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This comparative case analysis aims to understand what organizational conditions are related to the differences in the development of research among four traditional private universities in Latin America. Based on imprinting theory, the study analyzes how historical events and the founding conditions of each case study influence the processes of adaptation to local and global institutional pressures related to research development. Findings of the qualitative analysis of interviews with authorities of each case show that adaptative responses related to their policies and plans, allocation of universities' resources, tenure rules, and the development of a critical mass of professors with research capacities are influenced by their historical legacies: elements such as founding values, the stamps that the founders imprint, and the routines of selection of their members are maintained over time, intervening in the choice of the different options for the research development.

Introducción. Los datos sobre la prevalencia de coinfecciones o sobreinfecciones fúngicas en pacientes con COVID-19 son limitados. Objetivo. Describir la prevalencia de coinfecciones o sobreinfecciones fúngicas en pacientes con COVID-19, así como los factores de riesgo y las características demográficas, clínicas y microbiológicas. Material y métodos. Se incluyeron pacientes con diagnóstico confirmado de COVID-19, hospitalizados en la unidad de cuidados intensivos y con infección fúngica confirmada entre marzo del 2020 y diciembre del 2021. Del expediente clínico se obtuvieron datos sobre edad, sexo, comorbilidades, días de estancia hospitalaria, resultados de laboratorio (ferritina) y microbiológicos, tratamiento contra COVID-19, terapia antifúngica y desenlace. Resultados. Once de 740 pacientes cumplieron con los criterios de inclusión. La tasa de coinfección fue del 0,3 % y la de sobreinfección fue del 1,2 %. La población más afectada fue la de hombres adultos. Las coinfecciones o sobreinfecciones diagnosticadas fueron candiduria y candidemia, causadas por Candida albicans, C. tropicalis, C. glabrata, C. lusitaniae y Kluyveromyces marxianus (C. kefyr). Además, se encontró una traqueobronquitis por Aspergillus fumigatus. Los antifúngicos más administrados fueron fluconazol y caspofungina. La letalidad en pacientes con coinfecciones fue del 50 % y con sobreinfecciones fúngicas, del 22 %. El tiempo de estancia intrahospitalaria fue de 11 a 65 días. Ocho de los pacientes requirieron asistencia respiratoria mecánica y seis recibieron corticoides. La principal comorbilidad fue diabetes mellitus (81,8 %). Conclusiones. La tasa de coinfecciones o sobreinfecciones por hongos en pacientes con COVID-19 fue baja, pero la letalidad de estas requiere, con urgencia, la realización de pruebas de rutina para detectar hongos en pacientes con COVID-19 grave para diagnosticar oportunamente infecciones fúngicas que puedan comprometer aún más la vida del paciente

Abstract Pituitary neuroendocrine tumors (PitNET) represent the vast majority of sellar masses. Some behave aggressively, growing rapidly and invading surrounding tissues, with high rates of recurrence and resistance to therapy. Our aim was to establish patterns of genomic, transcriptomic and methylomic evolution throughout time in primary and recurrent tumors from the same patient. Therefore, we performed transcriptome- and exome-sequencing and methylome microarrays of aggressive, primary, and recurrent PitNET from the same patient. Primary and recurrent tumors showed a similar exome profile, potentially indicating a stable genome over time. In contrast, the transcriptome of primary and recurrent PitNET was dissimilar. Gonadotroph, silent corticotroph, as well as metastatic corticotroph and a somatotroph PitNET expressed genes related to fatty acid biosynthesis and metabolism, phosphatidylinositol signaling, glycerophospholipid and phospholipase D signaling, respectively. Diacylglycerol kinase gamma (DGKG), a key enzyme in glycerophospholipid metabolism and phosphatidylinositol signaling pathways, was differentially expressed between primary and recurrent PitNET. These alterations did not seem to be regulated by DNA methylation, but rather by several transcription factors. Molecular docking showed that dasatinib, a small molecule tyrosine kinase inhibitor used in the treatment of chronic lymphocytic and acute lymphoblastic leukemia, could target DGKG. Dasatinib induced apoptosis and decreased proliferation in GH3 cells. Our data indicate that pituitary tumorigenesis could be driven by transcriptomically heterogeneous clones, and we describe alternative pharmacological therapies for aggressive and recurrent PitNET.

