RESUMEN
Introduction: COVID-19 leads to severe clinical complications that culminate in respiratory failure and acute respiratory distress syndrome (ARDS). Despite reports of some comorbidities that contribute to the development of COVID-19-mediated ARDS, there is great variation in mortality rates among critical COVID-19 patients in the world. To date, no studies have described the incidence and comorbidities associated with ARDS due to COVID-19 in the northeastern region of Mexico. Aim of the study: To describe patients diagnosed with ARDS due to COVID-19 in the northeastern region of Mexico, as well as its variations in comparison with other regions of the country. Material and Methods: We conducted a prospective and observational study in a tertiary care center in Northeastern Mexico. All patients diagnosed with SARS-CoV-2 infection and requiring management in the intensive care unit were included. We developed a database that was updated daily with the patients' demographic information, pre-existing diseases, disease severity, and clinical variables. Results: The incidence of ARDS secondary to COVID-19 in HRAEV was high in comparison with other reports. Diabetes mellitus was the risk factor most associated with COVID-19-mediated ARDS. Conclusion: Based on our findings and those previously reported in the literature, there are differences that we discuss between northeastern and central Mexico, and analyze other areas evaluated around the world.
RESUMEN
OBJECTIVES: To compare the safety of Janus kinase inhibitors (JAKi) with that of tumour necrosis factor inhibitors (TNFi) and determine drug persistence among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We analysed data from patients included in BIOBADASER 3.0 and treated with JAKi or TNFi from 2015 to 2023 and estimated the incidence rate ratio (IRR) of adverse events and persistence. RESULTS: A total of 6826 patients were included. Of these, 52% had RA, 25% psoriatic arthritis and 23% axial SpA. Treatment was with TNFi in 86%. The mean duration of treatment was 2.2±2.0 years with TNFi versus 1.8±1.5 with JAKi. JAKis were prescribed in older patients with longer term disease, greater comorbidity and later treatment lines and more frequently as monotherapy. The IRR of all infections and gastrointestinal events was higher among patients with RA treated with JAKi. Drug persistence at 1, 2 and 3 years was 69%, 55% and 45% for TNFi and 68%, 54% and 45% for JAKi. Multivariate regression models showed a lower probability of discontinuation for JAKi (HR=0.85; 95% CI 0.78-0.92) and concomitant conventional synthetic disease-modifying antirheumatic drugs (HR=0.90; 95% CI 0.84-0.96). The risk of discontinuation increased with glucocorticoids, comorbidities, greater disease activity and later treatment lines. CONCLUSIONS: Infections, herpes zoster and gastrointestinal adverse events in patients with RA tended to be more frequent with JAKi. However, prognosis was poor in patients receiving JAKi. Persistence was similar for TNFi and JAKi, although factors associated with discontinuation differed by diagnostic group.
RESUMEN
Co-occurrence of paracoccidioidomycosis and strongyloidiasis in immunosuppressed patients, particularly those infected with human T-lymphotropic virus type 1/2, is infrequent. We describe the case of a Peruvian farmer from the central jungle with human T-lymphotropic virus type 1/2 infection, with 2 months of illness characterized by respiratory and gastrointestinal symptoms associated with fever, weight loss, and enlarged lymph nodes. Strongyloides stercoralis and Paracoccidioides brasiliensis were isolated in sputum and bronchoalveolar lavage samples, respectively. The clinical evolution was favorable after the patient received ivermectin and amphotericin B. We hypothesize that autoinfestation by S. stercoralis in human T-lymphotropic virus type 1/2-infected patients may contribute to the disseminated presentation of Paracoccidioides spp. Understanding epidemiological context is crucial for suspecting opportunistic regional infections, particularly those that may coexist in immunosuppressed patients.
