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This study presents the optimization of graphene oxide (GO) synthesis for arsenic (As) removal from contaminated groundwater in Mexico and Colombia, using the modified Hummers method. By applying response surface methodology (RSM), the concentrations of NaNO₃ and KMnO₄ were adjusted to maximize the density of oxygenated functional groups, significantly enhancing the adsorption capacity for As(V). Characterization results revealed a reduction in macroporosity and an increase in mesoporosity and microporosity, contributing to the superior adsorption performance. The optimized GO achieved an adsorption capacity of 99.13 mg g⁻¹ at 308 K under competitive conditions with other ions such as F⁻, CrO₄²⁻, Cl⁻, CO₃²⁻, and SO₄²⁻. Additionally, the synthesis process reduced toxic by-products, demonstrating sustainability for industrial-scale applications. These findings represent a significant advancement in the development of efficient and sustainable materials for groundwater remediation.

The CoCrMo alloy is a biomaterial that has been employed for the production of permanent orthopedic implants, however, the release of metallic ions from debris due to tribocorrosion is the main drawback for its extended application. In this paper, we propose the use of the ball burnishing process to improve the surface properties of the CoCrMo alloy. A 32 factorial design of experiments (DoE) was conducted to achieve a basic understanding of the relationship between the surface hardness, roughness and corrosion current (response variables) and the force and number of passes of the burnishing tool (input factors). Statistical analysis showed that force is the most significant factor for changing the surface properties. At the best experimental conditions, hardness was improved by 41.4%, the roughness was decreased by 72.7% and the corrosion rate was noticeably reduced by 92.4%. Microscopy and X-ray diffraction analysis showed that ball burnishing introduces changes in the microstructure, generating a surface layer with improved properties. It is concluded that the ball burnishing process is suitable for improving the surface properties of the CoCrMo alloy under an appropriate combination of experimental conditions.

Flash floods are a recurrent hazard for many developing Latin American regions due to their complex mountainous terrain and the rainfall characteristics in the tropics. These regions often lack the timely and high-quality information needed to assess, in real time, the threats to the vulnerable communities due to extreme hydrometeorological events. The systematic assessment of past extreme events allows us to improve our prediction capabilities of flash floods. In May 2015, a flash flood in the La Liboriana basin, municipality of Salgar, Colombia, caused more than 100 casualties and significant infrastructure damage. Despite the data scarcity, the climatological aspects, meteorological conditions, and first-order hydrometeorological mechanisms associated with the La Liboriana flash flood, including orographic intensification and the spatial distribution of the rainfall intensity relative to the basin's geomorphological features, are studied using precipitation information obtained using a weather radar quantitative precipitation estimation (QPE) technique, as well as from satellite products, in situ rain gauges from neighboring basins, quantitative precipitation forecasts (QPFs) from an operational Weather Research and Forecasting Model (WRF) application, and data from reanalysis products. The La Liboriana flash flood took place during a period with negative precipitation anomalies over most of the country as a result of an El Niño event. However, during May 2015, moist easterly flow towards the upper part of La Liboriana caused significant orographic rainfall enhancement. The overall evidence shows an important role of successive precipitation events in a relatively short period and of orography in the spatial distribution of rainfall and its intensification as convective cores approached the steepest topography. There were three consecutive events generating significant rainfall within the La Liboriana basin, and no single precipitation event was exceptionally large enough to generate the flash flood, but rather the combined role of precedent rainfall and the extreme hourly precipitation triggered the event. The results point to key lessons for improving local risk reduction strategies in vulnerable regions with complex terrain.

In this paper, we present the results of a non-enzymatic electrochemical glucose biosensor based on TiO2. An anatase working electrode was synthesized using the spin coating technique with the polymeric precursor method and dispersed TiO2 nanoparticles. Through scanning electron microscopy, it was observed that the electrode presented an irregular surface with clusters of nanoparticles. Electrochemical characterization indicated that the response was directly related to the morphology of the electrode. In the presence of glucose, the electrode exhibited adsorption behavior toward the molecules, enabling their recognition. The electrode was tested by employing PBS (phosphate buffer solutions) with varying pH values (from 4 to 9), demonstrating its electrochemical stability, even in the presence of glucose. Amperometric characterization was used to determine that the working region appeared from 0.2 mM to 2 mM, with a sensitivity of 4.46 μAcm−2mM−1 in PBS pH 7. The obtained results suggest that TiO2-based electrodes could be used for the detection of glucose concentration in sweat (0.277–1 mM) and saliva (0.23–1.77 mM).

Los pacientes con cáncer medular de tiroides avanzado tienen pocas opciones de tratamiento; las únicas terapias aceptadas a la fecha son el vandetanib y el cabozantinib. Sin embargo, al ser inhibidores multiquinasa tienen efectos adversos importantes, que pueden limitar su uso clínico. Con el vandetanib la prolongación del QT puede producir arritmias y requiere un uso cauteloso de medicamentos concomitantes. Con el cabozantinib, aparte de la hipertensión y el síndrome mano-pie, pueden aparecer fistulas y perforación gastrointestinal con riesgo de sangrado. Las alteraciones genéticas del proto-oncogén RET no solo están implicadas en el cáncer medular de tiroides, sino en otros tipos de cáncer, como el de pulmón. La inhibición específica del RET con los medicamentos LOXO-292 y BLU-677 es segura y no afecta otras tirosina quinasa. Por ende, su uso clínico parece ser prometedor, dado que tienen una buena respuesta clínica; además, tienen efectos adversos menos frecuentes y graves que los inhibidores de tirosina quinasa actuales.

