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Abstract Background Patients undergoing high-risk surgeries with acid-based disorders are associated with poor outcomes. The screening of mixed acid-based metabolic disorders by calculating delta anion gap (AG)/delta bicarbonate (Bic) has a clinically relevant role in patients with high AG metabolic acidosis (MA), however its utility in individuals facing high-risk surgical procedures remains unclear. Objective Characterize metabolic acidosis using delta-AG/delta-Bic and its associations in patients undergoing high-risk surgeries with possible outcome-related complications. Design Prospective observational multicentric study. Setting Three tertiary hospitals in Brazil. Patients Patients undergoing high-risk surgeries, aged 18 years or older, requiring postoperative critical care. Main outcome measures Patients undergoing high-risk surgeries monitored during the postoperative phase across three distinct intensive care units (ICUs), with assessment encompassing laboratory analyses upon admission and 24 h thereafter. Patients with MA and with elevated AG within 24 h were separated into 3 subgroups: [G1 – delta-AG/delta-Bic 1.6] MA associated with alkalosis. Primary endpoint was 30-day mortality. The secondary endpoints were cardiovascular, respiratory, renal, neurological, coagulation and infective complications. Results From the 621 surgical patients admitted to ICU, 421 (51.7%) had any type of acidosis. After 24 h, 140 patients remained with MA with elevated AG (G1: 101, G2: 18, and G3: 21). When compared to patients from subgroups 1 and 3, the subgroup with no mixed disorders 2 showed higher 30-day mortality (adjusted HR = 3.72; 95% CI 1.11–12.89, p = 0.001), cardiovascular complications (p = 0.001), ICU mortality (p = 0.03) and sum of all complications during the ICU period (p = 0.021). Conclusion In the postoperative time, patients with metabolic acidosis and no mixed disorders present higher ICU-Mortality and higher cardiovascular postoperative complications when compared with patients with combined hyperchloremia or alkalosis. Delta-AG/delta-Bic can be a useful tool to evaluate major clinical outcomes in this population.

Abstract Videos of magic tricks offer lots of opportunities to study the human mind. They violate the expectations of the viewer, causing prediction errors, misdirect attention, and elicit epistemic emotions. Herein we describe and share the Magic, Memory, and Curiosity (MMC) Dataset where 50 participants watched 36 magic tricks filmed and edited specifically for functional magnetic imaging (fMRI) experiments. The MMC Dataset includes a contextual incentive manipulation, curiosity ratings for the magic tricks, and incidental memory performance tested a week later. We additionally measured individual differences in working memory and constructs relevant to motivated learning. fMRI data were acquired before, during, and after learning. We show that both behavioural and fMRI data are of high quality, as indicated by basic validation analysis, i.e., variance decomposition as well as intersubject correlation and seed-based functional connectivity, respectively. The richness and complexity of the MMC Dataset will allow researchers to explore dynamic cognitive and motivational processes from various angles during task and rest.

Mexico City emits several thousands of tons of particle matter from transportation and other economic sectors. We collected PM2.5 samples from January to March 2015. The chemical analyses showed that PM2.5 is made up of 39% organic carbon, 12% elemental carbon, 23% metals (Al, Si, S, P, and K), and 5% heavy metals (Pb, Cr, Mn, Zn, and Hg). Ca and Fe were also present in trace concentrations, probably due to the resuspension of soils. Nitrate, sulfate, and ammonium suggest that the southwest of Mexico City, specifically the sampling site, receives more oxidated pollutants from vehicle emissions than other emissions. The chemical analyses show no significant changes in the composition or concentration of particle matter compared to previous studies.

Abstract Background The current EULAR definition of difficult-to-treat rheumatoid arthritis (D2T-RA) identifies patients with active disease refractory to multiple treatments at a single time point, without considering the persistence of this condition over time. The study aimed to assess difficult-to-treat rheumatoid arthritis (D2T-RA) over 12 months, considering persistence over time rather than a single time point, in a real-life cohort. Methods In a single-center real-life cohort, demographic and clinic data were cross-sectionally collected for each patient at baseline and retrospectively over the previous 12 months bimonthly. For each timepoint, the prevalence of D2T-RA patients was calculated, and patients meeting the EULAR definition for at least 6 months were defined as persistent D2T-RA (pD2T-RA). Finally, the clinical characteristics associated with the time-based definition of pD2T-RA were analyzed. Results Among 610 adult RA patients, 104 were refractory to ≥ 2 treatments. Initially, 41.3% met D2T-RA criteria, but only 27.9% fulfilled persistent D2T-RA (pD2T-RA) criteria over 6 months. The pD2T-RA group was associated with male gender, higher HAQ and Charlson Comorbidity Index scores, more failed treatments, and use of non-NSAID analgesics. Logistic regression linked pD2T-RA to higher SDAI and CRP values, and the use of glucocorticoids or analgesics. Chronic use of glucocorticoids was strongly associated with pD2T-RA. Conclusions The application of a temporal criterion allowed for the selection of a subgroup of pD2T-RA patients who differ from those who meet the definition of D2T-RA only episodically. Chronic use of glucocorticoids was the factor most strongly associated with pD2T-RA status.

Hypersensitivity reactions affecting the oral mucosa present a significant clinical challenge due to their diverse manifestations and the wide range of potential allergens involved. This article explores the types of allergic reactions commonly observed in the oral cavity, including contact allergies and systemic allergic reactions, emphasising their clinical presentations and diagnostic approaches. Common allergens such as metals and resin-based dental materials are highlighted, discussing their impact on oral health. Diagnostic strategies, including clinical examination, history taking, cutaneous patch testing and histopathological evaluation, are assessed for their efficacy in establishing the diagnosis of an allergic reaction and in identifying specific allergens. Management and treatment options are also reviewed, focusing on allergen avoidance, pharmacological interventions, and the selection of hypoallergenic dental materials. This article underscores the importance of a multidisciplinary approach in improving diagnostic accuracy and therapeutic outcomes for patients with oral mucosal allergies.

Abstract Emerging infectious diseases are a major threat to biodiversity and an important public health issue. Flaviviruses are the cause of several emerging vector-borne zoonotic arboviruses whose distribution is currently increasing in Europe. The evidence that West Nile virus (WNV) circulates in resident and migratory species has implications for both animal and public health and should therefore be studied in depth. USUTU (USUV), Bagaza (BAGV) and tick-borne encephalitis virus (TBEV) are other viruses that are beginning to spread more widely. An integrated surveillance program, namely in birds, is essential for reducing the risk of infection in human populations within the One Health principles. In the present study, wild birds admitted to wildlife rehabilitation centers in Portugal were sampled. Two hundred eight blood samples were assayed serologically for antibodies to flaviviruses by using a commercial ELISA kit. An overall seroprevalence of 19.6% (95% confidence interval [CI]: 13.7–26.7%) was observed. Antibodies against flaviviruses were detected in 13 (35.1%) different species of wild birds. Accipitriformes (26.7%; 95% CI: 18.5–36.2%) and Strigiformes (26.7%; 95% CI: 14.6–42.0%) were the orders with the highest seroprevalence rates recorded. There were no statistically significant differences (p = 0.725) between the geographical regions (NUTS II) studied, but a statistically significant difference (p = 0.017) was found between sex (male: 34.4%; female: 4.8%). A higher seroprevalence was detected in adults (32.1%) than in juvenile birds (9.3%) (p = 0.014), and age was considered a risk factor for flavivirus infection in wild birds (odds ratio 1.4; 95% CI: 0.5–4.0). More epidemiological studies are needed in Portugal since the actual spread of the genus Flavivirus throughout the country is unknown.

