, which enable tumor evasion and favors tumor progression. Among these, there are the myeloid-derived suppressor cells (MDSCs), their presence being associated with the poor clinical outcome of cancer patients. Tumor-derived prostaglandin E2 (PGE2) is known to mediate MDSC differentiation and the acquisition of pro-tumor features. In myeloid cells, PGE2 signaling is mediated via E-prostanoid receptor type 2 (EP2) and EP4. Although the suppressive role of PGE2 is well established in MDSCs, the role of EP2/4 on human MDSCs or whether EP2/4 modulation can prevent MDSCs suppressive features upon exposure to tumor-derived PGE2 is poorly defined. In this study, using an in vitro model of human monocytic-MDSCs (M-MDSCs) we demonstrate that EP2 and EP4 signaling contribute to the induction of a pro-tumor phenotype and function on M-MDSCs. PGE2 signaling via EP2 and EP4 boosted M-MDSC ability to suppress T and NK cell responses. Combined EP2/4 blockade on M-MDSCs during PGE2 exposure prevented the occurrence of these suppressive features. Additionally, EP2/4 blockade attenuated the suppressive phenotype of M-MDSCs in a 3D coculture with colorectal cancer patient-derived organoids. Together, these results identify the role of tumor-derived PGE2 signaling via EP2 and EP4 in this human M-MDSC model, supporting the therapeutic value of targeting PGE2-EP2/4 axis in M-MDSCs to alleviate immunosuppression and facilitate the development of anti-tumor immunity.

Impact on cerebral hemodynamics of the use of volume guarantee combined with high frequency oscillatory ventilation in a neonatal animal respiratory distress model.

High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. However, the possible impact of this new ventilation technique on cerebral hemodynamics is unknown. To evaluate the cerebral hemodynamics effect of HFOV combined with VG in an experimental animal model of neonatal respiratory distress syndrome (RDS) due to surfactant deficiency compared with HFOV and CMV+VG (control group). Eighteen newborn piglets were randomized, before and after the induction of RDS by bronchoalveolar lavage, into 3 mechanical ventilation groups: CMV, HFOV and HFOV with VG. Changes in cerebral oxygen transport and consumption and cerebral blood flow were analyzed by non-invasive regional cerebral oxygen saturation (CrSO2), jugular venous saturation (SjO2), the calculated cerebral oxygen extraction fraction (COEF), the calculated cerebral fractional tissue oxygen extraction (cFTOE) and direct measurement of carotid artery flow. To analyze the temporal evolution of these variables, a mixed-effects linear regression model was constructed. After randomization, the following statistically significant results were found in every group: a drop in carotid artery flow: at a rate of -1.7 mL/kg/min (95% CI: -2.5 to -0.81; p < 0.001), CrSO2: at a rate of -6.2% (95% CI: -7.9 to -4.4; p < 0.001) and SjO2: at a rate of -20% (95% CI: -26 to -15; p < 0.001), accompanied by an increase in COEF: at a rate of 20% (95% CI: 15 to 26; p < 0.001) and cFTOE: at a rate of 0.07 (95% CI: 0.05 to 0.08; p < 0.001) in all groups. No statistically significant differences were found between the HFOV groups. CONCLUSION: No differences were observed at cerebral hemodynamic between respiratory assistance in HFOV with and without VG, being the latter ventilatory strategy equally safe. WHAT IS KNOWN: • Preterm have a situation of fragility of cerebral perfusion wich means that any mechanical ventilation strategy can have a significant influence. High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. Several studies have compared CMV and HFOV and their effects at hemodynamic level. It is known that the use of high mean airway pressure in HFOV can cause an increase in pulmonary vascular resistance with a decrease in thoracic venous return. WHAT IS NEW: • The possible impact of VAFO + VG on cerebral hemodynamics is unknown. Due the lack of studies and the existing controversy, we have carried out this research project in an experimental animal model with the aim of evaluating the cerebral hemodynamic repercussion of the use of VG in HFOV compared to the classic strategy without VG.

Natural variation of immune epitopes reveals intrabacterial antagonism.

