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While the first infection of an emerging disease is often unknown, information on early cases can be used to date it. In the context of the COVID-19 pandemic, previous studies have estimated dates of emergence (e.g., first human SARS-CoV-2 infection, emergence of the Alpha SARS-CoV-2 variant) using mainly genomic data. Another dating attempt used a stochastic population dynamics approach and the date of the first reported case. Here, we extend this approach to use a larger set of early reported cases to estimate the delay from first infection to the Nth case. We first validate our framework by running our model on simulated data. We then apply our model using data on Alpha variant infections in the UK, dating the first Alpha infection at (median) August 21, 2020 (95% interpercentile range across retained simulations (IPR): July 23-September 5, 2020). Next, we apply our model to data on COVID-19 cases with symptom onset before mid-January 2020. We date the first SARS-CoV-2 infection in Wuhan at (median) November 28, 2019 (95% IPR: November 2-December 9, 2019). Our results fall within ranges previously estimated by studies relying on genomic data. Our population dynamics-based modelling framework is generic and flexible, and thus can be applied to estimate the starting time of outbreaks in contexts other than COVID-19.

IntroductionManagement of pediatric cancer patients involves invasive procedures such as punctures, injections, catheter placements, and chemotherapy which can generate fatigue, nausea, vomiting, anxiety, and pain. Virtual Reality (VR) is a nonpharmacological intervention classified as a cognitive-behavioral method to relieve symptoms.MethodsWe designed a crossover protocol and included 20 patients between 9 and 12 years old; ten were male. All patients had acute lymphoblastic leukemia diagnosis and were treatedwith St. Jude’s XV protocol in the maintenance phase. Pain and anxiety were measured with validated scales in the pediatric population.ResultsAlthough we used a small group of patients, we found statistical difference in the reduction of anxiety and perception of time.DiscussionThese results open a window to non-pharmacological treatments and show a strategy to improve quality of life in children inside the hospital.

Target 12.3 of the United Nations (UN) 2030 Agenda is as follows: “By 2030, halve per capita global food waste at the retail and consumer levels and reduce food losses along production and supply chains, including post-harvest losses.” The implementation of the specific targets of the UN 2030 Agenda, such as this one, presents a significant challenge, as they require immediate action, proper public policies, and unprecedented collaboration between private and public entities and countries. Target 12.3 is intrinsically related to many other targets, so its achievement has a direct impact on several of them. Therefore, it is vital to successfully achieve it, not only to reduce hunger but also to achieve many other Agenda targets and, in particular, to be able to reduce our environmental footprint. Preventing Food Losses and Waste (FLW) is a target within Circular Economy that can be considered to be most instrumental as Target 12.3 tries to prevent food overproduction with better redistribution that not only reduces inputs but also attempts to minimize waste by the donation of food products to Social Economy (SE) entities that help those in need. Circular Economy contributes to the resolution of the three most pressing environmental problems: overuse of resources or overexploitation, global warming, and biodiversity loss, in addition to all the negative impacts derived from these (UN Environment, 2019), preventing food losses and waste is also key to ensure the solution of both a deep social problem a public health one and the most important environmental ones. Even though the urgency of immediate action is clear, various academics, such as Martin Rio, Rogenhofer, and Sandoval Alvarado (2022), highlight that the attention this target receives from professionals remains scarce. Therefore, the purpose of this paper is to compare these policies on both sides of the Atlantic, to propose recommendations, and to help raise awareness of the problem of FLW, following a holistic approach for all possible actors involved, as communication is critical to achieve this target. Special attention is paid regarding tax policies in cases where food is donated to Social Economy Entities such as food banks, non-profit foundations, or soup kitchens as taxes can both act as barriers or facilitators to this aim; therefore, it is crucial to implement them correctly to ensure they act as true enablers to achieve the target. Thus, we will be able to assess the tax changes that can help do so by means of a comparison between the existing ones in the United States and the European Union.

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

La vasculitis asociada a ANCA denominada así por la presencia de anticuerpos anticitoplasma del neutrófilo es una enfermedad rara, crónica, inflamatoria con características clínicas inespecíficas y un diagnóstico por lo general tardío. Conlleva a que esta condición autoinmune se asocie con alta mortalidad y morbilidad. En el presente caso clínico se reporta una paciente femenina adulta mayor con más de un año de signos y síntomas caracterizadas por dolor pleurítico, pérdida de peso, neuropatía periférica, lesiones púrpuricas palpables secundaria a vasculitis asociada a ANCA. Por medio de tratamiento inmunosupresor con el uso inicial de esteroides intravenosos en bolos a altas dosis y ciclofosfamida por la vía oral, la paciente presenta rápida mejoría y control de su cuadro clínico. Se realizó una revisión de la literatura en cuanto a epidemiología, fisiopatología, hallazgos patológicos, manifestaciones clínicas, así como los hallazgos de laboratorio, las diferentes estrategias de tratamiento y la sobrevida de dicha enfermedad.

MAYO is a popular high-calorie condiment as well as an auspicious candidate in the ongoing NIST competition for additional post-quantum signature schemes achieving competitive signature and public key sizes. In this work, we present high-speed implementations of MAYO using the AVX2 and Armv7E-M instruction sets targeting recent x86 platforms and the Arm Cortex-M4. Moreover, the main contribution of our work is showing that MAYO can be even faster when switching from a bitsliced representation of keys to a nibble-sliced representation. While the bitsliced representation was primarily motivated by faster arithmetic on microcontrollers, we show that it is not necessary for achieving high performance on Cortex-M4. On Cortex-M4, we instead propose to implement the large matrix multiplications of MAYO using the Method of the Four Russians (M4R), which allows us to achieve better performance than when using the bitsliced approach. This results in up to 21% faster signing. For AVX2, the change in representation allows us to implement the arithmetic much faster using shuffle instructions. Signing takes up to 3.2x fewer cycles and key generation and verification enjoy similar speedups. This shows that MAYO is competitive with lattice-based signature schemes on x86 CPUs, and a factor of 2-6 slower than lattice-based signature schemes on Cortex-M4 (which can still be considered competitive).

Summary: Innate immune cells can undergo long-term functional reprogramming after certain infections, a process called trained immunity (TI). Here, we focus on antigens of Leishmania braziliensis, which induced anti-tumor effects via trained immunity in human monocytes. We reveal that monocytes exposed to promastigote antigens of L. braziliensis develop an enhanced response to subsequent exposure to Toll-like receptor (TLR)2 or TLR4 ligands. Mechanistically, the induction of TI in monocytes by L. braziliensis is mediated by multiple pattern recognition receptors, changes in metabolism, and increased deposition of H3K4me3 at the promoter regions of immune genes. The administration of L. braziliensis exerts potent anti-tumor capabilities by delaying tumor growth and prolonging survival of mice with non-Hodgkin lymphoma. Our work reveals mechanisms of TI induced by L. braziliensis in vitro and identifies its potential for cancer immunotherapy.

Se ha demostrado que las competencias matemáticas tempranas ejercen un rol importante en el aprendizaje de esta disciplina y que tanto la flexibilidad cognitiva como la planificación favorecen este proceso. Sin embargo, la mayoría de las investigaciones han relacionado las funciones ejecutivas con los resultados matemáticos generales, sin tomar en cuenta que esta disciplina incluye diversos componentes que varían en su complejidad cognitiva. Por lo tanto, el objetivo de esta investigación fue evaluar la capacidad predictiva de la flexibilidad cognitiva y la planificación en las competencias matemáticas lógico-relacionales y numéricas de 106 niños de educación inicial de escuelas chilenas, quienes fueron evaluados con dos tareas ejecutivas y un test de competencias matemáticas tempranas. Para el análisis de datos se realizaron correlaciones y modelos de regresión lineal múltiple. Los resultados mostraron que la flexibilidad cognitiva fue un predictor significativo de las competencias matemáticas tanto lógico-relacionales como numéricas, mientras que la planificación lo fue solo de las numéricas. Estos resultados confirman la importancia de la flexibilidad cognitiva y la planificación en el desarrollo de las competencias matemáticas tempranas, lo que podría propiciar intervenciones específicas sobre estas funciones ejecutivas y así favorecer el aprendizaje de las matemáticas en la educación inicial.