Abstract Understanding long-term coastal changes requires comprehensive records of morphological data spanning extended periods, ideally over multiple decades. Nevertheless, significant challenges arise from the restricted availability and accessibility of reliable data, especially in the case of complex coastal systems dominated by wave-current dynamics, such as ebb-tidal deltas (ETDs). This study introduces a new dataset for Tagus ETD in central Portugal, from 1845 to 1985 based on historic nautical charts available for the area. The data includes: (1) high-resolution bathymetric surfaces of ETD configuration for years 1845, 1879, 1893, 1929, 1939, 1960 and 1985; (2) shoreline position of three different indicators (Low-Water Line, High-Water Line and foredune dune seaward limit) at the adjacent coast for the same years; (3) rates-of-change for shoreline position of the High-Water Line indicator. Data also includes an uncertainty assessment for hydrographical and shoreline position information estimated from historic nautical charts. These data provide a valuable resource for describing, understanding, and modelling the long-term behaviour of ETDs not covered by other currently available datasets.

Abstract Aim Functional Management and Recovery is a standardized Psychoeducational Intervention, derived from “Integro”, an effective salutogenic-psychoeducational intervention for people in recovery journey, designed to improve recovery and functioning of individuals with psychotic disorders in Psychiatric Residential Facilities (PRFs). The aim of this study is to evaluate the primary and secondary outcomes of this intervention elaborated specifically for PRFs where evidence based structured interventions seem rare and desirable. Methods 66 individuals with psychotic disorders were recruited in 9 PRFs dislocated in the North, Center and South Italy and 63 underwent a multicenter follow-up study with a two time-point evaluation (t0, pre-treatment and t1, 6 months; ). At each time point, social functioning was assessed as primary outcome by the Personal and Social Performance scale (PSP); furthermore, psychopathological status was assessed by Brief Psychiatric Rating Scale (BPRS), Recovery by Recovery Assessment Scale (RAS), Cognitive Functioning by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Stress management by Stress-Scale, Cognitive Flexibility by Modified Five-Point Test (M-FPT), Emotional Intelligence by Emotional Intelligence Index (EI-I), the PRF Atmosphere and the Opinion of users about the PFR by an ad hoc questionnaire. The Abilities Knowledge, the Utility and Pleasantness of sessions were measured by an ad hoc list of items. Results 63 individuals out of 66, 52 (82,5%) affected by schizophrenia and 11 (17,5%) by bipolar I disorder with psychotic symptoms according to DSM-5-TR completed the study. At the end of the study, 43 (68,3%) were male, 57 (90.5%) were single, 5 (7.9%) engaged, 1 (1.6%) married; 45 (71.4%) unemployed. The total scores of PSP, RAS, BPRS, BANS, Stress management, Abilities Knowledge, Utility and Pleasantness of sessions showed a statistically significant improvement at t1 vs. t0. Two sub-scales out of 5 of M-FPT showed a statistically significant improvement. The Emotional Intelligence, the Unit Atmosphere and the Opinion of Users about PFR improved without statistical significance. Six months after the end of the follow-up study 22 individuals of the sample were dismissed with a very high turnover. Conclusions After a six-month follow-up (a short period of time), these results showed improvement in functioning, the primary outcome, as well as in the following secondary outcome variables: RAS, BPRS, BANS, Stress management, Abilities Knowledge, two sub-scales out of 5 of M-FPT, Utility and Pleasantness of sessions. Overall, a remarkable impact of psychoeducational structured intervention on the key Recovery variables is observed. Further studies are needed to address extent and duration of these improvements.

Abstract This study aimed to investigate if washing ram sperm from seminal plasma (SP) could be an effective tool to extend sperm lifespan in medium-term preservation in liquid form to optimize ovine artificial insemination protocols. To this end, in Experiment 1 SP was added to a sperm model without previous contact with this substance (ram epididymal sperm) at the beginning or the end of a 48-hour preservation protocol at 5 °C (n = 13). Sperm motility and kinetic parameters and sperm functionality in terms of sperm viability, apoptosis, mitochondrial activity and reacted acrosomes were assessed after 6 h of storage at 15 °C (standard liquid preservation method) and 24 and 48 h at 5 °C. Extended sperm showed better results after 48 h when stored in the absence than in the presence of SP in most sperm quality parameters. Moreover, the final SP supplementation of this experimental group resulted in the highest sperm motility and kinetic parameters, viability and mitochondrial activity. These results suggested that initial SP deprivation could be beneficial in a medium-term ram sperm preservation protocol in liquid form, as well as a final supplementation. Therefore, we conducted Experiment 2 to evaluate the effect of SP removal from freshly ejaculated ram semen under the same storage conditions as in Experiment 1 (n = 12). Surprisingly, SP withdrawal impaired sperm functionality, leading to increased apoptosis and decreased mitochondrial activity after 24 and 48 h at 5 °C. Conversely, SP supplementation at the end of the preservation protocol of the ejaculate processed as usual had a positive effect on sperm quality and fertility. To summarize, SP absence was beneficial for a medium-term preservation protocol (up to 48 h at 5 °C) of ram epididymal sperm, but the same preservation protocol for ram ejaculated sperm revealed a possible failure of the SP removal method in avoiding the sperm-SP interaction effect. Meanwhile, SP supplementation of ram semen at the end of the preservation protocol increased in vitro sperm quality and fertility after artificial insemination.

Purpose To highlight the rarity of the endothelial rejection line, also known as the Khodadoust line, as a manifestation following Descemet’s stripping automated endothelial keratoplasty (DSAEK). The objective is to present a meticulously detailed case, including imaging and anterior optical coherence tomography (OCT), to enhance understanding and recognition of this phenomenon. Methods A detailed case presentation involving a 50-year-old male, 3 years post-DSAEK transplantation for endothelial damage resulting from intraocular surgeries. The patient urgently sought consultation due to vision loss while under daily fluorometholone use. Clinical examination revealed acute graft rejection characterized by corneal edema, anterior chamber reaction, and the presence of keratic precipitates forming a Khodadoust line. The management approach included the initiation of a tapered dexamethasone regimen. Results The identified acute graft rejection, marked by the presence of a Khodadoust line, demonstrated favorable responsiveness to the initiated tapered dexamethasone regimen. Corneal OCT and imaging played crucial roles in providing detailed insights into the manifestation. Conclusions While the endothelial rejection line (Khodadoust line) is a rare occurrence following DSAEK, this case underscores its potential association with graft rejection. The successful management outlined in this report suggests the importance of prompt recognition and appropriate anti-inflammatory intervention in such cases to achieve positive outcomes.

ABSTRACTIntroduction Zebrafishes represent a proven model for human diseases and systems biology, exhibiting physiological and genetic similarities and having innate and adaptive immune systems. However, they are underexplored for human vaccinology, vaccine development, and testing. Here we summarize gaps and challenges.Areas covered Zebrafish models have four potential applications: 1) Vaccine safety: The past successes in using zebrafishes to test xenobiotics could extend to vaccine and adjuvant formulations for general safety or target organs due to the zebrafish embryos’ optical transparency. 2) Innate immunity: The zebrafish offers refined ways to examine vaccine effects through signaling via Toll-like or NOD-like receptors in zebrafish myeloid cells. 3) Adaptive immunity: Zebrafishes produce IgM, IgD,and two IgZ immunoglobulins, but these are understudied, due to a lack of immunological reagents for challenge studies. 4) Systems vaccinology: Due to the availability of a well-referenced zebrafish genome, transcriptome, proteome, and epigenome, this model offers potential here.Expert Opinion It remains unproven whether zebrafishes can be employed for testing and developing human vaccines. We are still at the hypothesis-generating stage, although it is possible to begin outlining experiments for this purpose. Through transgenic manipulation, zebrafish models could offer new paths for shaping animal models and systems vaccinology.

