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Abstract Freshwater systems provide key pathways for microplastic (MP) pollution, and although existing studies have demonstrated the susceptibility of freshwater biota to ingestion, translocation, and trophic transfer, specific challenges pertaining to methodological standardization remain largely unresolved, particularly with respect to isolating, characterizing, and assessing MPs. Here, a critical review is performed outlining the challenges and limitations currently faced by freshwater MP researchers, which may well apply across the MP research spectrum. Recommendations are provided for methodological standardization, particularly in MP characterization, quality assurance, and quality control (QA/QC) procedures as well as reporting. Considerations for the assessment of MPs in freshwater biota as a means of improving comparisons between studies are discussed. Technological advancements, including the improvement of laboratory infrastructure for identifying MPs within the smaller size range as well as methodological standardization are essential in providing policy makers with tools and measures necessary to determine the distribution of MPs within freshwater ecosystems, while also allowing for comparability and providing compliance for future monitoring requirements.

El presente artículo de investigación se desarrolló con el objetivo de conocer la innovación de enseñanzas y aprendizajes en las prácticas investigativas de docentes de la Ciudad de Medellín; Metodología. Desde el análisis de una investigación cualitativa, el desarrollo del estudio se alineo con el método hermenéutico interpretativo, fundamentado en el aprendizaje significativo, así como en los procesos de enseñanza y aprendizaje en prácticas investigativas de docentes. La información se obtuvo mediante las observaciones directas y entrevistas semiestructuradas a cuatro (4) docentes, los cuales fueron escogidos por su antigüedad dentro de las instituciones a las cuales pertenecen. La técnica de análisis empleada fue la triangulación de los datos. Resultados generales. La innovación implica un cambio intencional y se refiriere a un proceso orientado hacia la mejora, por ello, es fundamental para el estudio de la investigación escolar como una estrategia pedagógica que representa el último enfoque de investigación en el aula. Entre las reflexiones finales puede decirse que la innovación en instituciones educativas, tiene una íntima relación con el sector tecnológico; es el resultado, además, de acciones preestablecidas; que orientan hacia una adaptación flexible, hacia la experimentación, y el cambio guiado y por ello, los docentes han de estar en capacidad de alentar la investigación, la participación y la innovación en el alumnado

Pineal gland interstitial cells from 32 sheep embryos (from day 54 of gestation until birth ) and 18 sheep (from 1 month to >2 years) were analysed using ultrastructural and immunohistochemical techniques. From day 98 of gestation and throughout postnatal development, a second cell type was observed in addition to pinealocytes; these cells displayed uniform ultrastructural features similar to those of CNS astrocytes. Ultrastructural homogeneity was not matched by the results of histochemical and immunohistochemical analysis. Expression of phosphotungstic acid hematoxylin, glial fibrillary acidic protein and vimentin indicates that the second cell population in the developing ovine pineal gland is, in fact, a combination of glial-astrocyte cells at varying stages of maturity. Pineal interstitial cells started to show signs of functional activity evident in vascular tropism; such activity, evident from around day 98 of gestation, appeared to relate to the exchange of substances between the pineal parenchyma and blood vessels and, though it continued throughout postnatal development, was most evident in animals slaughtered between 9 months and 2 years of age (group II). Morphologically, functional activi- ty in interstitial cells in this age-group was apparent in: 1, formation of specific contact sites between interstitial cells and nerve fibres in the perivascular space; and 2, the presence of numerous gap junctions between the bulbous endings of cytoplasmic processes.

Cholesterol ester storage disease (CESD) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the LIPA gene, leading to reduced lysosomal acid lipase activity, cholesterol ester accumulation, and systemic manifestations including liver dysfunction and dyslipidemia. We report the case of a 25-year-old male presenting with subacute jaundice, hyperbilirubinemia (total bilirubin 51 mg/dL, predominantly direct), and dyslipidemia characterized by elevated total cholesterol and low HDL cholesterol levels. Initial diagnostic workup for acute hepatitis and liver dysfunction, including serological and imaging studies, was unremarkable. Liver biopsy revealed canalicular cholestasis and T-lymphocyte infiltration without fibrosis, raising suspicion for a metabolic or genetic etiology. Genetic analysis confirmed a heterozygous pathogenic mutation (c.894 G>A) in the LIPA gene, establishing the diagnosis of CESD. The patient required advanced management with a molecular adsorbent recirculating system to address refractory hyperbilirubinemia. CESD often mimics other metabolic and hepatic conditions, such as familial hypercholesterolemia or non-alcoholic fatty liver disease, necessitating high clinical suspicion and genetic confirmation for diagnosis. This case underscores the importance of recognizing CESD in patients with atypical dyslipidemia and persistent hepatic abnormalities, as early identification enables targeted therapeutic interventions, including Sebelipase alfa enzyme replacement therapy.