La conservación del patrimonio cultural subterráneo requiere documentación digital 3D de alta precisión. En Ecuador, este tipo de patrimonio se encuentra amenazado principalmente por eventos naturales de tipo sísmico. Las catacumbas de la Iglesia de Nuestra Señora de la Nieves (Sicalpa Viejo, Ecuador) tienen un alto valor patrimonial, ya que fueron construidas en la época colonial y han pasado por eventos sísmicos significativos, como el terremoto de 1797. La presente investigación presenta una metodología que usa tecnología vanguardista para la obtención de documentación digital considerando las particularidades de este tipo de construcciones subterráneas patrimoniales. Como resultado, se obtuvo el modelado 3D de todo el entorno de las catacumbas: nichos, osario, vestigios de huesos humanos de la época y detalles en piedra. Esta clase de documentación digital 3D es de gran utilidad para plantear proyectos de conservación del patrimonio cultural subterráneo antes o después de un evento sísmico. ENGLISH: The conservation of underground cultural heritage requires high-precision 3D digital documentation. In Ecuador, this type of heritage is mainly threatened by natural seismic events. The catacombs of the Church of Our Lady of the Snows, at Sicalpa Viejo, Ecuador, have a high heritage value, because they were built in colonial times and have been through significant seismic events, such as the earthquake of 1797. This research presents a methodology that uses cutting-edge technology to obtain digital documentation, taking into account the particularities of this type of underground heritage constructions. As a result, 3D modeling of the entire environment of the catacombs was obtained: niches, ossuary, vestiges of human bones of that time and details in stone. This kind of 3D digital documentation is very useful for planning conservation projects of underground cultural heritage before or after a seismic event.

En la actualidad, el patrimonio edificado enfrenta la amenaza de su deterioro, destrucción o desaparición debido a diversas causas, ya sean de origen natural o provocadas por actividades humanas. Ante este desafío surge la necesidad de utilizar herramientas tecnológicas vanguardistas que posibiliten la documentación exhaustiva de cada elemento arquitectónico histórico como medida para preservar el patrimonio tangible. Esta investigación se enfoca en el levantamiento HBIM («Historic Building Information Modeling») de la Iglesia de Balbanera (Colta, Ecuador) para su documentación. Esta iglesia fue seleccionada por su relevancia histórica y el alto nivel de detalle presente tanto en su estructura externa como en su interior. La metodología comprendió la planificación del levantamiento de información, el levantamiento «in situ» con tecnología de escáner láser 3D, el procesamiento de los datos obtenidos y la generación del modelo HBIM. Como resultado se obtuvo el modelo de la Iglesia de Balbanera, la cuantificación de materiales de obra y la documentación de planos arquitectónicos tanto en planta como en elevación, brindando a los profesionales información veraz y confiable para intervenciones futuras que garanticen la preservación del patrimonio edificado. ENGLISH: Today, built heritage faces the threat of deterioration, destruction or disappearance due to various causes, whether of natural origin or caused by human activities. Faced with this challenge, the need arises to use cutting-edge technological tools that enable the exhaustive documentation of each historical architectural element as a measure to preserve the tangible heritage. This research focuses on the HBIM (Historic Building Information Modeling) survey of the Balbanera Church (Colta, Ecuador) for its documentation. This church was selected for its historical relevance and the high level of detail present in both its external structure and its interior. The methodology included the planning of the information survey, in situ survey with 3D laser scanner technology, processing of the data obtained, and generation of the HBIM model. As a result, the model of the Balbanera Church, the quantification of work materials, and the documentation of architectural plans both in plan and elevation were achieved, providing professionals with accurate and reliable information for future interventions to ensure the preservation of the built heritage.