Asunto(s)
Infecciones por HTLV-I , Ivermectina , Paracoccidioidomicosis , Strongyloides stercoralis , Estrongiloidiasis , Humanos , Paracoccidioidomicosis/tratamiento farmacológico , Paracoccidioidomicosis/complicaciones , Paracoccidioidomicosis/diagnóstico , Estrongiloidiasis/tratamiento farmacológico , Estrongiloidiasis/complicaciones , Estrongiloidiasis/diagnóstico , Masculino , Infecciones por HTLV-I/complicaciones , Animales , Ivermectina/uso terapéutico , Strongyloides stercoralis/aislamiento & purificación , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Paracoccidioides/aislamiento & purificación , Coinfección , Infecciones por HTLV-II/complicaciones , Huésped Inmunocomprometido , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , AdultoRESUMEN
BACKGROUND/AIMS: Abexol is a mixture of primary aliphatic alcohols purified from beeswax (Apis mellifera), that produces anti-inflammatory, antioxidant and gastroprotective effects, as well as it is safe and well tolerated. To investigate and compare the efficacy and safety of Abexol (suspension versus tablets) in patients with gastrointestinal symptoms. METHODS: Monocentric study, open-label, randomized design, with two parallel groups receiving Abexol tablets (150 mg/d) or Abexol suspension (75 mg/d) for 8 weeks. Primary efficacy variable (significant improvement in the total score of Gastrointestinal Symptom Rating Scale [GSRS]). Significant reduction in the intensity of the gastrointestinal-symptoms and the reduction in the consumption of antacids are considered secondary efficacy variable. Short form-36 (SF-36) quality of life questiongenonaire was evaluated as collateral variable. Data were analyzed as per intention to treat. RESULTS: A significantly decrease in the overall score of the survey was observed with respect to the baseline level (p < 0.001) of 81.4% in the Abexol suspension group and 77.9% in the Abexol tablets group. At the end of the trial, most gastrointestinal- symptoms disappeared or reduced significantly. The frequency of consumption of neutralizing antacids was low. The significantly improvement in the perception of the state of health obtained in the Abexol is in correspondence with the improvement achieved in some of the components evaluate in the SF-36 questionnaire. Both treatments were safe and well tolerated. CONCLUSION: Abexol suspension showed efficacy and safety similar to Abexol tablets in patients with gastrointestinal symptoms, but using half the dose.
Asunto(s)
Antiácidos , Calidad de Vida , Animales , Humanos , Método Doble Ciego , Comprimidos , Resultado del TratamientoRESUMEN
La elección de una profesión constituye un momento crítico en la vida de los adolescentes. Es un proceso complejo en el que intervienen factores personales y sociales relacionados con la adquisición de conocimientos, habilidades, valores, así como con oportunidades laborales. Con el objetivo de estructurar los referentes teóricos sobre la orientación profesional vocacional hacia la carrera de Medicina en estudiantes de preuniversitario, se realizó una búsqueda actualizada sobre el tema, consultándose 30 referencias bibliográficas. Se abordaron aspectos generales del desarrollo de la orientación profesional-vocacional, reseñas históricas, conceptos, y etapas y desarrollo de este en Cuba hacia la carrera de Medicina. La etapa de la preparación para la selección profesional se dirige a preparar al educando para la selección profesional autodeterminada, y juega un papel fundamental dentro del sistema de influencias educativas que intervienen en el estudiante de preuniversitario, propiciando, desde la orientación profesional, el desarrollo de la motivación e interés del estudiante a niveles superiores. La formación de profesionales competentes y comprometidos con el desarrollo social constituye hoy día una misión esencial de la educación superior. Esta actividad cobra un extraordinario valor en la universidad médica actual, para asumir el compromiso social y obtener graduados con un alto nivel profesional.
Choosing a profession is a critical moment in adolescent lives. It is a complex process involving personal and social factors related to the acquisition of knowledge, skills, values, as well as job opportunities. With the aim of structuring the theoretical references on vocational professional orientation towards a career in Medicine in pre-university students, an updated search on the topic was carried out, consulting 30 bibliographic references. General aspects of the development of professional-vocational guidance, historical reviews, concepts, stages and development of this topic in Cuba towards the career of Medicine were addressed. The stage of preparation for professional selection is aimed at preparing the student for self-determined professional selection, and plays a fundamental role within the system of educational influences which impact on the pre-university student, promoting the development of student motivation and interest at higher levels through professional guidance. The training of competent professionals committed to social development is today an essential mission of higher education. This activity has extraordinary value in the current medical university, to assume social commitment and to have graduates with a high professional level.