Plants and animals detect biomolecules termed Microbe-Associated Molecular Patterns (MAMPs) and induce immunity. Agricultural production is severely impacted by pathogens which can be controlled by transferring immune receptors. However, most studies use a single MAMP epitope and the impact of diverse multi-copy MAMPs on immune induction is unknown. Here we characterized the epitope landscape from five proteinaceous MAMPs across 4,228 plant-associated bacterial genomes. Despite the diversity sampled, natural variation was constrained and experimentally testable. Immune perception in both Arabidopsis and tomato depended on both epitope sequence and copy number variation. For example, Elongation Factor Tu is predominantly single copy and 92% of its epitopes are immunogenic. Conversely, 99.9% of bacterial genomes contain multiple Cold Shock Proteins and 46% carry a non-immunogenic form. We uncovered a new mechanism for immune evasion, intrabacterial antagonism, where a non-immunogenic Cold Shock Protein blocks perception of immunogenic forms encoded in the same genome. These data will lay the foundation for immune receptor deployment and engineering based on natural variation.

The Fundamental Role of Oxime and Oxime Ether Moieties in Improving the Physicochemical and Anticancer Properties of Structurally Diverse Scaffolds.

The present review explores the critical role of oxime and oxime ether moieties in enhancing the physicochemical and anticancer properties of structurally diverse molecular frameworks. Specific examples are carefully selected to illustrate the distinct contributions of these functional groups to general strategies for molecular design, modulation of biological activities, computational modeling, and structure-activity relationship studies. An extensive literature search was conducted across three databases, including PubMed, Google Scholar, and Scifinder, enabling us to create one of the most comprehensive overviews of how oximes and oxime ethers impact antitumor activities within a wide range of structural frameworks. This search focused on various combinations of keywords or their synonyms, related to the anticancer activity of oximes and oxime ethers, structure-activity relationships, mechanism of action, as well as molecular dynamics and docking studies. Each article was evaluated based on its scientific merit and the depth of the study, resulting in 268 cited references and more than 336 illustrative chemical structures carefully selected to support this analysis. As many previous reviews focus on one subclass of this extensive family of compounds, this report represents one of the rare and fully comprehensive assessments of the anticancer potential of this group of molecules across diverse molecular scaffolds.

Randomized trial to assess the efficacy and safety of xyloglucan for the treatment of acute gastroenteritis in children.

Acute gastroenteritis is one of the most common diseases in children and an important cause of morbidity and mortality worldwide. No specific treatment is available; therefore, management is exclusively symptomatic. Xyloglucan has been approved in Europe as a class IIa medical device for restoration of the physiological functions of the intestinal wall. Our objective was to assess efficacy and safety of xyloglucan for the treatment of acute gastroenteritis in children. We performed a triple-blind, randomized placebo-controlled clinical trial in four primary care centers and one continued care hospital center. The study population comprised children with acute gastroenteritis aged >3 months and <5 years. Our primary endpoint was time (in hours) of resolution of diarrhea, defined as the time to resolution of stool consistency (Bristol Stool Form Scale ≤5 or Amsterdam Stool Form Scale B or C) or time until deposition frequency resumes to normality, whichever occurred first. We also recorded intravenous rehydration, hospitalization, stools per day, Vesikari scale, vomiting, relapse, weight loss, drugs prescribed, and adverse events. Eighty children were included in the intention-to-treat population (43 xyloglucan and 37 placebo) and 74 (93%) in the per-protocol population. Time to resolution of diarrhea was similar in both groups with (median, 95% CI) 24, 17-24 h in the xyloglucan group versus 24, 19-24 h in the placebo group, p = .680. Significant differences were observed for patients with moderate-to-severe diarrhea (Vesikari scale ≥9): xyloglucan group (20 [15-24] h) versus placebo group (85 [51-120] h) (p = .04). No other significant differences were found. Xyloglucan can be considered safe and other studies should be performed to confirm the usefulness in patients with moderate-to-severe diarrhea.

Preliminary data from a 4-year mirror-image and multicentre study of patients initiating paliperidone palmitate 6-monthly long-acting injectable antipsychotic: the Paliperidone 2 per Year study.

