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PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with Immune Checkpoint Inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS: /Patients. This retrospective, multicenter study was promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with head and neck cancer who initiated ICI between 01/01/2015 and 31/12/2021 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT, with secondary objectives including the analysis of their impact on survival and the identification of variables predictive of VTE/AT. RESULTS: A total of 143 patients with head and neck cancer were enrolled. The incidence of VTE/AT during follow-up (median 8.6 months) was 2.8%. Survival analysis showed no significant differences (p = 0.644) between the group that developed VTE/AT (median 7.13 months, 95% CI 0-22.9) and the group that did not (median 9.86 months, 95% CI 6.3-13.4). The presence of liver metastases was predictive of VTE/AT (p < 0.05). CONCLUSIONS: Thromboembolic disease associated with immunotherapy in patients with head and neck neoplasia does not significantly impact survival. The presence of liver metastases can predict these events.

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Cellulose modified hydrogels can be produced directly from raw biopolymers in novel cellulose solvents such as NaOH/urea aqueous solution. The effect of cellulose characteristics on the synthesis of a cellulose-graft-(net-poly(acrylamide-co-acrylic acid)) and its performance as water absorbent/methylene blue dye removal material is analyzed. Three cellulose samples, one analytical grade and two obtained from teak wood sawdust with different pretreatments (one alkaline and the other, a novel one known as (gas phase) acid pretreatment) were compared. The starting raw celluloses were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD) and viscosity in cupri ethylenediamine hydroxide (CED) solution, whereas the chemically modified materials were characterized by SEM, FTIR, and TGA. The pretreatment used influences composition, crystallinity index and degree of polymerization (DP) of the cellulose obtained. The modified material produced with cellulose from alkaline pretreatment showed the highest swelling ratio in water absorption tests at room temperature (12,714 %); in contrast, the one with cellulose from acid pretreatment showed the lowest swelling ratio (7,470 %). However, this difference is not so significative in dye removal tests, where absorption capacity is 139 and 140 mg/g, respectively. The results indicate that cellulose composition, particularly structures with significant hemicellulose and lignin remaining content, has a major effect on the performance of modified materials for water absorption, and degree of polymerization has a major effect on adsorption capacity of methylene blue.

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Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Asymptomatic EDSs, joint hypermobility without associated syndromes, EDSs, and hypermobility spectrum disorders are the commonest phenotypes associated with joint hypermobility. Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. JHS can be a sign of a more serious underlying genetic condition, such as EDS, which affects the cartilage, bone, fat, and blood. The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. Membrane proteins are a class of proteins embedded in the cell membrane and play a crucial role in cell signaling, transport, and adhesion. Dysregulated membrane proteins have been implicated in a variety of diseases, including cancer, cardiovascular disease, and neurological disorders; recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. This article presents an exploration of the causative factors contributing to musculoskeletal pain in individuals with hypermobility, based on research findings. It aims to provide an understanding of JHS and its association with membrane proteins, addressing the clinical manifestations, pathogenesis, diagnosis, and management of JHS.

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Background: Recurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL. Methods: A total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation. Results: We identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed. Discussion: Our findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.

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The main objective of the National Project for Research and Incidence of Childhood Leukemias is to reduce early mortality rates for these neoplasms in the vulnerable regions of Mexico. This project was conducted in the states of Oaxaca, Puebla, and Tlaxcala. A key strategy of the project is the implementation of an effective roadmap to ensure that leukemia patients are the target of maximum benefit of interdisciplinary collaboration between researchers, clinicians, surveyors, and laboratories. This strategy guarantees the comprehensive management of diagnosis and follow-up samples of pediatric patients with leukemia, centralizing, managing, and analyzing the information collected. Additionally, it allows for a precise diagnosis and monitoring of the disease through immunophenotype and measurable residual disease (MRD) studies, enhancing research and supporting informed clinical decisions for the first time in these regions through a population-based study. This initiative has significantly improved the diagnostic capacity of leukemia in girls, boys, and adolescents in the regions of Oaxaca, Puebla, and Tlaxcala, providing comprehensive, high-quality care with full coverage in the region. Likewise, it has strengthened collaboration between health institutions, researchers, and professionals in the sector, which contributes to reducing the impact of the disease on the community.