RESUMEN
Introduction: Brain death (BD) and steatosis are both risk factors for organ dysfunction or failure in liver transplantation (LT). Material and methods: Here, we examine the role of interleukin 6 (IL- 6) and IL-10 in LT of both non-steatotic and steatotic liver recovered from donors after brain death (DBDs), as well as the molecular signaling pathways underlying the effects of such cytokines. Results: BD reduced IL-6 levels only in nonsteatotic grafts, and diminished IL-10 levels only in steatotic ones. In both graft types, BD increased IL-1ß, which was associated with hepatic inflammation and damage. IL-6 administration reduced IL-1ß only in non-steatotic grafts and protected them against damage and inflammation. Concordantly, IL-1ß inhibition via treatment with an IL-1 receptor antagonist caused the same benefits in non-steatotic grafts. Treatment with IL-10 decreased IL-1ß only in steatotic grafts and reduced injury and inflammation specifically in this graft type. Blockading the IL-1ß effects also reduced damage and inflammation in steatotic grafts. Also, blockade of IL-1ß action diminished hepatic cAMP in both types of livers, and this was associated with a reduction in liver injury and inflammation, then pointing to IL-1ß regulating cAMP generation under LT and BD conditions. Additionally, the involvement of nitric oxide (NO) in the effects of interleukins was evaluated. Pharmacological inhibition of NO in LT from DBDs prompted even more evident reductions of IL-6 or IL-10 in non-steatotic and steatotic grafts, respectively. This exacerbated the already high levels of IL-1ß seen in LT from DBDs, causing worse damage and inflammation in both graft types. The administration of NO donors to non-steatotic grafts potentiated the beneficial effects of endogenous NO, since it increased IL-6 levels, and reduced IL-1ß, inflammation, and damage. However, treatment with NO donors in steatotic grafts did not modify IL-10 or IL-1ß levels, but induced more injurious effects tan the induction of BD alone, characterized by increased nitrotyrosine, lipid peroxidation, inflammation, and hepatic damage. Conclusion: Our study thus highlights the specificity of new signaling pathways in LT from DBDs: NO-IL-6-IL-1ß in non-steatotic livers and NO-IL-10-IL-1ß in steatotic ones. This opens up new therapeutic targets that could be useful in clinical LT.
Asunto(s)
Hígado Graso , Óxido Nítrico , Animales , Ratas , Encéfalo , Muerte Encefálica , Inflamación , Interleucina-6 , Donantes de Óxido NítricoRESUMEN
BACKGROUND: Actinomycosis is an unusual chronic bacterial infection, even rarer in people living with HIV. It is not considered an AIDS-defining disease. However, the role in co-presentation or overlap with other opportunistic conditions of advanced HIV is unknown. CASE PRESENTATION: A 49-year-old Peruvian male presented with a 4-month history of dysphagia, odynophagia, hyporexia and wasting. He underwent an upper digestive endoscopy, in which ulcers with a necrotic center were observed, therefore, the initial diagnostic assumption was esophageal cancer. Subsequent pathology report excluded neoplasms and confirmed the diagnosis of actinomycosis. Serology for human immunodeficiency virus was requested, yielding a positive result. Antimicrobial treatment with amoxicillin and antiretroviral therapy were indicated, with slow clinical improvement. After 4 months, epigastric discomfort presented, for which a new upper digestive endoscopy was performed, revealing a deep gastric ulcer, which was compatible with diffuse large B-cell non-Hodgkin lymphoma. CONCLUSION: Esophageal actinomycosis in people living with HIV is very rare. We suggest HIV-associated immunosuppression is not enough to allow for actinomycosis to develop, and masked underlying entities should be sought. The existence of such entities in people living with HIV should raise awareness of the possibility of unmasked immune reconstitution inflammatory syndrome once treatment has started.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Actinomicosis , Infecciones por VIH , Síndrome Inflamatorio de Reconstitución Inmune , Linfoma no Hodgkin , Humanos , Masculino , Persona de Mediana Edad , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , VIH , Síndrome Inflamatorio de Reconstitución Inmune/complicaciones , Actinomicosis/diagnóstico , Actinomicosis/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/tratamiento farmacológicoRESUMEN
High throughput drug screening is an established approach to investigate tumor biology and identify therapeutic leads. Traditional platforms use two-dimensional cultures which do not accurately reflect the biology of human tumors. More clinically relevant model systems such as three-dimensional tumor organoids can be difficult to scale and screen. Manually seeded organoids coupled to destructive endpoint assays allow for the characterization of treatment response, but do not capture transitory changes and intra-sample heterogeneity underlying clinically observed resistance to therapy. We present a pipeline to generate bioprinted tumor organoids linked to label-free, time-resolved imaging via high-speed live cell interferometry (HSLCI) and machine learning-based quantitation of individual organoids. Bioprinting cells gives rise to 3D structures with unaltered tumor histology and gene expression profiles. HSLCI imaging in tandem with machine learning-based segmentation and classification tools enables accurate, label-free parallel mass measurements for thousands of organoids. We demonstrate that this strategy identifies organoids transiently or persistently sensitive or resistant to specific therapies, information that could be used to guide rapid therapy selection.