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

Wastewater reuse could provide a substantial relief from water scarcity, particularly for agricultural and industrial purposes. To meet future legislation and environmental standards in this regard, organic micropollutants must be efficiently eliminated in the treated effluent. Innovative water treatment technologies can contribute to achieve this goal, but their environmental consequences must be controlled. The objective of this study is to assess the environmental hotspots of an enzyme-based wastewater treatment system for the removal of sulfamethoxazole (SMX) as a model pollutant. For this purpose, the Life Cycle Assessment and Product Environmental Footprint methodologies have been applied to a conceptual process design based on laboratory-scale data. In addition, we addressed the relevant process parameters (i.e., the stability and reuse of the enzyme and the impacts associated with its immobilization), the comparison with consolidated technologies (membrane and ozonation systems) and the geographical situation (such as the electricity mix and the water stress level). The main hotspot of the analyzed treatment process is the production of the unspecific peroxygenase used within the magnetic biocatalyst, contributing more than 36 % to all impact categories considered. Focusing on the magnetic biocatalyst synthesis, the enzyme production phase and the functionalization of the immobilization support are the most problematic (with percentages of up to 75 % in stratospheric ozone depletion and 65 % in terrestrial ecotoxicity, respectively). In relation to resource consumption, water demand has been estimated at 0.02 m3 per cubic meter of treated water, but water deprivation can be much higher depending on the country (∼0.5 m3). Therefore, the use of reclaimed water can offset the indirect effects of its treatment. This study serves as a roadmap for future research to achieve reduced emissions by reduction of energy requirements, the use of renewable energy but also by increasing the enzyme stability. Furthermore, the background environmental impacts of the production of the biocatalyst must be reduced to improve the competitiveness against implemented alternatives based on physical (membranes) and chemical (ozonation) processes.

Background: Systematic reviews suggest that animal-assisted therapy (AAT) and pet-robot interventions (PRI) achieve a reduction in mental health variables such as depressive symptoms. However, these systematic reviews include both randomised and non-randomised studies, which prevents an adequate assessment of the effect of confounding variables. Objective: This systematic review and meta-analysis aimed to evaluate the comparative effectiveness of AAT and PRI through randomized controlled trials (RCTs) in reducing depression in older adults. Methods: Our study is a systematic review. We searched three databases of scientific articles: SCOPUS, Web of Science and PubMed. We included studies that their population was older adults, aged 65 years or older, with or without a clinical condition, clinical diagnosis based on mental examination/test or documentation from medical records, accredited by the facilities' staff. We included trials in which the comparator was a passive intervention or an active intervention. We used the Cochrane risk-of-bias tool for randomised trials (RoB 2) to assess the risk of bias for each study. Our study was registered in PROSPERO (CRD42023393740). Results: Twenty-three studies were included in this systematic review. However, only 19 trials were included in the meta-analysis. At the overall risk of bias level, 78.9% of the studies were at high risk of bias (n = 15). We found that AAT (g= −0.72; 95%CI −1.13 to −0.31; p = 0.001) has a moderate and statistically significant effect as an intervention to reduce depressive symptoms in older adults. However, the PRIs do not show a significant effect on reducing depressive symptoms in older adults. In addition, a sub-analysis based on dog-assisted therapy (g= −0.65; 95%CI −1.21 to −0.08; p = 0.025), a specific type of AAT, showed a modest effect on reducing depressive symptoms. Conclusions: Our study concluded that AAT and DAT had a moderate and statistically significant effect as interventions to reduce depressive symptoms in older adults. On the other hand, PRI did not show a significant effect in reducing depressive symptoms.

Resumen: Introducción: la Medicina de Urgencia (MDU) es una especialidad en desarrollo a nivel mundial. En Chile se inició hace más de 2 décadas y aún está avanzando académicamente. Objetivo: explorar el estado actual del desarrollo curricular de la MDU en Chile e identificar formas de estandarizarlo y mejorarlo. Métodos: se realizó un estudio de caso cualitativo para explorar las perspectivas sobre el desarrollo del currículo de la MDU a través de entrevistas a residentes, graduados y directores de programas y análisis documental. Ambos conjuntos de datos fueron evaluados a través de análisis temático. Resultados: se analizaron 4 documentos y se realizaron 8 entrevistas. Surgieron 4 temas principales: estructura curricular, influencia del contexto, expectativas de un médico de urgencia, perspectivas de la MDU. Los programas actuales se centran en el aprendizaje en el lugar de trabajo y tiempo protegido para el aprendizaje; sin embargo, difieren en la exposición clínica y la calidad de la capacitación. Como prioridad, se identificó la colaboración, enfatizando la necesidad de que los programas trabajen juntos para garantizar la calidad. Conclusión: este estudio identifica el estado de situación del desarrollo curricular de la MDU en Chile, identificando similitudes y diferencias entre los programas y las áreas de mejora. Existe acuerdo sobre la necesidad de un currículo mínimo, considerando el contexto local y las necesidades de la sociedad. Abstract: Background: Emergency medicine (EM) is a developing specialty worldwide. In Chile, it has been developing for 25 years, however, there is a need for further progress. Aim: We aimed to explore the current postgraduate curriculum in Chile and identify ways to standardise and improve it. Methods: A qualitative case study approach was used to explore perspectives on EM curriculum development via interviewing residents, graduates and programme directors and documentary analysis of academic and governmental guidelines. Both data sets were evaluated through thematic analysis. Results: Four documents were analyzed, and eight interviews were conducted. Four main themes emerged: curricular structure, influence of context, expectations of an emergency physician, EM perspectives. Current programs focus on workplace learning and protected time for learning; however, they differ in clinical exposure and quality of training. Collaboration was identified as a priority, emphasizing the need for programs to work together to ensure quality. Conclusion: This study identifies the state of curriculum development of EM in Chile. It identifies similarities and differences between programs and areas for improvement. There is agreement on the need for a standardized curriculum, considering local context and societal needs.

Resumen: La fístula entero-colónica es una rara complicación de un linfoma de origen mesentérico y una causa inusual de diarrea crónica en pacientes que no tienen inmunosupresión ni enfermedad inflamatoria intestinal. Reportamos el caso de una paciente de 68 años con cuadro de dolor abdominal y diarrea crónica que a la evaluación imagenológica y endoscópica se evidenció una fístula yeyuno-colónica. Se realizó una resección quirúrgica en bloque y el análisis histológico e inmunohistoquímico de la pieza quirúrgica evidenció un linfoma no Hodgkin B de alto grado originado de un linfonodo del mesenterio con extensión secundaria a yeyuno y colon. El diagnóstico es desafiante debido al cuadro clínico inespecífico y el amplio diagnóstico diferencial, por lo que es imprescindible una adecuada anamnesis, examen físico y evaluación imagenológica que permita caracterizar la lesión y planificar la cirugía. El pronóstico y tratamiento adyuvante dependerá del tipo de tumor y el estadio en que se encuentre. Este es el primer reporte de caso local de un paciente con una fístula yeyuno-colónica secundaria a un linfoma no Hodgkin tipo B de alto grado originado de un linfonodo del mesenterio con extensión a intestino delgado y colon. Abstract: Enterocolonic fistula is a rare complication of lymphoma of mesenteric origin and an unusual cause of chronic diarrhea in patients without immunosuppression or inflammatory bowel disease. We report the case of a 68-year-old female patient with abdominal pain and chronic diarrhea that revealed a jejunocolonic fistula on imaging and endoscopic evaluation. Surgical block resection was performed and the histological and immunohistochemical analysis of the surgical specimen evidenced a high-grade B non-Hodgkin lymphoma originating from a lymph node of the mesentery with secondary extension to the jejunum and colon. The diagnosis is challenging due to the non-specific clinical picture and the wide differential diagnosis, for which an adequate anamnesis, physical examination and imaging evaluation are essential in order to characterize the lesion and schedule surgery. The prognosis and adjuvant treatment will depend on the type of tumor and its staging. This is the first local case report of a patient with a jejuno-colonic fistula secondary to a high-grade B-type non-Hodgkin lymphoma originating from a mesenteric lymph node with extension to the small intestine and colon.