Background: Melioidosis is endemic in Malaysia, the southwest of Thailand, and northern Australia. The incidence in Thailand is 4.4/1 000 000 inhabitants, where it causes 19% of community-acquired pneumonia (CAP) and 20% of bacteremic pneumonia, and the mortality is 50%. Sporadic cases have been described in Central and South America. The objective of this study was to describe the clinical and epidemiological features and ecological characteristics of melioidosis in Antioquia, Colombia. Methods: This is a case series description. Results: Seven cases were identified. Burkholderia pseudomallei was isolated from peripheral blood, pleural fluid, and urine and was identified by the automated system VITEK 2 (bioMérieux) and API 20NE biochemical kit. Five of the cases had a bacteremic form with shock and pulmonary compromise and two of these patients died. The non-bacteremic melioidosis cases had genitourinary, abdominal, and osteoarticular compromise. All patients had comorbidities and lived in rural hot and humid areas in the west central region of Colombia (Antioquia). Diabetes mellitus, renal insufficiency, and other chronic diseases are important risk factors for the development of severe forms. Conclusions: The cases presented here are similar to those occurring in endemic areas regarding comorbidity, risk factors, clinical presentation, and environmental conditions. It is necessary to establish whether melioidosis is an endemic and under-diagnosed disease or an emerging disease in Colombia.

This paper focuses on the particle size distribution (PSD) changes during nixtamalized corn kernels (NCK) as a function of the steeping time (ST). The process to obtain powder or corn flour from NCK was as follows: (i) the NCK with different STs were wet-milled in a stone mill, (ii) dehydrated by a Flash type dryer, and (iii) pulverized with a hammer mill and sieved with a 20 mesh. The powder was characterized by measuring the PSD percentage, calcium percentage (CP), peak viscosity at 90°C (PV), and crystallinity percentage (CP). The PSD of the powder as a function of ST was determined by sieving in Ro-TAP equipment. By sieving, five fractions of powder were obtained employing meshes 30, 40, 60, 80, and 100. The final weight of the PSD obtained from the sieving process follows a Gaussian profile with the maximum corresponding to the average particle obtained with mesh 60. The calcium percentage as a function of ST follows a behavior similar to the weight of the PSD. The study of crystallinity versus the mesh number shows that it decreases for smaller mesh number. A similar behavior is observed as steeping time increases, except around ST = 8 h where the gelatinization of starch is observed. The trend of increasing viscosity values of the powder samples occurs when increasing ST and decreasing particle size. The ST significantly changes the crystallinity and viscosity values of the powder and, in both cases, a minimum value is observed in the region 7–9 h. The experimental results show that the viscosity increases (decreases) if the particle size decreases (increases).

Cu-doped CdTe thin films were prepared by pulsed laser deposition on Corning glass substrates using powders as target. Films were deposited at substrate temperatures ranging from 100 to 300 °C. The X-ray diffraction shows that both the Cu-doping and the increase in the substrate temperature promote the presence of the hexagonal CdTe phase. For a substrate temperature of 300 °C a CdTe:Cu film with hexagonal phase was obtained. Raman and EDS analysis indicate that the films grew with an excess of Te, which indicates that CdTe:Cu films have p-type conductivity.

La tensión residual y la orientación molecular en un material proporcionan información importante de su comportamiento. La presencia o ausencia de tensión residual determina la calidad de los plásticos usados para el almacenamiento de información y otros. En el presente trabajo, se implementó un método de ensayo no destructivo para la evaluación de los discos compactos, así como el almacenamiento de información en los mismos mediante el análisis óptico de tensión residual. Además se hizo un análisis cuantitativo del estado de tensión de diferentes marcas de CD.

Interoperability is a software property for exchanging and using information between software systems. Some interoperability proposals are intended to use metamodels, models, and frameworks, in which visual representations are included. However, such proposals describe interoperability according to their point of view, focus of analysis, solution techniques, and specific level of interoperability; in addition, some of the visual representations use no standards, which lead to subjective interpretations by the reader. In this paper we propose a representation formalizing interoperability which includes essential elements and structural relationships among them. After a review of previous work, a summary of the analyzed literature is performed by using linguistic analysis in order to recognize the relationships among interoperability essential elements and mapping them to controlled language expressions. Finally, the mapping process is used to represent the interoperability essential elements and their relationships by using pre-conceptual schemas linked to the definition of each essential element. As a result, a pre-conceptual schema of the software system interoperability is proposed. Such a pre-conceptual schema is also used for explaining an interoperability lab study adapted from the literature. The proposed pre-conceptual schema explains the interoperability between two software systems and allows for characterizing interoperability problems and solutions. [ABSTRACT FROM AUTHOR]