Asunto(s)
Bioimpresión , Neoplasias , Humanos , Evaluación Preclínica de Medicamentos/métodos , Organoides/metabolismo , Neoplasias/patología , InterferometríaRESUMEN
Sarcomas are a family of rare malignancies composed of over 100 distinct histological subtypes. The rarity of sarcoma poses significant challenges in conducting clinical trials to identify effective therapies, to the point that many rarer subtypes of sarcoma do not have standard-of-care treatment. Even for established regimens, there can be substantial heterogeneity in responses. Overall, novel, personalized approaches for identifying effective treatments are needed to improve patient out-comes. Patient-derived tumor organoids (PDTOs) are clinically relevant models representative of the physiological behavior of tumors across an array of malignancies. Here, we use PDTOs as a tool to better understand the biology of individual tumors and characterize the landscape of drug resistance and sensitivity in sarcoma. We collected n=194 specimens from n=126 sarcoma patients, spanning 24 distinct subtypes. We characterized PDTOs established from over 120 biopsy, resection, and metastasectomy samples. We leveraged our organoid high-throughput drug screening pipeline to test the efficacy of chemotherapeutics, targeted agents, and combination therapies, with results available within a week from tissue collection. Sarcoma PDTOs showed patient-specific growth characteristics and subtype-specific histopathology. Organoid sensitivity correlated with diagnostic subtype, patient age at diagnosis, lesion type, prior treatment history, and disease trajectory for a subset of the compounds screened. We found 90 biological pathways that were implicated in response to treatment of bone and soft tissue sarcoma organoids. By comparing functional responses of organoids and genetic features of the tumors, we show how PDTO drug screening can provide an orthogonal set of information to facilitate optimal drug selection, avoid ineffective therapies, and mirror patient outcomes in sarcoma. In aggregate, we were able to identify at least one effective FDA-approved or NCCN-recommended regimen for 59% of the specimens tested, providing an estimate of the proportion of immediately actionable information identified through our pipeline. Highlights: Standardized organoid culture preserve unique sarcoma histopathological featuresDrug screening on patient-derived sarcoma organoids provides sensitivity information that correlates with clinical features and yields actionable information for treatment guidanceHigh-throughput screenings provide orthogonal information to genetic sequencingSarcoma organoid response to treatment correlates with patient response to therapyLarge scale, functional precision medicine programs for rare cancers are feasible within a single institution.
RESUMEN
Among the outstanding questions about the emergence of human-controlled fire is the systematic recurrence between the geochemical remains of fire and its preservation in the archaeological record, as the use of fire is considered a technological landmark, especially for its importance in food cooking, defensive strategies, and heating. Here we report fossil lipid biomarkers associated with incomplete combustion of organic matter at the Valdocarros II site, one of the largest European Acheulean sites in Spain dated to marine isotopic stage (MIS) 8/7 (~ 245 kya) allowing a multiproxy analysis of human-controlled fire use. Our results reveal isolated cases of highly concentrated and diverse polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs (APAHs), along with diagnostic conifer-derived triterpenoids in two hearth-like archaeological structures. The presence of combustion byproducts suggests the presence of anthropogenic (controlled) fires at Valdocarros-one of the oldest evidence of fire use in Europe-in association with Acheulean tools and bones. Hominins possibly used fire for two main activities, as a means of defense against predators and cooking. Our results help to better delineate major gaps in our current knowledge of human-controlled fire in the context of the Middle-Pleistocene in Europe and suggest that human ancestors were able to control fire before at least 250 kya.