Robotics applications are greatly needed in hazardous locations, e.g., fusion and fission reactors, where robots must perform delicate and complex tasks under ionizing radiation conditions. The drawback is that some robotic parts, such as active electronics, are susceptible to radiation. It can lead to unexpected failures and early termination of the robotic operation. This paper analyses the ionizing radiation effect from 0.09 to 1.5 Gy/s in robotic components (microcontrollers, servo motors and temperature sensors). The first experiment compares the performance of various microcontroller types and their actuators and sensors, where different mitigation strategies are applied, such as using Radiation-Hardened (Rad-Hard) microcontrollers or shielding. The second and third experiments analyze the performance of a 3-Degrees of Freedom (DoF) robotic arm, evaluating its componentsʼ responses and trajectory. This study enhances our understanding and expands our knowledge regarding radiationʼs impact on robotic arms and components, which is useful for defining the best strategies for extending the robotsʼ operational lifespan, especially when performing maintenance or inspection tasks in radiation environments.

Abstract Background The anterior minimally invasive (AMI) approach reduces soft tissue damage, risk of dislocation and enhances recovery, but it is associated with certain complications. The aim of this study is to compare the outcomes of patients who underwent total hip arthroplasty (THA) through posterolateral (PL) and AMI approaches performed by the same surgeon, in order to determine the learning curve associated with this new approach. Methods This retrospective cohort study included patients who underwent THA via PL and AMI approach between 2017 and 2022, with a minimum follow-up of 1 year. Hip fracture and oncologic patients were excluded. Demographic variables, functional scores and perioperative complications were assessed. A bivariate analysis was performed to identify differences between groups. Results Data of 124 AMI and 120 PL patients were analyzed. Demographic characteristics among groups were homogeneous. Functional outcomes at 3 months were superior for AMI (Oxford: 43 vs. 38; p

Musculoskeletal disorders of the upper extremity are among the most common occupational problems affecting nurses. The aim of this study was to analyze the prospective association between vitality and mental health and increased upper extremity pain intensity in female hospital nurses during a 1-year follow-up. A prospective cohort of 1185 female nurses from 19 hospitals in Denmark was conducted using baseline and 12-month follow-up questionnaires to identify potential associations between levels of vitality and mental health (SF-36 subscales) with pain intensity (0–10 scale) in the shoulder, elbow and hand/wrist regions. Associations were modeled using cumulative logistic regression. The fully adjusted model included the variables of age, baseline pain, body mass index, smoking status, years of occupation, leisure time physical activity level, number of daily patient transfers/handlings, as well as recognition and influence at work. The mean age was 48.3 (SD: 10.4) years. In the fully adjusted model, significant associations between low vitality levels and the odds of shoulder pain (OR = 1.96; 95%CI: 1.43–2.68) and hand/wrist pain (OR = 2.32; 95%CI: 1.58–3.42) were observed. Likewise, moderate levels of mental health was associated with increased odds of shoulder pain at follow-up (OR = 1.50; 95%CI: 1.16–1.93). These results provide an important incentive for nursing managers to assess vitality and mental health among hospital nurses and to consider this factor in prevention strategies to ensure good worker health and, by extension, high-quality care.

Abstract In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals “to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines”. The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing — making anonymised individual-level clinical trial data available to other investigators for further use — is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council’s Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.

SARS-CoV-2 infection (COVID-19) has had a significant impact on transplant activity in our country. Mortality and the risk of complications associated with COVID-19 in kidney transplant recipients (KT) were expected to be higher due to their immunosuppressed condition and the frequent associated comorbidities. Since the beginning of the pandemic in March 2020 we have rapidly improved our knowledge about the epidemiology, clinical features and management of COVID-19 post-transplant, resulting in a better prognosis for our patients. KT units have been able to adapt their programs to this new reality, normalizing both donation and transplantation activity in our country.This manuscript presents a proposal to update the general recommendations for the prevention and treatment of infection in this highly vulnerable population such as KT. Resumen: La infección por el SARS-CoV-2 (COVID-19) ha supuesto un importante impacto en la actividad trasplantadora en nuestro país. Era esperable que la mortalidad y el riesgo de complicaciones asociadas a la COVID-19 en el receptor de trasplante renal (TR) fueran mayores debido a su condición de inmunosupresión y a las frecuentes comorbilidades asociadas. Desde el inicio de la pandemia en marzo del 2020 hemos mejorado rápidamente nuestro conocimiento acerca de la epidemiología, características clínicas y manejo de la COVID-19 post-trasplante, redundando en un mejor pronóstico para nuestros pacientes. Las unidades de trasplante renal han sabido adaptar sus programas a esta nueva realidad, normalizándose la actividad tanto de donación como de trasplante en nuestro país.Este manuscrito presenta una propuesta de actualización de las recomendaciones generales para la prevención y el tratamiento de la infección en esta población tan vulnerable como son los receptores de un trasplante renal.

Los avances tecnológicos y sociales, derivados del uso masivo de las tecnologías de la información y la comunicación, están transformando todos los sectores, y la educación no es una excepción. Las organizaciones educativas deben adoptar una Transformación Digital (TD) para hacer frente a una nueva realidad cultural, social, medioambiental y económica de todos sus grupos de interés. De ahí que en este artículo se trazó como objetivo: analizar y entender la estructura intelectual, conceptual y social de la transformación digital en las organizaciones educativas. Como método se emplearon diferentes técnicas bibliométricas, que permitieron obtener como resultados y conclusión que en la estructura intelectual de la bibliografía aparecen tres temas; uno más teórico que explora la TD en las Instituciones de Educación Superior, alertando que ésta es más que un conjunto de herramientas digitales; un segundo clúster apunta a las tres dimensiones de la TD: tecnológica, pedagógica y organización; el tercer grupo analiza la implementación práctica de la TD y la importancia de gestionar las personas en el proceso. En estructura temática, destacan también 3 grupos: el de fundamentos teóricos y conceptual, que revela el COVID-19 como principal factor desencadenante de la TD, el segundo clúster investiga el proceso de aprendizaje a través de una docencia digital y el tercero destaca la importancia de la gestión del cambio cultural.

Abstract Reactive oxygen species (ROS) are an important source of cellular damage. When ROS intracellular levels increase, oxidative stress takes place affecting DNA stability and metabolic functions. To prevent these effects, stress-activated protein kinases (SAPKs) delay cell cycle progression and induce a transcriptional response that activates antioxidant mechanisms ensuring cell adaptation and survival. Fission yeast Cdc14-like phosphatase Flp1 (also known as Clp1) has a well-established role in cell cycle regulation. Moreover, Flp1 contributes to checkpoint activation during replication stress. Here, we show that Flp1 has a role in fine-tuning the cellular oxidative stress response. Phosphorylation-dependent nucleolar release of Flp1 in response to oxidative stress conditions plays a role in the cellular transcriptional response. Thus, Flp1 ablation increases the transcriptional response to oxidative stress, in both intensity and duration, upregulating both Atf1/Pcr1- and Pap1-dependent stress induced genes. Remarkably, we found that Flp1 interacts with the Atf1/Pcr1 complex with Pcr1 acting as a direct substrate. Our results provide evidence that Flp1 modulates the oxidative stress response by limiting the Atf1/Pcr1-mediated transcription.

