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The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell‐free DNA (cfDNA) methylomes as a potential source of biomarkers for the non‐invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high‐risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway‐specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate‐rich 1 (ERICH1) methylation discriminated high‐risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non‐invasive detection of colorectal serrated lesions.

Abstract Background Cell therapy has emerged as a revolutionary tool to repair damaged tissues by restoration of an adequate vasculature. Dental Pulp stem cells (DPSC), due to their easy biological access, ex vivo properties, and ability to support angiogenesis have been largely explored in regenerative medicine. Methods Here, we tested the capability of Dental Pulp Stem Cell-Conditioned medium (DPSC-CM), produced in normoxic (DPSC-CM Normox) or hypoxic (DPSC-CM Hypox) conditions, to support angiogenesis via their soluble factors. CMs were characterized by a secretome protein array, then used for in vivo and in vitro experiments. In in vivo experiments, DPSC-CMs were associated to an Ultimatrix sponge and injected in nude mice. After excision, Ultimatrix were assayed by immunohistochemistry, electron microscopy and flow cytometry, to evaluate the presence of endothelial, stromal, and immune cells. For in vitro procedures, DPSC-CMs were used on human umbilical-vein endothelial cells (HUVECs), to test their effects on cell adhesion, migration, tube formation, and on their capability to recruit human CD14+ monocytes. Results We found that DPSC-CM Hypox exert stronger pro-angiogenic activities, compared with DPSC-CM Normox, by increasing the frequency of CD31+ endothelial cells, the number of vessels and hemoglobin content in the Ultimatrix sponges. We observed that Utimatrix sponges associated with DPSC-CM Hypox or DPSC-CM Normox shared similar capability to recruit CD45− stromal cells, CD45+ leukocytes, F4/80+ macrophages, CD80+ M1-macrophages and CD206+ M2-macropages. We also observed that DPSC-CM Hypox and DPSC-CM Normox have similar capabilities to support HUVEC adhesion, migration, induction of a pro-angiogenic gene signature and the generation of capillary-like structures, together with the ability to recruit human CD14+ monocytes. Conclusions Our results provide evidence that DPSCs-CM, produced under hypoxic conditions, can be proposed as a tool able to support angiogenesis via macrophage polarization, suggesting its use to overcome the issues and restrictions associated with the use of staminal cells.

Abstract Background The Mendelian Disorders of Cornification (MeDOC) comprise a large number of disorders that present with either localised (palmoplantar keratoderma, PPK) or generalised (ichthyoses) signs. The MeDOC are highly heterogenic in terms of genetics and phenotype. Consequently, diagnostic process is challenging and before implementation of the next generation sequencing, was mostly symptomatic, not causal, which limited research on those diseases. The aim of the study was to genetically characterise a cohort of 265 Polish patients with MeDOC and to get insight into the skin lesions using transcriptome and lipid profile analyses. Results We detected causal variants in 85% (226/265) patients. In addition to the primary gene defect, a pathogenic variant in another gene involved in MeDOC pathology was identified in 23 cases. We found 150 distinct variants in 33 genes, including 32 novel and 16 recurrent (present in > 5 alleles). In 43 alleles large rearrangements were detected, including deletions in the STS, SPINK5, CERS3 and recurrent duplication of exons 10–14 in TGM1. The RNA analysis using samples collected from 18 MeDOC patients and 22 controls identified 1377 differentially expressed genes - DEG. The gene ontology analysis revealed that 114 biological processes were upregulated in the MeDOC group, including i.e. epithelial cell differentiation, lipid metabolic process; homeostasis; regulation of water loss via skin; peptide cross-linking. The DEG between TGM1 and ALOX12B patients, showed that RNA profile is highly similar, though fatty acid profile in epidermal scrapings of those patients showed differences e.g. for the very long chain fatty acids (VLCFAs; FAs ≥ C20), the very long-chain monounsaturated fatty acids (VLC-MUFAs, FAs ≥ C20:1) and the n6 polyunsaturated fatty acids (n6 PUFAs). Conclusion Our results show that NGS-based analysis is an effective MeDOC diagnostic tool. The Polish MeDOC patients are heterogenic, however recurrent variants are present. The novel variants and high number of TGM1 and SPINK5 copy number variations give further insight into molecular pathology of MeDOC. We show that secondary variants in MeDOC-related genes are present in a significant group of patients, which should be further investigated in the context of phenotype modifiers. Finally, we provide novel RNA and lipid data that characterise molecularly MeDOC epidermis.

Abstract Epilepsy, a widespread neural ailment considered by prolonged neuronal depolarization and repetitive discharge, has been linked to extreme stimulus of N-methyl-D-aspartate receptors (NMDARs). Despite the availability of approved anti-seizure medications (ASMs) in many developed nations, approximately 30% of epilepsy patients continue to experience drug-resistant seizures. Thus, a growing interest in discovering natural compounds as potential sources for new medications is growing. Sinapinic acid, a natural derivative of cinnamic acid found in food sources, is known for its neuroprotective properties. This study investigated how sinapinic acid interacts with NMDA receptors and its potential role in providing anticonvulsant effects. Male mice were randomly allocated into nine groups: a control group receiving normal saline (1 ml/kg), groups treated with sinapinic acid at doses of 1, 3, and 10 mg/kg, a group treated with diazepam at 10 mg/kg, a group treated with an NMDA agonist at 75 mg/kg, a group treated with an NMDA antagonist at 0.5 mg/kg, a group receiving the ineffective dose of sinapinic acid (1 mg/kg) along with the NMDA antagonist, and a group receiving the effective dose of sinapinic acid (10 mg/kg) along with the NMDA agonist. Sinapinic acid and other treatments were administered intraperitoneally 30 min prior to inducing seizures with PTZ injection. Seizure onset time was recorded following PTZ injection. Blood and brain samples were collected after anesthesia to determine serum and brain nitrite levels. Real-time PCR assessed NMDAR gene expression in the prefrontal cortex (PFC). Data were analyzed using Prism software. The time seizures began was notably extended in groups treated with sinapinic acid at doses of 3 and 10 mg/kg compared to those treated with saline (P

A pesar de los beneficios reconocidos de la Expresión Corporal, sigue siendo una materia poco impartida entre el profesorado de Educación Física en España. Se mencionan diversos motivos al respecto, entre otros, objetivos y metodologías ambiguos, estereotipos arraigados en cuanto a la motricidad expresiva, asociaciones al género femenino en particular y una formación inadecuada. El objetivo de este estudio fue evaluar el estado actual de la enseñanza de la Expresión Corporal en la educación secundaria en Cataluña. Para lograrlo, se adaptó un cuestionario que evaluaba las percepciones del profesorado en cuanto a la implementación de la Expresión Corporal a partir de un instrumento que ya empleaba la comunidad autónoma de Andalucía. Se llevaron a cabo una serie de procesos rigurosos de validación, entre otros, la valoración por parte de un panel de expertos que empleó el método Delphi y evaluaciones cuantitativas y cualitativas para validar su lógica, criterios, contenido y constructo. Asimismo, se realizaron una prueba piloto (n = 40) en otra población, una evaluación test-retest (n = 20) para garantizar la estabilidad y un análisis factorial exploratorio en el que participaron 418 docentes (42.8 % mujeres) para validar su coherencia interna y fiabilidad. Los hallazgos del estudio mostraron un coeficiente Kaiser-Meyer-Olkin (KMO) de .827, lo que indicó un nivel alto de idoneidad, junto con los valores de la prueba de esfericidad de Bartlett y de Chi-cuadrado, que confirmaron la continuidad del análisis factorial. En consecuencia, el Cuestionario de Opinión para Profesorado de Educación Física diseñado para evaluar la Expresión Corporal en la educación secundaria se validó correctamente. Este cuestionario validado puede ser una herramienta sólida para valorar y comprender las perspectivas del profesorado respecto a la implementación de la Expresión Corporal en las aulas de educación secundaria de Cataluña.