Hereditary haemorrhagic telangiectasia (HHT) is a rare genetic disease characterised by mucocutaneous telangiectasias and arteriovenous malformations that can affect multiple organs. Although rare, ischaemic cholangiopathy can occur, a serious complication that can even lead to death. We present the case of a patient with HHT disease with previous mucocutaneous and gastrointestinal manifestations in whom 8 weeks after cholecystectomy a saccular dilatation of the intrahepatic bile duct was observed.

Males have a higher incidence and mortality rate from colorectal cancer (CRC) compared with females. This review examines the reasons for these differences, including risk factors, screening participation, interpretation of screening tests, presentation and tumour types, pathophysiology (particularly the impact of sex hormones on tumour-related gene expression, microsatellite instability, micro-RNA expression, and the tumour microenvironment), and the efficacy and toxicity of treatment. Sex differences in hormones and body composition are responsible for some of the sexual dimorphism in CRC incidence and outcomes, particularly the pathophysiology, CRC presentation, the pharmacokinetics of cytotoxic therapies, and the impact of treatment on outcomes. However, gender differences also play a role, affecting risk factors, access to or participation in screening and treatment, and patients' experience of treatment (e.g. adverse events and sequelae). Sex and gender issues warrant further investigation in CRC to optimise treatment outcomes for patients., Competing Interests: Declarations. Conflict of interest: Rocio Garcia-Carbonero has provided scientific advice and/or received honoraria or funding for continuous medical education from AAA, Advanz Pharma, Amgen, Astellas, Bayer, BMS, Boerhringer, Esteve, Hutchmed, Ipsen, Midatech Pharma, MSD, Novartis, PharmaMar, Servier and Takeda, and has received research support from Pfizer, BMS and MSD. Elena Élez has received personal honoraria from Amgen, Bayer, BMS, Boehringer Ingelheim, Cure Teq AG, Hoffman La – Roche, Janssen, Lilly, Medscape, Merck Serono, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Repare Therapeutics Inc., RIN Institute Inc., Sanofi, Seagen International, GmbH, Servier, and Takeda. Ruth Vera García has received personal honoraria from ROCHE, Amgen, MSD, Merck Serono, Lilly, MSD, Novartis, Organon and Servier. Encarnación González-Flores, Eduardo Redondo-Cerezo, María José Safont have no conflicts of interest related to this work. Ethics approval and Informed consent: Ethical approval and informed consent would not apply to the current review article., (© 2025. The Author(s).)

Background: Antithrombotic drugs pose a dual challenge to acute upper gastrointestinal bleeding, with associated risks of bleeding complications and thromboembolic events upon withdrawal. We aimed to determine the impact of antithrombotic medications on in-hospital and delayed outcomes and whether suspension and resumption influenced delayed mortality., Methods: This study was a prospective registry analysis of patients between 2013-2021. Anticoagulants and antiplatelets were classified as antithrombotic. The examined outcomes included in-hospital mortality and delayed 6-month cardiovascular, bleeding, and mortality events., Results: A total of 1345 patients were included. 21.7% were taking anticoagulants and 19.1% were taking antiplatelets. Patients on antithrombotic therapy have a longer delay in endoscopic performance (11 ± 11 h vs. 9.6 ± 8 h; p  = 0.027) and less need for therapy (38.5% vs. 48.1%; p  = 0.002), with gastric erosion being more usual (14.2% vs. 9.1%; p  = 0.006).In-hospital mortality was higher in patients not taking antithrombotic (12% vs. 8%; p  = 0.022) and suspension < 72 h was associated with increased mortality (14.9% vs. 2.3%; p  = 0.001).Delayed mortality was higher in patients taking antithrombotic (9.4% vs. 6%; p =0.034) and in those who suspended them for more than 7days (17% vs. 8.7%; p =0.033), with no differences when it lasted<72h.Patients on antithrombotic therapy exhibited more delayed cardiovascular (13.7% vs. 3.4%; p <0.0001) and hemorrhagic events (22.9% vs. 12.9%; p <0.0001), with no differences observed in patients who withheld antithrombotic medication.Multivariate analysis identified ASA, disseminated malignancy, and NSAIDs as independent risk factors for in-hospital mortality, whereas antithrombotic therapy and hemoglobin levels were protective factors., Conclusion: Patients with upper gastrointestinal bleeding treated with antithrombotic drugs had lower in-hospital mortality despite increased comorbidities and older age. Conversely, delayed 6-month mortality was higher. Shorter antithrombotic suspension durations increased in-hospital mortality, whereas suspension for > 7 days increased delayed mortality.