Background: Paliperidone palmitate 6-monthly (PP6M) is the first long-acting antipsychotic injectable (LAI) to allow for only two medication administrations per year, though there is presently limited insight into its effectiveness and potential added value in real clinical practice conditions. Objectives: To present our ongoing study and draw its preliminary data on patient characteristics initiating PP6M and adherence during the first year of treatment. Methods: The paliperidone 2 per year (P2Y) study is a 4-year, multicentre, prospective mirror-image pragmatic study taking place at over 20 different sites in Europe. The mirror period covers 2 years either side of the PP6M LAI initiation. Retrospective data for the previous 2 years are collected for each patient from the electronic health records. Prospective data are recorded at baseline, 6, 12, 18 and 24 months of drug administration and also cover information on concomitant psychiatric medication, relapses, hospital admissions, side effects, discontinuation and its reasons. Meanwhile, here we present preliminary data from the P2Y study at basal and 6-month period (first and second PP6M administration). Results: At the point of PP6M initiation, the most frequent diagnosis was schizophrenia (69%), the clinical global impression scale mean score was 3.5 (moderately markedly ill) and the rate of previous hospital admissions per patient and year was 0.21. PP6M was initiated after a median of 3-4 years on previous treatment: 146 (73%) from paliperidone palmitate 3-monthly, 37 (19%) from paliperidone palmitate 1-monthly and 17 (9%) from other antipsychotics. The mean dose of the first PP6M was 1098.9 mg. The retention rate at 6 months and 1 year of treatment on PP6M in our cohort was 94%. Conclusion: Patient and clinician preference for LAIs with longer dosing intervals was the main reason for PP6M initiation/switching resulting in high treatment persistence. Future data are needed to evaluate the full impact of PP6M in clinical practice.

Planktonic and biofilm states of Staphylococcus aureus isolated from bone and joint infections and the in vitro effect of orally available antibiotics.

AIMS: To demonstrate the in vitro activity of orally available antibiotics against Staphylococcus aureus isolated from bone or orthopedic implant materials. The biofilm eradication of the combination of three antibiotics was also assessed. METHODS AND RESULTS: Clinical isolates from orthopedic infection samples were collected, and S. aureus isolates were classified according to their biofilm production and composition. Almost all S. aureus isolates (n = 36, 97.3%) produced biofilm and the major biofilm components were polysaccharides. Antimicrobial susceptibility was determined in planktonic (minimal inhibitory concentration; MIC) and biofilm cells (minimal biofilm eradication concentration; MBEC) using the MBEC Calgary Device. Overall, the MBEC ranged higher than the MIC. When combined at borderline-susceptible concentrations, moxifloxacin-rifampin and doxycycline-rifampin were both able to eradicate biofilms in a third of the strains whereas the doxycycline-moxifloxacin combination proved ineffective at eradicating biofilm, inhibiting it only in three strains. CONCLUSIONS: We propose rifampin in combination with moxifloxacin or doxycycline for the design of clinical trials of bone and/or orthopedic device infection without proper debridement or material retention.

Real-World Persistence and Treatment Patterns in Patients with Psoriatic Arthritis Treated with Anti-IL17 Therapy in Spain: The PerfIL-17 Study.

INTRODUCTION: Given the growing interest and use of interleukin-17 inhibitors (anti-IL17) for the treatment of psoriatic arthritis (PsA), an observational study has been conducted to characterize the patient profile, treatment patterns, and persistence of ixekizumab or secukinumab in patients with PsA receiving them as first anti-IL17. METHODS: This is a multicenter retrospective study, conducted at eight Spanish hospitals where data from adult patients with PsA were collected from electronic medical records. Three cohorts of patients, initiating treatment with an anti-IL17 [secukinumab 150 mg (SECU150), secukinumab 300 mg (SECU300), or ixekizumab (IXE)] between January 2019 and March 2021, were included. Demographic and clinical patient characteristics, treatment patterns, and persistence were analyzed descriptively. Continuous data were presented as mean [standard deviation (SD)] and categorical variables as frequencies with percentages. Persistence rates at 3, 6, and 12 months were calculated. RESULTS: A total of 221 patients with PsA were included in the study [SECU150, 103 (46.6%); SECU300, 38 (17.2%); and IXE, 80 (36.2%)]. Treatment patterns differed by clinical characteristics: SECU150 was initiated more frequently in patients with moderate PsA and less peripheral joint involvement, while patients on SECU300 included those with a higher rate of enthesitis and active skin psoriasis, and patients on IXE showed a longer time since PsA diagnosis, more frequent comorbidities, joint involvement, and diagnosed skin psoriasis. Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) were previously administered in 88.2% of patients and biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) were administered in 72.9%. The mean number of previous b/tsDMARDs was 2.4 (SD 1.5) in the IXE cohort, 1.7 (SD 0.9) in the SECU300 cohort, and 1.6 (SD 1.0) for those in the SECU150 cohort. The global persistence on all anti-IL17 was 97.2%, 88.4%, and 81.0% at 3, 6, and 12 months, respectively. The most frequent reason for discontinuation across the three cohorts was lack of effectiveness (16.7%; 37/221). CONCLUSIONS: Most of the patients with PsA treated with anti-IL17 in Spain had moderate to severe disease activity, high peripheral joint and skin involvement, and had received previous b/tsDMARDs. More than 80% of patients with a 1-year follow-up persisted on anti-IL17, with the highest rate observed in the IXE cohort, followed by the SECU150 then SECU300 cohorts.

