Microbial green synthesis of luminescent terbium sulfide nanoparticles using E. Coli: a rare earth element detoxification mechanism.

BACKGROUND: Rare-earth sulfide nanoparticles (NPs) could harness the optical and magnetic features of rare-earth ions for applications in nanotechnology. However, reports of their synthesis are scarce and typically require high temperatures and long synthesis times. RESULTS: Here we present a biosynthesis of terbium sulfide (TbS) NPs using microorganisms, identifying conditions that allow Escherichia coli to extracellularly produce TbS NPs in aqueous media at 37 °C by controlling cellular sulfur metabolism to produce a high concentration of sulfide ions. Electron microscopy revealed ultrasmall spherical NPs with a mean diameter of 4.1 ± 1.3 nm. Electron diffraction indicated a high degree of crystallinity, while elemental mapping confirmed colocalization of terbium and sulfur. The NPs exhibit characteristic absorbance and luminescence of terbium, with downshifting quantum yield (QY) reaching 28.3% and an emission lifetime of ~ 2 ms. CONCLUSIONS: This high QY and long emission lifetime is unusual in a neat rare-earth compound; it is typically associated with rare-earth ions doped into another crystalline lattice to avoid non-radiative cross relaxation. This suggests a reduced role of nonradiative processes in these terbium-based NPs. This is, to our knowledge, the first report revealing the advantage of biosynthesis over chemical synthesis for Rare Earth Element (REE) based NPs, opening routes to new REE-based nanocrystals.

Multi-model hydrological reference dataset over continental Europe and an African basin.

Although Essential Climate Variables (ECVs) have been widely adopted as important metrics for guiding scientific and policy decisions, the Earth Observation (EO) and Land Surface and Hydrologic Model (LSM/HM) communities have yet to treat terrestrial ECVs in an integrated manner. To develop consistent terrestrial ECVs at regional and continental scales, greater collaboration between EO and LSM/HM communities is needed. An essential first step is assessing the LSM/HM simulation uncertainty. To that end, we introduce a new hydrological reference dataset that comprises a range of 19 existing LSM/HM simulations that represent the current state-of-the-art of our LSM/HMs. Simulations are provided on a daily time step, covering Europe, notably the Rhine and Po river basins, alongside the Tugela river basin in Africa, and are uniformly formatted to allow comparisons across simulations. Furthermore, simulations are comprehensively validated with discharge, evapotranspiration, soil moisture and total water storage anomaly observations. Our dataset provides valuable information to support policy development and serves as a benchmark for generating consistent terrestrial ECVs through the integration of EO products.

A qualitative analysis of an Aß-monomer model with inflammation processes for Alzheimer's disease.

We introduce and study a new model for the progression of Alzheimer's disease (AD) incorporating the interactions of A ß -monomers, oligomers, microglial cells and interleukins with neurons through different mechanisms such as protein polymerization, inflammation processes and neural stress reactions. To understand the complete interactions between these elements, we study a spatially homogeneous simplified model that allows us to determine the effect of key parameters such as degradation rates in the asymptotic behaviour of the system and the stability of equilibrium. We observe that inflammation appears to be a crucial factor in the initiation and progression of AD through a phenomenon of hysteresis with respect to the oligomer degradation rate d . This means that depending on the advanced state of the disease (given by the value of the A ß -monomer degradation rate d : large value for an early stage and low value for an advanced stage) there exists a critical threshold of initial concentration of interleukins that determines if the disease persists or not in the long term. These results give perspectives on possible anti-inflammatory treatments that could be applied to mitigate the progression of AD. We also present numerical simulations that allow us to observe the effect of initial inflammation and monomer concentration in our model.

Incidence of intra-abdominal injuries in hemodynamically stable blunt trauma patients with a normal computed tomography scan admitted to the emergency department.