Mitoribosome biogenesis is a complex process involving RNA elements encoded in the mitochondrial genome and mitoribosomal proteins typically encoded in the nuclear genome. This process is orchestrated by extra‐ribosomal proteins, nucleus‐encoded assembly factors, which play roles across all assembly stages to coordinate ribosomal RNA processing and maturation with the sequential association of ribosomal proteins. Both biochemical studies and recent cryo‐EM structures of mammalian mitoribosomes have provided insights into their assembly process. In this article, we will briefly outline the current understanding of mammalian mitoribosome biogenesis pathways and the factors involved. Special attention is devoted to the recent identification of iron–sulfur clusters as structural components of the mitoribosome and a small subunit assembly factor, the existence of redox‐sensitive cysteines in mitoribosome proteins and assembly factors, and the role they may play as redox sensor units to regulate mitochondrial translation under stress.

Abstract Aims In low‐risk patients with severe aortic stenosis (AS), sutureless surgical aortic valve replacement (SU‐SAVR) may be an alternative to transcatheter aortic valve implantation (TAVI). The risk of heart failure hospitalization (HFH) after aortic valve replacement (AVR) in this population is incompletely characterized. This study aims to investigate the incidence, predictors, and outcomes of HFH in patients undergoing SU‐SAVR versus TAVI. Methods and results Patients referred for AVR between 2013 and 2020 at two centres were consecutively included. The decision for SU‐SAVR or TAVI was determined by a multidisciplinary Heart Team. Cox regression and competing risk analysis were conducted to assess adverse events. Of 594 patients (mean age 77.5 ± 6.4, 59.8% male), 424 underwent SU‐SAVR, while 170 underwent TAVI. Following a mean follow‐up of 34.1 ± 23.1 months, HFH occurred in 112 (27.8%) SU‐SAVR patients and in 8 (4.8%) TAVI patients (P

Abstract Aims Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). Methods and results Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow‐pressure relationship of the shunt. Open‐label patients from the RELIEVE‐HF trial underwent TEE at shunt implant and at 6 and 12 month follow‐up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans‐shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. Conclusions When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.

Abstract Inflammation is relevant in the pathogenesis and progression of heart failure (HF). Previous studies have shown that elevated high-sensitivity C-reactive protein (hsCRP) are associated with greater severity and may be associated with adverse outcomes. In this study, we sought to evaluate the prognostic role of hsCRP in a non-selected cohort of patients with acute HF. We prospectively included a multicenter cohort of 3,395 patients following an admission for acute HF. HsCRP levels were evaluated during the first 24 h following admission. Study endpoints were the risks of all-cause mortality, CV-mortality, and total HF readmissions. The mean age was 74.2 ± 11.2 years and 1,826 (53.8%) showed a left ventricular ejection fraction (LVEF) ≥ 50%. Median hsCRP was 12.9 mg/L (5.4–30 mg/L). Over a median follow-up of 1.8 (0.6–4.1) years, 1,574 (46.4%) patients died, and 1,341 (39.5%) patients were readmitted for worsening HF. After multivariable adjustment, hsCRP values were significantly and positively associated with a higher risk of all-cause and CV mortality (p = 0.003 and p = 0.001, respectively), as well as a higher risk of recurrent HF admissions (p

Although preslaughter feed withdrawal is commonly used in the livestock industry to reduce the risk of viscera puncture during evisceration, the optimal feed withdrawal time (FWT) appears to be species dependent and is not yet well defined in rabbits. This study aimed to evaluate the impact of three preslaughter FWTs while considering the effect of sex on physiological response and meat quality of rabbits. Three FWTs (4, 11 and 18 h) were tested using 144 recently weaned Grimaud rabbits fed until they reached an average commercial slaughter live body weight of 2.5±0.2 kg. Rabbits were allocated into 24 cages, with six animals in each cage. Eight cages (four cages for females and four cages for males) were assigned to each of the three FWTs. Blood lactate concentrations measured at exsanguination did not raise concerns related to stress. Female rabbits subjected to 4 h FWT had a higher gastrointestinal tract weight compared to male rabbits and to other females subjected to 11 and 18 h FWT (P=0.04). Stomach content weights were lower after 18 h FWT compared to 4 and 11 h (P=0.002) for both sexes, while caecum weights were not affected by FWT. Caecum pH was higher after 11 and 18 h FWT compared to 4 h (P=0.02). Technological meat quality was not particularly affected by FWT, except for Longissimus lumborum drip loss which was lower for rabbits after 18 h FWT compared to 4 h FWT (P=0.005). With respect to microbiological meat quality, the end of shelf life was reached after 10 days for vacuum-packed hind legs from rabbits after 11 h FWT, as Escherichia coli cell counts for four out of the eight hind legs analysed were higher than 3 Log10 colony-forming units (CFU)/10 g. For the other two FWT groups, the end of shelf life was reached after 15 d, at which point the cell counts for all hind legs were ≥3 Log10 CFU/10 g for E. coli and ≥7 Log10 CFU/g for total aerobic mesophilic and presumptive lactic acid bacteria (the maximum threshold concentrations according to current regulations). Our results demonstrate that when transport (30 min) and lairage (30 min) times are short (1 h in total), an 18-h preslaughter feed withdrawal for both male and female rabbits can allow the gut to empty properly with limited effect on meat quality.

Abstract Aim The objective of this study was to assess the therapeutic effects of corticosteroids in adult patients hospitalized with viral community-acquired pneumonia. Methods This is a retrospective analysis of data collected prospectively from November 1996 to June 2024. All adult patients with viral community-acquired pneumonia were enrolled. The primary outcome was 30-day mortality. Secondary outcomes included all-cause in-hospital mortality, ICU admission, length of ICU and hospital stay, mechanical ventilation, and 1-year mortality. Propensity score matching (PSM) was used to obtain balance among the baseline variables in the two groups. Results Of the 524 patients with viral pneumonia, 30 (6%) received corticosteroids and 494 (94%) did not. Patients were primarily male (n = 299, 57%), with a median [Q1-Q3] age of 66.9 [55–81] years. The 3:1 propensity matching procedure identified 90 patients not treated with corticosteroid (CS-) as controls. After PSM, no difference in 30-day mortality was found [7% (95%CI 1 to 22%) vs. 4% (95%CI 1 to 11%), p = 0.639]. The risk of death at 30 days did not differ significantly in unmatched and matched cohorts [Hazard Ratio (HR) 1.33 (0.32–5.63), p = 0.695 vs. HR 1.51 (0.28–8.27), p = 0.632, respectively]. Nor were differences found in hospital length of stay, ICU admission and length of stay, or mechanical ventilation requirement and duration between matched and unmatched CS + and CS-. Conclusions There were no significant differences in the primary and secondary outcomes regarding the use of corticosteroids in patients with viral pneumonia.