Asunto(s)
Hominidae , Hidrocarburos Policíclicos Aromáticos , Animales , Humanos , España , Europa (Continente) , Fósiles , ArqueologíaRESUMEN
Yeast fungi of the genus Trichosporon spp. can colonize the gastrointestinal tract in humans. In recent decades, the pathogenic role of Trichosporon asahii has been increasingly acknowledged especially in the setting of neutropenic patients with hematological malignancies. However, non-neutropenic patients who are immunosuppressed for other reasons are also at risk of developing invasive forms of this mycosis. We present the case of a 62-year-old male, with a history of ulcerative colitis under immunosuppressive treatment and previous exposure to antibiotics for various bacterial infections, who was admitted to the emergency department with a mycotic aneurysm of the abdominal aorta and left common iliac secondary to T. asahii infection. A multidisciplinary approach of the case (both early medical and surgical interventions) allowed the patient's favorable outcome. The patient was followed for more than two years with no evidence of relapse. We postulate that the diagnosis of invasive Trichosporonosis should be considered in patients with inflammatory bowel disease (IBD) under immunosuppressive treatment and with prior exposure to antibiotics.
RESUMEN
BACKGROUND: Major depressive disorders (MDDs) occurs frequently in patients with tuberculosis (TB). Elevated serum pro-inflammatory cytokine levels in MDD patients is a well-established fact. Therefore, an integrated clinical practice should be considered. However, the inflammatory status of MDD-TB patients is unknown. In this study, we analyze cytokines in activated-cells and sera from MDD-TB, TB, MDD patients, and healthy controls. METHODS: Flow cytometry was used to evaluate the intracellular production of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, and IL-10 by peripheral blood mononuclear cells after a polyclonal stimulation. A Bio-Plex Luminex system was used to measure serum cytokine and chemokine levels in the study groups. RESULTS: We observed a 40.6% prevalence of MDD in TB patients. The proportion of IFN-gamma-producing cells was higher in MDD-TB patients than other pathological groups. Nevertheless, the percentage of TNF-alpha- and IL-12-producing cells was similar between MDD-TB and TB patients. Likewise, MDD-TB and TB patients showed similar serum pro-inflammatory cytokine and chemokine levels, which were significantly lower than those in MDD patients. By multiple correspondence analyses, we observed that low levels of serum IL-4, IL-10, and IL-13 were powerfully associated with TB comorbidities with MDD. CONCLUSIONS: A high frequency of IFN-γ-producing cells is associated with low levels of serum anti-inflammatory cytokines in MDD-TB patients.
RESUMEN
Antimicrobials are routinely used in human and veterinary medicine. With repeated exposure, antimicrobials promote antibiotic resistance, which poses a threat to public health. In this study, we aimed to determine the susceptibility patterns, virulence factors, and phylogroups of E. coli isolates during the killing process in a bovine slaughterhouse. We analyzed 336 samples (from water, surfaces, carcasses, and feces), and 83.3% (280/336) were positive for E. coli. The most common phenotypic resistances that we detected were 50.7% (142/280) for tetracycline, 44.2% (124/280) for cephalothin, 34.6% (97/280) for streptomycin, and 36.7% (103/280) for ampicillin. A total of 82.4% of the isolates had resistance for at least one antimicrobial, and 37.5% presented multiresistance. We detected a total of 69 different phenotypic resistance patterns. We detected six other resistance-related genes, the most prevalent being tetA (22.5%) and strB (15.7%). The prevalence values of the virulence genes were 5.4% in hlyA, 1.4% in stx1, and 0.7% in stx2. The frequencies of the pathogenic strains (B2 and D) were 32.8% (92/280) and 67.1% (188/280) as commensals A and B1, respectively. E. coli isolates with pathogenic potential and multiresistance may represent an important source of dissemination and a risk to consumers.