OBJECTIVES: Blunt abdominal trauma is a common cause of emergency department admission. Computed tomography (CT) scanning is the gold standard method for identifying intra-abdominal injuries in patients experiencing blunt trauma, especially those with high-energy trauma. Although the diagnostic accuracy of this imaging technique is very high, patient admission and prolonged observation protocols are still common practices worldwide. We aimed to evaluate the incidence of intra-abdominal injury in hemodynamically stable patients with high-energy blunt trauma and a normal abdominal CT scan at a Level-1 Trauma Center in Colombia, South America, to assess the relevance of a prolonged observation period. METHODS: We performed a retrospective study of patients admitted to the emergency department for blunt trauma between 2021 and 2022. All consecutive patients with high-energy mechanisms of trauma and a normal CT scan at admission were included. Our primary outcomes were the incidence of intra-abdominal injury identified during a 24-hour observation period or hospital stay, ICU admission, and death. RESULTS: We included 480 patients who met the inclusion criteria. The median age was 33 (IQR 25.5, 47), and 74.2% were male. The most common mechanisms of injury were motor vehicle accidents (64.2%), falls from height (26%), and falls from bikes (3.1%). A total of 99.2% of patients had a Revised Trauma Score of 8. Only 1 patient (0.2%) (95% CI: 0.01-1.16) presented with an abdominal injury during the observation period. No ICU admissions or deaths were reported. CONCLUSION: The incidence of intra-abdominal injury in patients with hemodynamically stable blunt trauma and a negative abdominal CT scan is extremely low, and prolonged observation may not be justified in these patients.

Dacriocistocele bilateral congénito: reporte de un caso / Congenital bilateral dacryocystocele: case report

Introducción: el dacriocistocele es una malformación congénita rara, secundaria a la obstrucción del conducto nasolagrimal; tiene una incidencia de 0,1 % de pacientes con obstrucción congénita del conducto nasolagrimal y se encuentra bilateralmente hasta en 25 % de casos. Caso clínico: lactante femenina de dos meses con celulitis periorbitaria derecha preseptal no asociada con lesión de entrada y diagnóstico inicial de dacriocistitis derecha. Al examen físico de ingreso, en el ojo derecho se evidencia gran masa abscedada en saco lagrimal; en el ojo izquierdo, un área indurada y leve reflujo a la presión del saco lagrimal. Se realiza tomografía computarizada de órbitas con hallazgos compatibles con dacriocistocele bilateral. Discusión y conclusiones: conocer la presentación y posibles complicaciones asociadas con esta patología previene una morbilidad importante al paciente. La mayoría de los casos de dacriocistocele se pueden manejar médicamente, sin embargo, aquellos asociados con complicaciones requieren de manejo quirúrgico oportuno.

Introduction: Dacryocystocele is a rare congenital malformation secondary to na-solacrimal duct obstruction. It has an incidence of 0.1% of patients with congenital nasolacrimal duct obstruction, being found bilaterally in up to 25% of cases. Case Report: Two-month-old female infant with preseptal right periorbital cellulitis not associated with an entrance lesion, with an initial diagnosis of right dacryocystitis. On physical examination, a large abscessed mass in the lacrimal sac was eviden-ced in the right eye; in the left eye, there was an indurated area and slight reflux to the lacrimal sac pressure. Computed tomography of the orbits was performed with findings compatible with bilateral dacryocystocele. Discussion and conclusions: Knowing the presentation and possible complications associated with this pathology prevents significant patient morbidity. Most cases of dacryocystocele can be mana-ged medically, however, cases associated with complications require timely surgical management.

Breast Cancer in Pregnant Young Women: Clinicopathological Profile, Survival, and Pregnancy Outcomes.

