Diagnostic difficulties in congenital tumor with positive antibodies for skeletal muscle. Lipofibromatosis case report

Neonatos con Tumores congénitos de partes blandasIntroduction: Congenital soft tissue tumors are uncommon; proper diagnosis calls for histopathological experience and ancillary techniques based upon immunohistochemial, cytogenetic, and molecular biology. Following excision, intermediately aggressive soft tumors tend to local recurrence, which significantly impacts prognosis; some cases occur close to malignity; subsequently, diagnostic implications are enormous for the patient. Case report: A 26-day old neonate with a posterior left thigh mass entered hospital. Initial biopsy analysis could not rule out either striated muscle origin or malignancy; resection and classification of surgical piece followed. Pursuant to resection, using immunohistochemistry panel, tumor analysis and classification took place. Conclusion: Soft tumor diagnosis is a complex process, even more so for newborns. Infrequent occurrence requires that examiners have ample histopathological experience in the handling of ancillary techniques. Furthermore, as in lipofibromatosis, determining the presence of trapped vs. malignant tissue hinders proper classification, which, in turn, has profound implications for the patient. We include a standard diagnostic algorithm based on clinical and histological characteristics for this type of congenital lesions.https://orcid.org/0000-0003-3507-7596https://orcid.org/0000-0001-8932-4877https://orcid.org/0000-0002-7147-425Xhttps://orcid.org/0000-0001-7982-4552Revista Internacional - No indexadaN

Natural Variation in Diauxic Shift between Patagonian Saccharomyces eubayanus Strains

The study of natural variation can untap novel alleles with immense value for biotechnological applications. Saccharomyces eubayanus Patagonian isolates exhibit differences in the diauxic shift between glucose and maltose, representing a suitable model to study their natural genetic variation for novel strains for brewing. However, little is known about the genetic variants and chromatin regulators responsible for these differences. Here, we show how genome-wide chromatin accessibility and gene expression differences underlie distinct diauxic shift profiles in S. eubayanus. We identified two strains with a rapid diauxic shift between glucose and maltose (CL467.1 and CBS12357) and one strain with a remarkably low fermentation efficiency and longer lag phase during diauxic shift (QC18). This is associated in the QC18 strain with lower transcriptional activity and chromatin accessibility of specific genes of maltose metabolism and higher expression levels of glucose transporters. These differences are governed by the HAP complex, which differentially regulates gene expression depending on the genetic background. We found in the QC18 strain a contrasting phenotype to those phenotypes described in S. cerevisiae, where hap4D, hap5D, and cin5D knockouts significantly improved the QC18 growth rate in the glucose-maltose shift. The most profound effects were found between CIN5 allelic variants, suggesting that Cin5p could strongly activate a repressor of the diauxic shift in the QC18 strain but not necessarily in the other strains. The differences between strains could originate from the tree host from which the strains were obtained, which might determine the sugar source preference and the brewing potential of the strain.Fil: Molinet, Jennifer. Universidad de Santiago de Chile; ChileFil: Eizaguirre, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales. Universidad Nacional del Comahue. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales; ArgentinaFil: Quintrel, Pablo. Universidad de Santiago de Chile; ChileFil: Bellora, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Instituto de Tecnologías Nucleares para la Salud; ArgentinaFil: Villarroel, Carlos A.. Universidad de Talca; ChileFil: Villarreal, Pablo. Universidad de Santiago de Chile; ChileFil: Benavides Parra, José. Universidad de Santiago de Chile; ChileFil: Nespolo, Roberto F.. Universidad Austral de Chile; ChileFil: Libkind Frati, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales. Universidad Nacional del Comahue. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales; ArgentinaFil: Cubillos, Francisco A.. Universidad de Santiago de Chile; Chil

Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing.

Following central nervous system (CNS) demyelination, adult oligodendrocyte progenitor cells (OPCs) can differentiate into new myelin-forming oligodendrocytes in a regenerative process called remyelination. Although remyelination is very efficient in young adults, its efficiency declines progressively with ageing. Here we performed proteomic analysis of OPCs freshly isolated from the brains of neonate, young and aged female rats. Approximately 50% of the proteins are expressed at different levels in OPCs from neonates compared with their adult counterparts. The amount of myelin-associated proteins, and proteins associated with oxidative phosphorylation, inflammatory responses and actin cytoskeletal organization increased with age, whereas cholesterol-biosynthesis, transcription factors and cell cycle proteins decreased. Our experiments provide the first ageing OPC proteome, revealing the distinct features of OPCs at different ages. These studies provide new insights into why remyelination efficiency declines with ageing and potential roles for aged OPCs in other neurodegenerative diseases

Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study

Background Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. Methods All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. Results A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5–14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. Conclusions Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.Q1Q1Los factores de riesgo de resistencia a los carbapenémicos en las infecciones del torrente sanguíneo por Enterobacterales entre niños con cáncer o después de un TCMH no se han explorado a fondo. Métodos Se examinaron retrospectivamente todos los niños con cáncer o post-TCMH que desarrollaron infecciones del torrente sanguíneo por Enterobacterales en dos centros de referencia de cáncer en las principales ciudades de Colombia entre 2012 y 2021. Cuando ocurrió el episodio de infección, se evaluaron los mecanismos de resistencia a los carbapenémicos según los métodos disponibles. Los datos se dividieron en un conjunto de entrenamiento (80%) y un conjunto de prueba (20%). Se crearon tres modelos de predicción de Enterobacterales resistentes a carbapenémicos (CRE) validados internamente: un modelo de regresión logística multivariante y dos técnicas de minería de datos. El rendimiento del modelo se evaluó calculando el promedio del AUC, la sensibilidad, la especificidad y los valores predictivos. Resultados Se produjeron un total de 285 episodios de infección del torrente sanguíneo por Enterobacterales (229 susceptibles a carbapenémicos y 56 resistentes a carbapenémicos) [mediana de edad (RIQ), 9 (3,5 a 14) años; 57% hombres]. El riesgo de CRE fue 2,1 veces mayor cuando la infección fue causada por Klebsiella spp. y 5,8 veces mayor cuando se había utilizado un carbapenem durante ≥3 días en el mes anterior. Un modelo que incluía estas dos variables predictivas tuvo un rendimiento discriminatorio del 77% en la predicción de la resistencia a los carbapenémicos. El modelo tuvo una especificidad del 97% y un valor predictivo negativo del 81%, con baja sensibilidad y valor predictivo positivo. Conclusiones Incluso en entornos con una alta prevalencia de CRE, estas dos variables pueden ayudar a la identificación temprana de pacientes en quienes los agentes activos de CRE son innecesarios y resaltar la importancia de fortalecer las estrategias de administración de antibióticos dirigidas a prevenir el uso excesivo de carbapenémicos.N/AS

CHARITY: Chagas cardiomyopathy bisoprolol intervention study: a randomized double-blind placebo force-titration controlled study with Bisoprolol in patients with chronic heart failure secondary to Chagas cardiomyopathy [NCT00323973]

BACKGROUND: Chagas' disease is the major cause of disability secondary to tropical diseases in young adults from Latin America, and around 20 million people are currently infected by T. cruzi. Heart failure due to Chagas cardiomyopathy is the main clinical presenation in Colombia. Heart failure due to Chagas' disease may respond to digoxin, diuretics and vasodilator therapy. Beta-adrenoreceptor antagonism seems to protect against the increased risk of cardiac arrhythmia and sudden death due to chronic sympathetic stimulation. The aim of this study is to evaluate the effects of the selective beta-adrenergic receptor blocker Bisoprolol on cardiovascular mortality, hospital readmission due to progressive heart failure and functional status in patients with heart failure secondary to Chagas' cardiomyopathy. METHODS/DESIGN: A cohort of 500 T. cruzi seropositive patients (250 per arm) will be selected from several institutions in Colombia. During the pretreatment period an initial evaluation visit will be scheduled in which participants will sign consent forms and baseline measurements and tests will be conducted including blood pressure measurements, twelve-lead ECG and left ventricular ejection fraction assessment by 2D echocardiography. Quality of life questionnaire will be performed two weeks apart during baseline examination using the "Minnesota living with heart failure" questionnaire. A minimum of two 6 minutes corridor walk test once a week over a two-week period will be performed to measure functional class. During the treatment period patients will be randomly assigned to receive Bisoprolol or placebo, initially taking a total daily dose of 2.5 mgrs qd. The dose will be increased every two weeks to 5, 7.5 and 10 mgrs qd (maximum maintenance dose). Follow-up assessment will include clinical check-up, and blood collection for future measurements of inflammatory reactants and markers. Quality of life measurements will be obtained at six months. This study will allow us to explore the effect of beta-blockers in chagas' cardiomyopathy

Lipid bodies containing oxidatively truncated lipids block antigen cross-presentation by dendritic cells in cancer

Tumor-associated dendritic cells are defective in their ability to cross-present antigens, and they accumulate lipid bodies. Here the authors show that this defect is due to an impaired trafficking of peptide-MHC class I caused by the interaction of electrophilic lipids with chaperone heat shock protein 70

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Atypical Streptococcal Meningitis with Fatal Cerebrovascular Complications: A Case Report

Bacterial meningitis is an infectious pathology that remains a public health challenge. The most frequent etiological agent is Streptococcus pneumoniae, which is also associated with higher rates of mortality and sequels. However, less is known about the clinical presentation of atypical non-pneumoniae streptococcal meningitis. Here, we studied a 23-year-old man with no medical background who presented with projectile vomiting, states of consciousness alteration, unilateral cranial nerve palsy, and meningeal signs. Neuroimaging showed tonsillar herniation, regions of empyema, right transverse and sigmoid sinuses thrombosis, and multiple arterial subcortical infarcts. Cerebrospinal fluid suggested bacterial infection; blood and abscess cultures were positive for Streptococcus constellatus. The patient received antibiotics with no clinical improvement. He deteriorated over the following days, the abolishment of brainstem reflexes was observed, and brain death was declared. Streptococcal meningitis produced by atypical species is a potential cause of lethal cerebrovascular complications, even in immunocompetent patients

Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing.

Following central nervous system (CNS) demyelination, adult oligodendrocyte progenitor cells (OPCs) can differentiate into new myelin-forming oligodendrocytes in a regenerative process called remyelination. Although remyelination is very efficient in young adults, its efficiency declines progressively with ageing. Here we performed proteomic analysis of OPCs freshly isolated from the brains of neonate, young and aged female rats. Approximately 50% of the proteins are expressed at different levels in OPCs from neonates compared with their adult counterparts. The amount of myelin-associated proteins, and proteins associated with oxidative phosphorylation, inflammatory responses and actin cytoskeletal organization increased with age, whereas cholesterol-biosynthesis, transcription factors and cell cycle proteins decreased. Our experiments provide the first ageing OPC proteome, revealing the distinct features of OPCs at different ages. These studies provide new insights into why remyelination efficiency declines with ageing and potential roles for aged OPCs in other neurodegenerative diseases