La investigación tuvo por objetivo determinar la autopercepción de la alfabetización digital en la comunicación y gestión del conocimiento de profesores de la Facultad de Filosofía, Letras y Ciencias de la Educación de la Universidad de Guayaquil, Ecuador. Para ello se asumió el enfoque cuantitativo con nivel descriptivo, diseño de campo, no experimental y transversal. La muestra fue de 74 docentes de esta Facultad, durante el primer período de 2023, empleando un cuestionario de 42 ítems distribuidos en nueve dimensiones. Los resultados develaron el nivel de dominio de las competencias digitales en las áreas de alfabetización digital y de comunicación que auto perciben los docentes e identificar de qué manera gestionan el conocimiento entre la comunidad educativa. En conclusión, estos docentes poseen un intermedio nivel de competencias digitales que les permite gestionar del conocimiento e información digital, lo cual tiene la posibilidad de influir de forma favorable en la calidad de la educación superior de Ecuador.

Abstract The open‐source programming language ‘R' has become a standard tool in the palaeobiologist's toolkit. Its popularity within the palaeobiological community continues to grow, with published articles increasingly citing the usage of R and R packages. However, there are currently a lack of agreed standards for data preparation and available frameworks to support the implementation of such standards. Consequently, data preparation workflows are often unclear and not reproducible, even when code is provided. Moreover, due to a lack of code accessibility and documentation, palaeobiologists are often forced to ‘reinvent the wheel’ to find solutions to issues already solved by other members of the community. Here, we introduce palaeoverse, a community‐driven R package to aid data preparation and exploration for quantitative palaeobiological research. The package is freely available and has three core principles: (1) streamline data preparation and analyses; (2) enhance code readability; and (3) improve reproducibility of results. To develop these aims, we assessed the analytical needs of the broader palaeobiological community using an online survey, in addition to incorporating our own experiences. In this work, we first report the findings of the survey, which shaped the development of the package. Subsequently, we describe and demonstrate the functionality available in palaeoverse and provide usage examples. Finally, we discuss the resources we have made available for the community and our future plans for the broader Palaeoverse project. palaeoverse is a community‐driven R package for palaeobiology, developed with the intention of bringing palaeobiologists together to establish agreed standards for high‐quality quantitative research. The package provides a user‐friendly platform for preparing data for analysis with well‐documented open‐source code to enhance transparency. The functionality available in palaeoverse improves code reproducibility and accessibility, which is beneficial for both the review process and future research.

Abstract Mesial temporal lobe epilepsy, one of the most common forms of epilepsy, is often linked with drug resistance. Surgical intervention is a reliable and safe treatment option, though research into postsurgical outcomes in our locality remains limited. We performed a retrospective observational study included 91 patients with mesial temporal lobe epilepsy and hippocampal sclerosis who had undergone anterior temporal lobectomy between 2012 and 2020 at a surgical epilepsy center located in Lima, Peru. Postoperative outcomes were analyzed using bivariate and multivariate analysis based on the Engel classification. We found that after 12 months of follow‐up, 78.65% of the 91 patients achieved an Engel IA classification, while 9.09% attained Engel IB classification and 11.24% were designated as Engel II, with only 1.12% classified as Engel IVA. The median QOLIE31 score was 84 (IQR: 75–90), with 74.16% of the participants successfully reintegrating into academic or employment activities. After 24 months, only 68 patients completed the follow‐up, with 69.12% achieving an Engel IA classification. Individuals with a secondary education or higher were more likely to achieve an Engel IA classification at 12 months (OR: 5.11; P = 0.005; CI: 1.63–16.01), after adjusting for sex and age. We concluded that most patients exhibited favorable outcomes after 1 year of follow‐up. However, lower educational attainment was linked to worse postsurgical outcomes.

Resumen: La infección por el SARS-CoV-2 (COVID-19) ha supuesto un importante impacto en la actividad trasplantadora en nuestro país. Era esperable que la mortalidad y el riesgo de complicaciones asociadas a la COVID-19 en el receptor de trasplante renal (TR) fueran mayores debido a su condición de inmunosupresión y a las frecuentes comorbilidades asociadas. Desde el inicio de la pandemia en marzo del 2020 hemos mejorado rápidamente nuestro conocimiento acerca de la epidemiología, características clínicas y manejo de la COVID-19 postrasplante, redundando en un mejor pronóstico para nuestros pacientes. Las unidades de TR han sabido adaptar sus programas a esta nueva realidad, normalizándose la actividad tanto de donación como de trasplante en nuestro país.Este manuscrito presenta una propuesta de actualización de las recomendaciones generales para la prevención y el tratamiento de la infección en esta población tan vulnerable como son los receptores de un trasplante renal. Abstract: SARS-CoV-2 infection (COVID-19) has had a significant impact on transplant activity in our country. Mortality and the risk of complications associated with COVID-19 in kidney transplant (KT) recipients were expected to be higher due to their immunosuppressed condition and the frequent associated comorbidities. Since the beginning of the pandemic in March 2020 we have rapidly improved our knowledge about the epidemiology, clinical features and management of COVID-19 post-transplant, resulting in a better prognosis for our patients. KT units have been able to adapt their programs to this new reality, normalizing both donation and transplantation activity in our country.This manuscript presents a proposal to update the general recommendations for the prevention and treatment of infection in this highly vulnerable population such as KT.

Abstract Sarcomas constitute a heterogeneous group of rare and difficult-to-treat tumors that can affect people of all ages, representing one of the most common forms of cancer in childhood and adolescence. Little is known about the molecular entities involved in sarcomagenesis. Therefore, the identification of processes that lead to the development of the disease may uncover novel therapeutic opportunities. Here, we show that the MEK5/ERK5 signaling pathway plays a critical role in the pathogenesis of sarcomas. By developing a mouse model engineered to express a constitutively active form of MEK5, we demonstrate that the exclusive activation of the MEK5/ERK5 pathway can promote sarcomagenesis. Histopathological analyses identified these tumors as undifferentiated pleomorphic sarcomas. Bioinformatic studies revealed that sarcomas are the tumors in which ERK5 is most frequently amplified and overexpressed. Moreover, analysis of the impact of ERK5 protein expression on overall survival in patients diagnosed with different sarcoma types in our local hospital showed a 5-fold decrease in median survival in patients with elevated ERK5 expression compared with those with low expression. Pharmacological and genetic studies revealed that targeting the MEK5/ERK5 pathway drastically affects the proliferation of human sarcoma cells and tumor growth. Interestingly, sarcoma cells with knockout of ERK5 or MEK5 were unable to form tumors when engrafted into mice. Taken together, our results reveal a role of the MEK5/ERK5 pathway in sarcomagenesis and open a new scenario to be considered in the treatment of patients with sarcoma in which the ERK5 pathway is pathophysiologically involved.

Suicidal behavior and Non-Suicidal Self-Injuries (NSSIs) are a major health problem in the adolescent population. New technologies can contribute to the development of innovative interventions in suicide prevention. Here, we present the SmartCrisis-Teen study protocol. The study consists of a randomized clinical trial which aims to evaluate the effectiveness of a digital safety plan to prevent suicidal behavior and NSSIs in adolescents. This is a multicentric study which will be conducted among the adolescent population, both in clinical and student settings, with a target sample of 1080 participants. The intervention group will receive an Ecological Momentary Intervention (EMI) consisting of a digital safety plan on their mobile phone. All participants will receive their Treatment As Usual (TAU). Participants will be followed for six months, with weekly and monthly telephone visits and face-to-face visits at three and six months. Participants will be assessed using traditional questionnaires as well as Ecological Momentary Assessment (EMA) and Implicit Association Tests (IATs). With this intervention, we expect a reduction in NSSIs through the acquisition of coping strategies and a decrease in suicidal behavior over the course of follow-up. This study provides a novel, scalable digital intervention for preventing suicidal behavior and NSSIs in adolescents, which could contribute to improving adolescent mental health outcomes globally.