Background Breast cancer is one of the most common cancer types diagnosed during pregnancy; the presence of any neoplasm in pregnant women faces clinical dilemmas and challenges in cancer and pregnancy management. Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during pregnancy or within one year after delivery. The aim of this study was to describe tumor clinicopathological characteristics and pregnancy outcomes in PABC patients. Materials and methods This is a retrospective cohort assessing PABC patients. Qualitative variables were compared using Fisher's exact test. Kaplan-Meier method was used to calculate survival. Cox regression and logistic regression methods were used to estimate the hazard ratio (HR) and odds ratio (OR), respectively. Results We assessed 16 PABC patients. Women ≤ 35 years of age were mainly diagnosed at advanced stage (88.8%) with ER-negative disease (77.8%). Patients with >4 pathological lymph nodes (25%; p = 0.001) and ER-negative disease (50%; p = 0.646) showed poor five-year overall survival (OS). In the multivariate analysis, nodal involvement was the main predictor associated with poorer OS (HR = 1.4, 90% confidence interval [CI]: 1.14 to 1.8). The following risk factors might influence the risk of preterm delivery: maternal older age, gestational age at diagnosis, and intrauterine exposure to chemotherapy, but an adjusted OR of 0.61 (90% CI: 0.34 to 1), 0.80 (90% CI: 0.66 to 0.9), and 0.013 (90% CI: 0.00 to 0.9), respectively, did not statistically support such an effect. Conclusions Younger women with PABC had a more aggressive pathological profile that might partly explain the poor OS. Obstetrical adverse events related to preterm delivery should be avoided with better planning of specialized strategies.

No seroconversion among healthcare workers exposed to SARS-CoV-2 during the early phase of the pandemic.

BACKGROUND: The SARS-CoV-2 pandemic is associated with morbidity, hospitalizations, absenteeism, and mortality among healthcare workers (HCW). AIM: To evaluate the seroconversion rate in HCW exposed to SARS-CoV-2 in the early pandemic phase in 2020 at a regional reference hospital. MATERIAL AND METHODS: One hundred seventy-nine HCW working at a regional hospital were invited to a longitudinal study performed between April-July 2020. A serological analysis by ELISA IgG for viral nucleoprotein and protein S with a secondary analysis by ELISA IgG protein S1/S2 for samples with positive or doubtful result was carried out together with a complementary online survey to inquire about occupational or community exposures to SARS-CoV-2. RESULTS: Two cases with baseline infection were detected (1.1%, one symptomatic and one asymptomatic) and no cases of seroconversion were detected. During the study period, there were 136 patients hospitalized with COVID-19, and regional weekly COVID-19 incidence ranged from 2.7 to 24.4 per 100,000 inhabitants. No SARS-CoV-2 cases were detected by PCR among 27 HCW who consulted for respiratory symptoms in the period. Online surveys confirmed direct care of COVID-19 patients and also detected a high degree of unprotected social interaction at work. CONCLUSIONS: There was no evidence of seroconversion in this group of HCW exposed to the risk of infection by SARS-CoV-2 during the onset of the COVID-19 pandemic. Personal protective equipment and other measures used by the HCW were extremely useful for their protection in the initial phase of the pandemic.

Registro de síndromes coronarios agudos en centros de alta complejidad de Argentina. ReSCAR 2022 / Acute Coronary Syndromes in High Complexity Centers of Argentina. The ReSCAR Registry