Microbiome modulation is one of the novel strategies in medicine with the greatest future to improve the health of individuals and reduce the risk of different conditions, including metabolic, immune, inflammatory, and degenerative diseases, as well as cancer. Regarding the latter, many studies have reported the role of the gut microbiome in carcinogenesis, formation and progression of colorectal cancer (CRC), as well as its response to different systemic therapies. Likewise, obesity, one of the most important risk factors for CRC, is also well known for its association with gut dysbiosis. Moreover, obesity and CRC display, apart from microbial dysbiosis, chronic inflammation, which participates in their pathogenesis. Although human and murine studies demonstrate the significant impact of the microbiome in regulating energy metabolism and CRC development, little is understood about the contribution of the microbiome to the development of obesity-associated CRC. Therefore, this systematic review explores the evidence for microbiome changes associated with these conditions and hypothesizes that this may contribute to the pathogenesis of obesity-related CRC. Two databases were searched, and different studies on the relationship among obesity, intestinal microbiota and CRC in clinical and preclinical models were selected. Data extraction was carried out by two reviewers independently, and 101 studies were finally considered. Findings indicate the existence of a risk association between obesity and CRC derived from metabolic, immune, and microbial disorders., (© 2024 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: The use of real-time ultrasound has become the standard of care for percutaneous central venous access and shown to decrease overall number of attempts and complication rates., Material and Method: A retrospective analysis of a prospective database was done focusing on three types of central access: non-tunneled, tunneled, and implantable, placed via ultrasound-guided Brachiocephalic Vein (BCV) between January 2019 and January 2023. Data were recorded: gender, age, weight, side (left or right), number of puncture attempts, arterial puncture, change of operator or puncture side, and mechanical complications (pneumothorax and hemothorax)., Results: A total of 1028 non-tunneled, tunneled, and implantable central lines were placed. Five hundred and eighty seven were Male. The children were aged from 0 to 18 years and their weights ranged from 1 to 113 kg. Nine hundred and thirty-five were left BCV. Right BCV was cannulated in 93 patients. Failure to cannulate left BCV was recorded in seven cases. Three arterial punctures were recorded. Cannulation success rate was 97.2% (999/1028) and was higher in left BCV than right BCV ( p  < 0.001)., Discussion: Based on the above, we believe that ultrasound-guided BCV is an easy and secure method to cannulate children, in our series left BCV showed a higher cannulation success rate rather than right BCV., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Enrolling children with cancer in early phase trials is crucial to access innovative treatments, contributing to advancing pediatric oncology research and providing tailored therapeutic options. Our objective is to analyze the impact of these trials on patient outcomes and safety, and to examine the evolution and feasibility of trials in pediatric cancer over the past decade., Methods: All patients recruited in pediatric anticancer phase I/II clinical trials from January 2014 to December 2022 were included. Clinical records and trial protocols were analyzed., Results: A total of 215 patients (median age 11.2 years, range 1-29.5) were included in 52 trials (258 inclusions). Patients with extracranial solid tumors (67%), central nervous system (CNS) tumors (24%), and leukemia (9%) were included. The most common investigational drugs were small molecules (28.3%) and antibodies (20.5%). Serious adverse events were experienced by 41% of patients, 4.4% discontinued treatment because of toxicity and two had toxic deaths. Median event-free survival was 3.7 months (95%CI: 2.8-4.5), longer in phase II trials than in phase I (2 vs. 6.3 months; p  ≤ 0.001). Median overall survival was 12 months (95%CI: 9-15), higher in target-specific vs. non-target-specific trials (14 vs. 6 months; p  ≤ 0.001)., Discussion: A significant and increasing number of patients have been included in early clinical trials, suggesting that both oncologists and families consider it valuable to be referred to specialized Units to access new therapies. Moreover, our data suggests that participation in early clinical trials, although not without potential toxicities, might have a positive impact on individual outcomes., Competing Interests: AR-S-S had a consulting role for EusaPharma, Sanofi and SERB. She received honoraria from EusaPharma and Roche. FB has been a member of a data monitoring committee (DMC) in a clinical trial sponsored by Sanofi, had a consulting or advisory role for Bayer, Amgen, Roche Genentech, EusaPharma and Eisai and received honoraria from Servier (through his current affiliation). LM is member of a Data Monitoring Committee (DMC) for clinical trials sponsored by Novartis, Actuate Therapeutics, Shionogi, Incyte, the University of Southampton and the Royal Marsden NHS Foundation Trust; had a consulting role for Novartis, Bayer, BMS, Merck, Gilead and Shionogi, has received travel expenses from Recordati Rare Diseases and is member of the Executive Committee of SIOPEN (European neuroblastoma research cooperative group), organization which receives royalties for the sales of dinutuximab beta. His institution receives funding from sponsors for DMC participation, advisory role or conducting industry-sponsored clinical trials. LS received honoraria as consultant from Sobi, Agios, Novartis, Amgen and Rocket Pharmaceuticals Inc. He has also licensed medicinal products from Rocket Pharmaceuticals Inc. JV-A received honoraria from EusaPharma, Jazz Pharmaceuticals and Servier. M Ramirez has received honoraria for participation in advisory boards from Amplicell and stock options from Orgenesis. AL received honoraria from Servier, Alexion, and Lilly. BH received honoraria from Servier, Novartis and Pfizer. MA received honoraria from Servier and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Pujol Manresa, Buendía López, Andión, Herrero, Lassaletta, Ramirez, Ruano, Hernández-Marqués, Varo, de Rojas, Cortés Hernández, Verdú-Amorós, Martín Prado, Artigas, Redondo, Ruiz Pato, Herreros López, Sevilla, Madero, Moreno, Bautista Sirvent and Rubio-San-Simón.)