The aim of this systematic review was to determine whether autogenous tooth grafting material (ATGM) is as safe and effective as other bone substitutes used for maxillary sinus augmentation procedures, evaluating histomorphometric and/or histological data, implant primary stability, associated complications and radiographic bone height measurements. An automated electronic search was conducted using four databases (Medline/PubMed, Scopus, Web of Science and Cochrane Library), supplemented by a manual search, to identify clinical human studies using particulate ATGM for the aforementioned procedure. The included studies had a sample size of at least four patients and were published before 31st July 2024. The Newcastle–Ottawa scale (NOS) and Joanna Briggs Institute (JBI) Critical Appraisal Checklist were used to assess the risk of bias in cohort studies and case series, respectively. Seven studies were included in the descriptive analysis, obtaining 128 participants (46.8% only treated with ATGM) and 192 placed implants. Due to the heterogeneity of the studies, meta-analysis could not be performed. The authors concluded that ATGM appears to be a feasible and safe alternative for maxillary sinus augmentation procedures. These results should be interpreted with caution due to the limited amount of scientific evidence on this topic and the heterogeneity between the included studies.

This study investigates electromyography activation and force development differences in key lower limb muscles between female football players with previous anterior cruciate ligament injuries compared with healthy players. Twenty-two semi-professional players were divided into ACL-injured (n = 11) and non-injured groups (n = 11). Participants underwent maximal voluntary isometric contractions while electromyography activation, peak and average, and peak torque of force were measured. Results indicated significant differences in electromyography activation patterns between anterior cruciate ligament players and non-injured players, particularly in biceps femoris and gluteus maximus muscles. These differences were also evident when comparing between limbs within anterior cruciate ligament players. Interestingly, both groups exhibited similar peak torque of force during maximal contractions, suggesting a compensatory neuromuscular strategy that supports a return to sport based on kinetic and kinematic factors. However, these findings underscore persistent muscle integration imbalances potentially contributing to the high rate of anterior cruciate ligament reinjury. In conclusion, this study highlights the importance of evaluating electromyography activation alongside force development in understanding neuromuscular adaptations post anterior cruciate ligament injury. These insights emphasize the need for comprehensive rehabilitation strategies that address muscle imbalance to mitigate the risk of recurrent anterior cruciate ligament injuries in female football players.

Decision-making systems allow artificial agents to adapt their behaviours, depending on the information they perceive from the environment and internal processes. Human beings possess unique decision-making capabilities, adapting to current situations and anticipating future challenges. Autonomous robots with adaptive and anticipatory decision-making emulating humans can bring robots with skills that users can understand more easily. Human decisions highly depend on dopamine, a brain substance that regulates motivation and reward, acknowledging positive and negative situations. Considering recent neuroscience studies about the dopamine role in the human brain and its influence on decision-making and motivated behaviour, this paper proposes a model based on how dopamine drives human motivation and decision-making. The model allows robots to behave autonomously in dynamic environments, learning the best action selection strategy and anticipating future rewards. The results show the model’s performance in five scenarios, emphasising how dopamine levels vary depending on the robot’s situation and stimuli perception. Moreover, we show the model’s integration into the Mini social robot to provide insights into how dopamine levels drive motivated autonomous behaviour regulating biologically inspired internal processes emulated in the robot.

Aneurysmal subarachnoid hemorrhage (aSAH) is caused by abnormal blood vessel dilation and subsequent rupture, resulting in blood pooling in the subarachnoid space. This neurological insult results in the activation of the inflammasome, a multiprotein complex that processes pro-inflammatory interleukin (IL)-1 cytokines leading to morbidity and mortality. Moreover, increases in inflammasome proteins are associated with clinical deterioration in many neurological diseases. Limited studies have investigated inflammasome protein expression following aSAH. Reliable markers of the inflammatory response associated with aSAH may allow for earlier detection of patients at risk for complications and aid in the identification of novel pharmacologic targets. Here, we investigated whether inflammasome signaling proteins may serve as potential biomarkers of the inflammatory response in aSAH. Serum and cerebrospinal fluid (CSF) from fifteen aSAH subjects and healthy age-matched controls and hydrocephalus (CSF) no-aneurysm controls were evaluated for levels of inflammasome signaling proteins and downstream pro-inflammatory cytokines. Protein measurements were carried out using Simple Plex and Single-Molecule Array (Simoa) technology. The area under the curve (AUC) was calculated using receiver operating characteristics (ROCs) to obtain information on biomarker reliability, specificity, sensitivity, cut-off points, and likelihood ratio. In addition, a Spearman r correlation matrix was performed to determine the correlation between inflammasome protein levels and clinical outcome measures. aSAH subjects demonstrated elevated caspase-1, apoptosis-associated speck-like protein with a caspase recruiting domain (ASC), IL-18 and IL-1β levels in serum, and CSF when compared to controls. Each of these proteins was found to be a promising biomarker of inflammation in aSAH in the CSF. In addition, ASC, caspase-1, and IL-1β were found to be promising biomarkers of inflammation in aSAH in serum. Furthermore, we found that elevated levels of inflammasome proteins in serum are useful to predict worse functional outcomes following aSAH. Thus, the determination of inflammasome protein levels in CSF and serum in aSAH may be utilized as reliable biomarkers of inflammation in aSAH and used clinically to monitor patient outcomes.

The Japanese plum tree (Prunus salicina Lindl.) is mainly cultivated in temperate areas of China and some European countries. Certain amounts of wood (from pruning works) are generated every year from this crop of worldwide commercial significance. The main objective of this work was to value this agricultural woody residue, for which the chemical composition of pruning wood extracts from six Japanese plum cultivars was investigated, and the antiproliferative activity of extracts and pure phenolics present in those extracts was measured. For the chemical characterization, total phenolic content and DPPH radical-scavenging assays and HPLC‒DAD/ESI‒MS analyses were performed, with the procyanidin (−)-ent-epicatechin-(2α→O→7,4α→8)-epicatechin (5) and the propelargonidin (+)-epiafzelechin-(2β→O→7,4β→8)-epicatechin (7) being the major components of the wood extracts. Some quantitative differences were found among plum cultivars, and the content of proanthocyanidins ranged from 1.50 (cv. ‘Fortune’) to 4.44 (cv. ‘Showtime’) mg/g of dry wood. Regarding the antitumoral activity, eight wood extracts and four phenolic compounds were evaluated in MCF-7 cells after 48 h of induction, showing the wood extract from cv. ‘Songold’ and (‒)-annphenone (3), the best antiproliferative activity (IC50: 424 μg/mL and 405 μg/mL, respectively).

Background: Tension-type headache (TTH) is the most prevalent primary headache. Pressure pain thresholds (PPTs) reflect the pressure pain sensitivity of the tissues. Women with TTH have showed greater pressure hypersensitivity in some muscles compared to men. The aim of this study was to compare the PPTs from myofascial trigger points in cervical and cranial muscles which might contribute to headaches between men and women with TTH. Methods: An observational and correlation cross-sectional study was performed. PPTs were evaluated bilaterally and compared between men and women in the following muscles: upper trapezius, splenius capitis and cervicis, semispinalis, rectus capitis posterior major, obliquus capitis superior and inferior, occipitofrontalis posterior and anterior, temporalis, masseter, clavicular and sternal head of sternocleidomastoid, zygomaticus major, and levator scapulae. The mean PPT was calculated as well. Results: Significant differences showing lower PPTs in women compared to men were found in the mean PPT (p = 0.000) and in all the points except in the left clavicular head of the sternocleidomastoid (p = 0.093) and in the left masseter (p = 0.069). Conclusions: Lower PPTs from myofascial trigger points in cervical and cranial muscles, which might contribute to headaches, were observed in women compared to men with TTH. The mean PPT was also lower in women than in men, suggesting the need for gender-specific approaches in the treatment of TTH.