RESUMEN Introducción : Realizamos un registro multicéntrico para analizar el abordaje diagnóstico y terapéutico de todos los tipos de síndromes coronarios agudos; este registro es el primero en abordar en detalle aquellos cuadros que cursan sin enfermedad coronaria epicárdica significativa. Es importante conocer la realidad del actual accionar médico con el objeto de hallar oportunidades de mejora. Material y métodos : Se registraron en forma prospectiva pacientes hospitalizados por síndrome coronario agudo en 15 centros de Argentina, con diagnóstico con troponina ultrasensible, servicio de unidad coronaria y hemodinamia disponible las 24 horas, entre enero y agosto de 2022. Resultados : Se incluyeron 984 pacientes consecutivos, un 22,2% con angina inestable, 39,1% con infarto agudo de miocardio sin elevación del segmento ST (IAMSEST) y 24,1% con infarto agudo de miocardio con elevación del segmento ST (IAMCEST). Por otro lado, el 4,1% se presentó como IAM tipo 2, 1,2% como miocarditis, 0,7% como síndrome de Takotsubo y 8,6% como infarto de miocardio con enfermedad coronaria no obstructiva (MINOCA). La mediana (rango intercuartílico, RIC) de edad fue de 66 años (56,5-74), con un 75,3% de pacientes de sexo masculino. El manejo inicial de los pacientes sin elevación del segmento ST fue invasivo en el 84%, con una tasa de enfermedad coronaria significativa del 76,5%. En cuanto a la evolución intrahospitalaria, las complicaciones isquémicas más relevantes fueron el reinfarto (2,84%), angina recurrente (2,4%), angina post infarto (2%) y trombosis intra stent (0,5%). El porcentaje de eventos hemorrágicos totales fue de 4,4% y la mortalidad intrahospitalaria total fue de 3,76%. Conclusiones : El registro tiene una buena representación del espectro de pacientes con sospecha inicial de síndrome coronario agudo, manejados en centros con una estrategia inicial principalmente invasiva, con una baja tasa de complicaciones hospitalarias y una mortalidad global aceptable.

ABSTRACT Background : We conducted a multicenter registry to analyze the diagnostic and therapeutic approach to all types of acute coronary syndromes; this registry is the first to provide detailed information on conditions without significant epicardial coronary artery disease. Knowing the reality of current medical practice is important to find opportunities for improvement. Methods : Patients hospitalized for acute coronary syndrome between January and August 2022 in 15 centers of Argentina, with high-sensitivity cardiac troponin, coronary care unit, and catheterization laboratory available 24 hours, were prospectively recorded. Results : A total of 984 consecutive patients were included, 22.2% with unstable angina, 39.1% with non-ST-segment elevation myocardial infarction (NSTEMI) and 24.1% with ST-segment elevation myocardial infarction (STEMI). Additionally, 4.1% presented as type 2 AMI, 1.2% as myocarditis, 0.7% as Takotsubo syndrome and 8.6% as myocardial infarction with non-obstructive coronary arteries (MINOCA). Median age was 66 years [interquartile range (IQR) 56.5-74] and 75.3% were men. An early invasive management was used in 84% of patients without ST segment elevation, and 76.5% of them had significant coronary artery disease. During hospitalization, 2.84% of the patients presented reinfarction, 2.43% recurrent angina, 2% postinfarction angina and 0.5% stent thrombosis. Bleeding events occurred in 4.4% of the patients, and overall in-hospital mortality was 3.76%. Conclusions : The registry has a good representation of the spectrum of patients with initial suspicion of "acute coronary syndrome", managed in centers with an invasive initial strategy and with low rate of in-hospital complications and acceptable overall mortality.

A single-step, rapid, and versatile method for simultaneous detection of cell surface glycan profiles using fluorochrome-conjugated lectins.

Cell surface glycans play essential roles in diverse physiological and pathological processes and their assessment has important implications in biomedicine and biotechnology. Here we present a rapid, versatile, and single-step multicolor flow cytometry method for evaluation of cell surface glycan signatures using a panel of selected fluorochrome-conjugated lectins. This procedure allows simultaneous detection of cell surface glycans with a 10-fold reduction in the number of cells required compared with traditional multistep lectin staining methods. Interestingly, we used this one-step lectin array coupled with dimension reduction algorithms in a proof-of-concept application for discrimination among different tumor and immune cell populations. Moreover, this procedure was also able to unveil T-, B-, and myeloid cell subclusters exhibiting differential glycophenotypes. Thus, we report a rapid and versatile lectin cytometry method to simultaneously detect a particular repertoire of surface glycans on living cells that can be easily implemented in different laboratories and core facilities.

Why do patients with antiphospholipid syndrome bleed? A clinical paradox.