IntroductionChronic obstructive pulmonary disease (COPD) is one of the world’s major public health problems. It is characterized by a major inflammatory response, where vitamin D, due to its role in regulating the immune system, and genetic variants involved in its metabolism may play an essential role. The aim of this study is to evaluate the association between 13 polymorphisms related to vitamin D metabolism and the COPD risk.Material and methodsA retrospective longitudinal study was designed in which 152 cases of COPD diagnosed at the University Hospital Virgen de las Nieves and 456 controls without the pathology, matched by age and sex, were included. The determination of the 13 polymorphisms was carried out using TaqMan™ probes.ResultsStatistical analysis showed that the AA genotype and the A allele of the CYP27B1 rs4646536 polymorphism may be associated with an increased risk of developing COPD according to genotypic models (OR = 2. 6; 95% CI = 1.38-5.22; p = 0.004), dominant (OR = 1.69; 95% CI = 1.15-2.5; p = 0.008), recessive (OR = 2.24; 95% CI = 1.22-4.41; p = 0.013) and additive (OR = 1.56; 95% CI = 1.18-2.08; p = 0.020) models. Likewise, the AA genotype and the A allele of the CYP2R1 rs10741657 polymorphism were also associated with the risk of developing COPD according to the genotypic (OR = 1.9; 95% CI = 1.06-3.36; p = 0.028) and additive (OR = 1.37; 95% CI = 1.04-1.81; p = 0.027) models. Likewise, an association was found between GATG (p = 0.002; OR = 2.05; 95%CI = 1.32-3.20) and AGGT (p < 0.0001; OR = 2.1e46; 95%CI = 2.1e46-2.1e46) haplotypes and an increased risk of COPD.ConclusionsWe can therefore conclude that those variants could be used in the early detection of the disease in the future.

Acute Myeloid Leukemia is mainly a disease of the elderly: however, the knowledge on the outcomes of treatment in core binding factor AML (CBFAML) in older population, is limited. We retrospectively collected data on 229 patients with CBF- AML followed long-term in the last two decades. A 5-year overall survival (OS) of 44.2% (95%CI, 39.9-47.5) and a 5-year event – free survival (EFS) of 32.9% (95%CI, 25.5-40.1) was observed. In a subgroup of >70-year patients who completed intensive therapy (induction + >3 courses of consolidation including autologous stem cell transplant: 10 patients) the median EFS was 11.8 months (95%CI, 9.4 – 15.2) and OS was 40.0% (95%CI, 36.4 – 44.1) at 5yr. In univariate analysis, age >70 (hazard ratio (HR) 1.78, [95%CI, 1.15 – 2.54], p=.008), failure to achieve remission following induction (HR, 8.96 [95%CI, 5.5 – 13.8], p=

La incorporación de actividades de trabajo en equipo en los programas de formación universitaria es esencial, ya que es una de las habilidades más valoradas para los profesionales en el campo de la ingeniería. La selección de los grupos de trabajo por parte del profesor es una estrategia que puede conducir a un mejor desempeño en las tareas colaborativas. Este estudio presenta los resultados de una investigación sobre los criterios conscientes para la selección de grupos de trabajo basados en los roles de los estudiantes. La investigación tuvo como objetivo analizar las dinámicas de trabajo en equipo entre estudiantes de diversas disciplinas dentro de los cursos de ingeniería. Se examinaron las opiniones de más de 600 estudiantes matriculados en 10 programas de grado y posgrado. Los resultados indican que los estudiantes de cursos avanzados se sienten más cómodos asumiendo el papel de líder, mientras que los estudiantes de primer año no tienen un perfil claramente definido. La evaluación de los estudiantes con esta metodología también muestra ciertas variaciones dependiendo del año y el tipo de actividad. En general, en los grupos con mejor rendimiento, la mayoría de los miembros reciben evaluaciones similares de sus compañeros. Abstract The incorporation of teamwork activities in university training programs is essential, as it is one of the most valued skills for professionals in the field of engineering. The selection of working groups by the teacher is a strategy that can lead to better performance in collaborative tasks. This study presents the results of research on the conscious selection criteria for group work based on students’ roles. The research aimed to analyze teamwork dynamics among students from various disciplines within engineering courses. The opinions of over 600 students enrolled in 10 undergraduate and postgraduate programs were examined. The results indicate that students in advanced courses feel more comfortable taking on the role of leader, while first-year students do not have a well-defined profile. The evaluation of students using this methodology also shows certain variations depending on the year and type of activity. Overall, in the highest-performing groups, most members receive similar evaluations from their peers.

Acromegaly is a rare endocrine disorder characterized by the excessive production of growth hormone (GH) in adulthood. Currently, it is understood that certain pituitary neuroendocrine tumors (PitNETs) exhibit a hereditary predisposition. These tumors’ genetic patterns fall into two categories: isolated and syndromic tumors. The isolated forms are characterized by molecular defects that predispose exclusively to PitNETs, including familial isolated pituitary adenomas (FIPAs) and sporadic genetic defects not characterized by hereditary predisposition. All the categories involve either germline or somatic mutations, or both, each associated with varying levels of penetrance and different phenotypes. This highlights the importance of genetic testing and the need for a more comprehensive view of the whole disease. Despite the availability of multiple treatment options, diagnosis often occurs after several years, and management is still difficult. Early detection and intervention are crucial for preventing complications and enhancing the quality of life for affected individuals. This review aims to elucidate the molecular, clinical, and histological characteristics of GH-secreting PitNETs, providing insights into their prevalence, treatment nuances, and the benefits of genetic testing for each type of genetic disorder associated with acromegaly.

Abstract Hand visibility affects motor control, perception, and attention, as visual information is integrated into an internal model of somatomotor control. Spontaneous brain activity, i.e., at rest, in the absence of an active task, is correlated among somatomotor regions that are jointly activated during motor tasks. Recent studies suggest that spontaneous activity patterns not only replay task activation patterns but also maintain a model of the body's and environment's statistical regularities (priors), which may be used to predict upcoming behavior. Here, we test whether spontaneous activity in the human somatomotor cortex as measured using fMRI is modulated by visual stimuli that display hands vs. non-hand stimuli and by the use/action they represent. A multivariate pattern analysis was performed to examine the similarity between spontaneous activity patterns and task-evoked patterns to the presentation of natural hands, robot hands, gloves, or control stimuli (food). In the left somatomotor cortex, we observed a stronger (multivoxel) spatial correlation between resting state activity and natural hand picture patterns compared to other stimuli. No task-rest similarity was found in the visual cortex. Spontaneous activity patterns in somatomotor brain regions code for the visual representation of human hands and their use.

Abstract ASCT2 is an obligate exchanger of neutral amino acids, contributing to cellular amino acid homeostasis. ASCT2 belongs to the same family (SLC1) as Excitatory Amino Acid Transporters (EAATs) that concentrate glutamate in the cytosol. The mechanism that makes ASCT2 an exchanger rather than a concentrator remains enigmatic. Here, we employ cryo-electron microscopy and molecular dynamics simulations to elucidate the structural basis of the exchange mechanism of ASCT2. We establish that ASCT2 binds three Na+ ions per transported substrate and visits a state that likely acts as checkpoint in preventing Na+ ion leakage, both features shared with EAATs. However, in contrast to EAATs, ASCT2 retains one Na+ ion even under Na+-depleted conditions. We demonstrate that ASCT2 cannot undergo the structural transition in TM7 that is essential for the concentrative transport cycle of EAATs. This structural rigidity and the high-affinity Na+ binding site effectively confine ASCT2 to an exchange mode.