Abstract The continued advancement of electrochemical technologies requires an increasingly detailed understanding of the microscopic processes that control their performance, inspiring the development of new multi-modal diagnostic techniques. Here, we introduce a neutron imaging approach to enable the quantification of spatial and temporal variations in species concentrations within an operating redox flow cell. Specifically, we leverage the high attenuation of redox-active organic materials (high hydrogen content) and supporting electrolytes (boron-containing) in solution and perform subtractive neutron imaging of active species and supporting electrolyte. To resolve the concentration profiles across the electrodes, we employ an in-plane imaging configuration and correlate the concentration profiles to cell performance with polarization experiments under different operating conditions. Finally, we use time-of-flight neutron imaging to deconvolute concentrations of active species and supporting electrolyte during operation. Using this approach, we evaluate the influence of cell polarity, voltage bias and flow rate on the concentration distribution within the flow cell and correlate these with the macroscopic performance, thus obtaining an unprecedented level of insight into reactive mass transport. Ultimately, this diagnostic technique can be applied to a range of (electro)chemical technologies and may accelerate the development of new materials and reactor designs.

Biochar is a carbon-rich material that can be produced from waste biomass, making it a sustainable alternative to activated carbon. Biochar production is a carbon capture and storage strategy, and its physicochemical characteristics make it a useful additive for many processes, including the biological treatment of organic waste. Particularly, biochar has a high adsorbent capacity due to its high porosity, surface area and functional groups, which makes this material especially attractive in technologies with the presence of known inhibitors or that imply the emission of polluting compounds. In anaerobic digestion, its application improves the stability of the system against inhibition, increases the efficiency of the process, and allows the purification of biogas in situ. In composting, it reduces greenhouse gas and odor emissions and improves the quality of the compost obtained, increasing the nutrient content, immobilizing heavy metals, and reducing the presence of pathogenic microorganisms. Even so, the use of biochar in the biological treatment of organic waste is still an incipient field that requires research and consensus on key aspects such as the optimal dose of biochar, the transformation of the organic material over time, and its subsequent application as an amendment for the improvement of agricultural soils.

Background and objective: The depth of the prostate-specific antigen (PSA) decline after androgen receptor pathway inhibitor (ARPI) treatment combined with androgen deprivation therapy for patients with metastatic hormone-sensitive prostate cancer (mHSPC) may affect prognosis. The primary objective in our study was the correlation between the PSA response at 3 mo and radiologic progression-free survival (rPFS) at 24 mo. Three groups were defined according to the PSA decline: complete response (PSA ≤0.02 ng/ml), partial response (PSA >0.02 and ≤0.2 ng/ml), and incomplete response (PSA >0.2 ng/ml). Secondary objectives were correlation between the PSA response at 3 mo and overall survival, and the development of a model predicting complete PSA response. Methods: We conducted a retrospective multicenter study of patients with mHSPC treated with apalutamide from May 2018 to September 2023 registered in the Real-World Evidence APA registry across 20 centers. Key findings and limitations: We included 633 patients with mHSPC. The median age at diagnosis was 68 yr (interquartile range [IQR] 63–75) and median PSA was 16 ng/ml (IQR 7.5–64). Some 63% of the short had low-volume disease, 51% had de novo disease, 48% had recurrent disease. At 3 mo, 27% had a complete response, 42% a partial response, and 31% an incomplete response, with corresponding rRFS rates at 24 mo of 92%, 86%, and 63%. According to the predictive model, a complete PSA response at 3 mo was associated with the use of next-generation imaging and PSA

Abstract Background Ventilation management may differ between COVID–19 ARDS (COVID–ARDS) patients and patients with pre–COVID ARDS (CLASSIC–ARDS); it is uncertain whether associations of ventilation management with outcomes for CLASSIC–ARDS also exist in COVID–ARDS. Methods Individual patient data analysis of COVID–ARDS and CLASSIC–ARDS patients in six observational studies of ventilation, four in the COVID–19 pandemic and two pre–pandemic. Descriptive statistics were used to compare epidemiology and ventilation characteristics. The primary endpoint were key ventilation parameters; other outcomes included mortality and ventilator–free days and alive (VFD–60) at day 60. Results This analysis included 6702 COVID–ARDS patients and 1415 CLASSIC–ARDS patients. COVID–ARDS patients received lower median VT (6.6 [6.0 to 7.4] vs 7.3 [6.4 to 8.5] ml/kg PBW; p

Abstract Apalutamide is a selective androgen receptor signalling inhibitor that is used in the treatment of prostate cancer. Skin rash is one of the most common adverse events with apalutamide. Although the majority of rash events are grade 1 and 2, the appearance of skin rash during treatment can lead to dose reduction, a pause in treatment or even treatment discontinuation, especially if patients present late when the rash has become severe. This in turn can result in a significant delay or even a permanent discontinuation in the patient’s treatment of prostate cancer. As apalutamide is a generally well tolerated and an effective treatment for many men with advanced prostate cancer, it is extremely important to make attempts to prevent skin problems or to manage them at the earliest stage possible. We therefore have developed practical guidance for the management of apalutamide-related rash, including an infographic with recommendations for rash management by grade. Central to this approach is patient education and awareness. Encouraging patients to proactively care for their skin from the start of treatment and informing them of the risk of rash with apalutamide therapy are essential. If the patient observes any skin changes, they should be advised to report it straight away to their cancer care team. Adopting this simple, proactive approach of patient education and increased vigilance from the care team is expected to lead to early identification of rash and subsequent intervention to allow for quicker resolution and enable patients to continue their cancer treatment with a drug that can delay disease progression and increase survival in patients with prostate cancer.

Abstract Background The aim of this study was to assess the contribution of the reflective multidisciplinary discussion in determining the value contribution of innovative drugs through the multi-criteria decision analysis (MCDA). This methodology considers all relevant criteria for healthcare decision-making in a global, transparent, and systematic manner and from the perspective of relevant stakeholders. The determination of value contribution of tabelecleucel for the treatment of Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) compared to salvage therapy was used as an example. Results Tabelecleucel obtained a value contribution score of 0.63 and increased to 0.75 after the reflective discussion. EBV+ PTLD was considered a life-threatening disease (5.0 ± 0.0), with a significant unmet need for an approved treatment (5.0 ± 0.0). Tabelecleucel was perceived as bringing improvements in terms of efficacy (4.2 ± 0.8) and safety (3.8 ± 0.8) compared to the salvage therapy. Most experts considered that the high efficacy and safety results could represent an improvement in the quality of life of patients (2.3 ± 1.2) along with savings in medical costs (2.3 ± 2.0) and non-medical costs (2.7 ± 1.6) compared to the salvage therapy. However, others emphasized the need of more evidence to confirm these improvements and savings over time. Tabelecleucel was regarded as potentially modifying the clinical course of the disease (4.3 ± 0.8) and supported by high-quality evidence (3.2 ± 0.4). All contextual criteria were valued highly positively for tabelecleucel. "Safety/Tolerability" and "Other medical costs" were the criteria that experienced the highest change in the re-test conducted after the reflective discussion. The reflective discussion allowed resolving doubts or misinterpretations of the experts, so the re-test obtained more accurate and consistent results of the value contribution of tabelecleucel. Conclusions The study shows that the MCDA methodology is a useful tool for decision-making on innovative treatments for the management of rare diseases. It also highlights the importance of reflective multidisciplinary discussion for its ability to resolve doubts or misinterpretations of experts, subsequently allowing to obtain more consistent and reliable results on the value contribution of the drug, being potentially more positive.