Background/Objectives: Early identification of patients at risk of developing severe acute pancreatitis (SAP) is still an issue. Dynamic assessment of clinical and laboratory parameters within the first 48 h of admission may offer valuable insights into the prediction of unfavorable outcomes such as SAP and death. Methods: A prospective observational study was conducted on a cohort of patients admitted for AP at a tertiary referral hospital. Clinical and laboratory data were collected on admission and at 48 h. Patients were classified based on the Revised Atlanta classification. Logistic regression analysis was performed to identify independent risk factors for SAP. Likelihood ratios and post-test probabilities were calculated to assess the clinical usefulness of predictive markers. Results: 227 patients were included, with biliary etiology being the most common and a prevalence of SAP and death of 10.7% and 5.7%, respectively. BISAP ≥ 2 on admission, presence of SIRS after 48 h, rise in heart rate over 20 bpm, and any increase in BUN after 48 h were independent risk factors for SAP. The combination of these factors increased the post-test probability of SAP and death, with BISAP ≥ 2 combined with the presence of SIRS after 48 h showing the highest probability (82% and 73%, respectively). Conclusions: Dynamic assessment of BUN, heart rate, and SIRS within the first 48 h of admission can aid in predicting the development of SAP and death in patients with AP. These findings underscore the importance of continuous monitoring, although multicenter studies are warranted to refine predictive models for SAP.