Thermoplastic starch (TPS) has gained considerable attention during the last few years in developing starch-based biodegradable food packaging materials or edible coatings due to its high availability and low cost. TPS is manufactured from starch plasticized with food-grade plasticizers, making it suitable for food contact applications. In addition, TPS is bio-based and biodegradable, which, from an environmental perspective, closes the circle of the circular economy. However, the industrial application of TPS is somewhat limited due to its poor mechanical performance and low water resistance. However, the low water resistance could increase the water sensitivity of TPS, which could be advantageous for coating application or food encapsulation. The present work aims to tailor the water sensitivity of TPS by adding peach gum polysaccharide to obtain water-soluble films. With this aim, peach gum polysaccharide (PGP) was extracted from peach gum (PG) using the thermal hydrolysis method. Films of TPS-PG and TPS-PGP were prepared and characterized by their water sensitivity and mechanical, microstructural, and thermal properties. The results show that PGP allows the obtaining of films with water sensitivities higher than 70% but also improves TPS elongation at break, making the material more suitable for application as film.

La agricultura es una de las principales fuentes de contaminación difusa, cuya contaminación por nitrógeno y sedimentos de las son los principales impactos ambientales. Es por ello, que una adecuada gestión de estas zonas es necesaria. El presente estudio se llevó a cabo en la cuenca más meridional del Mar Menor, que se encuentra amenazado por la exportación difusa de nutrientes y sedimentos. Es por ello que este estudio evalúa la efectividad de varias actuaciones basadas en la Ley 3/2020, de recuperación y protección del Mar Menor para el control de las descargas de nitrógeno y sedimentos a la laguna. Los resultados de estas simulaciones mostraron que con el cumplimiento completo de la Ley 3/2020 es posible reducir de forma significativa la producción de sedimentos a la laguna, así como la exportación de nitrógeno en superficie y la lixiviación de nitratos.

In this work, we present a comprehensive overview of the genetic and non-genetic complexity of eosinophilic granulomatosis with polyangiitis (EGPA). EGPA is a rare complex systemic disease that occurs in people presenting with severe asthma and high eosinophilia. After briefly introducing EGPA and its relationship with the anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAVs), we delve into the complexity of this disease. At first, the two main biological actors, ANCA and eosinophils, are presented. Biological and clinical phenotypes related to ANCA positivity or negativity are explained, as well as the role of eosinophils and their pathological subtypes, pointing out their intricate relations with EGPA. Then, the genetics of EGPA are described, providing an overview of the research effort to unravel them. Candidate gene studies have investigated biologically relevant candidate genes; the more recent genome-wide association studies and meta-analyses, able to analyze the whole genome, have confirmed previous associations and discovered novel risk loci; in the end, family-based studies have dissected the contribution of rare variants and the heritability of EGPA. Then, we briefly present the environmental contribution to EGPA, reporting seasonal events and pollutants as triggering factors. In the end, the latest omic research is discussed and the most recent epigenomic, transcriptomic and microbiome studies are presented, highlighting the current challenges, open questions and suggesting approaches to unraveling this complex disease.

Abstract Background In standard weaning from mechanical ventilation, a successful spontaneous breathing test (SBT) consisting of 30 min 8 cmH2O pressure-support ventilation (PSV8) without positive end-expiratory pressure (PEEP) is followed by extubation with continuous suctioning; however, these practices might promote derecruitment. Evidence supports the feasibility and safety of extubation without suctioning. Ultrasound can assess lung aeration and respiratory muscles. We hypothesize that weaning aiming to preserve lung volume can yield higher rates of successful extubation. Methods This multicenter superiority trial will randomly assign eligible patients to receive either standard weaning [SBT: 30-min PSV8 without PEEP followed by extubation with continuous suctioning] or lung-volume-preservation weaning [SBT: 30-min PSV8 + 5 cmH2O PEEP followed by extubation with positive pressure without suctioning]. We will compare the rates of successful extubation and reintubation, ICU and hospital stays, and ultrasound measurements of the volume of aerated lung (modified lung ultrasound score), diaphragm and intercostal muscle thickness, and thickening fraction before and after successful or failed SBT. Patients will be followed for 90 days after randomization. Discussion We aim to recruit a large sample of representative patients (N = 1600). Our study cannot elucidate the specific effects of PEEP during SBT and of positive pressure during extubation; the results will show the joint effects derived from the synergy of these two factors. Although universal ultrasound monitoring of lungs, diaphragm, and intercostal muscles throughout weaning is unfeasible, if derecruitment is a major cause of weaning failure, ultrasound may help clinicians decide about extubation in high-risk and borderline patients. Trial registration The Research Ethics Committee (CEIm) of the Fundació Unió Catalana d’Hospitals approved the study (CEI 22/67 and 23/26). Registered at ClinicalTrials.gov in August 2023. Identifier: NCT05526053.

Abstract Morgana is a ubiquitous HSP90 co-chaperone protein coded by the CHORDC1 gene. Morgana heterozygous mice develop with age a myeloid malignancy resembling human atypical myeloid leukemia (aCML), now renamed MDS/MPN with neutrophilia. Patients affected by this pathology exhibit low Morgana levels in the bone marrow (BM), suggesting that Morgana downregulation plays a causative role in the human malignancy. A decrease in Morgana expression levels is also evident in the BM of a subgroup of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients showing resistance or an incomplete response to imatinib. Despite the relevance of these data, the mechanism through which Morgana expression is downregulated in patients’ bone marrow remains unclear. In this study, we investigated the possibility that Morgana expression is regulated by miRNAs and we demonstrated that Morgana is under the control of four miRNAs (miR-15a/b and miR-26a/b) and that miR-15a may account for Morgana downregulation in CML patients.

Apresentação ao dossiê dedicado ao antropólogo, filósofo e historiador das religiões italiano Ernesto de Martino (1908- 1965), uma figura central na história do pensamento europeu do século XX, quase desconhecida no Brasil.

La fine del Mondo é o título que Ernesto de Martino queria dar a uma obra na qual trabalhou intensamente durante vários anos, a partir do final da década de 1950 e que a morte prematura, em 1965, não permitiu terminar. O densíssimo material composto por anotações, análises críticas de uma enorme literatura, trechos já completos da obra em projeto, foi publicado uma primeira vez em 1977 e numa segunda edição francesa, totalmente reorganizada, em 2016. O tema do Fim do Mundo é analisado pelo autor em seu duplo aspecto: como tema cultural historicamente determinado (na escatologia protocristã, nos movimentos proféticos e milenaristas dos povos oprimidos) e como risco antropológico permanente, dramaticamente ilustrado pela literatura psicopatológica. A partir da perspectiva comparativa, de Martino reflete sobre os significados dos apocalipses em vários momentos e lugares, trazendo a análise antropológica para o coração da própria cultura ocidental.