Maize (Zea mays L.) may be infected by Fusarium verticillioides and F. proliferatum, and consequently contaminated with fumonisins (FBs), as well as the co-products of bioethanol intended for animal feed. Laccase enzymes have a wide industrial application such as mycotoxin degradation. The aims were to isolate and identify fungal laccase-producing strains, to evaluate laccase production, to determine the enzymatic stability under fermentation conditions, and to analyse the effectiveness in vitro of enzymatic extracts (EEs) containing laccases in degrading FB1. Strains belonging to Funalia trogii, Phellinus tuberculosus, Pleurotus ostreatus, Pycnoporus sanguineus and Trametes gallica species showed laccase activity. Different isoforms of laccases were detected depending on the evaluated species. For the FB1 decontamination assays, four enzymatic activities (5, 10, 15 and 20 U/mL) were tested, in the absence and presence of vanillic acid (VA) and 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) as redox mediators (1 and 10 mM). Trametes gallica B4-IMICO-RC EE was the most effective strain in buffer, achieving a 60% of FB1 reduction. Laccases included in EEs remained stable at different alcoholic degrees in maize steep liquor (MSL), but no significant FB1 reduction was observed under the conditions evaluated using MSL. This study demonstrate that although laccases could be good candidates for the development of a strategy to reduce FB1, further studies are necessary to optimise this process in MSL.

The nutritional composition of food for animal production can be enhanced using olive tree and plant by-products due to their high content of bioactive compounds such as pentacyclic triterpenes. Here, we present a novel application of near-infrared spectroscopy (NIRS) for the prediction of the total or individual [maslinic acid (MA), oleanolic acid (OA), and uvaol (UO)] pentacyclic triterpene concentrations in a feed additive obtained from a plant mixture. The oxygen radical absorbance capacity of these types of samples demonstrated the existence of a high antioxidant capacity. The conventional determination methods of pentacyclic triterpene concentration are costly, labor-intensive, and not practical for analyzing several lines within a limited timeframe at the factory level. The optimal regression model developed in our work demonstrated high correlation values for the calibration and validation sets, along with a high residual prediction deviation value. We used 63 samples for the development of the model. The NIRS method can be applied directly to dried powder and makes extraction and high-performance liquid chromatography (HPLC) analysis unnecessary. Our results also demonstrate that NIRS can accurately quantify pentacyclic triterpenes even at low concentrations in food additives. It can be used at the factory level to directly determine the pentacyclic triterpene concentrations in the additive powder at the same time that the powder is produced.

A description of new antimicrobial agents suitable for food industries has become necessary, and natural compounds are being considered as promising sources of new active derivatives to be used with the aim of improving food safety. We have previously described desirable antimicrobial and antibiofilm activities against foodborne bacteria by analogs to A-type proanthocyanidins (PACs) with a nitro (NO2) group at carbon 6 of the A-ring. We report herein the synthesis of eight additional analogs with chloro and bromo atoms at the A-ring and the systematic study of their antimicrobial and antioxidant activities in order to evaluate their possible application as biocides or food preservatives, as well as to elucidate new structure–activity relationships. The results from this study show that halogenated analogs to natural A-type proanthocyanidins rise above the nitro derivatives previously reported in their antimicrobial activities. Gram-positive bacteria are the most sensitive to all the analogs and combinations assayed, showing MICs from 10 to 50 μg/mL in most cases, as well as reductions in biofilm formation and the disruption of preformed biofilms of at least 75%. Some structure–activity relationships previously described have also been corroborated. Analogs with just one OH group at the B-ring show better antimicrobial activities than those with two OH groups, and those analogs with two or three OH groups in the whole structure are more active than those with four OH groups. In addition, the analogs with two OH groups at the B-ring and chloro at the A-ring are the most effective when antibiofilm activities are studied, especially at low concentrations.

This study aims to evaluate the biocontrol potential of Meyerozyma guilliermondii (CECT13190), an endophytic yeast, and its role in mitigating the adverse effects of abiotic and biotic stress in cucumber plants. The relevance of this study lies in addressing the threat of Fusarium wilt, a major fungal disease that impacts cucumber crop productivity, as well as the exacerbation of food scarcity caused by climate change-induced abiotic stress factors such as high temperatures and drought. The study was conducted in a greenhouse environment where Cucumis sativus seedlings were exposed to biotic (F. oxysporum inoculation) and abiotic stress conditions (heat and water deficit). The impact of M. guilliermondii on treated plants’ physiology, growth, development, and flowering was assessed. The study confirmed the biocontrol activity of M. guilliermondii against F. oxysporum and highlighted its positive effects as a plant growth promoter. It enhanced overall plant health, activated natural defense mechanisms against F. oxysporum, and alleviated the detrimental impacts of abiotic stress. Notably, M. guilliermondii also induced early flowering in cucumber plants. This research underscores the potential of M. guilliermondii as a biocontrol agent for managing Fusarium wilt, enhancing stress tolerance, promoting early flowering, and offering promising prospects for sustainable crop production amidst fungal diseases and climate change-induced stressors. The findings emphasize the importance of utilizing M. guilliermondii to improve cucumber crop productivity and address food scarcity challenges.

Background/Objectives: Childhood and adolescence are important stages of life for acquiring healthy habits. There is a high prevalence of sedentary lifestyles worldwide during these ages, which negatively impacts health. This is attributed, in part, to excessive time spent engaging in sedentary behaviors. The aim of this study was to assess the time spent on sedentary behaviors and their relationship with physical activity levels in children and adolescents in the Community of Madrid. Methods:A total of 26,729 participants aged 10–17 from various schools and institutes took part in this study. The International Physical Activity Questionnaire Short Form (IPAQ-SF) was used, and they were asked about the time they spent on different leisure time habits (specific sedentary behaviors and organized physical activity). A generalized linear model was used to analyze the association between the time spent in sedentary activities and the time spent in physical activity. Results: The results revealed that children and adolescents engage in low levels of physical activity and most of them spend considerable time in sedentary behaviors such as studying, watching television, or using social media. Completing school homework (Coef: 1.23, 95% CI: −0.51 to 2.97, p = 0.167) or using social media for more than 2 h (Coef: 1.29, 95% CI: −2.98 to 0.40, p = 0.133) compared to not dedicating time to them did not show a significant association with daily physical activity time. Watching television for more than 2 h was associated with a decrease of 2.60 min (95% CI: −4.41 to −0.78, p = 0.005). Thus, no or only irrelevant associations were found between time spent in sedentary activities and physical activity time. Conclusions: Despite the drawbacks of spending time engaging in sedentary behaviors, they seem to be compatible with physical activity levels. Therefore, it is important to continue research on physical activity adherence strategies to promote overall health and well-being.

The disadvantages of some conventional drugs, including their low bioavailability, poor targeting efficiency, and important side effects, have led to the rational design of drug delivery systems. In particular, the introduction of drug delivery systems is a potential approach to enhance the uptake of therapeutic agents and deliver them at the right time and in the right amount of concentration at the required site, as well as open new strategies for effective illness treatment. In this review, we provide a basic understanding of drug delivery systems with an emphasis on the use of cyclodextrin-, polymer- and surfactant-based delivery systems. These systems are very attractive because they are biocompatible and biodegradable nanomaterials with multifunctional components. We also provide some details on their design considerations and their use in a variety of medical applications by employing several routes of administration.