For the conservation of species, especially those endemic or vulnerable, it is necessary to deepen the knowledge about their ecological dynamic and to find adequate techniques for multiplication. Ramorinoa girolae, "chica", is an endemic woody species of the xerophytic flora from western Argentine arid regions, with a restricted occupation area and fragmented communities. The lack of records makes relevant the conduction of research underpinning knowledge of the species, regeneration mechanisms and multiplication techniques. The objective of this work was to study the behavior of seeds of three populations under germination conditions and the response for different pre-germinative treatments. Germination trials were made in the laboratory with different pre-germinative techniques using the seeds of three populations under a completely aleatory design. Results confirm the presence of physical dormancy in seeds restricting the imbibing process for their rapid germination. The treatments, hot water scarification and mechanical scarification with sandpaper, increase significantly the germination percentages. The best treatment is mechanical scarification with sandpaper, reaching values of 92% of germination at five days from the beginning of the treatment. The uneven response of germination of the different populations confirms the different behavior of local populations and results interesting for ecosystem studies and future lines of investigation and management of this species. These technical aspects appear as relevant for the application of reforestation and environmental restoration programs. Para la conservación de las especies, especialmente endémicas o vulnerables, es necesario profundizar el conocimiento de su dinámica ecológica y encontrar técnicas adecuadas de multiplicación. Ramorinoa girolae, "chica", es una especie leñosa endémica de la flora xerófila del oeste árido argentino, con restringida área de ocupación y distribución fragmentada. La falta de antecedentes hace relevante realizar investigaciones que fundamenten el conocimiento de la especie, los mecanismos de regeneración y las técnicas para su multiplicación. El objetivo de este trabajo fue estudiar el comportamiento de semillas de tres poblaciones en condiciones de germinación y la respuesta a diferentes tratamientos pregerminativos. Se realizaron ensayos de germinación en laboratorio con distintas técnicas pregerminativas utilizando semillas de tres poblaciones bajo un diseño completamente aleatorizado. Los resultados confirman la presencia de dormición física en las semillas que restringen el proceso de imbibición para su rápida germinación. Los tratamientos ensayados, escarificación con agua caliente y mecánica con lija, incrementan significativamente los porcentajes de germinación. El tratamiento que produce mejores resultados es la escarificación mecánica con lija, alcanzando valores del 92% de germinación a los cinco días de comenzado el tratamiento. La desigual respuesta de germinación de distintas poblaciones confirma el comportamiento diferente de poblaciones locales que resulta de interés en los estudios ecosistémicos y futuras líneas de investigación y gestión de esta especie. Estos conocimientos son relevantes en la propagación de la especie y la aplicación de programas reforestación y restauración ambiental. [ABSTRACT FROM AUTHOR]

Abstract: In this work the electronic behavior of hydrogen impurities in lanthanum (La), scandium (Sc) and yttrium (Y) matrices is studied. For each one of the systems some fundamental physical properties are determined, as the induced screening electron density, the volume of solution of hydrogen, the solution heat and the variation of the density of electronic states, using the formalism of the density functional theory (DFT) and the Jellium model. We propose a new parameterization for the solution heat in terms of the change of total energy of the system, obtaining an excellent agreement with experimental values reported in the literature. One of the main features of this model is that it yields accurate values of those properties of the system which are strongly dependent on the density of free electrons. The results obtained by this method are compared with experimental data available in the literature, as well as with more sophisticated theoretical models. [Copyright &y& Elsevier]

A modified method for in vitro production of conidia from two isolates of Mycosphaerella fijiensis is described. Conidial production was notably stimulated by brush harvesting mycelial cultures in three batches of Petri dishes at three intervals: batch 1, every 5 days [5, 10 and 15 days post-inoculation (dpi)]; batch 2, every 6 days (6, 12 and 18 dpi); and batch 3, every 7 days (7, 14 and 21 dpi). Significant cumulative conidial production was observed after the second harvest at all intervals. Conidial viability was verified indirectly by inoculating conidial suspensions onto Musa acuminata leaf fragments and monitoring infection with light and scanning electron microscopes. [ABSTRACT FROM AUTHOR]

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The Electronic Health Record used in the public primary care network of Buenos Aires City has a specific module for the vaccines registration. The present study explores the factors of EHR adoption by nurses. We found 5 barriers and one facilitator for adoption. Barriers are related with organize the flow of patients especially during vaccine campaigns, adapt the work stations and integrate the records with the vaccine central program. [ABSTRACT FROM AUTHOR]

Background: Some cancer survivors experience difficulties with concentration, attention, and memory; however, there are no studies on neurodevelopment in patients under 5 years of age who are undergoing cancer treatment. Our aim was to evaluate neurodevelopment in cancer patients under 5 years of age using the Early Development Instrument (EDI) test, considering factors such as nutritional status, type of cancer, and treatment effect. Methods: A cross-sectional study was conducted from February 2018 to March 2019. Patients with cancer diagnoses outside the central nervous system in any phase of cancer treatment were included. Results: A total of 45 patients were included. Regarding fine motor skills, 28% of patients with retinoblastoma and 23% of patients with leukemia or lymphoma had a risk of developmental delay compared to 0% of patients with solid tumors (p = 0.025). The final results showed that 19 (42.2%) patients had normal neurodevelopment (gray), 7 (15.5%) had a delay in neurodevelopment (light gray), and 19 (42.2%) had a risk of developmental delay (black). Regarding developmental delay, 52% of patients in the leukemia and lymphoma group, 71% in the retinoblastoma group, and 23% in the solid tumor group presented developmental delay (p = 0.06). Conclusions: The risk of delay and lag in neurodevelopment is common in cancer patients under 5 years of age undergoing treatment. However, more studies are required to evaluate the effect of treatment on this group of patients as it may be affected by various factors.