La Educación para la Ciudadanía Mundial (ECM) ha evolucionado como un enfoque holístico para desarrollar una comunidad global comprometida con el desarrollo sostenible. Esta investigación evalúa su aplicación en dos fases: una histórica, explorando su evolución desde los inicios de la Unesco hasta hoy, y otra centrada en los resultados actuales de informes de la Unesco sobre la ECM en su aplicación en leyes, planes de estudio, evaluación y formación. Se concluye que, pese a su reciente consolidación en los Objetivos de Desarrollo Sostenible, la ECM está en una etapa inicial en la acción política. Aunque la mayoría de los países muestran compromiso, se necesitan mayores esfuerzos en todas las áreas evaluadas para una integración más sólida y efectiva.

The study aimed to present the characteristics of the three most prevalent oral potentially malignant disorders, leukoplakia, oral lichen planus (OLP), and actinic cheilitis, using data from 62 patients collected at the “Sfântul Spiridon” Emergency Clinical Hospital in Iași, Romania, between January 2015 and January 2023. The results revealed a higher prevalence of these lesions among older adults, particularly those over 50 years old, and a significant gender disparity in the incidence of actinic cheilitis, which was more common in males (68%). Leukoplakia was frequently observed on the tongue and lower lip, whereas OLP commonly affected the buccal mucosa. Actinic cheilitis was primarily noted on the lower lip, attributed to chronic sun exposure. The study highlighted the importance of early detection and regular monitoring of these conditions to prevent malignant transformation.

Oral lichen planus (OLP) is a chronic inflammatory condition that poses significant therapeutic challenges. Emerging evidence suggests that topical Janus Kinase (JAK) inhibitors could represent a novel treatment paradigm for OLP. This review explores the pathophysiology of OLP, highlighting the role of the JAK-STAT pathway in its pathogenesis. We discuss the current landscape of topical JAK inhibitors, including their mechanism of action, efficacy, and safety profile. The review also examines recent clinical trials and observational studies that shed light on the potential of these agents in managing OLP. Finally, we provide a perspective on the future of JAK inhibitors in the context of OLP treatment, considering both their therapeutic potential and the need for further research.

Resumen: Los y las profesionales que trabajan con mujeres víctimas de violencia de género se enfrentan con situaciones emocionales difíciles, y es importante ser consciente de las emociones y sentimientos que generan las actitudes y comportamiento de las mujeres y sus agresores, porque pueden convertirse en barreras para la comunicación y afectar seriamente a la relación profesional con las víctimas. Además, pueden producir situaciones de estrés mantenido que pueden llegar al agotamiento emocional y afectar a su salud, a su vida y a su desempeño laboral. Describimos las consecuencias, los factores de riesgo y las señales de alarma, así como los factores de protección o resiliencia, que es importante conocer, y, finalmente, enumeramos los retos actuales y algunas recomendaciones para los y las profesionales y la administración a fin de ayudar a prevenir estos efectos y mejorar el desempeño profesional sin riesgos para la salud. Abstract: Professionals who work with women victims of gender violence face difficult emotional situations, and it is important to be aware of the emotions and feelings that the attitudes and behaviour of victims and aggressors generate in them. These emotions can become barriers to communication and seriously affect the professional's relationship with victims. Furthermore, they can generate situations of sustained stress, lead to emotional exhaustion, and affect their health, life, and work performance. We describe the consequences, risk factors and warning signs, as well as protective or resilience factors, that are important to know, and we list the current challenges and some recommendations for professionals and management in order to help prevent such effects and improve professional performance without health risks.

IntroductionImmunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC).MethodsOpen-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study.Results125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) (p

Purpose: In this study, we aimed to compare closure of the incision for external dacryocystorhinostomy (ext-DCR) by suturing with 6-0 Prolene versus closure with 2-octyl cyanoacrylate and assess the results in terms of the aesthetic and functional aspects of the scar, operating time, postoperative symptoms and complications, and the economic cost of the two techniques. Methods: Sixty-three patients with distal lacrimal obstruction and indication of ext-DCR were initially enrolled in a longitudinal prospective cohort study. Patients underwent ophthalmologic evaluations including lacrimal probing, external examination with photograph, measurement of the surgical wound, timing the cutaneous closure phase of the surgery, recording postoperative wound pain using visual analog scale (VAS), and recording the patient’s and clinician’s subjective satisfaction with the scar using Patient and Observer Scar Assessment Scale (POSAS) at 6 months postsurgery. The 63 eyes were divided into two groups: the wounds in group 1 were closed with 6-0 Prolene using continuous locking suture and the wounds in group 2 were closed with 2-octyl cyanoacrylate. Results: There was no difference in baseline characteristics (age, sex, and race), and no statistically significant differences were found in wound length, POSAS score, VAS score, or serious complications of the wound between the two groups. There were differences in surgery time and economic cost for group 2 compared to group 1 of -2.39 min and -€5.37/operation, respectively. Conclusion: This is the first study in the literature that compares 6-0 Prolene versus Dermabond®. The latter one presents advantages compared to Prolene, given that it reduces the length of surgery, reduces costs, and allows for greater flexibility in postoperative follow-up visits.

In theory, geopolitical risk and political uncertainty can directly affect energy markets. Fluctuations lead to the cost of clean energy sources as they compete with traditional energy. The purpose of this study is to analyse financial integration and test the diversifying asset hypothesis between clean energy indices, specifically the Clean Energy Fuels (CLNE), Nasdaq Clean Edge Green Energy (CELS), S&P Global Clean Energy (SPGTCLEN), TISDALE Clean Energy (TCEC.CN), Wilderhill (ECO) and West Texas Intermediate (WTI) stock indices, over the period from 1 January 2018 to 23 November 2023. Analysing the results reveals a scenario where most of the clean energy indices show cointegration with each other, indicating long-term relationships that reflect common trends in the clean energy sector. However, the relative independence of the WTI suggests that Oil still acts as an important and potentially diversifying external factor for investors focused on sustainable energy. Structural breaks in 2021 and 2022 in several indices point to significant events that have altered market dynamics, possibly including changes in environmental policies, technological innovations and the impacts of the COVID-19 pandemic. The cointegration evidence and structural breaks provide valuable information for building investment portfolios. Investors can consider the WTI to diversify portfolios dominated by clean energy assets, taking advantage of Oil’s relative independence. On the other hand, the high correlation between clean energy indices suggests that, within this sector, diversification options are more limited, requiring careful analysis of the specific characteristics of each index and the macroeconomic forces affecting them.

People with injuries to the peripheral nervous system suffer from paralysis of the facial muscles, fingers and hands or toes and feet, often for the rest of their lives, due to its poor functional regeneration. Therefore, to improve patients’ quality of life, there is an urgent need for conduits that effectively support the healing of large defects in nerve pathways through specific guidance of nerve cells. This paper describes two specific methods for achieving directed growth of Schwann cells, a type of glial cells that can support the regeneration of the nerve pathway by guiding the neuronal axons in the direction of their alignment. One method uses aligned polyamide-6 (PA-6) nanofibers produced via electrospinning on a very fast rotating structured collector, which enables easy nanofiber detachment, without additional effort. The other method implies the exposure of a poly(ethylene terephthalate) (PET) foil to a KrF* laser beam, that renders a nanorippled surface topography. Schwann cell growth on these substrates was inspected after one week of cultivation by means of scanning electron microscopy (SEM). For both methods we show that Schwann cells grow in a certain direction, predetermined by nanofiber and nanoripple orientation. In contrast, cells cultivated on randomly oriented nanofibers or unstructured surfaces, show an omnidirectional growth behavior. These two methods can be used to produce nerve conduits for the treatment of injuries to the peripheral nervous system.