Although worldwide-known criteria of antiphospholipid syndrome include thrombotic and obstetric events, a moderate number of patients manifest with bleeding episodes during course of the disease, which is typically attributed to the long-term anticoagulation. However, these haemorrhagic manifestations sometimes are part of pathophysiological changes that might occur secondary to the disease that involves endothelial activation, platelets dysfunction and blood clot factors misfunction. Recognizing these mechanisms of bleeding is crucial not only due to the need of treatment change or adding, but also because of changes in the disease' prognosis. In this review, we attempted to explain those complications, from its mechanism to a treatment approach, in order for physicians to be able to recognize patients with antiphospholipid syndrome and haemorrhagic manifestations, and to understand that, beyond over-anticoagulation, there are some other mechanisms that can trigger this complication and thus carry out a better diagnostic and therapeutic approach.

High-throughput screening method for discovering CatSper inhibitors using membrane depolarization caused by external calcium chelation and fluorescent cell barcoding.

The exclusive expression of CatSper in sperm and its critical role in sperm function makes this channel an attractive target for contraception. The strategy of blocking CatSper as a male, non-hormonal contraceptive has not been fully explored due to the lack of robust screening methods to discover novel and specific inhibitors. The reason for this lack of appropriate methodology is the structural and functional complexity of this channel. We have developed a high-throughput method to screen drugs with the capacity to block CatSper in mammalian sperm. The assay is based on removing external free divalent cations by chelation, inducing CatSper to efficiently conduct monovalent cations. Since Na+ is highly concentrated in the extracellular milieu, a sudden influx depolarizes the cell. Using CatSper1 KO sperm we demonstrated that this depolarization depends on CatSper function. A membrane potential (Em) assay was combined with fluorescent cell barcoding (FCB), enabling higher throughput flow cytometry based on unique fluorescent signatures of different sperm samples. These differentially labeled samples incubated in distinct experimental conditions can be combined into one tube for simultaneous acquisition. In this way, acquisition times are highly reduced, which is essential to perform larger screening experiments for drug discovery using live cells. Altogether, a simple strategy for assessing CatSper was validated, and this assay was used to develop a high-throughput drug screening for new CatSper blockers.

No seroconversion among healthcare workers exposed to SARS-CoV-2 during the early phase of the pandemic / Ausencia de seroconversión en trabajadores de la salud expuestos a SARS-CoV-2 durante la primera fase de la pandemia

BACKGROUND: The SARS-CoV-2 pandemic is associated with morbidity, hospitalizations, absenteeism, and mortality among healthcare workers (HCW). AIM: To evaluate the seroconversion rate in HCW exposed to SARS-CoV-2 in the early pandemic phase in 2020 at a regional reference hospital. MATERIAL AND METHODS: One hundred seventy-nine HCW working at a regional hospital were invited to a longitudinal study performed between April-July 2020. A serological analysis by ELISA IgG for viral nucleoprotein and protein S with a secondary analysis by ELISA IgG protein S1/S2 for samples with positive or doubtful result was carried out together with a complementary online survey to inquire about occupational or community exposures to SARS-CoV-2. RESULTS: Two cases with baseline infection were detected (1.1%, one symptomatic and one asymptomatic) and no cases of seroconversion were detected. During the study period, there were 136 patients hospitalized with COVID-19, and regional weekly COVID-19 incidence ranged from 2.7 to 24.4 per 100,000 inhabitants. No SARS-CoV-2 cases were detected by PCR among 27 HCW who consulted for respiratory symptoms in the period. Online surveys confirmed direct care of COVID-19 patients and also detected a high degree of unprotected social interaction at work. CONCLUSIONS: There was no evidence of seroconversion in this group of HCW exposed to the risk of infection by SARS-CoV-2 during the onset of the COVID-19 pandemic. Personal protective equipment and other measures used by the HCW were extremely useful for their protection in the initial phase of the pandemic.