Background Melanoma, the most lethal form of skin cancer, has undergone a transformative treatment shift with the advent of checkpoint blockade immunotherapy (CBI). Understanding the intricate network of immune cells infiltrating the tumor and orchestrating the control of melanoma cells and the response to CBI is currently of utmost importance. There is evidence underscoring the significance of tissue-resident memory (TRM) CD8 T cells and classic dendritic cell type 1 (cDC1) in cancer protection. Transcriptomic studies also support the existence of a TCF7+ (encoding TCF1) T cell as the most important for immunotherapy response, although uncertainty exists about whether there is a TCF1+TRM T cell due to evidence indicating TCF1 downregulation for tissue residency activation.Methods We used multiplexed immunofluorescence and spectral flow cytometry to evaluate TRM CD8 T cells and cDC1 in two melanoma patient cohorts: one immunotherapy-naive and the other receiving immunotherapy. The first cohort was divided between patients free of disease or with metastasis 2 years postdiagnosis while the second between CBI responders and non-responders.Results Our study identifies two CD8+TRM subsets, TCF1+ and TCF1−, correlating with melanoma protection. TCF1+TRM cells show heightened expression of IFN-γ and Ki67 while TCF1− TRM cells exhibit increased expression of cytotoxic molecules. In metastatic patients, TRM subsets undergo a shift in marker expression, with the TCF1− subset displaying increased expression of exhaustion markers. We observed a close spatial correlation between cDC1s and TRMs, with TCF1+TRM/cDC1 pairs enriched in the stroma and TCF1− TRM/cDC1 pairs in tumor areas. Notably, these TCF1− TRMs express cytotoxic molecules and are associated with apoptotic melanoma cells. Both TCF1+ and TCF1− TRM subsets, alongside cDC1, prove relevant to CBI response.Conclusions Our study supports the importance of TRM CD8 T cells and cDC1 in melanoma protection while also highlighting the existence of functionally distinctive TCF1+ and TCF1− TRM subsets, both crucial for melanoma control and CBI response.

AbstractGram-negative folliculitis may be the result of prolonged antibacterial treatments in patients with acne and rosacea. It is caused by alteration of facial skin flora and the nasal mucous, a decrease of Gram-positive bacteria and a proliferation of Gram-negative bacteria (for example Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Klebsiella sp. and Proteus mirabilis). It should be considered in patients with acne who have not had a clinical improvement after 3-6 months of treatment with tetracyclines. The disease is underestimated, probably because bacteriological studies are rarely requested and the increased use of oral isotretinoin for acne management. One of the most effective treatments for Gram-negative folliculitis is oral isotretinoin (0.5-1 mg / kg / day for 4-5 months). We report the case of Gram negative folliculitis successfully treated with oral isotretinoin.

Objectives: Evaluate the efficacy and tolerability of itraconazole plus terbinafine for refractory onychomycosis. This is a prospective clinical trial. Patients with proven Trychophyton rubrum onychomycosis of toenails were enrolled; the treatment consisted of weekly administration: itraconazole 200mg/day and terbinafine 250mg/day, for four months. Results: Thirty-two patients with onychomycosis were studied. Twenty-eight cases had distal subungual onychomycosis and 4 total dystrophic onychomycosis. At the end of the follow-up 17/32 patients had clinical and mycologic cure (53.12%), 5 had clinical improvement only (15.6%), and 10 (31.2%) failed. Conclusion: Weekly alternate therapy with itraconazole + terbinafine represents a safe rescue treatment.

IntroductionSeveral effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system.MethodsThis study aims to analyze the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations.ResultsOur findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-γ) in both CD4+ and CD8+ T-cells.DiscussionThe AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.