En el español de Canarias parece que el estándar nacional coexiste con una norma regional, la canaria, aún por definir en el nivel morfosintáctico. Carecemos de estudios empíricos que informen sobre el estatus variacional de muchas construcciones que se vienen registrando en el archipiélago desde hace décadas y que son diferenciales respecto al estándar europeo. El objetivo principal de este trabajo es plantear los problemas de desorientación normativa que se derivan de esta situación. Para ello se analiza el proceso de normalización lingüística iniciado en Canarias, se presenta una nómina de fenómenos morfosintácticos de estatus indefinido y, en el caso de tres variables, los resultados obtenidos en un cuestionario sociolingüístico dirigido a estudiantes universitarios canarios.

Accurately modelling the propagation of radiant intensity in aqueous environments poses significant challenges for both academia and industry, due to complex interactions like absorption, scattering, and reflection. This study aims to improve the accuracy of optical modeling in water-based systems by comparing experimental data with numerical simulation techniques, addressing the need for more reliable simulation methods in multiple applications like treatment of water and environmental monitoring.Implementation has been done by analyzing how the method compares with the discrete ordinate method, radiometry, and actinometry. The study further quantifies the effect of the photoreactor quartz tube on measured intensity for multiple wavelengths. Losses in light intensity are estimated to be 10 ± 0.5% for FX-1 265 source. In contrast, the simulation in a water medium showed an increase of up to 64% in the light intensity delivered to the central part of the tube due to internal reflections and scattering. Model predictions from ray tracing successfully compared with the Discrete Ordinate Method (DOM) and experimental data (within ± 6%), ensuring the accurate design of complex systems for water disinfection. The data from simulations is seen to tackle challenges faced in complex radiation modeling and demonstrates that the method can be utilized as a useful tool for optimization and prediction.

Long-term tolerance in the absence of immunosuppressive drugs is a major goal in the transplantation field, not yet attained. Recent research on the role of commensal microbiota in the control of immunity has opened new avenues for the search of novel clinical interventions. Indeed, products of intestinal metabolism generated by both host cells and the microbiota have been identified as modulators of the immune response. Among these, tryptophan (Trp) and its derivatives are being investigated to understand their impact on alloimmunity and their potential usefulness as therapeutic targets to improve allograft survival. Here, we reviewed the latest findings on the contribution of Trp metabolic pathways to transplant outcomes.

ABSTRACT Purpose: Illicit cosmetic injections remain highly prevalent and can cause serious complications, including death. We aimed to explore existing literature regarding the use of illicit cosmetic injections globally. Methods: We searched six databases with no language restriction from inception to 2022. We included all articles focused on adult patients of any gender who received any illicit cosmetic injection. Screening and data extraction followed standards from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews guidelines. Results: After screening 629 abstracts and 193 full texts, 142 citations were included. We identified articles from 28 countries and three multi-country studies. Most were from high-income (75.3%) and upper-middle-income countries (21.8%). Of all patients whose gender identity was described, 49.9% were transgender women, and 40.8% were cisgender women. The anatomic regions most frequently injected were the buttocks (35%) and the breast (13.3%). The most frequently described complications were granuloma (41.5%), dermatological problems (41.5%), infection (35.9%), and pulmonary complications (34.5%). Conclusions: We observed the impact of illicit silicone injections, particularly on cisgender women and transgender individuals. Existing barriers must be addressed, including healthcare prejudice and inadequate knowledge about care for gender minorities. This will require educating at-risk groups and enhancing policies to regulate these procedures.

ABSTRACT The study aimed to describe the epidemiology of multidrug-resistant (MDR) bacteria among solid cancer (SC) patients with bloodstream infections (BSIs), evaluating inappropriate empiric antibiotic treatment (IEAT) use and mortality trends over a 25-year period. All BSI occurrences in adult SC patients at a university hospital were analyzed across five distinct five-year intervals. MDR bacteria were classified as extended-spectrum beta-lactamases (ESBL)-producing and/or Carbapenem-resistant Enterobacterales, non-fermenting Gram-negative bacilli (GNB) resistant to at least three antibiotic classes, methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococci. A multivariate regression model identified the risk factors for MDR BSI. Of 6,117 BSI episodes, Gram-negative bacilli (GNB) constituted 60.4% (3,695/6,117), being the most common are Escherichia coli with 26.8% (1,637/6,117), Klebsiella spp. with 12.4% (760/6,117), and Pseudomonas aeruginosa with 8.6% (525/6,117). MDR-GNB accounted for 644 episodes (84.8% of MDR or 644/759), predominantly ESBL-producing strains (71.1% or 540/759), which escalated significantly over time. IEAT was administered in 24.8% of episodes, mainly in MDR BSI, and was associated with higher mortality (22.9% vs. 14%, P < 0.001). Independent factors for MDR BSI were prior antibiotic use [odds ratio (OR) 2.93, confidence interval (CI) 2.34–3.67], BSI during antibiotic treatment (OR 1.46, CI 1.18–1.81), biliary (OR 1.84, CI 1.34–2.52) or urinary source (OR 1.86, CI 1.43–2.43), admission period (OR) 1.28, CI 1.18–1.38, and community-acquired infection (OR 0.57, CI 0.39–0.82). The study showed an increase in MDR-GNB among SC patients with BSI. A quarter received IEAT, which was linked to increased mortality. Improving risk assessment for MDR infections and the judicious prescription of empiric antibiotics are crucial for better outcomes.IMPORTANCEMultidrug-resistant (MDR) bacteria pose a global public health threat as they are more challenging to treat, and they are on the rise. Solid cancer patients are often immunocompromised due to their disease and cancer treatments, making them more susceptible to infections. Understanding the changes and trends in bloodstream infections in solid cancer patients is crucial, to help physicians make informed decisions about appropriate antibiotic therapies, manage infections in this vulnerable population, and prevent infection. Solid cancer patients often require intensive and prolonged treatments, including surgery, chemotherapy, and radiation therapy. Infections can complicate these treatments, leading to treatment delays, increased healthcare costs, and poorer patient outcomes. Investigating new strategies to combat MDR infections and researching novel antibiotics in these patients is of paramount importance to avoid these negative impacts.

We evaluated response to VEN/HMA in 46 patients with acute myeloid leukemia (AML) characterized by extramedullary disease (EMD). Median age was 65 (range, 19-81) years. Patients had a median of two EMD sites (range, 1-5) and 35 (76%) patients had concurrent bone marrow involvement. Twenty (43%) patients had highrisk genetic features according to the European Leukemia Net 2022 classification. Twenty-nine (63%) were relapsed or refractory after intensive chemotherapy (CTX) including 13 (28%) with prior allogeneic hematopoietic cell transplantation (allo-HCT). Patients received a median of 2 cycles of VEN/HMA (range, 1-31). Twenty (43%) patients achieved complete remission (CR) or CR with incomplete hematological recovery (CRi) after VEN/HMA and five (11%) achieved a partial remission (PR). Six patients were subsequently consolidated with allo-HCT (CR/CRi, n=4; PR, n=2). Median follow-up was 49.1 months (95%-CI, 26.1 months - not reached) and median overall survival (OS) 6.4 months (95%-CI, 5.1-11 months). One-year and 2-years OS rates were 29.3% (95%-CI, 18.6-46.2%) and 12.3% (95%-CI, 5.5-27.6%), respectively. Age with a cut-off of 60 years had no impact on OS (P=0.90). Relapse occurred in 12 of 20 (60%) patients who achieved CR/CRi after VEN/HMA treatment. Of those, all except one succumbed to their disease. Six (30%) patients were in CR/CRi at last follow-up and 2 (10%) died in CR. In our cohort of patients with AML with EMD with high-risk features, treatment with VEN/HMA resulted in an encouraging ORR of 54% with a CR/CRi rate of 43.5%. However, VEN/HMA alone may not be effective in maintaining disease control.