RESUMEN
Introducción: la información a incluir en el hiperentorno de aprendizaje con contenidos histológicos, y la funcionalidad de este para el trabajo independiente del estudiante, deben ser concebidas integradamente, en una comunión de intereses donde el programa de la asignatura aporte el flujograma pedagógico. Objetivo: diseñar un hiperentorno de aprendizaje que contribuya al desarrollo del trabajo independiente del estudiante, con los contenidos histológicos del proceso de enseñanza-aprendizaje de la asignatura Célula, Tejidos, Sistema Tegumentario, de la carrera de Medicina, en la Universidad de Ciencias Médicas de Matanzas. Materiales y métodos: como método rector se empleó la dialéctica materialista de la filosofía marxista-leninista. Métodos teóricos: histórico-lógico, analítico-documental, inductivo-deductivo, sistémico estructural funcional, modelación. Métodos empíricos: encuesta a estudiantes, entrevista a profesores, observación a clases, selección de expertos. La población estuvo conformada por 10 profesores de la asignatura y una muestra de 290 estudiantes. El trabajo realizado abarcó dos etapas y tres fases: diagnóstico, diseño y valoración de los resultados. Resultados: con relación a requisitos de diseño, la dimensión mejor evaluada fue la usabilidad (4,98). En lo referido a habilidades cognitivas, se destaca, con buenos resultados, el indicador desarrollo de habilidades de navegación en la búsqueda de información, con un valor de 9,30. Conclusiones: el hiperentorno de aprendizaje diseñado es factible, muestra facilidad de uso y funcionalidad al dar respuesta a las necesidades de los estudiantes en la asignatura; se adapta a las posibilidades del estudiante.
Introduction: the information to be included in the learning hyper-environment with histological contents, and its functionality for the student's independent work, must be conceived in an integrative way, in communion of interests where the program of the subject contributes the pedagogical flowchart. Objective: to design a learning hyper-environment that contributes to the development of the student's independent work, with the histological contents of the teaching-learning process of the subject Cell, Tissues, Integumentary System, of the Medicine degree, at the Matanzas University of Medical Sciences of Matanzas. Materials and methods: the materialist dialectics of the Marxist-Leninist philosophy was used as the guiding method. Theoretical methods: historical-logical, analytical-documentary, inductive-deductive, systemic structural functional, modeling. Empirical methods: students survey, teachers interview, observation of classes, selection of experts. The population consisted of 10 teachers of the subject and a sample of 250 students. The work carried out covered two stages and three phases: diagnosis, design and evaluation of the results. Results: regarding design requirements, the best evaluated dimension was usability (4.98). In terms of cognitive skills, the development of navigation skills indicator in the search for information stands out with good results, and a value of 9.30. Conclusions: the designed learning hyper-environment is feasible, shows ease of use and functionality by responding to the needs of students in the subject; it adapts to the possibilities of the student.
RESUMEN
This work examines the possible behaviour of Neanderthal groups at the Cueva Des-Cubierta (central Spain) via the analysis of the latter's archaeological assemblage. Alongside evidence of Mousterian lithic industry, Level 3 of the cave infill was found to contain an assemblage of mammalian bone remains dominated by the crania of large ungulates, some associated with small hearths. The scarcity of post-cranial elements, teeth, mandibles and maxillae, along with evidence of anthropogenic modification of the crania (cut and percussion marks), indicates that the carcasses of the corresponding animals were initially processed outside the cave, and the crania were later brought inside. A second round of processing then took place, possibly related to the removal of the brain. The continued presence of crania throughout Level 3 indicates that this behaviour was recurrent during this level's formation. This behaviour seems to have no subsistence-related purpose but to be more symbolic in its intent.
Asunto(s)
Hombre de Neandertal , Animales , Herbivoria , Cráneo , Arqueología , España , MamíferosRESUMEN
Systematic identification of signaling pathways required for the fitness of cancer cells will facilitate the development of new cancer therapies. We used gene essentiality measurements in 1,086 cancer cell lines to identify selective coessentiality modules and found that a ubiquitin ligase complex composed of UBA6, BIRC6, KCMF1, and UBR4 is required for the survival of a subset of epithelial tumors that exhibit a high degree of aneuploidy. Suppressing BIRC6 in cell lines that are dependent on this complex led to a substantial reduction in cell fitness in vitro and potent tumor regression in vivo. Mechanistically, BIRC6 suppression resulted in selective activation of the integrated stress response (ISR) by stabilization of the heme-regulated inhibitor, a direct ubiquitination target of the UBA6/BIRC6/KCMF1/UBR4 complex. These observations uncover a novel ubiquitination cascade that regulates ISR and highlight the potential of ISR activation as a new therapeutic strategy. SIGNIFICANCE: We describe the identification of a heretofore unrecognized ubiquitin ligase complex that prevents the aberrant activation of the ISR in a subset of cancer cells. This provides a novel insight on the regulation of ISR and exposes a therapeutic opportunity to selectively eliminate these cancer cells. See related commentary Leli and Koumenis, p. 535. This article is highlighted in the In This Issue feature, p. 517.