Adoptive T cellular immunotherapies have emerged as relevant approaches for treating cancer patients who have relapsed or become refractory (R/R) to traditional cancer treatments. Chimeric antigen receptor (CAR) T-cell therapy has improved survival in various hematological malignancies. However, significant limitations still impede the widespread adoption of these therapies in most cancers. To advance in this field, six research groups have created the “NEXT Generation CART MAD Consortium” (NEXT CART) in Madrid’s Community, which aims to develop novel cell-based immunotherapies for R/R and poor prognosis cancers. At NEXT CART, various basic and translational research groups and hospitals in Madrid concur to share and synergize their basic expertise in immunotherapy, gene therapy, and immunological synapse, and clinical expertise in pediatric and adult oncology. NEXT CART goal is to develop new cell engineering approaches and treatments for R/R adult and pediatric neoplasms to evaluate in multicenter clinical trials. Here, we discuss the current limitations of T cell-based therapies and introduce our perspective on future developments. Advancement opportunities include developing allogeneic products, optimizing CAR signaling domains, combining cellular immunotherapies, multi-targeting strategies, and improving tumor-infiltrating lymphocytes (TILs)/T cell receptor (TCR) therapy. Furthermore, basic studies aim to identify novel tumor targets, tumor molecules in the tumor microenvironment that impact CAR efficacy, and strategies to enhance the efficiency of the immunological synapse between immune and tumor cells. Our perspective of current cellular immunotherapy underscores the potential of these treatments while acknowledging the existing hurdles that demand innovative solutions to develop their potential for cancer treatment fully.

Background: Langerhans cell histiocytosis (LCH) is a rare neoplastic disease characterized by clonal proliferation of dendritic cells. It is Mexico’s ninth most frequent malignancy in patients under 18 years of age. The aim of the study was to determine the clinical characteristics, treatment, and survival of Mexican pediatric patients diagnosed with LCH treated from January 2010 to December 2018. Methods: We conducted a retrospective study of LCH using data from 19 accredited hospitals throughout the Mexican Republic. Patients < 18 years who were diagnosed with LCH between January 2010 and December 2018 were included (253 patients) in the study. Results: All patients had a histopathological diagnosis, and extension studies were performed at their treatment centers. The median age at diagnosis was 19 months. The most frequently affected sites included the bone (178 cases; 70%) and the skin (131 cases; 51.7%). Of the patients in Group 1, 48 (42%) had bone marrow involvement, 62 (53%) had splenomegaly, and 39 (34.8%) had liver involvement. Of the patients who underwent chemotherapy treatment, 61.2% exhibited a complete response, and 36 patients (14.2%) relapsed after complete remission. The most frequent sites of relapse were the skin, bone, lymph nodes, and liver. The overall survival rate was 91.3% and was lower for patients in Group 1 (77%) compared with those in Groups 2 (97%) and 3 (100%), p = 0.001. Conclusion: The current report aims to demonstrate the findings of a multicenter study conducted on Mexican children with LCH; consequently, these treatment results for a relatively infrequent disease merit further research.

IntroductionAcute lymphoblastic Leukemia (ALL) is the most common pediatric malignancy. While the survival rate for childhood ALL exceeds 90% in high-income countries, the estimated survival in low-and middle-income countries ranges from 22-79%, depending on the region and local resources.MethodsThis study retrospectively reviewed demographic, biological, and clinical parameters of children under 18 years of age with newly diagnosed ALL presenting between 2013-2017 across five pediatric centers in 4 countries in South America. Survival analyses were estimated using the Kaplan-Meier method.ResultsAcross the five centers, 752 patients were analyzed (Bolivia [N=9], Ecuador [N=221], Paraguay [N=197], Peru [N=325]) and 92.1% (n=690) patients were diagnosed with B-cell and 7.5% (n= 56) with T-cell ALL. The median age was 5.5 years old (IQR 7.29). At diagnosis, 47.8% of patients were categorized as standard and 51.9% as high risk per their institutional regimen. Advanced diagnostics availability varied between modalities. MRD was evaluated in 69.1% of patients; molecular testing was available for ETV6-RUNX, BCR-ABL1, TCF3-PBX1, and KMT2A-rearranged ALL in 75-81% of patients; however, karyotyping and evaluation for iAMP21 were only performed in 42-61% of patients. Central nervous system (CNS) involvement was evaluated at diagnosis in 57.3% (n=429) patients; of these, 93.7% (n=402) were CNS 1, 1.6% (n=7) were CNS 2, 0.7% (n=11) were CNS3, 1.9% (n=8) had cranial nerve palsy, and 2.1% (n=9) results unavailable. Chemotherapy delays >2 weeks were reported in 56.0% (n=421) patients during treatment. Delays were attributed to infection in 63.2% (n=265), drug-related toxicities in 47.3% (n=198), and resource constraints, including lack of bed availability in 23.2% (n=97) of patients. The 3-year Abandonment-sensitive EFS and OS were 61.0±1.9% and 67.2±1.8%, respectively. The 3-year EFS and OS were 71.0±1.8% and 79.6±1.7%, respectively.DiscussionThis work reveals opportunities to improve survival, including addressing severe infections, treatment interruptions, and modifications due to drug shortages. In 2018, healthcare professionals across South America established the Pediatric Oncology Latin America (POLA) group in collaboration with St. Jude Children’s Research Hospital. POLA collaborators developed an evidence-based, consensus-derived, adapted treatment guideline, informed by preliminary results of this evaluation, to serve as the new standard of care for pediatric ALL in participating institutions.

At certain depths, the elastic properties of the ground are not affected by seismic waves. However, as they reach the surface, the soil density decreases and so does its elastic limit. This means that the expected ground motion acting at the foundation of a structure cannot be adequately described without considering the inelastic response of the soil near the surface. Therefore, one of the key elements in characterizing the seismic response of civil structures is the site effect. These depend mainly on the parameters of the soil beneath the structure and the features of the ground motion acting at the depth, where non-linear effects are negligible. Therefore, the main objective of this paper is to find an intensity measure that incorporates the information provided by the soil profile under the structure and the ground motion acting at the bedrock level. Due to the random nature of both elements, a probabilistic framework using Monte Carlo simulation has been developed to analyze this problem. For this purpose, random soil profiles have been generated to obtain a representative sample of likely scenarios of the study area. A large database of Colombian ground motion records has been used to model the seismic hazard. Finally, power functions capable of relating the input variables to the dynamic response of a large set of reinforced concrete structures have been derived by considering multi-regression analysis. It has been observed that, in several cases, intensity measures extracted from the displacement spectrum appear in the mathematical arrangements. These functions could be used to improve the efficiency of seismic risk prediction at the urban level.