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Introduction: Acute leukemias (AL) are the main types of cancer in children worldwide. In Mexico, they represent one of the main causes of death in children under 20 years of age. Most of the studies on the incidence of AL in Mexico have been developed in the urban context of Greater Mexico City and no previous studies have been conducted in the central-south of the country through a population-based study. The aim of the present work was to identify the general and specific incidence rates of pediatric AL in three states of the south-central region of Mexico considered as some of the marginalized populations of Mexico (Puebla, Tlaxcala, and Oaxaca). Methods: A population-based study was conducted. Children aged less than 20 years, resident in these states, and newly diagnosed with AL in public/private hospitals during the period 2021-2022 were identified. Crude incidence rates (cIR), standardized incidence rates (ASIRw), and incidence rates by state subregions (ASIRsr) were calculated. Rates were calculated using the direct and indirect method and reported per million children under 20 years of age. In addition, specific rates were calculated by age group, sex, leukemia subtype, and immunophenotype. Results: A total of 388 cases with AL were registered. In the three states, the ASIRw for AL was 51.5 cases per million (0-14 years); in Puebla, it was 53.2, Tlaxcala 54.7, and Oaxaca de 47.7. In the age group between 0-19 years, the ASIRw were 44.3, 46.4, 48.2, and 49.6, in Puebla, Tlaxcala, and Oaxaca, respectively. B-cell acute lymphoblastic leukemia was the most common subtype across the three states. Conclusion: The incidence of childhood AL in the central-south region of Mexico is within the range of rates reported in other populations of Latin American origin. Two incidence peaks were identified for lymphoblastic and myeloid leukemias. In addition, differences in the incidence of the disease were observed among state subregions which could be attributed to social factors linked to the ethnic origin of the inhabitants. Nonetheless, this hypothesis requires further investigation.

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The gene dosage compensation hypothesis presents a mechanism through which the expression of certain genes is modulated to compensate for differences in the dose of genes when additional chromosomes are present. It is one of the means through which cancer cells actively cope with the potential damaging effects of aneuploidy, a hallmark of most cancers. Dosage compensation arises through several processes, including downregulation or overexpression of specific genes and the relocation of dosage-sensitive genes. In cancer, a majority of compensated genes are generally thought to be regulated at the translational or post-translational level, and include the basic components of a compensation loop, including sensors of gene dosage and modulators of gene expression. Post-translational regulation is mostly undertaken by a general degradation or aggregation of remaining protein subunits of macromolecular complexes. An increasingly important role has also been observed for transcriptional level regulation. This article reviews the process of targeted gene dosage compensation in cancer and other biological conditions, along with the mechanisms by which cells regulate specific genes to restore cellular homeostasis. These mechanisms represent potential targets for the inhibition of dosage compensation of specific genes in aneuploid cancers. This article critically examines the process of targeted gene dosage compensation in cancer and other biological contexts, alongside the criteria for identifying genes subject to dosage compensation and the intricate mechanisms by which cells orchestrate the regulation of specific genes to reinstate cellular homeostasis. Ultimately, our aim is to gain a comprehensive understanding of the intricate nature of a systems-level property. This property hinges upon the kinetic parameters of regulatory motifs, which we have termed "gene dosage sensor loops." These loops have the potential to operate at both the transcriptional and translational levels, thus emerging as promising candidates for the inhibition of dosage compensation in specific genes. Additionally, they represent novel and highly specific therapeutic targets in the context of aneuploid cancer.