More studies should adopt a combined approach to modifiable lifestyle behaviors because of their potential synergistic effects on health. This study aims to • observe how boys and girls allocate their time on different activities, during week and weekend days, • investigate the time inter-relations between different leisure activities, and • analyze how child and familial characteristics are associated with children’s time use in multiple activities. In 2016/17, a validated questionnaire collected data from 3-10-year-old Portuguese children (n = 8,472). Parents reported their children’s time use in different behaviors: sleep, study, screen media use, indoor and outdoor play, and school commute, as well as children’s participation in sports, and socio-economic characteristics of the family. A combination of statistical analysis (e.g., t-tests, pairwise correlations and multiple linear regression) revealed that: • boys reportedly have higher screen time than girls, but they also accumulate more time in outdoor play; • the time spent in different activities was determined by a set of family sociodemographic factors, such as urbanization and parental employment; and • exists some inter-relation between leisure activities with high screen time being significantly associated with less sport participation and less sleep duration. Identifying time spent in multiple activities that differ by sex (and associated determinants) is critical for the development of activity promotion strategies, and may help to inform evidence-based policies designed to increase physical activity and decrease sedentary behavior in young children. Present findings highlight the growing importance of electronic media in children’s life and how they can displace other leisure activities.

Nurseries and greenhouses face challenges of limited water supply and increased demand for irrigation efficiency to minimize runoff and mitigate water loss to the environment. Overhead irrigation systems are among the most widely used methods for container plants, particularly in small container sizes. However, there is a lack of research examining the distribution uniformity (DU) of the most used sprinklers in nursery settings. Our study investigated the DU of different overhead sprinkler types and models commonly used in outdoor nurseries in the United States to guide greater adoption of higher irrigation efficiency technology. Catch-can experiments compared ten different sprinkler models in small (4.6 m × 4.6 m) and large (9.1 m × 9.1 m) square experimental plots in Irvine, California. We measured water volume, wind speed, and operating pressure, and calculated the application rate for 189 test runs conducted between Mar 2020 and May 2023. Our results show that of the models tested, the greatest DU was achieved by the Hunter MP2000 at 276 kPa (DU = 0.78 ± 0.05) in the small spacing, and the Senninger Xcel Wobbler with a 3.97 mm nozzle at 172 kPa (DU = 0.76 ± 0.06) in the large spacing. Wind speed and operating conditions affected the DU and spatial uniformity of irrigation among the ten models, highlighting the importance of maintaining operating pressures at the manufacturer's recommendations to ensure optimal application rates and DU. Together these results offer a quantitative comparison of sprinkler performance at different operating pressure and in a wide range of wind speeds, allowing users to select sprinkler models that best fit their operation and maximize water conservation.

Resumen: Objetivo: Describir los problemas relacionados con la medicación (PRM) detectados y su resolución tras la intervención farmacéutica en la revisión del tratamiento de pacientes mayores polimedicados institucionalizados. Diseño: Estudio descriptivo de una cohorte de seguimiento retrospectivo, de enero a octubre de 2022. Emplazamiento: Doce centros residenciales de la Comunidad de Madrid. Participantes: Se incluyeron 295 pacientes de 65 o más años con 5 o más medicamentos prescritos de forma crónica. Intervenciones: Revisiones de tratamiento realizadas por el farmacéutico de atención primaria con posterior valoración de las propuestas de mejora, en reuniones presenciales con el médico de atención primaria y médico del centro residencial. Mediciones principales: Problemas relacionados con la medicación, tipos y resolución. Sexo, edad, número de medicamentos antes y después de la intervención. Subgrupos farmacológicos según la clasificación anatómica terapéutica química (ATC) y principios activos implicados en los PRM. Resultados: Se detectaron 1.425 PRM, con una media de 4,85 (DE: 3,33) PRM/paciente. El PRM más frecuente fue el error de conciliación (32,52%), seguido de pauta y posología (15,72%). De las 1425 propuestas de mejora, se aceptaron el 86,73%. Se observaron diferencias estadísticamente significativas entre el número de fármacos después de la revisión (10,20) y antes de la revisión (12,29) con una diferencia de medias de 2,09 (IC 95%: 1,98-2,21; p

ABSTRACT Objectives: to validate the content of a guidance guide on self-care in the postoperative period of breast surgery for breast cancer. Methods: a methodological study with content validity, carried out with 15 expert nurses and physiotherapists, between May and July 2022. Recruitment took place from the Lattes Platform, using snowball sampling. The level of relevance and representativeness for each item was verified using the Content Validity Index (CVI). It was considered valid when CVI was equal to or greater than 78% (0.78). Results: from the initial total of 37 items, two were excluded, as they had insufficient practical relevance and theoretical relevance, and another five items which, although presenting a CVI lower than the established cut-off, were suggested to be rewritten and grouped with other similar items. Conclusions: thirty items were considered valid and demonstrated important and significant characteristics, constituting suitable material for application in clinical practice.

Wildfires are natural phenomena for most ecosystems on Earth. Many soil properties are impacted by fire, including soil hydraulic properties. We used a laboratory experiment to replicate the temperatures reached by a natural wildfire and documented the effects on soil hydraulic properties. This study hypothesizes that the impact of heating on soil hydrological properties can be explained by the interaction of a number of variables especially organic matter content (OM), cation exchange capacity (CEC), texture, pH, and electrical conductivity (EC). The main objective of this study is to explore the interconnections between soil hydraulic, chemical, and physical properties, focusing on understanding how these relationships change across different ecoregions and temperatures. Sixteen soils were collected across 16 sites susceptible to forest fires in the Central Zone of Chile and heated to 100 °C and 300 °C for two hours. These sites were representative of two distinct ecoregions: the Chilean Matorral (CM) and the Valdivian Temperate Forests (VTF). Chemical, physical, and hydraulic soil properties were measured before and after heating. At 100 °C, there were no significant changes in chemical, physical, or hydraulic soil properties. At 300 °C, significant changes were observed in most soil properties in soils from both ecoregions. The OM content and CEC decreased, whereas pH and electrical conductivity increased. In addition, clay content and water aggregate stability (WSA) decreased, while all hydraulic properties increased their values. The aforementioned results demonstrate that infiltration increased after the soil was heated. This can be attributed primarily to decreases in clay content. At the same time, the water repellency (R) index decreased, allowing water to more easily wet the soil particles. Correlations revealed that CEC and clay are the main factors ruling soil hydraulic properties at all temperatures. Clay mineralogy also contributes to the soil hydraulic behavior observed. Nonlinear models were developed to estimate hydraulic properties at 100 °C and 300 °C, using the main soil properties. The models illustrated that the soils of the CM ecoregion, which are characterized by lower OM and influence of clay/CEC ratio, would be less affected by fire compared to the soils of VTF. The water holding capacity would decrease in both ecoregions. However, due to the greater changes in OM and clay in VTF, the impact would be greater than in CM.11 Ca2+ = Calcium cations (meq/ 100g); CEC = Cation exchange capacity (meq/ 100g); CM = Chilean Matorral; EC = Electrical conductivity (μS/cm); I = Cumulative infiltration (cm); K = Unsaturated hydraulic conductivity (mm/h); K+ = Potassium cations (meq/ 100g); Ks = Saturated hydraulic conductivity (mm/h); Mg2+ = Magnesium cations (meq/100g); Na+ = Sodium cations (meq/100g); OM = Organic matter (g/100g); R index = Water repellency index; Se = Ethanol sorptivity (cm/s05); Sw = Water sorptivity (cm/s05); VTF = Valdivian Temperate Forest; WSA = Water-stable aggregates (%).