Asunto(s)
Carcinoma , Humanos , Ubiquitinación , Línea Celular , Transducción de Señal , UbiquitinasRESUMEN
Introducción: El cáncer colorectal constituye en la actualidad la segunda neoplasia maligna más frecuente. La mayoría son esporádicos, otra pequeña proporción corresponde a formas hereditarias. Sin embargo, se estima que en un 15 % a 20 % de casos pueden existir un componente hereditario asociado. Los familiares de primer grado de pacientes con cáncer colorrectal, constituyen un universo de mayor riesgo que la población general de padecer esta enfermedad, por lo que se recomienda el cribado en estos individuos. Objetivo: Determinar la frecuencia de pólipos adenomatosos en individuos con familiares de primer grado diagnosticados con cáncer de colon. Métodos: Se realizó un estudio descriptivo, de corte transversal, que incluyó a 126 adultos con familiares de primer grado de consanguinidad con cáncer de colon, a los que se les realizó colonoscopia en el Instituto de Gastroenterología entre diciembre de 2019 y diciembre 2021. Se describen las características de los pólipos adenomatosos encontrados. Resultados: La media para la edad fue de 55,9 ± 10,6, predominaron las mujeres. Se encontraron pólipos adenomatosos; 27 eran sésiles y 12 pediculados; en 26 (66,7 %), el tamaño era menor de 10 mm. La mayoría de los pólipos, fueron del tipo tubular. Se observó diversidad en cuanto a la localización de las lesiones, sin que existiera un predominio en ningún segmento anatómico. Conclusiones: Lesiones precursoras del cáncer colorrectal, como los pólipos adenomatosos, son frecuentes en individuos asintomáticos con familiares de primer grado de consanguinidad que padecieron esta neoplasia maligna.
Introduction : Colorectal cancer is currently the second most frequent neoplasm. Most of them are sporadic, another small proportion corresponds to hereditary forms. However, it is estimated that in 15-20% of cases there may be an associated hereditary component. First-degree relatives of patients with colorectal cancer constitute a universe with a higher risk of developing this disease than that of the general population, so screening is recommended in these individuals. Objective : To determine the frequency of adenomatous polyps in individuals with first-degree relatives diagnosed with colon cancer. Methods : A descriptive, cross-sectional study was carried out, including 126 adult relatives with first-degree blood relatives with colon cancer, who underwent colonoscopy at the Institute of Gastroenterology between December 2019 and December 2021. The characteristics of the adenomatous polyps found are described. Results : The mean for age was 55.9 ± 10.6, women predominated: 94 (74.6 %). Thirty-nine (30.9 %) adenomatous polyps were found; 27 (69.2 %) were sessile and 12 (30.7 %) pedunculated; in 26 (66.7 %) the size was less than 10 mm. The majority, 37 (94.8 %), were of the tubular type. Diversity was observed as to the location of the lesions, with no predominance in any anatomical segment. Conclusions : Precursor lesions of colorectal cancer, such as adenomatous polyps, are common in asymptomatic individuals with first-degree relatives who have had this malignancy.
RESUMEN
While conducting recombinant DNA technology procedures, such as DNA purification, agarose gel electrophoresis is often used for identification, characterization and quantification of DNA. The collection of data for experiments involving such techniques frequently involves capturing images using systems that are expensive and/or proprietary, such that they are not user-serviceable when they malfunction or become antiquated. In response to these limitations, work was done to replace the authors' existing aging Mac OS-based modular system with open-source software and generic hardware. Several versions of a modular imaging system that can be adjusted to fit nearly all use cases are described. The systems developed can accommodate diverse uses from research laboratories to educational environments where commercial systems could be unaffordable.