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Atherosclerosis is the leading cause of cardiovascular diseases in Mexico and worldwide. The membrane transporters ABCA1 and ABCG1 are involved in the reverse transport of cholesterol and stimulate the HDL synthesis in hepatocytes, therefore the deficiency of these transporters promotes the acceleration of atherosclerosis. MicroRNA-33 (miR-33) plays an important role in lipid metabolism and exerts a negative regulation on the transporters ABCA1 and ABCG1. It is known that by inhibiting the function of miR-33 with antisense RNA, HDL levels increase and atherogenic risk decreases. Therefore, in this work, a genetic construct, pPEPCK-antimiR-33-IRES2-EGFP, containing a specific antimiR-33 sponge with two binding sites for miR-33 governed under the PEPCK promoter was designed, constructed, and characterized, the identity of which was confirmed by enzymatic restriction, PCR, and sequencing. Hep G2 and Hek 293 FT cell lines, as well as a mouse hepatocyte primary cell culture were transfected with this plasmid construction showing expression specificity of the PEPCK promoter in hepatic cells. An analysis of the relative expression of miR-33 target messengers showed that the antimiR-33 sponge indirectly induces the expression of its target messengers (ABCA1 and ABCG1). This strategy could open new specific therapeutic options for hypercholesterolemia and atherosclerosis, by blocking the miR-33 specifically in hepatocytes.

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An iterative analysis of Imparfinis, combining phylogenetic analysis based on cytochrome oxidase gene and multivariate morphometrics, revealed a new cryptic species from the Andean tributaries of the Orinoco River basin, which is described here. The new species is sister to a clade constituted by Imparfinis hasemani and Imparfinis pijpersi, both from the river basins of the Guiana Shield, being also the most geographically proximate species. Nonetheless, the new species is most similar in general appearance to Imparfinis guttatus from the Madeira and Paraguay River drainages, being almost undistinguishable by conventional characters of external morphology, differing only by morphometric attributes overall. The new species can be distinguished from the remaining congeners by a unique combination of characters, including lower lobe of caudal fin darker than upper lobe, maxillary barbel reaching or surpassing pelvic-fin insertion, 12-15 gill rakers on first gill arch, 40-42 total vertebrae and 9-10 ribs. The new species constitutes the only representative from the Orinoco River basin belonging to Imparfinis sensu stricto.

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We recorded Pimelodella bockmanni and P. serrata for the first time for Colombia, based on specimens collected in tributaries from the main channel of the Amazonas River, in the so-called Trapecio Amazónico, in the southernmost region of this country. We also present morphometric, meristic, and osteological data of the examined material, and provide a complementary morphological description of the poorly known P. serrata, a species known only from the Madeira River drainage in Bolivia and Brazil.

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There are little data on pentamidine as a treatment for paediatric cutaneous leishmaniasis (CL). The objective of this study was to describe the effectiveness and safety of pentamidine over a 10-year period. Every child seen in French Guiana between 2010 and 2020 with proven CL and treated with pentamidine was included. In total, 55 children met the inclusion criteria - 23 girls and 32 boys. There were 38 patients (38/55, 69%) with a > 50% improvement at 1 month after pentamidine treatment and a complete cure at 3 months; 16 children had a < 50% improvement at 1 month and were given a second dose. Of these 16, 8 showed a complete cure at 3 months, 5 were lost to follow-up and 3 showed therapeutic failure at 3 months. The overall cure rate was 84% (46/55) after one or two doses. In terms of the safety of pentamidine, no severe adverse events (grade ≥ 3) were reported.

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Introducción: Son muy escasos los estudios publicados sobre el efecto de infiltraciones con células madres en seudoartrosis aséptica posquirúrgicas. Asimismo, los métodos tradicionales de tratamiento coadyuvante para favorecer la consolidación (esteroides anabólicos y bifosfonatos) representan elevados riesgos, rechazo e incluso abandono del tratamiento por parte del paciente. Objetivo: Jerarquizar las variables más influyentes para el tratamiento con células madre en la seudoartrosis aséptica posquirúrgica en el servicio de Ortopedia y Traumatología del Hospital General Docente "Dr. Agostinho Neto" del municipio de Guantánamo en el período de enero 2022 a enero 2023, con el empleo de la herramienta fuzzy TOPSIS. Método: Se aplicó un estudio descriptivo, con el apoyo de los métodos de proceso de jerarquía analítica difusa (fuzzy AHP) y técnica para el cumplimiento de órdenes por similitud con la solución ideal difusa (fuzzy TOPSIS), con datos del departamento de Ortopedia y Traumatología del hospital antes mencionado. El universo estuvo constituido por 50 pacientes, la muestra del estudio quedó conformada por n ꓿ 44. Resultados: Se pudieron obtener las principales variables que intervienen en un tratamiento con células madre en la seudoartrosis para garantizar el éxito en la implementación de dicho tratamiento, ellas fueron: trazo de la fractura, causa de la seudoartrosis, tipo de terapia empleada, tiempo de consolidación y grado de consolidación. Conclusiones: La jerarquización de las variables obtenidas constituirá una guía donde los servicios de Ortopedia y Traumatología del Hospital General Docente "Dr. Agostinho Neto", del municipio de Guantánamo, podrá incidir en la efectividad del tratamiento con células madre en la seudoartrosis.