Interoperability is a property of software quality that is related to the cooperation between software systems for exchanging information. However, this concept is not well explained or understood. A theory would be useful to explain interoperability in terms of its essential elements and propositions. Theoretical contributions of interoperability are intended to formalize this concept by using common frameworks, models, and meta-models. However, tentative contributions developed in the past have failed to propose a theory of interoperability due to four reasons: (1) a disunified vocabulary is used, (2) the essential elements for describing interoperability are not well identified, (3) only a single level of interoperability is assessed, and (4) interoperability principles are not well formalized. This paper tentatively proposes an axiomatic theory of interoperability as a complementary approach to the existing knowledge. The proposed theory seeks to better formalize the concepts of interoperability and suggest actions aimed at establishing interoperability. After a brief review of related works and the state of the art, a set of axioms and propositions is presented. This theory is evaluated by a group of experts, and an example is presented to illustrate its use. Conclusions and future works are outlined at the end of the paper.

Introducción: Las enfermedades cardiovasculares en las gestantes son desafiantes, con alta morbimortalidad materna y perinatal, por lo que se recomienda un equipo cardio-obstétrico para su atención. Aun así, pocos datos evalúan el impacto de estos equipos. Por lo tanto, el presente estudio tiene como objetivo comparar los resultados obstétricos, maternos y neonatales del seguimiento semiestructurado (SSE) en una clínica cardio-obstétrica con respecto a un seguimiento usual o seguimiento no estructurado (SNE) en gestantes con enfermedad cardiaca. Métodos: Se realizó un registro prospectivo de gestantes con cardiopatías. Se compararon las pacientes con SSE por un equipo cardio-obstétrico, contra aquellas con evaluación única o SNE. Se calculó el riesgo de eventos según la clasificación de la Organización Mundial de la Salud modificado (OMSm) y la escala del Cardiac Disease in Pregnancy Study II (CARPREG-II) y se evaluaron los desenlaces cardiacos, obstétricos y neonatales. Resultados: Se evaluaron 168 pacientes, 37 con SSE y 131 con evaluación única (SNE). Los principales diagnósticos fueron cardiopatía congénita, arritmias y valvulopatías. La media del CARPREG-II en pacientes de SNE fue 2.48 (DE: 2.3) y en pacientes de SSE fue 3.37 (DE: 2.45; p = 0.041). La media de la OMSm en pacientes de SNE fue 2.1 (DE: 1.6) y con SSE fue 2.65 (DE: 0.95; p = 0.0052). No hubo diferencias significativas en los desenlaces cardiacos primarios (13.8% en SNE vs. 5.4% en SSE; p = 0.134), cardiacos secundarios (5.3 en SNE vs. 2.7 en SSE; p = 0.410), obstétricos (10% en SNE vs. 16.2% en SSE; p = 0.253) y neonatales (35.9% en SNE y 40.5% en SSE; p = 0.486) a pesar de que las pacientes con SSE tenían un riesgo mayor que las pacientes con SNE según las escalas de la OMSm y el CARPREG- II. Conclusiones: En gestantes con cardiopatía, un SSE comparado con un SNE por un equipo cardio-obstétrico no mostró diferencias estadísticamente significativas en los desenlaces cardiovasculares, obstétricos y neonatales, a pesar de que las pacientes con SSE tenían un riesgo significativamente más alto de desenlaces adversos por las escalas de la OMSm y el CARPREG-II. Esto sugiere que el SSE logra al menos equiparar los desenlaces a pesar del mayor riesgo de eventos adversos que tenían las pacientes de este grupo.

Microplastics are contaminants of emerging concern, not least due to their global presence in marine surface waters. Unsurprisingly, microplastics have been reported in salts harvested from numerous locations. We extracted microplastics from 13 European sea salts through 30% H2O2 digestion and filtration over 5-µm filters. Filters were visually inspected at magnifications to x100. A subsample of potential microplastics was subjected to Raman spectroscopy. Particle mass was estimated, and human dose exposure calculated. After blank corrections, median concentrations were 466 ± 152 microplastics kg-1 ranging from 74 to 1155 items kg-1. Traditionally harvested salts contained fewer microplastics than most industrially harvested ones (t-test, p

Objetivo: Sintetizar y valorar críticamente las recomendaciones sobre manejo neurocognitivo del paciente con cardiopatía congénita presentadas en guías de práctica clínica y declaraciones científicas. Método: Revisión sistemática de recomendaciones de práctica (PROSPERO CRD42020205202). Se realizó una búsqueda en PubMed, SCOPUS, Ovid/Cochrane, y LILACS y se revisaron repositorios de sociedades científicas y referencias de los documentos incluidos. La valoración crítica se hizo mediante el AGREE-II (escenario ideal) para las guías y declaraciones, y mediante el AGREE-REX para las recomendaciones (escenarios ideal y local). Se presentan la matriz de recomendaciones y el análisis de barreras potenciales para su implementación en Colombia. Resultados: Se incluyeron 18 recomendaciones relacionadas. La media en el AGREEII fue 89.6. La media en el AGREE-REX fue 90.1 en el escenario ideal y 69.9 en el escenario local. Las recomendaciones incluidas se centran en vigilancia, tamizaje, evaluación y consejería; no se identificaron recomendaciones sobre intervención neurocognitiva. Las principales barreras de implementación en Colombia son la no disposición a pagar por parte del sistema de salud y la ausencia de oferta integral de atención para el manejo neurocognitivo en cardiopatía congénita. Conclusión: Las recomendaciones identificadas podrían ser adaptadas en una guía de práctica colombiana, realizando modificaciones en reconocimiento del contexto local.