The use of arbuscular mycorrhizal fungi (AMF) offers promising benefits to agriculture in the Amazon regions, where soils are characteristically acidic and nutrient-poor. The purpose of this research was to investigate the potential effects of two recently described species of AMF (Nanoglomus plukenetiae and Rhizoglomus variabile) native to the Peruvian Amazon for improving the plant growth of Plukenetia volubilis (inka nut or sacha inchi) and protecting the roots against soil pathogens. Two assays were simultaneously conducted under greenhouse conditions in Peru. The first focused on evaluating the biofertilizer effect of AMF inoculation, while the second examined the bioprotective effect against the root knot nematode, Meloidogyne incognita. Overall, the results showed that AMF inoculation of P. volubilis seedlings positively improved their development, particularly their biomass, height, and the leaf nutrient contents. When seedlings were exposed to M. incognita, plant growth was also noticeably higher for AMF-inoculated plants than those without AMF inoculation. Nematode reproduction was significantly suppressed by the presence of AMF, in particular R. variabile, and especially when inoculated prior to nematode exposure. The dual AMF inoculation did not necessarily lead to improved crop growth but notably improved P and K leaf contents. The findings provide strong justification for the development of products based on AMF as agro-inputs to catalyze nutrient use and uptake and protect crops against pests and diseases, especially those that are locally adapted to local crops and cropping conditions.

Rifampicin is one of the mainstays in treating staphylococcal prosthetic joint infection (PJI). However, discontinuation due to intolerance, drug interactions, and adverse events is common. Two-stage revision surgery remains the gold standard, with the number of revision arthroplasties steadily increasing. This study aims to evaluate the effectiveness and safety of a novel two-stage revision protocol for staphylococcal prosthetic joint infection (PJI) utilizing bone cement spacers loaded with multiple high doses of antibiotics. Additionally, it seeks to analyze outcomes in patients ineligible for rifampicin treatment. A retrospective review of 43 cases of staphylococcal hip and knee prosthetic joint infections (PJIs) from 2012 to 2020 was conducted. In all instances, a commercial cement containing 1 g of gentamicin and 1 g of clindamycin, augmented with 4 g of vancomycin and 2 g of ceftazidime, was employed to cast a spacer manually after thorough surgical debridement. We report an eradication rate of 82%, with no significant differences observed (p = 0.673) between patients treated with (84%, n = 19) and without rifampicin (79%, n = 24). There were no disparities in positive culture rates (7%), spacer replacement (18%), or survival analysis (p = 0.514) after an average follow-up of 68 months (range 10–147) in the absence of systemic toxicity and surgical complications superimposable to those previously reported. In conclusion, two-stage revision with local high doses of ceftazidime, vancomycin, gentamicin, and clindamycin demonstrates high effectiveness in treating staphylococcal PJIs. Notably, systemic rifampicin does not influence the outcomes. This protocol, with multiple high doses of antibiotics loaded into the bone cement spacer, is presented as a viable and safe alternative for patients unsuitable for rifampicin treatment.

Bridges are one of the most critical and costly structures on road networks. Thus, their integrity and operation must be preserved to prevent safety concerns and connectivity losses after seismic events. Recent large-magnitude earthquakes have revealed a series of vulnerabilities in multi-span highway bridges. In particular, skewed bridges have been severely damaged due to their susceptibility to developing excessive in-plane deck rotations and span unseating. Although seismic design codes have been updated to prescribe larger seating lengths and have incorporated unseating prevention devices, such as shear keys and cable restrainers, research on the seismic performance of skewed bridges with passive energy-dissipation devices is still limited. Therefore, this study focuses on assessing the effectiveness of implementing hysteretic dampers on skewed bridges. With that aim, dampers with and without recentering capabilities are designed and incorporated in representative Chilean skewed bridges to assess their contribution to seismic performance. Three-dimensional nonlinear finite element models, multiple-stripe analysis, and fragility curves are utilized to achieve this objective. The results show that incorporating bidirectional dampers can effectively improve the seismic performance of skewed bridges at different hazard levels by limiting in-plane deck rotations independently of their skew angle. Additionally, the influence of external shear keys and damper hysteretic behavior is analyzed, showing that these parameters have a low influence on bridge performance when bidirectional dampers are incorporated.

Introducción. La esporotricosis es una micosis de implantación causada por Sporothrix spp. Este se encuentra distribuido mundialmente y se puede encontrar en la vegetación y en el suelo. La ruta más frecuente de adquisición de la infección es por traumatismos con elementos contaminados con propágulos del hongo. Los gatos domésticos son los animales más afectados y pueden transmitirla a los humanos, por lo que es considerada una zoonosis. Las formas clínicas incluyen: la linfangítica nodular, la cutánea fija, la pulmonar (poco habitual) y la diseminada (excepcional). Objetivo. Analizar la epidemiología de la esporotricosis en Argentina entre los años 2010 y 2022. Describir la presentación clínica, los métodos de diagnóstico y el tratamiento de los casos diagnosticados en este período. Conocer los genotipos circulantes y observar su relación con el lugar geográfico de adquisición de la infección. Materiales y métodos. Se llevó a cabo un estudio analítico, retrospectivo y observacional, en el que se analizaron las historias clínicas de los pacientes con esporotricosis de 12 instituciones de salud de Argentina, entre los años 2010 y 2022. Resultados. Se presentan 54 casos en los que la forma clínica más frecuente fue la linfangítica nodular y el tratamiento de elección fue el itraconazol. En todos los casos se realizó diagnóstico convencional. El cultivo de las muestras clínicas resultó más sensible que el examen directo, ya que permitió el desarrollo de Sporothrix spp. en los 54 casos. En 22 casos se hizo identificación molecular y Sporothrix schenkii sensu stricto fue la especie más frecuentemente aislada. Conclusiones. Este estudio permitió conocer la epidemiología de esta micosis en Argentina, así como la disponibilidad de métodos diagnósticos y el tratamiento de elección.

Introduction. Fungal infections in patients with COVID-19 was one of the most debated topics during the pandemic. Objectives. To analyze the clinical characteristics and evolution of people living with HIV/AIDS and coinfection with cryptococcus and COVID-19 (group A) or without it (group B). Materials and methods. This is an analytical and retrospective study. We reviewed medical records of patients with meningeal cryptococcosis between April 2020 and May 2021. Results. We studied 65 people living with HIV/AIDS and with cryptococcosis infection diagnosed from April 2020 to May 2021. Fifteen patients with HIV/AIDS suffered from cryptococcosis and COVID-19, and out of these, 14 presented meningitis (group A), while 28 suffered from meningeal cryptococcosis, but did not have COVID-19 (group B). Conclusions. No statistically significant differences were observed between the two groups (A and B) considering: intracranial hypertension, presence of Cryptococcus antigens in cerebrospinal fluid, sensorium deterioration or mortality. The detection of Cryptococcus antigens in serum by lateral flow assay was highly effective to rapidly diagnose cryptococcosis in patients with HIV/AIDS who also developed COVID-19. Patients of both groups consulted for cryptoccocosis sometime after, in comparison with the pre-pandemic cases related to this infection.

Abstract Background Structural descriptions of complete genomes have elucidated evolutionary processes in angiosperms. In Cactaceae (Caryophyllales), a high structural diversity of the chloroplast genome has been identified within and among genera. In this study, we assembled the first mitochondrial genome (mtDNA) for the short-globose cactus Mammillaria huitzilopochtli. For comparative purposes, we used the published genomes of 19 different angiosperms and the gymnosperm Cycas taitungensis as an external group for phylogenetic issues. Results The mtDNA of M. huitzilopochtli was assembled into one linear chromosome of 2,052,004 bp, in which 65 genes were annotated. These genes account for 57,606 bp including 34 protein-coding genes (PCGs), 27 tRNAs, and three rRNAs. In the non-coding sequences, repeats were abundant, with a total of 4,550 (179,215 bp). In addition, five complete genes (psaC and four tRNAs) of chloroplast origin were documented. Negative selection was estimated for most (23) of the PCGs. The phylogenetic tree showed a topology consistent with previous analyses based on the chloroplast genome. Conclusions The number and type of genes contained in the mtDNA of M. huitzilopochtli were similar to those reported in 19 other angiosperm species, regardless of their phylogenetic relationships. Although other Caryophyllids exhibit strong differences in structural arrangement and total size of mtDNA, these differences do not result in an increase in the typical number and types of genes found in M. huitzilopochtli. We concluded that the total size of mtDNA in angiosperms increases by the lengthening of the non-coding sequences rather than a significant gain of coding genes.