Introduction: Currently there are very few published studies concerning the effect of implantations with stem cells in post-surgical aseptic pseudoarthrosis. In addition, the traditional methods of adjuvant treatment in order to improve efficacy (anabolic steroids and bisphosphonates) represent high risks, rejection and even treatment abandonment by patients. Objective: Hierarchalising the most influential variables for treatment with stem cells in post-surgical aseptic pseudoarthrosis in the Orthopedics and Traumatology service of the Hospital General Docente "Dr. Agostinho Neto", Guantánamo, from January 2022 to January 2023, with the application of the TOPSIS fuzzy method. Method: A descriptive study was applied, with the application of Fuzzy Analytical Hierarchy process methods (Fuzzy AHP) and the Technique for Order of Preference by Similarity to Ideal Solution (fuzzy TOPSIS), with information gathered from the Orthopedics and Traumatology department of the aforementioned hospital. The universe of study consisted of 50 patients. The study sample included n꓿44. Results: It was possible to obtain the main variables involved in the stem cell treatment for pseudarthrosis, variables with great contribution in the success of implementation of such treatment, which were as follow: fracture trace, cause of pseudarthrosis, type of therapy used, time of bone consolidation and degree in bone consolidation. Conclusions: The hierarchization of the variables obtained will constitute a guide where the Orthopedics and Traumatology services of the Hospital General Docente "Dr. Agostinho Neto", in Guantánamo municipality, will be able to influence in the efficacy of stem cell treatment for pseudarthrosis.

Introdução: Existem poucos estudos publicados sobre o efeito de infiltrações com células-tronco em pseudoartrose asséptica pós-cirúrgica. Da mesma forma, os métodos tradicionais de tratamento adjuvante para promover a consolidação (esteróides anabolizantes e bisfosfonatos) representam riscos elevados, rejeição e até abandono do tratamento por parte do paciente. Objetivo: Priorizar as variáveis de maior influência para o tratamento com células-tronco na pseudoartrose asséptica pós-cirúrgica no serviço de Ortopedia e Traumatologia do Hospital General Docente "Dr. Agostinho Neto" do município de Guantánamo no período de janeiro de 2022 a janeiro de 2023, com a utilização da ferramenta fuzzy TOPSIS. Método: Foi aplicado um estudo descritivo, com apoio dos métodos de processo hierárquico analítico fuzzy (fuzzy AHP) e da técnica de atendimento de pedidos por similaridade com a solução fuzzy ideal (fuzzy TOPSIS), com dados do Departamento de Ortopedia e Traumatologia do referido hospital. O universo foi constituído por 50 doentes, a amostra do estudo foi constituída por n꓿44. Resultados: Foi possível obter as principais variáveis que intervêm num tratamento com células estaminais na pseudoartrose para garantir o sucesso na implementação do referido tratamento, elas foram eles: linha de fratura, causa da pseudoartrose, tipo de terapia utilizada, tempo de consolidação e grau de consolidação. Conclusões: A hierarquização das variáveis obtidas constituirá um guia onde os serviços de Ortopedia e Traumatologia do Hospital General Docente "Dr. Agostinho Neto", município de Guantánamo, poderá influenciar a eficácia do tratamento com células-tronco na pseudoartrose.