Abstract Background In the hospital environment, carbapenemase-producing Pseudomonas aeruginosa (CPPA) may lead to fatal patient infections. However, the transmission routes of CPPA often remain unknown. Therefore, this case study aimed to trace the origin of CPPA ST357, which caused a hospital-acquired pneumonia in a repatriated critically ill patient suffering from Guillain-Barré Syndrome in 2023. Methods Antimicrobial susceptibility of the CPPA isolate for 30 single and combination therapies was determined by disk-diffusion, Etest or broth microdilution. Whole-genome sequencing was performed for three case CPPA isolates (one patient and two sinks) and four distinct CPPA ST357 patient isolates received in the Dutch CPPA surveillance program. Furthermore, 193 international P. aeruginosa ST357 assemblies were collected via three genome repositories and analyzed using whole-genome multi-locus sequence typing in combination with antimicrobial resistance gene (ARG) characterization. Results A Dutch patient who carried NDM-1-producing CPPA was transferred from Kenya to the Netherlands, with subsequent dissemination of CPPA isolates to the local sinks within a month after admission. The CPPA case isolates presented an extensively drug-resistant phenotype, with susceptibility only for colistin and cefiderocol-fosfomycin. Phylogenetic analysis showed considerable variation in allelic distances (mean = 150, max = 527 alleles) among the ST357 isolates from Asia (n = 92), Europe (n = 58), Africa (n = 21), America (n = 16), Oceania (n = 2) and unregistered regions (n = 4). However, the case isolates (n = 3) and additional Dutch patient surveillance program isolates (n = 2) were located in a sub-clade of isolates from Kenya (n = 17; varying 15–49 alleles), the United States (n = 7; 21–115 alleles) and other countries (n = 6; 14–121 alleles). This was consistent with previous hospitalization in Kenya of 2/3 Dutch patients. Additionally, over half of the isolates (20/35) in this sub-clade presented an identical resistome with 9/17 Kenyan, 5/5 Dutch, 4/7 United States and 2/6 other countries, which were characterized by the bla NDM-1, aph(3’)-VI, ARR-3 and cmlA1 ARGs. Conclusion This study presents an extensively-drug resistant subclone of NDM-producing P. aeruginosa ST357 with a unique resistome which was introduced to the Netherlands via repatriation of critically ill patients from Kenya. Therefore, the monitoring of repatriated patients for CPPA in conjunction with vigilance for the risk of environmental contamination is advisable to detect and prevent further dissemination.

Abstract Background Trimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death. Methods Adults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6–29) and 28-day all-cause mortality (Days 1–29). Results One-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable. A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (

Abstract To explore preoperative and operative risk factors for red blood cell (RBC) transfusion requirements during liver transplantation (LT) and up to 24 h afterwards. We evaluated the associations between risk factors and units of RBC transfused in 176 LT patients using a log-binomial regression model. Relative risk was adjusted for age, sex, and the model for end-stage liver disease score (MELD) (adjustment 1) and baseline hemoglobin concentration (adjustment 2). Forty-six patients (26.14%) did not receive transfusion. Grafts from cardiac-death donors were used in 32.61% and 31.54% of non-transfused and transfused patients, respectively. The transfused group required more reoperation for bleeding (P = 0.035), longer mechanical ventilation after LT (P

Penelitian ini merupakan Implementasi model pembelajaran contextual teaching and learning (CTL) dalam meningkatkan hasil belajar siswi kelas XI pada materi sistem koloid di SMA Islam Darul Muhibbien Binuang bertujuan untuk meningkatkan aktivitas siswi, hasil belajar dan tanggapan siswi terhadap penerapan model pemebelajaran contextual teaching and learning (CTL). Pendekatan yang digunakan adalah kuantitatif dan quasi ekperimen. Subjek penelitian adalah siswa kelas XIB sebanyak 20 siswi sebagai kelas eksperimen dan kelas XIC sebanyak 20 siswi sebagai kelas kontrol. Aktivitas siswi tergolong sangat tinggi dengan persentase rata-rata 91,25%, hasil penelitian menunjukkan bahwa hasil belajar meningkat dengan persentase hasil belajar yang diperoleh 15% nilai sebelum menggunakan model CTL, sedangkan siswi telah menggunakan model CTL persentase yang diperoleh 95%. Tanggapan siswi adalah positif sebanyak 94%, sedangkan yang bertanggapan negatif 6%. Hasil penelitian ini menyimpulkan bahwa penerapan model pembelajaran CTL dapat meningkatkan aktivitas siswi, hasil belajar, dan minat belajar siswi.

Mata pelajaran kimia merupakan suatu mata pelajaran yang memerlukan strategi agar lebih mudah untuk dimengerti oleh siswa terutama pada materi redoks. Salah satu model pembelajaran yang dapat memudahkan siswa dalam menerima konsep yang diberikan oleh guru adalah model pembelajaran inkuiri terbimbing. Penelitian ini bertujuan untuk mengetahui apakah terdapat perbedaan hasil belajar kimia kelas X SMA Islam Darul Muhibbien pada materi redoks dengan menggunakan model pembelajaran inkuiri terbimbing. Dalam penelitian ini penulis menggunakan metode eksperimen (quasi experimen) dan menggunakan pendekatan kuantitatif dengan desain penelitian yang digunakan yaitu pretest-posstest control grup design. Hasil penelitian menunjukkan bahwa pada uji hipotesis hasil nilai signifikan yang didapat adalah 0,000 < 0,05 yang artinya terdapat perbedaan hasil belajar siswa pada kelas eksperimen dengan kelas kontrol dengan penggunaan model pembelajaran inkuiri terbimbing dan konvensional, dengan persentase nilai belajar kelas eksperimen 80% dan 55% pada kelas kontrol.

Abstract piRNAs are crucial for transposon silencing, germ cell maturation, and fertility in male mice. Here, we report on the genetic landscape of piRNA dysfunction in humans and present 39 infertile men carrying biallelic variants in 14 different piRNA pathway genes, including PIWIL1, GTSF1, GPAT2, MAEL, TDRD1, and DDX4. In some affected men, the testicular phenotypes differ from those of the respective knockout mice and range from complete germ cell loss to the production of a few morphologically abnormal sperm. A reduced number of pachytene piRNAs was detected in the testicular tissue of variant carriers, demonstrating impaired piRNA biogenesis. Furthermore, LINE1 expression in spermatogonia links impaired piRNA biogenesis to transposon de-silencing and serves to classify variants as functionally relevant. These results establish the disrupted piRNA pathway as a major cause of human spermatogenic failure and provide insights into transposon silencing in human male germ cells.