Abstract Background Advanced colorectal cancer (CRC) is difficult to treat. For that reason, the development of novel therapeutics is necessary. Here we describe a potentially actionable plasma membrane target, the amino acid transporter protein subunit CD98hc. Methods Western blot and immunohistochemical analyses of CD98hc protein expression were carried out on paired normal and tumoral tissues from patients with CRC. Immunofluorescence and western studies were used to characterize the action of a DM1-based CD98hc-directed antibody–drug conjugate (ADC). MTT and Annexin V studies were performed to evaluate the effect of the anti-CD98hc-ADC on cell proliferation and apoptosis. CRISPR/Cas9 and shRNA were used to explore the specificity of the ADC. In vitro analyses of the antitumoral activity of the anti-CD98hc-ADC on 3D patient-derived normal as well as tumoral organoids were also carried out. Xenografted CRC cells and a PDX were used to analyze the antitumoral properties of the anti-CD98hc-ADC. Results Genomic as well proteomic analyses of paired normal and tumoral samples showed that CD98hc expression was significantly higher in tumoral tissues as compared to levels of CD98hc present in the normal colonic tissue. In human CRC cell lines, an ADC that recognized the CD98hc ectodomain, reached the lysosomes and exerted potent antitumoral activity. The specificity of the CD98hc-directed ADC was demonstrated using CRC cells in which CD98hc was decreased by shRNA or deleted using CRISPR/Cas9. Studies in patient-derived organoids verified the antitumoral action of the anti-CD98hc-ADC, which largely spared normal tissue-derived colon organoids. In vivo studies using xenografted CRC cells or patient-derived xenografts confirmed the antitumoral activity of the anti-CD98hc-ADC. Conclusions The studies herewith reported indicate that CD98hc may represent a novel ADC target that, upon well-designed clinical trials, could be used to increase the therapeutic armamentarium against CRC.

Abstract To analyze and compare the accuracy and root contact prevalence, comparing a conventional freehand technique and two navigation techniques based on augmented reality technology for the orthodontic self-drilling mini-implants placement. Methods Two hundred and seven orthodontic self-drilling mini-implants were placed using either a conventional freehand technique (FHT) and two navigation techniques based on augmented reality technology (AR TOOTH and AR SCREWS). Accuracy across different dental sectors was also analyzed. CBCT and intraoral scans were taken both prior to and following orthodontic self-drilling mini-implants placement. The deviation angle and horizontal were then analyzed; these measurements were taken at the coronal entry point and apical endpoint between the planned and performed orthodontic self-drilling mini-implants. In addition, any complications resulting from mini-implant placement, such as spot perforations, were also analyzed across all dental sectors. Results The statistical analysis showed significant differences between study groups with regard to the coronal entry-point (p

Abstract A hallmark of many malignant tumors is dedifferentiated (immature) cells bearing slight or no resemblance to the normal cells from which the cancer originated. Tumor dedifferentiated cells exhibit a higher capacity to survive to chemo and radiotherapies and have the ability to incite tumor relapse. Inducing cancer cell differentiation would abolish their self-renewal and invasive capacity and could be combined with the current standard of care, especially in poorly differentiated and aggressive tumors (with worst prognosis). However, differentiation therapy is still in its early stages and the intrinsic complexity of solid tumor heterogeneity demands innovative approaches in order to be efficiently translated into the clinic. We demonstrate here that microRNA 203, a potent driver of differentiation in pluripotent stem cells (ESCs and iPSCs), promotes the differentiation of mammary gland tumor cells. Combining mouse in vivo approaches and both mouse and human-derived tridimensional organoid cultures, we report that miR-203 influences the self-renewal capacity, plasticity and differentiation potential of breast cancer cells and prevents tumor cell growth in vivo. Our work sheds light on differentiation-based antitumor therapies and offers miR-203 as a promising tool for directly confronting the tumor-maintaining and regeneration capability of cancer cells.

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients. Inclusion criteria: patients older than 18 years on HD in the CAM, excluding patients diagnosed with any other hereditary disease with renal involvement different from FD, that sign the Informed Consent (IC). Exclusion criteria: underaged patients or not agreeing or not being capable of signing the IC. Results: 3470 patients were included, 63% males and with an average age of 67.9 ± 9.7 years. 2357 were HD-prevalent patients and 1113 HD-incident patients. For HD-prevalent patients, average time in HD was 45.2 months (SD 51.3), in HD-incident patients proteinuria was present in 28.4%. There were no statistical differences in plasmatic alpha-galactosidase A (α-GAL-A) activity or Lyso-GL-3 values when comparing HD-prevalent and HD-incident populations and neither between males and females. A genetic study was performed in 87 patients (2.5% of patients): 60 male patients with decreased enzymatic activity and 27 female patients either with a decreased GLA activity, increased Lyso-Gl3 levels or both. The genetic variants identified were: p.Asp313Tyr (4 patients), p.Arg220Gln (3 patients) and M290I (1 patient). None of the identified variants is pathogenic. Conclusions: 76% of HD Centers of the CAM participated in the study. This is the first publication to describe the prevalence of FD in the HD-population of a region of Spain as well as its average α-GAL-A-activity and plasmatic Lyso-Gl3 levels. It is also the first study that combines a cross-sectional design with a prospective follow-up design. This study has not identified any FD patient. Resumen: El objetivo del estudio ha sido realizar un mapa descriptivo de la enfermedad de Fabry (EF) en la Comunidad de Madrid, así como realizar un despistaje de la EF a todo paciente incidente durante un período de 3 años. Criterios de inclusión: Pacientes mayores de 18 años, excluyendo aquellos diagnosticados de cualquier otra enfermedad hereditaria con afectación renal diferente de la EF, que firmaran el consentimiento informado. Criterios de exclusión: pacientes menores de edad, no estar de acuerdo o no ser capaces de firmar el consentimiento informado. Resultados: Se incluyeron 3.470 pacientes (63% hombres), con una edad media de 67,9 ± 9,7 años, de los cuales 2.357 eran pacientes prevalentes y 1.113 incidentes. En el caso de los pacientes prevalentes, el tiempo medio en hemodiálisis (HD) fue de 45,2 (DE 51,3) meses. En pacientes incidentes, la proteinuria estuvo presente en el 28,4%. No hubo diferencias estadísticamente significativas en la actividad plasmática de alfa-galactosidasa A o valores de Lyso-Gl3 al comparar las poblaciones de incidentes y de prevalentes, y tampoco entre hombres y mujeres. Se realizó estudio genético en 87 pacientes (2,5% de los pacientes): 60 varones con disminución de la actividad enzimática y 27 mujeres con una disminución de la actividad enzimática, aumento de los niveles de Lyso-Gl3 o ambos. Las variantes genéticas identificadas fueron: p.Asp313Tyr (4 pacientes), p.Arg220Gln (3 pacientes) y M290I (un paciente). Ninguna de las variantes identificadas fue patógena. Conclusiones: El 76% de los centros de HD de la Comunidad de Madrid participaron en el estudio. Este es el primer estudio epidemiológico prospectivo de EF en la población de HD de una región de España. También es la primera vez que se describen niveles de alfa-galactosidasa A y Lyso-Gl3 en HD, sin embargo, en este estudio no se han identificado pacientes con EF.