Tri-Butyl Tin (TBT) remains as a legacy pollutant in the benthic environments. Although the toxic impacts and endocrine disruption caused by TBT to gastropod molluscs have been established, the changes in energy reserves allocated to maintenance, growth, reproduction and survival of European oysters Ostrea edulis, a target species of concerted benthic habitat restoration projects, have not been explored. This study was designed to evaluate the effect of TBT chloride (TBTCl) on potential ions and relevant metabolomic pathways and its association with changes in physiological, biochemical and reproductive parameters in O. edulis exposed to environmental relevant concentrations of TBTCl. Oysters were exposed to TBTCl 20 ng/L (n = 30), 200 ng/L (n = 30) and 2000 ng/L (n = 30) for nine weeks. At the end of the exposure, gametogenic stage, sex, energy reserve content and metabolomic profiling analysis were conducted to elucidate the metabolic alterations that occur in individuals exposed to those compounds. Metabolite analysis showed significant changes in the digestive gland biochemistry in oysters exposed to TBTCl, decreasing tissue ATP concentrations through a combination of the disruption of the TCA cycle and other important molecular pathways involved in homeostasis, mitochondrial metabolism and antioxidant response. TBTCl exposure increased mortality and caused changes in the gametogenesis with cycle arrest in stages G0 and G1. Sex determination was affected by TBTCl exposure, increasing the proportion of oysters identified as males in O. edulis treated at 20ng/l TBTCl, and with an increased proportion of inactive stages in oysters treated with 2000 ng/l TBTCl. The presence and persistence of environmental pollutants, such as TBT, could represent an additional threat to the declining O. edulis populations and related taxa around the world, by increasing mortality, changing reproductive maturation, and disrupting metabolism. Our findings identify the need to consider additional factors (e.g. legacy pollution) when identifying coastal locations for shellfish restoration.

Authoritative, trustworthy, continual, automatic hourly air quality monitoring is a relatively recent innovation. The task of reliably identifying long-term trends in air quality is therefore very challenging, as well as complex. Ports are major sources of atmospheric pollution, which is linked to marine traffic and increased road traffic congestion. This study investigated the long-term trends and drivers of atmospheric pollution in the port cities of Houston, London, and Southampton in 2000–2019. Authoritative air quality and meteorological data for seven sites at these three locations were meticulously selected alongside available traffic count data. Data were acquired for sites close to the port and sites that were near the city centre to determine whether the port emissions were influencing different parts of the city. Openair software was used for plots and statistical analyses. Pollutant concentrations at Houston, Southampton and Thurrock (London) slowly reduced over time and did not exceed national limits, in contrast to NO2 and PM10 concentrations at London Marylebone Road. Drivers of atmospheric pollution include meteorology, geographical and temporal variation, and traffic flow. Statistically significant relationships (p < 0.001) between atmospheric pollution concentration and meteorology across most sites were found, but this was not seen with traffic flows in London and Southampton. However, port emissions and the other drivers of atmospheric pollution act together to govern the air quality in the city.

Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities. Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia. Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses. Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p

Abstract Background In the search for novel antibody-drug conjugates (ADCs) with therapeutic potential, it is imperative to identify novel targets to direct the antibody moiety. CD13 seems an attractive ADC target as it shows a differential pattern of expression in a variety of tumors and cell lines and it is internalized upon engagement with a suitable monoclonal antibody. PM050489 is a marine cytotoxic compound tightly binding tubulin and impairing microtubule dynamics which is currently undergoing clinical trials for solid tumors. Methods Anti-CD13 monoclonal antibody (mAb) TEA1/8 has been used to prepare a novel ADC, MI130110, by conjugation to the marine compound PM050489. In vitro and in vivo experiments have been carried out to demonstrate the activity and specificity of MI130110. Results CD13 is readily internalized upon TEA1/8 mAb binding, and the conjugation with PM050489 did not have any effect on the binding or the internalization of the antibody. MI130110 showed remarkable activity and selectivity in vitro on CD13-expressing tumor cells causing the same effects than those described for PM050489, including cell cycle arrest at G2, mitosis with disarrayed and often multipolar spindles consistent with an arrest at metaphase, and induction of cell death. In contrast, none of these toxic effects were observed in CD13-null cell lines incubated with MI130110. Furthermore, in vivo studies showed that MI130110 exhibited excellent antitumor activity in a CD13-positive fibrosarcoma xenograft murine model, with total remissions in a significant number of the treated animals. Mitotic catastrophes, typical of the payload mechanism of action, were also observed in the tumor cells isolated from mice treated with MI130110. In contrast, MI130110 failed to show any activity in a xenograft mouse model of myeloma cells not expressing CD13, thereby corroborating the selectivity of the ADC to its target and its stability in circulation. Conclusion Our results show that MI130110 ADC combines the antitumor potential of the PM050489 payload with the selectivity of the TEA1/8 monoclonal anti-CD13 antibody and confirm the correct intracellular processing of the ADC. These results demonstrate the suitability of CD13 as a novel ADC target and the effectiveness of MI130110 as a promising antitumor therapeutic agent.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) comprise a group of illnesses marked by memory and behavioral dysfunction that can occur in up to 50% of HIV patients despite adequate treatment with combination antiretroviral drugs. Iron dyshomeostasis exacerbates HIV-1 infection and plays a major role in Alzheimer’s disease pathogenesis. In addition, persons living with HIV demonstrate a high prevalence of neurodegenerative disorders, indicating that HAND provides a unique opportunity to study ferroptosis in these conditions. Both HIV and combination antiretroviral drugs increase the risk of ferroptosis by augmenting ferritin autophagy at the lysosomal level. As many viruses and their proteins exit host cells through lysosomal exocytosis, ferroptosis-driving molecules, iron, cathepsin B and calcium may be released from these organelles. Neurons and glial cells are highly susceptible to ferroptosis and neurodegeneration that engenders white and gray matter damage. Moreover, iron-activated microglia can engage in the aberrant elimination of viable neurons and synapses, further contributing to ferroptosis-induced neurodegeneration. In this mini review, we take a closer look at the role of iron in the pathogenesis of HAND and neurodegenerative disorders. In addition, we describe an epigenetic compensatory system, comprised of bromodomain-containing protein 4 (BRD4) and microRNA-29, that may counteract ferroptosis by activating cystine/glutamate antiporter, while lowering ferritin autophagy and iron regulatory protein-2. We also discuss potential interventions for lysosomal fitness, including ferroptosis blockers, lysosomal acidification, and cathepsin B inhibitors to achieve desirable therapeutic effects of ferroptosis-induced neurodegeneration.