Abstract Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression of prototypical LXR targets and leads macrophages to a less inflammatory phenotype with a profibrotic gene signature. These studies underscore the role of LDs as reservoirs and metabolic hubs of bioactive lipids, and suggest that LDAH favorably modulates macrophage activation and protects against atherosclerosis via lipolytic mobilization of regulatory sterols.

Abstract Aims The objective of this study was to perform a cost–benefit analysis of the CardioMEMS HF System (Abbott Laboratories, Abbott Park, IL, USA) in a heart failure (HF) clinic in Spain by evaluating the real‐time remote monitoring of pulmonary artery pressures, which has been shown to reduce HF‐related hospitalizations and improve the quality of life for selected HF patients. Particularly, the study aimed to determine the value of CardioMEMS in Southern Europe, where healthcare costs are significantly lower and its effectiveness remains uncertain. Methods and results This single‐centre study enrolled all consecutive HF patients (N = 43) who had been implanted with a pulmonary artery pressure sensor (CardioMEMS HF System); 48.8% were females, aged 75.5 ± 7.0 years, with both reduced and preserved left ventricular ejection fraction; 67.4% of them were in New York Heart Association Class III. The number of HF hospitalizations in the year before and the year after the sensor implantation was compared. Quality‐adjusted life years gained based on a literature review of previous studies were calculated. The rate of HF hospitalizations was significantly lower at 1 year compared with the year before CardioMEMS implantation (0.25 vs. 1.10 events/patient‐year, hazard ratio 0.22, P = 0.001). At the end of the first year, the usual management outperformed the CardioMEMS HF System. By the end of the second year, the CardioMEMS system is estimated to reduce costs compared with usual management (net benefits of €346). Conclusions Based on the results, we suggest that remote monitoring of pulmonary artery pressure with the CardioMEMS HF System represents a midterm and long‐term efficient strategy in a healthcare setting in Southern Europe.

Many new construction techniques have been developed in recent years, one of them is Three-Dimensional Concrete Printing (3DCP). It offers many advantages such as reduced human error, minimum manpower usage, and shorter construction period. This technique, however, still needs to be studied further to ensure good quality of constructions. This experimental study aims to investigate the bond strength of embedded steel reinforcement in vibration-based 3DCP mortar. The parameters varied are reinforcement diameter and direction of printing. It is found that average bond stress decreases as reinforcement diameter increases. Furthermore, 3DCP specimens with bars placed parallel to the printing direction have relatively higher bond stresses as compared to the ones with bars placed perpendicularly. As compared to conventional cast specimens, 3DCP specimens have higher bond stresses which might be due to vibration-based 3DCP mortar. Moreover, building code formulas significantly underestimate the bond stresses of vibration-based 3DCP specimens tested in this study.

The Andean Condor (Vultur gryphus) is a globally threatened species. Its highly mobile capability presents important challenges for conservation planning, especially in extremely geographically complex regions such as Colombia, where little is known about its ecology. Over the past three decades, financial and technical conservation efforts have primarily focussed on reintroduction and local management strategies. However, these initiatives did not properly prioritize the various conservation measures undertaken. We utilized roosting locations across Colombia to identify suitable roosting distribution with high risk because of the anthropogenic impact on a Systematic Planning Tool for decision-making based on robust spatial habitat modelling to define where and how should focus the Andean condor conservation actions in the country. Specifically, we aimed to develop a conservation planning tool to facilitate spatially explicit decision-making. Our results showed that Colombia has at least 19,571.33 km2 of suitable roosting habitat for this species, but over 30% of this area is currently considered to be under conservation risk due to severe anthropogenic impacts. Considering this, we suggested different actions for each proposed area according to potential threats generated by human communities.

Introduction The use of emerging tobacco and nicotine products affects tobacco use behaviors among college students. Thus, we aimed to examine transitions in tobacco use patterns and identify their predictors among smokers in a cohort of nursing students in Catalonia (Spain). Methods We conducted a prospective longitudinal study of Catalan nursing students between 2015–2016 and 2018–2019. We examined transitions in tobacco use patterns between baseline and follow-up among smokers from: 1) daily to nondaily smoking, 2) non-daily to daily smoking, 3) cigarette-only use to polytobacco use, 4) poly-tobacco use to cigarette-only use, 5) between products, 6) reducing consumption by ≥5 cigarettes per day (CPD); and 7) quitting smoking. We applied a Generalized Linear Model with a log link (Poisson regression) and robust variance to identify predictors of reducing cigarette consumption by ≥5 CPD and quitting smoking, obtaining both crude and adjusted (APR) prevalence ratios and their 95% confidence intervals (CIs). Results Among daily smokers at baseline, 12.1% transitioned to non-daily smoking at follow-up, while 36.2% of non-daily smokers shifted to daily smoking. Among cigarette-only users, 14.2% transitioned to poly-tobacco use, while 48.4% of polytobacco users switched to exclusive cigarette use. Among all smokers (daily and non-daily smokers), 60.8% reduced their cigarette consumption by ≥5 CPD and 28.3% quit smoking. Being a non-daily smoker (APR=0.33; 95% CI 0.19–0.55) and having lower nicotine dependence (APR=0.78; 95% CI 0.64–0.96) were inversely associated with reducing cigarette consumption, while being a non-daily smoker (APR=1.19; 95% CI: 1.08–1.31) was directly associated with quitting smoking. Conclusions Nursing students who smoked experienced diverse transitions in tobacco use patterns over time. Evidence-based tobacco use preventive and cessation interventions are needed to tackle tobacco use among future nurses.

El text recull les principals disposicions sobre els usos, els drets lingüístics i el règim jurídic de la llengua publicades al Diari Oficial de la Unió Europea (DOUE) de l’1 de juliol al 31 de desembre de 2023. L’ordre en què apareixen les disposicions esmentades és el que s’estableix cronològicament al DOUE i, quant a la jurisprudència, la data en què les sentències del TJUE són pronunciades. La sigla EEE correspon a Espai Econòmic Europeu, àrea d’integració comercial que associa en un únic mercat interior la Unió Europea (UE) amb Noruega, Islàndia i Liechtenstein.

Abstract We continue our work on the light-front formulation of quarkonium γ ∗ γ transition form factors, extending the formalism to J PC = 2++ tensor meson states. We present an analysis of γ ∗ γ → χ c2 transition amplitude and the pertinent helicity form factors. Our relativistic formalism is based on the light-front quark-antiquark wave function of the quarkonium. We calculate the two-photon decay width as well as three independent γ ∗ γ transition form factors for J z = 0, 1, 2 as a function of photon virtuality Q 2. We compare our results for the two-photon decay width to the recently measured ones by the Belle and BES III collaborations. Even when including relativistic corrections, a very small Γ(λ = 0)/Γ(λ = 2) ~ 10 −3 ratio is found which is beyond present experimental precision. We also present the form factors as a function of photon virtuality and compare them to the sparse experimental data on the so-called off-shell width. The formalism presented here can be used for other 2++ mesons, excited charmonia or bottomonia or even light q q ¯ $$ q\overline{q} $$ -mesons.