Waste management is now a major global concern. Therefore, the circular economy (CE) and sustainable technology have become the necessary means of achieving sustainable business development. In this study, we conduct an analysis of the waste recovery sector in Spain to determine whether the most innovative and socially aware companies complied with sustainable development goal (SDG) 5 (gender equality) and SDG 8 (decent work and growth) during the period 2019–2021 (pre-Coronavirus Disease 2019, (pre-COVID-19), during COVID-19, and post-COVID-19). To this end, based on factors comprising economic and financial variables, the companies were grouped via a cluster analysis using the k-means method; they were linked to the SDGs (5 and 8) in order to determine the compliance of this sector. The results indicate that the technological transformations carried out by the waste valorization companies were reflected in their financial performance, with an increase in revenues of 61 % between 2019 and 2021; all clusters complied with SDG 8. However, despite promoting business transformation, social change, sustainable technology, and CE, these companies are far from compliant with SDG 5; indeed, a setback in social development was observed, with a significant decline in the number of women in positions of power after COVID-19. This therefore constitutes one of the greatest challenges for companies in this sector.

Abstract In the past, several wild plants were widely consumed as food by humans. Dandelion [Taraxacum officinale (L.) Weber ex F.H. Wigg] is a wild species with remarkable nutritional and medicinal properties. Many studies have investigated the chemical components of the plant for human health. Nonetheless, little research has been carried out on the cultivation and related production of this species. With this study, we intend to investigate some cultural practices to start defining an efficient protocol for dandelion cultivation in northern Italy. Two seeding rates (0.14 and 0.55 g m−2) and two harvest regimes (when leaves reached a length of 20 cm and 1 week later) were compared. Leaf fresh weight yield was determined at each harvest, and the following morphological parameters were measured: plant height, number of plants per square meter, number of leaves per square meter, leaf area index, number of leaves per plant, leaf weight, and specific leaf weight. The productivity of dandelion was found to be unaffected by the seeding rate, and no significant differences were found between harvest regimes. The delayed harvest regime was only advantageous at the first cut as it allowed for a longer establishment phase, resulting in a higher yield. The nitrate content in the leaves differed between the first two cuts and the third and fourth cuts with both harvest regimes and both sowing rates.

IntroductionSlip-related falls are a significant concern, particularly for vulnerable populations such as the elderly and individuals with gait disorders, necessitating effective preventive measures. This manuscript presents a biomechanical study of how the lower limbs react to perturbations that can trigger a slip-like fall, with the ultimate goal of identifying target specifications for developing a wearable robotic system for slip-like fall prevention.MethodsOur analysis provides a comprehensive understanding of the natural human biomechanical response to slip perturbations in both slipping and trailing legs, by innovatively collecting parameters from both the sagittal and frontal plane since both play pivotal roles in maintaining stability and preventing falls and thus provide new insights to fall prevention. We investigated various external factors, including gait speed, surface inclination, slipping foot, and perturbation intensity, while collecting diverse data sets encompassing kinematic, spatiotemporal parameters, electromyographic data, as well as torque, range of motion, rotations per minute, detection, and actuation times.ResultsThe biomechanical response to slip-like perturbations by the hips, knees, and ankles of the slipping leg was characterized by extension, flexion, and plantarflexion moments, respectively. In the trailing leg, responses included hip flexion, knee extension, and ankle plantarflexion. Additionally, these responses were influenced by gait speed, surface inclination, and perturbation intensity. Our study identified target range of motion parameters of 85.19°, 106.34°, and 95.23° for the hips, knees, and ankles, respectively. Furthermore, rotations per minute values ranged from 17.85 to 51.10 for the hip, 21.73 to 63.80 for the knee, and 17.52 to 57.14 for the ankle joints. Finally, flexion/extension torque values were estimated as −3.05 to 3.22 Nm/kg for the hip, −1.70 to 2.34 Nm/kg for the knee, and −2.21 to 0.90 Nm/kg for the ankle joints.DiscussionThis study contributes valuable insights into the biomechanical aspects of slip-like fall prevention and informs the development of wearable robotic systems to enhance safety in vulnerable populations.

IntroductionThere has been a dramatic global surge in dengue fever (DF) in recent years, with a projected 100-400 million cases annually and large outbreaks expected every 3-4 years. This concerning scenario is in sharp contrast to the very low availability of dengue vaccines to meet this spiraling demand, particularly affecting developing countries in Latin America and Africa. In our study, we aim to identify current vaccine development constraints, from a technological perspective, based on clinical trials and patent landscape data.MethodsThis study was conducted in a two-step methodology. First, candidates and launched products and methods used in the development or as part of DF vaccines were identified from the Cortellis Drug Discovery Intelligence (CDDI) platform. Second, the Derwent Innovation database was used to retrieve patent documents related to dengue vaccines. Data were collected in the period 2014-2024 (to identify the candidate and or launched vaccines) and 2018-2022 (to identify patent documents) with claims involving applications for dengue vaccine development. We presented these descriptive data in the following format: quantitative and qualitative assessments describing the vaccine development scenario and the claimed vaccine technologies.ResultsOur study indicated that 65% of dengue vaccines are still in phase 1 of development. The few current dengue vaccines that have reached phase 3 (1) and launched (2) have shown limited levels of individual protection for one or more dengue serotypes and there is an anemic pipeline of the next generation of more effective tetravalent dengue vaccines. Although the intelligent use of multiple dengue vaccine formulations in immunization campaigns can result in effective protection against all serotypes at the population level, the implementation of this is complex and challenging. The results of our study thus provide evidence of a worrisome global situation regarding the development of new dengue vaccine candidates.ConclusionTo reverse this scenario, there is an urgent need to implement new knowledge governance approaches and business models to stimulate an exponential increase in global vaccine development funding for dengue and several other vaccines.

Abstract Melanoma heterogeneity is a hurdle in metastatic disease management. Although the advent of targeted therapy has significantly improved patient outcomes, the occurrence of resistance makes monitoring of the tumor genetic landscape mandatory. Liquid biopsy could represent an important biomarker for the real-time tracing of disease evolution. Thus, we aimed to correlate liquid biopsy dynamics with treatment response and progression by devising a multiplatform approach applied to longitudinal melanoma patient monitoring. We conceived an approach that exploits Next Generation Sequencing (NGS) and droplet digital PCR, as well as the FDA-cleared platform CellSearch, to analyze circulating tumor DNA (ctDNA) trend and circulating melanoma cell (CMC) count, together with their customized genetic and copy number variation analysis. The approach was applied to 17 stage IV melanoma patients treated with BRAF/MEK inhibitors, followed for up to 28 months. BRAF mutations were detected in the plasma of 82% of patients. Single nucleotide variants known or suspected to confer resistance were identified in 70% of patients. Moreover, the amount of ctDNA, both at baseline and during response, correlated with the type and duration of the response itself, and the CMC count was confirmed to be a prognostic biomarker. This work provides proof of principle of the power of this approach and paves the way for a validation study aimed at evaluating early ctDNA-guided treatment decisions in stage IV melanoma. The NGS-based molecular profile complemented the analysis of ctDNA trend and, together with CMC analysis, revealed to be useful in capturing tumor evolution.