IntroductionInnate immune training is a metabolic, functional, and epigenetic long-term reprogramming of innate cells triggered by different stimuli. This imprinting also reaches hematopoietic precursors in the bone marrow to sustain a memory-like phenotype. Dendritic cells (DCs) can exhibit memory-like responses, enhanced upon subsequent exposure to a pathogen; however, whether this imprinting is lineage and stimulus-restricted is still being determined. Nevertheless, the functional consequences of DCs training on the adaptive and protective immune response against non-infectious diseases remain unresolved.MethodsWe evaluated the effect of the nontoxic cholera B subunit (CTB), LPS and LTA in the induction of trained immunity in murine DCs revealed by TNFa and LDH expression, through confocal microscopy. Additionally, we obtained bone marrow DCs (BMDCs) from mice treated with CTB, LPS, and LTA and evaluated training features in DCs and their antigen-presenting cell capability using multiparametric cytometry. Finally, we design an experimental melanoma mouse model to demonstrate protection induced by CTB-trained DCs in vivo.ResultsCTB-trained DCs exhibit increased expression of TNFa, and metabolic reprogramming indicated by LDH expression. Moreover, CTB training has an imprint on DC precursors, increasing the number and antigen-presenting function in BMDCs. We found that training by CTB stimulates the recruitment of DC precursors and DCs infiltration at the skin and lymph nodes. Interestingly, training-induced by CTB promotes a highly co-stimulatory phenotype in tumor-infiltrating DCs (CD86+) and a heightened functionality of exhausted CD8 T cells (Ki67+, GZMB+), which were associated with a protective response against melanoma challenge in vivo.ConclusionOur work indicates that CTB can induce innate immune training on DCs, which turns into an efficient adaptive immune response in the melanoma model and might be a potential immunotherapeutic approach for tumor growth control.

El objetivo de esta presentación es dar a conocer el manejo de la miositis piógena del músculo obturador interno en un paciente pediátrico que fue tratado mediante un drenaje percutáneo guiado por ecografía. Se trata de un niño de 5 años de edad, con manifestaciones clínicas y valores de laboratorio de infección muscular profunda en el obturador interno. Se identificó específicamente con resonancia magnética, es un área de difícil acceso quirúrgico, por lo cual se realizó un tratamiento percutáneo guiado por ecografía que permitió drenar el contenido purulento de la zona afectada. La resonancia magnética hizo posible lograr un diagnóstico más acertado en los casos de infección piógena temprana y, a su vez, decidir la vía de abordaje más adecuada. En ocasiones, se puede optar por la guía ecográfica con la cual se evita el abordaje quirúrgico formal y así disminuyen las complicaciones de la herida y la mayor morbimortalidad. La adición de procedimientos percutáneos guiados por imágenes es una herramienta muy útil para tratar enfermedades infecciosas y una gran ayuda para el ortopedista.

Abstract The difficulty in predicting fatal outcomes in patients with coronavirus disease 2019 (COVID‐19) impacts the general morbidity and mortality due to severe acute respiratory syndrome‐coronavirus 2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre‐existing comorbidities. A cohort of 147 patients hospitalized for severe COVID‐19 was included in a descriptive, observational, single‐center, and prospective study. Patients were recruited during the first COVID‐19 pandemic wave (April–November 2020). Data were collected from the clinical history whereas immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leucocyte. Patients were grouped according to the outcome in survivors or non‐survivors. The prognostic value of leucocyte, cytokines or HLA‐DR, CD39, and CD73 was calculated. Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the deceased patient group. Mixed hypercytokinemia, including inflammatory (IL‐6) and anti‐inflammatory (IL‐10) cytokines, was more evident in deceased patients. In the deceased patient group, lymphopenia with a higher neutrophil‐lymphocyte ratio (NLR) value was present. HLA‐DR expression and the percentage of CD39+ cells were higher than non‐COVID‐19 patients but remained similar despite the outcome. Receiver operating characteristic analysis and cutoff value of NLR (69.6%, 9.4), percentage NLR (pNLR; 71.1%, 13.6), and IL‐6 (79.7%, 135.2 pg/mL). The expression of HLA‐DR, CD39, and CD73, as many serum cytokines (other than IL‐6) and chemokines levels do not show prognostic potential, were compared to NLR and pNLR values.

IntroductionThe 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.MethodsBy 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 discussionOur 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.