Abstract Background There exists consistent empirical evidence in the literature pointing out ample heterogeneity in terms of the clinical evolution of patients with COVID-19. The identification of specific phenotypes underlying in the population might contribute towards a better understanding and characterization of the different courses of the disease. The aim of this study was to identify distinct clinical phenotypes among hospitalized patients with SARS-CoV-2 pneumonia using machine learning clustering, and to study their association with subsequent clinical outcomes as severity and mortality. Methods Multicentric observational, prospective, longitudinal, cohort study conducted in four hospitals in Spain. We included adult patients admitted for in-hospital stay due to SARS-CoV-2 pneumonia. We collected a broad spectrum of variables to describe exhaustively each case: patient demographics, comorbidities, symptoms, physiological status, baseline examinations (blood analytics, arterial gas test), etc. For the development and internal validation of the clustering/phenotype models, the dataset was split into training and test sets (50% each). We proposed a sequence of machine learning stages: feature scaling, missing data imputation, reduction of data dimensionality via Kernel Principal Component Analysis (KPCA), and clustering with the k-means algorithm. The optimal cluster model parameters –including k, the number of phenotypes– were chosen automatically, by maximizing the average Silhouette score across the training set. Results We enrolled 1548 patients, each of them characterized by 92 clinical attributes (d=109 features after variable encoding). Our clustering algorithm identified k=3 distinct phenotypes and 18 strongly informative variables: Phenotype A (788 cases [50.9% prevalence] – age $$\sim$$ ∼ 57, Charlson comorbidity $$\sim$$ ∼ 1, pneumonia CURB-65 score $$\sim$$ ∼ 0 to 1, respiratory rate at admission $$\sim$$ ∼ 18 min-1, FiO2 $$\sim$$ ∼ 21%, C-reactive protein CRP $$\sim$$ ∼ 49.5 mg/dL [median within cluster]); phenotype B (620 cases [40.0%] – age $$\sim$$ ∼ 75, Charlson $$\sim$$ ∼ 5, CURB-65 $$\sim$$ ∼ 1 to 2, respiration $$\sim$$ ∼ 20 min-1, FiO2 $$\sim$$ ∼ 21%, CRP $$\sim$$ ∼ 101.5 mg/dL); and phenotype C (140 cases [9.0%] – age $$\sim$$ ∼ 71, Charlson $$\sim$$ ∼ 4, CURB-65 $$\sim$$ ∼ 0 to 2, respiration $$\sim$$ ∼ 30 min-1, FiO2 $$\sim$$ ∼ 38%, CRP $$\sim$$ ∼ 152.3 mg/dL). Hypothesis testing provided solid statistical evidence supporting an interaction between phenotype and each clinical outcome: severity and mortality. By computing their corresponding odds ratios, a clear trend was found for higher frequencies of unfavourable evolution in phenotype C with respect to B, as well as more unfavourable in phenotype B than in A. Conclusion A compound unsupervised clustering technique (including a fully-automated optimization of its internal parameters) revealed the existence of three distinct groups of patients – phenotypes. In turn, these showed strong associations with the clinical severity in the progression of pneumonia, and with mortality.

Abstract Glutamatergic neurotransmission and oxidative stress are involved in the pathophysiology of seizures. Some anticonvulsants exert their effects through modulation of these pathways. Trigonelline (TRG) has been shown to possess various pharmacological effects like neuroprotection. Therefore, this study was performed to determine TRG’s anticonvulsant effects, focusing on its potential effects on N-methyl-D-aspartate (NMDA) receptors, a type of glutamate receptor, and oxidative stress state in the prefrontal cortex (PFC) in PTZ-induced seizure in mice. Seventy-two male mice were randomly divided into nine groups. The groups included mice that received normal saline, TRG at doses of 10, 50, and 100 mg/kg, diazepam, NMDA (an agonist), ketamine (an antagonist), the effective dose of TRG with NMDA, as well as sub-effective dose of TRG with ketamine, respectively. All agents were administrated intraperitoneally 60 min before induction of seizures by PTZ. Latency to seizure, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels in serum and PFC were measured. Furthermore, the gene expression of NR2A and NR2B, subunits of NMDA receptors, was measured in the PFC. TRG administration increased the latency to seizure onset and enhanced TAC while reducing MDA levels in both the PFC and serum. TRG also decreased the gene expression of NR2B in the PFC. Unexpectedly, the findings revealed that the concurrent administration of ketamine amplified, whereas NMDA mitigated, the impact of TRG on latency to seizure. Furthermore, NMDA diminished the positive effects of TRG on antioxidant capacity and oxidative stress, while ketamine amplified these beneficial effects, indicating a complex interaction between TRG and NMDA receptor modulation. In the gene expression of NMDA receptors, results showed that ketamine significantly decreased the gene expression of NR2B when co-administrated with a sub-effective dose of TRG. It was found that, at least partially, the anticonvulsant effect of TRG in PTZ-induced seizures in male mice was mediated by the attenuation of glutamatergic neurotransmission as well as the reduction of oxidative stress.

Abstract Background The Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disorders and metabolic processes. Hypothesizing that eCBs and NAEs will be biomarkers of a MedDiet intervention and will be related to the cognitive response, we investigated this relationship according to sex and apolipoprotein E (APOE) genotype, which may affect eCBs and cognitive performance. Methods This was a prospective cohort study of 102 participants (53.9% women, 18.8% APOE-ɛ4 carriers, aged 65.6 ± 4.5 years) from the PREDIMED-Plus-Cognition substudy, who were recruited at the Hospital del Mar Research Institute (Barcelona). All of them presented metabolic syndrome plus overweight/obesity (inclusion criteria of the PREDIMED-Plus) and normal cognitive performance at baseline (inclusion criteria of this substudy). A comprehensive battery of neuropsychological tests was administered at baseline and after 1 and 3 years. Plasma concentrations of eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and N-docosahexaenoylethanolamine (DHEA), were also monitored. Baseline cognition, cognitive changes, and the association between eCBs/NAEs and cognition were evaluated according to gender (crude models), sex (adjusted models), and APOE genotype. Results At baseline, men had better executive function and global cognition than women (the effect size of gender differences was − 0.49, p = 0.015; and − 0.42, p = 0.036); however, these differences became nonsignificant in models of sex differences. After 3 years of MedDiet intervention, participants exhibited modest improvements in memory and global cognition. However, greater memory changes were observed in men than in women (Cohen’s d of 0.40 vs. 0.25; p = 0.017). In men and APOE-ε4 carriers, 2-AG concentrations were inversely associated with baseline cognition and cognitive changes, while in women, cognitive changes were positively linked to changes in DHEA and the DHEA/AEA ratio. In men, changes in the OEA/AEA and OEA/PEA ratios were positively associated with cognitive changes. Conclusions The MedDiet improved participants’ cognitive performance but the effect size was small and negatively influenced by female sex. Changes in 2-AG, DHEA, the OEA/AEA, the OEA/PEA and the DHEA/AEA ratios were associated with cognitive changes in a sex- and APOE-dependent fashion. These results support the modulation of the endocannabinoid system as a potential therapeutic approach to prevent cognitive decline in at-risk populations. Trial registration ISRCTN89898870.