ANTECEDENTES: La pandemia de SARS-CoV-2 está asociada a morbilidad, hospitalizaciones, ausentismo y mortalidad entre el personal de salud (PS). OBJETIVO: Evaluar la tasa de seroconversión en el PS expuesto al SARS-CoV-2 en la fase pandémica inicial el 2020 en un hospital regional de referencia. MATERIAL Y MÉTODOS: Ciento setenta y nueve trabajadores de la salud fueron invitados a un estudio longitudinal realizado entre abril-julio de 2020. Se efectuó un análisis serológico por ELISA IgG para nucleoproteína viral y proteína S con un análisis secundario por ELISA IgG proteína S1 / S2 para muestras con resultado positivo o dudoso junto a encuestas complementarias en línea para preguntar sobre exposiciones ocupacionales o comunitarias al SARS-CoV-2. RESULTADOS: Se detectaron dos casos con infección basal (1,1%, uno sintomático y uno asintomático) sin casos de seroconversión. Durante el período de estudio, hubo 136 pacientes hospitalizados con COVID-19, y la incidencia semanal regional de COVID-19 osciló entre 2,7 y 24,4 por 100.000 habitantes. No se detectaron casos de SARS-CoV-2 por PCR entre los 27 funcionarios que consultaron por síntomas respiratorios en este período. Las encuestas en línea confirmaron la atención directa de los pacientes con COVID-19 y también detectaron un alto grado de interacción social desprotegida en el trabajo. CONCLUSIONES: No hubo evidencia de seroconversión en un grupo de funcionarios expuestos al riesgo de infección por SARS-CoV-2 durante el inicio de la pandemia de COVID-19. Los equipos de protección personal y otras medidas utilizadas por el PS fueron de suma utilidad para su protección en la fase inicial de la pandemia.

Galectin-7 reprograms skin carcinogenesis by fostering innate immune evasive programs.

Non-melanoma skin cancer (NMSC) has risen dramatically as a result of chronic exposure to sunlight ultraviolet (UV) radiation, climatic changes and clinical conditions associated with immunosuppression. In spite of considerable progress, our understanding of the mechanisms that control NMSC development and their associated molecular and immunological landscapes is still limited. Here we demonstrated a critical role for galectin-7 (Gal-7), a ß-galactoside-binding protein preferentially expressed in skin tissue, during NMSC development. Transgenic mice (Tg46) overexpressing Gal-7 in keratinocytes showed higher number of papillomas compared to WT mice or mice lacking Gal-7 (Lgals7-/-) when subjected to a skin carcinogenesis protocol, in which tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA) and tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were sequentially administered. RNAseq analysis of Tg46 tumor lesions revealed a unique profile compatible with cells of the myelomonocytic lineage infiltrating these tumors, an effect that was substantiated by a higher number of CD11b+Gr1+ cells in tumor-draining lymph nodes. Heightened c-Met activation and Cxcl-1 expression in Tg46 lesions suggested a contribution of this pathway to the recruitment of these cells. Remarkably, Gal-7 bound to the surface of CD11b+Ly6ChiLy6Glo monocytic myeloid cells and enhanced their immunosuppressive activity, as evidenced by increased IL-10 and TGF-ß1 secretion, and higher T-cell inhibitory activity. In vivo, carcinogen-treated Lgals7-/- animals adoptively transferred with Gal-7-conditioned monocytic myeloid cells developed higher number of papillomas, whereas depletion of these cells in Tg46-treated mice led to reduction in the number of tumors. Finally, human NMSC biopsies showed increased LGALS7 mRNA and Gal-7 protein expression and displayed transcriptional profiles associated with myeloid programs, accompanied by elevated CXCL1 expression and c-Met activation. Thus, Gal-7 emerges as a critical mediator of skin carcinogenesis and a potential therapeutic target in human NMSC.