Osteomielitis primaria de esternón / Primary sternal osteomyelitis

La osteomielitis primaria de esternón es muy infrecuente en niños, con menos de 100 casos publicados hasta la actualidad. Su presentación clínica es a menudo inespecífica, lo que causa un retraso en el diagnóstico. Se presentan dos nuevos casos de osteomielitis primaria de esternón. Ambos referían un cuadro de fiebre, malestar general, dolor torácico y rechazo del decúbito, con eritema preesternal en uno de los casos. La velocidad de sedimentación globular y la proteína C-reactiva estaban elevadas en ambos casos. El diagnóstico se confirmó mediante estudios de imagen y en un caso se aisló Staphylococcus aureus sensible a meticilina en el hemocultivo. Ambos se recuperaron sin complicaciones con tratamiento antibiótico. Debe tenerse en cuenta la osteomielitis primaria de esternón en el diagnóstico diferencial del dolor torácico, especialmente si se acompaña de fiebre, signos inflamatorios locales, intolerancia al decúbito o elevación de reactantes de fase aguda.

Primary sternal osteomyelitis is very rare in children, with less than 100 cases published to date. Its clinical presentation is often non-specific, which results in a diagnostic delay. Here we describe 2 new cases of primary sternal osteomyelitis. Both referred fever, malaise, chest pain, and refusal to lie down, with pre-sternal erythema in one of the cases. The erythrocyte sedimentation rate and C-reactive protein values were high in both cases. The diagnosis was confirmed by imaging studies; methicillin-sensitive Staphylococcus aureus was isolated in the blood culture of one of them. Both recovered without complications with antibiotic treatment. Primary sternal osteomyelitis should be considered in the differential diagnosis of chest pain, especially if accompanied by fever, local inflammatory signs, intolerance to lying down, or increased acute phase reactants.

Efecto de la duración del decúbito prono en pacientes con SDRA durante la pandemia por SARS-CoV-2 / Effect of duration of prone position in ARDS patients during SARS-CoV-2 pandemic

Objetivo: Describir las características de los pacientes con síndrome de distrés respiratorio agudo por neumonía bilateral por COVID-19 en ventilación mecánica invasiva (VMI) y analizar el efecto del decúbito prono prolongado>24h (DPP) respecto al decúbito prono<24h (DP). Diseño: Estudio observacional retrospectivo descriptivo. Análisis uni y bivariante. Ámbito: Servicio de Medicina Intensiva del Hospital General Universitario de Elche. Participantes: Pacientes con neumonía por SARS-CoV-2 (2020-2021) en VMI por síndrome de distrés respiratorio agudo moderado-severo. Intervenciones: VMI. Maniobras de DP. Variables de interés principales: Sociodemográficas; analgosedación; bloqueo neuromuscular; DP (duración), estancia y mortalidad en UCI, días de VMI; complicaciones no infecciosas; infecciones asociadas a la asistencia sanitaria. Resultados: Cincuenta y un pacientes precisaron DP y de ellos 31 (69,78%) requirieron DPP. No se encontraron diferencias en las características iniciales de los pacientes (sexo, edad, comorbilidades, gravedad inicial, o en el tratamiento antiviral y antiinflamatorio recibido). Los pacientes con DPP presentaron menor tolerancia a la ventilación en decúbito supino (61,29 vs. 89,47%, p=0,031), mayor estancia hospitalaria (41 vs. 30 días, p=0,023), más días de VMI (32 vs. 20 días, p=0,032), mayor duración del tratamiento con bloqueo neuromuscular (10,5 vs. 3 días, p=0,0002), así como un mayor porcentaje de episodios de obstrucción del tubo orotraqueal (48,39 vs. 15%, p=0,014). Conclusiones: El DPP se asoció con mayor uso de recursos y complicaciones en pacientes con síndrome de distrés respiratorio agudo moderado-severo por COVID-19. (AU)