Purpose: Protocol description for renal perfusion study using thermographic technology and description of the thermographic and clinical behavior of the transplanted kidneys before and after unclamping., Methods: Infrared thermographic images of renal grafts are obtained before kidney reperfusion, 10 min after and just before closing the surgical wound. Thermographic data is evaluated together with the type of graft and donor, cold ischemia time, hypovascularized areas determined by the surgeon during surgical intervention, alterations in vascular flow in postoperative echo-Doppler, time at the beginning of graft function and serum creatinine monitoring during postoperative follow-up., Results: 17 grafts were studied. The mean temperature of the grafts before reperfusion, 10 min after and at the end of the surgery were 18.7 °C (SD 6.27), 32.36 °C (SD1.47) and 32.07 °C (SD1.78) respectively. 4 grafts presented hypoperfused areas after reperfusion. These areas presented a lower temperature compared to the well perfused parenchyma surface using thermographic images., Conclusion: The study of the usefulness and applicability of thermography can allow the development of tools that provide additional objective information on organ perfusion in real time and non-invasive manner. Our protocol and initial results can contribute to provide new evidence. Further analyses should be developed to shed light on the role of this technology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ex vivo expansion of human CD34+ hematopoietic stem and progenitor cells remains a challenge due to rapid differentiation after detachment from the bone marrow niche. In this study, we assessed the capacity of an inducible fusion protein to enable sustained ex vivo proliferation of hematopoietic precursors and their capacity to differentiate into functional phagocytes. We fused the coding sequences of an FK506-Binding Protein 12 (FKBP12)-derived destabilization domain (DD) to the myeloid/lymphoid lineage leukemia/eleven nineteen leukemia (MLL-ENL) fusion gene to generate the fusion protein DD-MLL-ENL and retrovirally expressed the protein switch in human CD34+ progenitors. Using Shield1, a chemical inhibitor of DD fusion protein degradation, we established large-scale and long-term expansion of late monocytic precursors. Upon Shield1 removal, the cells lost self-renewal capacity and spontaneously differentiated, even after 2.5 y of continuous ex vivo expansion. In the absence of Shield1, stimulation with IFN-γ, LPS, and GM-CSF triggered terminal differentiation. Gene expression analysis of the obtained phagocytes revealed marked similarity with naïve monocytes. In functional assays, the novel phagocytes migrated toward CCL2, attached to VCAM-1 under shear stress, produced reactive oxygen species, and engulfed bacterial particles, cellular particles, and apoptotic cells. Finally, we demonstrated Fcγ receptor recognition and phagocytosis of opsonized lymphoma cells in an antibody-dependent manner. Overall, we have established an engineered protein that, as a single factor, is useful for large-scale ex vivo production of human phagocytes. Such adjustable proteins have the potential to be applied as molecular tools to produce functional immune cells for experimental cell-based approaches., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Massive gastrointestinal bleeding is a life-threatening condition without a well-established definition. We aimed to analyze the characteristics, risk factors, and outcomes of patients with massive upper gastrointestinal bleeding., Methods: Our study analyzed a prospective registry of patients admitted between 2013 and 2020 with variceal and non-variceal causes. Severe bleeding was defined as ongoing bleeding requiring transfusion of more than 2 units of packed red blood cells within 24 hours, accompanied by signs of shock. The main outcomes were 30-day and 6-month mortality, rebleeding within 7 days, persistent bleeding, and severe complications during admission., Results: Out of 1213 patients, 171 had massive gastrointestinal bleeding, with a predominance of males. The massive bleeding group had higher rates of chronic kidney disease, cirrhosis, in-patient status, disseminated malignancy, alcoholism, and ASA score ≥3. All major outcomes, including 30-day mortality, 6-month mortality, rebleeding, persistent bleeding, and severe complications, were more common in the massive bleeding group. Multivariate logistic regression identified inpatient status, systemic diseases, malignancy, active bleeding in endoscopy, and severe complications as risk factors for massive bleeding and mortality., Conclusions: Inpatient status and comorbidities, especially systemic diseases, and malignancies, were associated with a higher risk of massive bleeding. Mortality was linked to chronic kidney disease, cirrhosis, severe comorbidities, and alcohol consumption. We observed increased 6-months mortality, probably related to a health status in which gastrointestinal bleeding heralded poor outcomes, some of them potentially preventable. Innovative healthcare interventions, such as Emergency Department-based intermediate care areas or Intensive Care Units, and multidisciplinary follow-up, could potentially improve survival., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to declare., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in adults, particularly older adults and those with underlying medical conditions. Vaccination has emerged as a potential key strategy to prevent RSV-related morbidity and mortality. This Neumoexperts Prevention (NEP) Group scientific paper aims to provide an evidence-based positioning and RSV vaccination recommendations for adult patients. We review the current literature on RSV burden and vaccine development and availability, emphasising the importance of vaccination in the adult population. According to our interpretation of the data, RSV vaccines should be part of the adult immunisation programme, and an age-based strategy should be preferred over targeting high-risk groups. The effectiveness and efficiency of this practice will depend on the duration of protection and the need for annual or more spaced doses. Our recommendations should help healthcare professionals formulate guidelines and implement effective vaccination programmes for adult patients at risk of RSV infection now that specific vaccines are available., (Copyright © 2024 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)