A case of tinea corporis by Trichophyton indotineae observed in Argentina is presented. The patient had a history of having spent 18 months in Tulum, Mexico. She was suffering from tinea corporis in the anterior region of both thighs and the gluteal area. A mycological study was performed and T. mentagrophytes complex was isolated. The fungus was later identified as T. indotineae by DNA sequencing and treatment with SUBA-itraconazole was initiated with good clinical response.

Introducción. Los pacientes con diabetes mellitus de tipo 2 son propensos a adquirir infecciones por Candida spp., en ocasiones, causadas por más de una especie. La resistencia de algunas de ellas puede resultar en complicaciones médicas por falla del tratamiento. Objetivos. Determinar la frecuencia y las variedades clínicas de la candidiasis oral mixta en pacientes con diabetes mellitus de tipo 2, las especies de Candida involucradas y sus espectros de sensibilidad a los antifúngicos utilizados como tratamiento. Material y métodos. Se hizo un estudio transversal analítico en pacientes con diabetes mellitus de tipo 2, hiperglucemia (superior o igual al 7 % de la hemoglobina glucosilada, HbA1C) y con diagnóstico clínico de candidiasis oral. Mediante técnicas microbiológicas, se identificaron las especies causales de la candidiasis oral. Las pruebas de sensibilidad se llevaron a cabo con el método de difusión en placa con tiras (E-test®). Resultados. Se incluyeron 72 pacientes: 32 (44 %) hombres y 40 (56 %) mujeres, clasificados en tres grupos de edad: jóvenes adultos (17 %), adultos (74 %) y ancianos (9 %), con una media de 51 años. No se encontraron diferencias significativas en la candidiasis oral según los grupos de sexo y edad, ni entre las candidiasis orales mixtas y el sexo, el porcentaje de HbA1C, el tratamiento antihiperglucemiante o el tiempo de diagnóstico de la diabetes mellitus de tipo 2. En el grupo etario de adultos, se encontró una correlación con las candidiasis mixtas o simples. Se encontraron 8 (13 %) casos de candidiasis mixtas: siete con coinfección por dos especies de Candida y uno con coinfección por tres especies. Las especies identificadas en ellos, fueron: Candida albicans, C. glabrata, C. dubliniensis, C. kefyr, C. tropicalis y C. krusei. La mayoría de estas especies presentó sensibilidad a ketoconazol y fluconazol, y mayor resistencia a itraconazol. Conclusiones. Las candidiasis orales mixtas se presentan, aproximadamente, en el 10 % de los pacientes con diabetes mellitus de tipo 2 y el tratamiento puede ser ineficaz cuando no se identifica el agente etiológico.

Epilepsy is the most common neurological disorder with a worldwide incidence of 20% and a treatment failure rate of 25–30%. The fluctuation in serum levels, efficacy and safety of antiepileptic drugs can be attributed to single nucleotide polymorphisms of genes encoding their respective proteins involved in drug metabolism. The present study attempted to evaluate the pharmacogenetic variants of CYP2C9 and CYP2C19 associated with adverse reactions induced by antiepileptic drugs used in Peru. Few studies were found to significantly associate the CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3 single nucleotide polymorphisms with elevated serum levels of valproic acid and carbamazepine, and valproic acid induction of hyperammonemia, and adverse reactions cutaneous for carbamazepine. There is further evidence of a significant association of CYP2C9*2/CYP2C9*3 with severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and epidermal necrolysis (TEN) phenytoin-induced. CYP2C9*3 may be a pharmacogenetic biomarker for such a drug. It is proposed to reduce the dose of drugs for intermediate and poor metabolizers. No pharmacogenetic studies were found in patients with epilepsy in Peruvian populations. It is concluded that this review could help physicians in the prediction and prevention of adverse reactions induced by antiepileptic drugs, as well as to improve their pharmacotherapeutic results. It could also be used as scientific evidence to carry out pharmacogenetic and precision medicine studies in Peruvian patients with epilepsy, due to their tricontinental and Latin American ancestry.