Abstract Improved phenotyping in pneumonia is necessary to strengthen risk assessment. Via a feasible and multidimensional approach with basic parameters, we aimed to evaluate the effect of host response at admission on severity stratification in COVID-19 and community-acquired pneumonia (CAP). Three COVID-19 and one CAP multicenter cohorts including hospitalized patients were recruited. Three easily available variables reflecting different pathophysiologic mechanisms—immune, inflammation, and respiratory—were selected (absolute lymphocyte count [ALC], C-reactive protein [CRP] and, SpO2/FiO2). In-hospital mortality and intensive care unit (ICU) admission were analyzed as outcomes. A multivariable, penalized maximum likelihood logistic regression was performed with ALC ( 60 mg/L), and, SpO2/FiO2 (

Abstract Background and aims Stroke is the leading cause of adult-onset disability. Although clinical factors influence stroke outcome, there is a significant variability among individuals that may be attributed to genetics and epigenetics, including DNA methylation (DNAm). We aimed to study the association between DNAm and stroke prognosis. Methods and results To that aim, we conducted a two-phase study (discovery-replication and meta-analysis) in Caucasian patients with ischemic stroke from two independent centers (BasicMar [discovery, N = 316] and St. Pau [replication, N = 92]). Functional outcome was assessed using the modified Rankin Scale (mRS) at three months after stroke, being poor outcome defined as mRS > 2. DNAm was determined using the 450K and EPIC BeadChips in whole-blood samples collected within the first 24 h. We searched for differentially methylated positions (DMPs) in 370,344 CpGs, and candidates below p-value

IntroductionIt is estimated that 1.4 billion quails are reared each year for their eggs and meat, but animal welfare assessment protocols for this species have yet to be established. The objective of this study was to devise an animal welfare assessment protocol developed through a multidimensional approach that contained a number of animal-based indicators (ABIs) for quails (Coturnix japonica) reared for meat production.MethodsDuring 2021 and 2022, the identical auditor visited and audited 14 Spanish farms in their initial year of integration into an animal welfare certification scheme. The protocol is categorised into 4 principles and 12 criteria. The “good feeding” principle includes 6 indicators (1 ABI), “good housing” includes 10 indicators (5 ABIs), “good health” includes 12 indicators (9 ABIs), and “appropriate behaviour” contains 8 indicators (5 ABIs). The final welfare assessment is calculated at the farm level using scores from the on-farm recordings. The assessment is a step-by-step weighted sum of the scores from the various indicators, with the final score ranging between 0 and 100.Results and discussionThe main welfare issues found on all farms were a lack of temperature and humidity records, a poor lighting pattern, and the absence of an outdoor range or access to one. To a lesser degree, it was also found that there were excessive numbers of birds per feeder, the presence of improperly functioning drinkers (i.e., not working, inadequate water flow, or dripping water), poor litter quality, and a high prevalence of birds with dirty plumage and lameness. Despite this, the farms achieved a good overall score, being classified as “enhanced” (n = 11) and “acceptable” (n = 3). The tool proved helpful in identifying specific welfare issues at the farm level and conducting benchmarking.

Summary: CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Background Bipolar disorder is highly prevalent and consists of biphasic recurrent mood episodes of mania and depression, which translate into altered mood, sleep and activity alongside their physiological expressions. Aims The IdenTifying dIgital bioMarkers of illnEss activity and treatment response in BipolAr diSordEr with a novel wearable device (TIMEBASE) project aims to identify digital biomarkers of illness activity and treatment response in bipolar disorder. Method We designed a longitudinal observational study including 84 individuals. Group A comprises people with acute episode of mania (n = 12), depression (n = 12 with bipolar disorder and n = 12 with major depressive disorder (MDD)) and bipolar disorder with mixed features (n = 12). Physiological data will be recorded during 48 h with a research-grade wearable (Empatica E4) across four consecutive time points (acute, response, remission and episode recovery). Group B comprises 12 people with euthymic bipolar disorder and 12 with MDD, and group C comprises 12 healthy controls who will be recorded cross-sectionally. Psychopathological symptoms, disease severity, functioning and physical activity will be assessed with standardised psychometric scales. Physiological data will include acceleration, temperature, blood volume pulse, heart rate and electrodermal activity. Machine learning models will be developed to link physiological data to illness activity and treatment response. Generalisation performance will be tested in data from unseen patients. Results Recruitment is ongoing. Conclusions This project should contribute to understanding the pathophysiology of affective disorders. The potential digital biomarkers of illness activity and treatment response in bipolar disorder could be implemented in a real-world clinical setting for clinical monitoring and identification of prodromal symptoms. This would allow early intervention and prevention of affective relapses, as well as personalisation of treatment.

ABSTRACT Since March 2022, an increase was observed in multidrug-resistant microorganisms (MDRO), associated with the hospital transfer of Ukrainian patients. The goal was to collect phenotypic susceptibility data and assess clinical implications. Carbapenemase-producing Enterobacterales (CPE, n = 96), Pseudomonas aeruginosa (CPPA, n = 20), and carbapenem-resistant Acinetobacter baumannii–calcoaceticus (CRAB, n = 6) from Ukrainian patients were obtained from March to December 2022 from the Dutch MDRO surveillance. Antimicrobial susceptibility testing was performed using broth microdilution (BMD) when available, fosfomycin agar dilution, disk diffusion (DD) for cefiderocol, and diverse gradient strips. All isolates were sequenced with Illumina next-generation sequencing. For meropenem, aminoglycosides, ceftazidime–avibactam, ceftolozane–tazobactam, and imipenem–relebactam, susceptibility rates were low (0%–30%), due to the high number of blaNDM-positive isolates (79/122; 65%). For cefiderocol, results depended on reading with or without microcolonies, applying EUCAST or CLSI breakpoints, and whether DD or BMD was used; e.g., for Klebsiella pneumoniae, 30%–97% were susceptible. For colistin, 103/111 (93%) non-intrinsically resistant CPE/CPPA/CRAB isolates were susceptible. For most CPE, a low minimal inhibitory concentration (MIC) of

Although an increased effectiveness has been suggested when phages and antibiotics are combined, this approach has not been tested against a mature biofilm on an endotracheal tube (ETT) surface. This study evaluated the effect of short- and long-term combined phage-antibiotic therapy in a control of a mature biofilm on an ETT surface. Pseudomonas aeruginosa strains, including susceptible and resistant clinical samples, were used to develop the ETT biofilm. Biofilm was treated with 108PFU/mL of phage_2, phage_18 or 5 μg/mL of ceftolozane/tazobactam, alone or in combination with phages. The sequential combination of the two different phages and ceftolozane/tazobactam was also tested. Biofilm viability was assessed after short (2, 4, 24 h) and long-(48, 72 h) term treatment exposure using colony forming unit measurement. For long-term exposition, a new treatment shot was added every 24 h. In the sequential combination, the phage type was switched at 24 h of treatment. Regarding the susceptible strains, the treatments had limited antibiofilm effect after 2, 4 and 24 h. After 48 and 72 h, administering phages alone had no effect on biofilm viability, indicating the emergence of phage-resistant phenotypes. Nonetheless, the combined phage-antibiotic treatment reduced the biofilm viability in about 5-log, whilst antibiotic alone reduced in about 3-log. The sequential combination of phages and antibiotic reduced the biofilm viability in about 6-log. With respect to the resistant strains, no antibiofilm activity was observed regarding the treatment arms. The combination of phages and ceftolozane/tazobactam showed a synergism strain-dependent, being more apparent in susceptible strains.