This paper proposes a control scheme for a wave energy conversion system based on a linear generator and a cascaded multilevel converter. The mechanical conversion system is composed of a buoy connected directly to a linear generator. The windings of the generator are individually controlled by a cascaded multilevel power converter using independent maximum power point tracking to improve energy harvesting. The output of the cascaded converter is controlled to keep the DC capacitors balanced and generate a multilevel voltage at the output terminals which reduces the losses in the underwater transmission line. Experimental results show the performance of the proposed control scheme maximizing the power generation by imposing a current with the same waveform of the induced voltage and balancing the DC capacitors.

Background: The association between childhood cancer and socioeconomic status has been widely studied. However, none of the results are conclusive. This study aimed to analyze the association between the Human Development Index (HDI) and the acute lymphoblastic leukemia (ALL) incidence in children under the Popular Medical Insurance Care. Methods: We conducted an observational, descriptive, and population-based study covering 55% of the Mexican population (58 million). Results: The most impoverished states were located in the south east region of Mexico, while the north was more homogeneous, with HDIs varying between 0.73 and 0.79. Our findings emphasize that the metropolitan area of Mexico City and the State of Nuevo Leon have the highest levels of HDI. Regions were graded from I to IV according to their HDIs in ascending order. The HDIs varied from 0.667 to 0.830/100,000 children/year, with a national average of 0.746. The leukemia incidence for regions I, II, III, and IV was 6.12, 6.53, 4.96, and 9.95. An analysis of ALL incidence in Mexico showed significant differences for region IV in comparison with the other regions based on the HDI values (p = 0.0001). Conclusions: Further in-depth studies, including the economic aspects of the different geographic regions and their ethnographic characteristics, would give a more comprehensive panorama.

BackgroundEvidence shows that medical education includes a variety of basic and clinical skills. Ethical and human values are not typically considered in medical school curricula, and this is evident in medical practice in certain scenarios such as decision-making at pediatric cancer patients' end of life.MethodsThis study explores a bioethical approach to address complex decision-making at the end of life in children and adolescents with cancer. We are a cross-functional group of scientists from several academic disciplines who conducted a systematic review of the literature using our newly developed meta-bioethical analysis and synthesis of findings. The search was carried out in five databases, resulting in 10 research papers. Following quality screening, seven articles were ultimately selected for further analysis.ResultsOur focus is on the state of the art to better understand the bioethical deliberation at the end of life in pediatric oncology. Here, we report a systematic review that includes (i) classification of the screened articles by the type of decision-making they use, ii) the system values that are at the core of the decision-making at the end of life, and iii) bioethical and ethical discernment queries. We conclude with a discussion regarding the best practices of ethical discernment and decision-making at the end of life.This study highlights the need to develop more research to better understand the influence and origin of these multidimensional factors determining critical decisions that define the quality of life of patients in a highly sensitive moment.ConclusionWe conclude that personal aspects of the physician define their actions more than knowledge or organized structure. It is thus necessary that pediatric oncologists receive ethics and humanistic education.

Myalgic encephalomyelitis/chronic fatigue syndrome is a serious illness of unknown etiology, characterized by debilitating exhaustion, memory impairment, pain and sleep abnormalities. Viral infections are believed to initiate the pathogenesis of this syndrome although the definite proof remains elusive. With the unfolding of COVID-19 pandemic, the interest in this condition has resurfaced as excessive tiredness, a major complaint of patients infected with the SARS-CoV-2 virus, often lingers for a long time, resulting in disability, and poor life quality. In a previous article, we hypothesized that COVID-19-upregulated angiotensin II triggered premature endothelial cell senescence, disrupting the intestinal and blood brain barriers. Here, we hypothesize further that post-viral sequelae, including myalgic encephalomyelitis/chronic fatigue syndrome, are promoted by the gut microbes or toxin translocation from the gastrointestinal tract into other tissues, including the brain. This model is supported by the SARS-CoV-2 interaction with host proteins and bacterial lipopolysaccharide. Conversely, targeting microbial translocation and cellular senescence may ameliorate the symptoms of this disabling illness.

Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) is a heterogeneous disease consisting of at least two separate subtypes, based on the mutation status of the immunoglobulin heavy chain variable gene (IGHV) sequence. Exposure to antigens seems to play a role in malignant transformation and in the selection and expansion of more aggressive CLL clones. Furthermore, a biased usage of particular IGHV gene subgroups and the existence of stereotyped B-cell receptors (BCRs) are distinctive characteristics of human CLL. We have previously described that Traf2DN/BCL2 double-transgenic (tg, +/+) mice develop CLL/SLL with high incidence with aging. In this model, TNF-Receptor Associated Factor (TRAF)-2 deficiency cooperates with B cell lymphoma (BCL)-2 in promoting CLL/SLL in mice by specifically enforcing marginal zone (MZ) B cell differentiation and rendering B cells independent of BAFF for survival. In this report, we have performed the sequencing of the IGHV-D-J rearrangements of B cell clones from the Traf2DN/BCL2-tg+/+ mice with CLL/SLL. The results indicate that these mice develop oligoclonal and monoclonal B cell expansions. Allotransplantation of the oligoclonal populations into immunodeficient mice resulted in the preferential expansion of one of the parental clones. The analysis of the IGHV sequences indicated that 15% were mutated (M) and 85% unmutated (UM). Furthermore, while the Traf2DN/BCL2-tg-/- (wild-type), -/+ (BCL2 single-tg) and +/- (Traf2DNDN single-tg) littermates showed the expression of various IGHV gene subgroups, the CLL/SLL expanded clones from the Traf2DN/BCL2-tg+/+ (double-transgenic) mice showed a more restricted IGHV gene subgroup usage and an overrepresentation of particular IGHV genes. In addition, the HCDR3-encoded protein sequence indicates the existence of stereotyped immunoglobulin (Ig) in the BCRs and strong similarities with BCR recognizing autoantigens and pathogen-associated antigens. Altogether, these results highlight the remarkable similarities between the CLL/SLL developed by the Traf2DN/BCL2-tg+/+ mice and its human counterpart.

In this paper we propose a modular multilevel converter for a linear generator for a wave energy converter. The coils of this generator are individually controlled to improve energy harvesting performance. This topology involves two stages. The first stage uses a full-bridge to control the harvested current with a reference generated by means of an MPPT method. The second stage uses a half-bridge to control the voltage of the DC-link and the output current. Furthermore, multilevel modular converters allow the generation of a medium DC voltagethat reduces the losses in energy transmission lines from offshore to a coupling common point on the shore.

Agonistic monoclonal antibodies (mAbs) targeting the co-stimulatory receptor 4-1BB are among the most effective immunotherapeutic agents across pre-clinical cancer models. However, clinical development of full-length 4-1BB agonistic mAbs, has been hampered by dose-limiting liver toxicity. We have previously developed an EGFR-targeted 4-1BB-agonistic trimerbody (1D8N/CEGa1) that induces potent anti-tumor immunity without systemic toxicity, in immunocompetent mice bearing murine colorectal carcinoma cells expressing human EGFR. Here, we study the impact of human EGFR expression on mouse liver in the toxicity profile of 1D8N/CEGa1. Systemic administration of IgG-based anti-4-1BB agonist resulted in nonspecific immune stimulation and hepatotoxicity in a liver-specific human EGFR-transgenic immunocompetent mouse, whereas in 1D8N/CEGa1-treated mice no such immune-related adverse effects were observed. Collectively, these data support the role of FcγR interactions in the major off-tumor toxicities associated with IgG-based 4-1BB agonists and further validate the safety profile of EGFR-targeted Fc-less 4-1BB-agonistic trimerbodies in systemic cancer immunotherapy protocols.

Se estudiaron las adaptaciones morfológicas de Ramorinoa girolae Speg. (Fabaceae) a condiciones ambientales áridas en los estadios vegetativos cotiledonar y segundo nomófilo expandido. Semillas provenientes de una población natural de la provincia de La Rioja se pusieron a germinar a temperatura ambiente de ± 20° C para registrar y evaluar los eventos en la evolución de la germinación y desarrollo de plántula. Se realizaron cortes transversales a mano alzada de los órganos vegetativos los cuales teñidos con azul de astra y safranina se fotografiaron con microscopio binocular y cámara digital Nikon. Las plántulas presentaron una germinación fanerocotiledonar con una extensa raíz principal. A partir del primer y segundo nudo se observaron hojas con disposición alterna prontamente caducas, cumpliendo los tallos la función de fotosíntesis. En su anatomía presenta raíz tetrarca, rizodermis uniestratificada y parénquima cortical con endodermis en estadío primario. El hipocótilo tiene contorno circular a subcircular, cutícula delgada con epidermis uniestratificada, hacecillos vasculares abiertos distribuidos en eustela y médula parenquimática con amiloplastos. En el primer entrenudo del epicótilo se observó una epidermis uniestratificada con gruesa cutícula. La corteza presenta colénquima laminar intercalado con clorénquima en empalizada, hay una división de haces vasculares y desarrollo del cambium. En el segundo entrenudo el epicótilo presenta contorno circular, epidermis biestratificada con cutícula engrosada, tricomas unicelulares aglandulares y pequeñas costillas debido a la presencia de estomas hundidos. Subepidérmicamente muestra una hipodermis colenquimatosa. La corteza está constituida por clorénquima en empalizada. Los haces vasculares presentan floema con un casquete de fibras gelatinosas. Las hojas presentan una epidermis uniestratificada con tricomas unicelulares aglandulares en la cara adaxial y mesófilo dorsiventral. Se concluye que los caracteres morfológicos de la plántula de Ramorinoa girolae descritos en este estudio nos permite exponer caracteres adaptativos de la especie a condiciones ambientales áridas.