Objective: To describe the characteristics of patients with acute respiratory distress syndrome due to bilateral COVID-19 pneumonia on invasive mechanical ventilation (IMV) and analyze the effect of prolonged prone decubitus>24h (PPD) compared to prone decubitus<24h (PD). Design: Retrospective observational descriptive study. Uni and bivariate analysis. Setting: Department of Intensive Care Medicine. General University Hospital of Elche. Participants: Patients with SARS-CoV-2 pneumonia (2020–2021) in VMI for moderate-severe acute respiratory distress syndrome, ventilated in PD. Interventions: IMV. PD maneuvers. Main variables of interest: Sociodemographic; analgo-sedation; neuromuscular blockade; PD (duration), ICU stay and mortality, days of IMV; non-infectious complications; health care-associated infections. Results: Fifty-one patients required PD and of these 31 (69.78%) required PPD. No differences were found in patient characteristics (sex, age, comorbidities, initial severity, antiviral and anti-inflammatory treatment received). Patients on PPD had lower tolerance to supine ventilation (61.29 vs. 89.47%, p=0.031), longer hospital stay (41 vs. 30 days, p=0.023), more days of IMV (32 vs. 20 days, p=0.032), longer duration of neuromuscular blockade (10.5 vs. 3 days, p=0.0002), as well as a higher percentage of episodes of orotracheal tube obstruction (48.39 vs. 15%, p=0.014). Conclusions: PPD was associated with higher resource use and complications in patients with moderate-severe acute respiratory distress syndrome by COVID-19. (AU)

Understanding plant pathogen interactions using spatial and single-cell technologies.

Plants are in contact with diverse pathogens and microorganisms. Intense investigation over the last 30 years has resulted in the identification of multiple immune receptors in model and crop species as well as signaling overlap in surface-localized and intracellular immune receptors. However, scientists still have a limited understanding of how plants respond to diverse pathogens with spatial and cellular resolution. Recent advancements in single-cell, single-nucleus and spatial technologies can now be applied to plant-pathogen interactions. Here, we outline the current state of these technologies and highlight outstanding biological questions that can be addressed in the future.

Serologic evolution and follow-up to IgG antibodies of infants born to mothers with gestational COVID.

BACKGROUND: It is known that SARS-CoV-2 antibodies from pregnant women with SARS-CoV-2 infection during pregnancy cross the placenta but the duration and the protective effect of these antibodies in infants is scarce. METHODS: This prospective study included mothers with SARS-COV-2 infection during pregnancy and their infants from April 2020 to March 2021. IgG antibodies to SARS-CoV-2 spike protein were performed on women and infants at birth and at two and six months during follow-up. Anthropometrical measures and physical and neurological examinations and a clinical history of symptoms and COVID-19 diagnosis were collected. Simple linear regression was performed to compare categorical and continuous variables. To compare the mother's and infant's antibody titers evolution, a mixed linear regression model was used. A predictive model of newborn antibody titers at birth has been established by means of simple stepwise linear regression. RESULTS: 51 mother-infant couples were included. 45 (90%) of the mothers and 44 (86.3%) of the newborns had a positive serology al birth. These antibodies were progressively decreasing and were positive in 34 (66.7%) and 7 (13.7%) of infants at 2 and 6 months, respectively. IgG titers of newborns at birth were related to mothers' titers, with a positive moderate correlation (Pearson's correlation coefficient: 0.82, p < 0,001). Fetal/maternal antibodies placental transference rate was 1.3 (IQR: 0.7-2.2). The maternal IgG titers at delivery and the type of maternal infection (acute, recent, or past infection) was significantly related with infants' antibody titers at birth. No other epidemiological or clinical factors were related to antibodies titers. Neurodevelopment, psychomotor development, and growth were normal in 94.2% of infants in the third follow-up visit. No infants had a COVID-19 diagnosis during the follow-up period. CONCLUSIONS: Transplacental transfer of maternal antibodies is high in newborns from mothers with recent or past infection at delivery, but these antibodies decrease after the first months of life. Infant's IgG titers were related to maternal IgG titers at delivery. Further studies are needed to learn about the protective role of maternal antibodies in infants.

Microwave-assisted autohydrolysis of avocado seed for the recovery of antioxidant phenolics and glucose.