Rius, Mercè (2024) Discurs contrafeminista València: Editorial Afers, 85 p. ISBN 978-84-18618-75-8

Biorefineries are emerging facilities that are planned to transform existing waste treatment plants based on composting and/or anaerobic digestion into complex installations where biological and physicochemical processes coexist to maximize the recovery of renewable energy and valuable bioproducts. Biorefineries are mainly based on the use of several typologies of organic waste as starting material. This feature, together with the fact that biorefineries are supposed to be carbon neutral, has provoked that two biotechnologies arise as the key to have a successful biorefinery in economic and environmental terms: anaerobic digestion, a consolidated renewable energy provider, and solid-state fermentation, an emerging technology, derived from composting, to act as a supplier of a new generation of biorefinery products that include enzymes, bioplastics, biopesticides, biosurfactants and bioestimulants, among others. This review explores the importance of the role of anaerobic digestion and solid-state fermentation in novel biorefineries, highlighting their obvious advantages and their main challenges, in a specific moment where anaerobic digestion and, in consequence, digestate, are undergoing an exponential increase as a renewable energy source and a predominant organic waste.

Este texto describe y analiza el proceso de elaboración y validación del Código Deontológico (CD) de la Red Española de Asociaciones de Diseño (READ) desde una perspectiva participativa y consensual. Partiendo de un núcleo impulsor inicial, se ha implicado a grupos focales en formato taller, encuestas, correcciones colectivas y validación por votación. Los resultados evidencian que con un proceso participativo podemos identificar los valores éticos, las buenas y las malas prácticas de READ y que podemos proponer una nueva estructura formal del Código.

Many women have sought alternative therapies to address menopause. Recently, a multi-ingredient supplement (MIS) containing L-histidine, L-carnosine, L-serine, and L-cysteine has been shown to be effective at ameliorating hepatic steatosis (HS) in ovariectomized (OVX) rats, a postmenopausal oestrogen deficiency model. Considering that HS frequently accompanies obesity, which often occurs during menopause, we aimed to investigate the effects of this MIS for 8 weeks in OVX rats. Twenty OVX rats were orally supplemented with either MIS (OVX-MIS) or vehicle (OVX). Ten OVX rats received vehicle orally along with subcutaneous injections of 17β-oestradiol (OVX-E2), whereas 10 rats underwent a sham operation and received oral and injected vehicles (control group). MIS consumption partly counteracted the fat mass accretion observed in OVX animals, leading to decreased total fat mass, adiposity index and retroperitoneal white adipose tissue (RWAT) adipocyte hypertrophy. OVX-MIS rats also displayed increased lean mass and lean/fat ratio, suggesting a healthier body composition, similar to the results reported for OVX-E2 animals. MIS consumption decreased the circulating levels of the proinflammatory marker CRP, the total cholesterol-to-HDL-cholesterol ratio and the leptin-to-adiponectin ratio, a biomarker of diabetes risk and metabolic syndrome. RWAT transcriptomics indicated that MIS favourably regulated genes involved in adipocyte structure and morphology, cell fate determination and differentiation, glucose/insulin homeostasis, inflammation, response to stress and oxidative phosphorylation, which may be mechanisms underlying the beneficial effects described for OVX-MIS rats. Our results pave the way for using this MIS formulation to improve the body composition and immunometabolic health of menopausal women.

BackgroundExisting literature on moral conflicts that healthcare professionals encounter in dementia care has explored, amongst others, issues related to autonomy, decision-making capacity, privacy, and more. Notably, conflicts related to healthcare professionals who support informal dementia caregiving and who are confronted with family members being overburdened with their care responsibly remains an underexplored topic in the current literature, particularly in the context of Low-and Middle-Income Countries. The present paper introduces such an encounter, presenting an ethical case analysis of a conflict that occurred during a larger research project conducted in North Macedonia.Case to be studiedDue to the absence of formal care services that could have relieved an overburdened family caregiver, healthcare professionals felt compelled to reach out to the uninvolved adult daughters, requesting them to participate in their parents’ care. Wondering about whether their reaching out to the daughters might count as an attempt of pressure and undue interference, professionals conflicted over the appropriateness of their action. This paper follows up on their concern, ethically assessing the professionals’ action. To answer the question on whether the healthcare professionals acted appropriately or not, and to what extent, theories of filial duties are applied, embedding their action in the larger context of dementia care in North Macedonia.Results and conclusionIt is argued that the lack of formal care services in North Macedonia is of utmost relevance to the conflict. Thus, the conclusion is that the ethical inappropriateness of the case is to be located not so much with the action of the healthcare professionals but with the state because of its failure to provide professional care services that allow healthcare professionals to take ethically sound actions to counteract overarching burdens that family members face when providing informal dementia care

Resumen: La simulación clínica (SC) en Medicina se encuentra en crecimiento y es actualmente complementaria a la formación convencional, siendo ambos enfoques necesarios. Dispone de evidencia y aceptación por la comunidad científica. Ofrece ventajas educativas y evaluativas, permitiendo a través del análisis crítico, una práctica segura, con igualdad de oportunidades para los participantes y puede promover tanto competencias técnicas como humanísticas. Los avances tecnológicos suponen una oportunidad, facilitan escenarios más realistas y permiten la práctica repetitiva. A pesar de los desafíos económicos, la simulación clínica contribuye a la formación de profesionales de una forma más completa, equitativa y segura. Abstract: Clinical Simulation (SC) in Medicine is growing and is currently complementary to conventional learning, both approaches being necessary. There is evidence and is widely accepted by the scientific community. It offers educational and evaluative advantages, allowing trough critical analysis, a safe practice, with equal opportunities for participants, and promoting both technical and humanistic competencies. Technological advances provide an opportunity by facilitating more realistic scenarios and repetitive practice. Despite economic challenges, Clinical Simulation contributes to the training of professionals in a more complete, equitable and safe way.

The ratification of the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) and the passage of Indonesia’s first national law based on disability rights, No. 8 of 2016 on Persons with Disabilities, have laid the groundwork for a paradigm shift in understanding and approaching disability in the country. Based on descriptive analysis and long-term observation, this article argues that advances in the legal frameworks that govern disability policies have yet to result in significant improvements in the lives of Indonesians with disabilities. A lack of budget commitment, regulatory discord, and insufficient awareness of disability rights in the public and private sectors all point to a half-hearted approach to disability inclusion. This article illustrates this argument by focusing on three crucial aspects of the realisation of human rights for people with disabilities in Indonesia: the rights to education, health and employment.