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Temperature measuring is a daily procedure carried out worldwide in practically all environments of human activity, but it takes particular relevance in industrial, scientific, medical, and food processing and production areas. The characteristics and performance of the temperature sensors required for such a large universe of applications have opened the opportunity for a comprehensive range of technologies and architectures capable of fulfilling the sensitivity, resolution, dynamic range, and response time demanded. In this work, a highly sensitive fiber optic temperature sensor based on a double-cavity Fabry-Perot interferometer (DCFPI) is proposed and demonstrated. Taking advantage of the Vernier effect, we demonstrate that it is possible to improve the temperature sensitivity exhibited by the polymer-capped fiber Fabry-Perot interferometer (PCFPI) up to 39.8 nm/°C. The DCFPI is sturdy, reconfigured, and simple to fabricate, consisting of a semi-spherical polymer cap added to the surface of the ferrule of a commercial single-mode fiber connector (SMF FC/PC) placed in front of a mirror at a proper distance. The length of the air cavity (Lair) was adjusted to equal the thickness of the polymer cap (Lpol) plus a distance δ to generate the most convenient Vernier effect spectrum. The DCFPI was packaged in a machined, movable mount that allows the adjustment of the air cavity length easily but also protects the polymer cap and simplifies the manipulation of the sensor head.

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Introduction: The decisive key to disease-free survival in B-cell precursor acute lymphoblastic leukemia in children, is the combination of diagnostic timeliness and treatment efficacy, guided by accurate patient risk stratification. Implementation of standardized and high-precision diagnostic/prognostic systems is particularly important in the most marginalized geographic areas in Mexico, where high numbers of the pediatric population resides and the highest relapse and early death rates due to acute leukemias are recorded even in those cases diagnosed as standard risk. Methods: By using a multidimensional and integrated analysis of the immunophenotype of leukemic cells, the immunological context and the tumor microenvironment, this study aim to capture the snapshot of acute leukemia at disease debut of a cohort of Mexican children from vulnerable regions in Puebla, Oaxaca and Tlaxcala and its potential use in risk stratification. Results and discussion: Our findings highlight the existence of a distinct profile of ProB-ALL in children older than 10 years, which is associated with a six-fold increase in the risk of developing measurable residual disease (MRD). Along with the absence of CD34+ seminal cells for normal hematopoiesis, this ProB-ALL subtype exhibited several characteristics related to poor prognosis, including the high expression level of myeloid lineage markers such as MPO and CD33, as well as upregulation of CD19, CD34, CD24, CD20 and nuTdT. In contrast, it showed a trend towards decreased expression of CD9, CD81, CD123, CD13, CD15 and CD21. Of note, the mesenchymal stromal cell compartment constituting their leukemic niche in the bone marrow, displayed characteristics of potential suppressive microenvironment, such as the expression of Gal9 and IDO1, and the absence of the chemokine CXCL11. Accordingly, adaptive immunity components were poorly represented. Taken together, our results suggest, for the first time, that a biologically distinct subtype of ProB-ALL emerges in vulnerable adolescents, with a high risk of developing MRD. Rigorous research on potential enhancing factors, environmental or lifestyle, is crucial for its detection and prevention. The use of the reported profile for early risk stratification is suggested.

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The resident and tourist population in the Mexican Caribbean has grown exponentially, increasing the availability of dissolved inorganic nutrients in coastal waters through submarine groundwater discharge (SGD). Recently, a new massive drift of Sargassum spp. has occurred that can provide new organic matter and enrich coastal water with nutrients. In different sites in the Mexican Caribbean, the chemical composition of the water was analyzed, and the δ15N of Thalassia testudinum was determined between 2016 and 2019. Evidence of SGD was observed in Akumal Bay due to high silicate concentrations and its negative correlation with salinity. Seasonal and interannual variation in NH4+ concentration was observed at these sites. In October 2018, SGD contributed ∼70 times more nitrogen and ∼194 times more phosphorus than the decomposition of the pelagic macroalgae Sargassum spp. The δ15N data showed that Akumal Bay received nitrogen of anthropogenic origin and that nitrogen fixation processes or probably assimilation of nitrogen of the leachates of pelagic Sargassum spp were dominant at Mahahual and Xahuayxol.

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