This study describes the valorization of avocado seed (AS) within a green biorefinery concept using microwave-assisted autohydrolysis. After the treatment at temperatures of 150-230 °C for 5 min, the resulting solid and liquor were characterized. The temperature of 220 °C led to the simultaneous optimal values of antioxidant phenolics/flavonoids (42.15 mg GAE/g AS, 31.89 RE/g AS, respectively) and glucose + glucooligosaccharides (38.82 g/L) in the liquor. Extraction with ethyl acetate allowed the recovery of the bioactive compounds while maintaining the polysaccharides in the liquor. The extract was rich in vanillin (99.02 mg/g AS) and contained several phenolic acids and flavonoids. The solid phase and the phenolic-free liquor were subjected to enzymatic hydrolysis to produce glucose, reaching values of 9.93 and 105 g glucose/L, respectively. This work demonstrates that microwave-assisted autohydrolysis is a promising technology to obtain fermentable sugars and antioxidant phenolic compounds from avocado seeds following a biorefinery scheme.

[Effect of duration of prone position in ARDS patients during SARS-CoV-2 pandemic]. / Efecto de la duración del decúbito prono en pacientes con SDRA durante la pandemia por SARS-CoV-2.

Objective: To describe the characteristics of patients with acute respiratory distress syndrome due to bilateral COVID-19 pneumonia on invasive mechanical ventilation (IMV) and analyze the effect of prolonged prone decubitus > 24 h (PPD) compared to prone decubitus < 24 h (PD). Design: Retrospective observational descriptive study. Uni and bivariate analysis. Setting: Department of Intensive Care Medicine. General University Hospital of Elche. Participants: Patients with SARS-CoV-2 pneumonia (2020-2021) in VMI for moderate-severe acute respiratory distress syndrome, ventilated in PD. Interventions: IMV. PD maneuvers. Main variables of interest: Sociodemographic; analgo-sedation; neuromuscular blockade; PD (duration), ICU stay and mortality, days of IMV; non-infectious complications; health care-associated infections. Results: Fifty-one patients required PD and of these 31 (69.78%) required PPD. No differences were found in patient characteristics (sex, age, comorbidities, initial severity, antiviral and anti-inflammatory treatment received). Patients on PPD had lower tolerance to supine ventilation (61.29 vs. 89.47%, p = 0.031), longer hospital stay (41 vs. 30 days, p = 0.023), more days of IMV (32 vs. 20 days, p = 0.032), longer duration of neuromuscular blockade (10.5 vs. 3 days, p = 0.0002), as well as a higher percentage of episodes of orotracheal tube obstruction (48.39 vs. 15%, p = 0.014). Conclusions: PPD was associated with higher resource use and complications in patients with moderate-severe acute respiratory distress syndrome by COVID-19.

Effect of the duration of prone position in ARDS patients during the SARS-CoV-2 pandemic.

OBJECTIVE: To describe the characteristics of patients with acute respiratory distress syndrome (ARDS) due to bilateral COVID-19 pneumonia on invasive mechanical ventilation (IMV), and to analyze the effect of prone position >24 h (prolonged) (PPP) compared to prone decubitus <24 h (PP). DESIGN: A retrospective observational descriptive study was carried out, with uni- and bivariate analyses. SETTING: Department of Intensive Care Medicine. Hospital General Universitario de Elche (Elche, Alicante, Spain). PARTICIPANTS: Patients with SARS-CoV-2 pneumonia (2020-2021) on IMV due to moderate-severe ARDS, ventilated in prone position (PP). INTERVENTIONS: IMV. PP maneuvers. MAIN VARIABLES OF INTEREST: Sociodemographic characteristics, analgo-sedation, neuromuscular blockade (NMB), PD duration, ICU stay and mortality, days of IMV, non-infectious complications, healthcare associated infections. RESULTS: Fifty-one patients required PP, and of these, 31 (69.78%) required PPP. No differences were observed in terms of patient characteristics (gender, age, comorbidities, initial severity, antiviral and antiinflammatory treatment received). Patients on PPP had poorer tolerance to supine ventilation (61.29% vs 89.47%, p = 0.031), longer hospital stay (41 vs 30 days, p = 0.023), more days of IMV (32 vs 20 days, p = 0.032), longer duration of NMB (10.5 vs 3 days, p = 0.0002), as well as a higher percentage of episodes of orotracheal tube obstruction (48.39% vs 15%, p = 0.014). CONCLUSIONS: PPP was associated with greater resource use and complications in patients with moderate-severe ARDS due to COVID-19.

TP53-mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease.

Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP) are associated with an increased risk of hematologic malignancy, coronary artery disease, and all-cause mortality. Here we analyze the relation between CHIP status and incident peripheral artery disease (PAD) and atherosclerosis, using whole-exome sequencing and clinical data from the UK Biobank and Mass General Brigham Biobank. CHIP associated with incident PAD and atherosclerotic disease across multiple beds, with increased risk among individuals with CHIP driven by mutation in DNA Damage Repair (DDR) genes such as TP53 and PPM1D. To model the effects of DDR-induced CHIP on atherosclerosis, we used a competitive bone marrow transplantation strategy, and generated atherosclerosis-prone Ldlr-/- chimeric mice carrying 20% p53-deficient hematopoietic cells. The chimeric mice were analyzed 13-weeks post-grafting and showed increased aortic plaque size and accumulation of macrophages within the plaque, driven by increased proliferation of p53-deficient plaque macrophages. In summary, our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system beyond the coronary arteries, and provide genetic and experimental support for a direct causal contribution of TP53-mutant CHIP to atherosclerosis.

A New Functional Food Ingredient Obtained from Aloe ferox by Spray Drying.

Aloe mucilages of Aloe ferox (A. ferox) and Aloe vera (A. vera) were spray-dried (SD) at 150, 160 and 170 °C. Polysaccharide composition, total phenolic compounds (TPC), antioxidant capacity and functional properties (FP) were determined. A. ferox polysaccharides were comprised mainly of mannose, accounting for >70% of SD aloe mucilages; similar results were observed for A. vera. Further, an acetylated mannan with a degree of acetylation >90% was detected in A. ferox by 1H NMR and FTIR. SD increased the TPC as well as the antioxidant capacity of A. ferox measured by both ABTS and DPPH methods, in particular by ~30%, ~28% and ~35%, respectively, whereas in A. vera, the antioxidant capacity measured by ABTS was reduced (>20%) as a consequence of SD. Further, FP, such as swelling, increased around 25% when A. ferox was spray-dried at 160 °C, while water retention and fat adsorption capacities exhibited lower values when the drying temperature increased. The occurrence of an acetylated mannan with a high degree of acetylation, together with the enhanced antioxidant capacity, suggests that SD A. ferox could be a valuable alternative raw material for the development of new functional food ingredients based on Aloe plants.

Association of the Interleukin 1B-31*C Proinflammatory Allele with the Severity of COVID-19 Patients: A Preliminary Report.

Individuals with no known comorbidities or risk factors may develop severe coronavirus disease 2019 (COVID-19). The present study assessed the effect of certain host polymorphisms and viral lineage on the severity of COVID-19 among hospitalized patients with no known comorbidities in Mexico. The analysis included 117 unrelated hospitalized patients with COVID-19. Patients were stratified by whether they required intensive care unit (ICU) admission: the ICU group (n = 40) and non-ICU group (n = 77). COVID-19 was diagnosed on the basis of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) assay and clinical and radiographic criteria. The presence of the IL1B-31 (T/C) polymorphism was determined for all patients using PCR and nucleotide sequencing. Genotyping of the IL-4 (-590, T/C) and IL-8 (-251, T/A) polymorphisms was performed by the amplification refractory mutation system-PCR method. Genotyping of IL1-RN was performed using PCR. Viral genome sequencing was performed using the ARTIC Network amplicon sequencing protocol using a MinION. Logistic regression analysis identified the carriage of IL-1 B*-31 *C as an independent potential risk factor (odds ratio [OR] = 3.1736, 95% confidence interval [CI] = 1.0748-9.3705, p = 0.0366) for ICU admission and the presence of IL-RN*2 as a protective factor (OR = 0.4371, 95% CI = 0.1935-0.9871, p = 0.0465) against ICU admission. Under the codominant model, the CC genotype of IL1B-31 significantly increased the risk of ICU admission (OR: 6.38, 95% CI: 11.57-25.86, p < 0.024). The IL1B-31 *C-IL-4-590 *T haplotype increased the risk of ICU admission (OR = 2.53, 95% CI = 1.02-6.25, p = 0.047). The 42 SARS-CoV-2 genomes sequenced belonged to four clades, 20A-20D. No association was detected between SARS-CoV-2 clades and ICU admission or death. Thus, in patients with no known comorbidities or risk factors, the IL1B-31*C proinflammatory allele was observed to be associated with the risk of ICU admission owing to COVID-19.