[Associating prognostic factors with clinical results in locally advanced breast cancer]. / Asociando factores pronósticos con resultados clínicos en cáncer de mama localmente avanzado.

Background: Breast cancer is the most frequent malignant tumor in women. Objective: To identify clinico-pathological and molecular markers as predictors of survival in patients with locally advanced breast cancer (LABC). Methods: Retrospective and observational study. The clinical factors of clinico-pathological and molecular predictors in relation with overall survival (OS) were assessed by the survival function, baseline hazard with smoothing and Cox regression. Results: 126 patients were assessed. OS at five years was significantly superior in patients with clinical stage IIIA (87%; p < 0.001), grade 2 tumor (81%; p < 0.001), pathological node stage (ypN0: 90%; p < .001), low-risk Nottingham prognostic index (86%; p < 0.001) and luminal A subtype (88%; p = 0.022). Baseline hazard with smoothing exhibited an increase in the mortality rate at 50 months for the luminal B/ HER2+ subtype compared with other subtypes. The multivariate analysis ascertained that the stage ypN2-3 (hazard ratio [HR] = 7.3; 95% confidence interval [95% CI]: 2.2 to 23.9) and the HER2+ nonluminal (HR = 7.8; 95% CI: 2 to 29.6) and triple negative (HR = 5.4; 95% CI: 1.7 to 17.2) subtypes were associated with a poor OS. Conclusions: The comprehensive evaluation of the molecular marker and clinico-pathological factors provides more accurate predictive and prognostic information. The nodal stage and molecular subtype are suitable clinical parameters on survival for LABC patients.

Introducción: el cáncer de mama es el tumor maligno más frecuente en las mujeres. Objetivo: identificar marcadores clínico-patológicos y moleculares como predictores de la supervivencia en pacientes con cáncer de mama localmente avanzado (CMLA). Material y métodos: estudio retrospectivo y observacional. Los factores clínico-patológicos y moleculares fueron evaluados en relación con la supervivencia global (SG) mediante la función de supervivencia, riesgo basal con suavizamiento y regresión de Cox. Resultados: 126 pacientes fueron evaluadas. La SG a cinco años fue significativamente superior en pacientes con estadio clínico IIIA (87%; p < 0.001), tumor de grado 2 (81%; p < 0.001), ausencia de ganglios patológicos (ypN0: 90%; p < 0.001) y en el subtipo luminal A (88%; p = 0.022). El riesgo basal con suavizamiento exhibió un incremento en la tasa de mortalidad a los 50 meses para el subtipo luminal B/ HER2+ comparado con los otros subtipos. En el análisis multivariado, el estadio ypN2-3 (razón de riesgo [RR] = 7.3; intervalo de confianza del 95% [IC 95%]: 2.2 a 23.9) y los subtipos HER2+ (RR = 7.8; IC 95%: 2 a 29.6) y triple negativo (RR= 5.4; IC 95%: 1.7 a 17.2) se asociaron con una pobre SG. Conclusiones: la evaluación integral del marcador molecular y de los factores clínico-patológicos proporciona información predictiva y pronóstica más precisa. El estadio ganglionar y subtipo molecular son parámetros adecuados con un impacto pronóstico en la SG para las pacientes con CMLA.

Tumor-Experienced Human NK Cells Express High Levels of PD-L1 and Inhibit CD8+ T Cell Proliferation.

Natural Killer (NK) cells play a key role in cancer immunosurveillance. However, NK cells from cancer patients display an altered phenotype and impaired effector functions. In addition, evidence of a regulatory role for NK cells is emerging in diverse models of viral infection, transplantation, and autoimmunity. Here, we analyzed clear cell renal cell carcinoma (ccRCC) datasets from The Cancer Genome Atlas (TCGA) and observed that a higher expression of NK cell signature genes is associated with reduced survival. Analysis of fresh tumor samples from ccRCC patients unraveled the presence of a high frequency of tumor-infiltrating PD-L1+ NK cells, suggesting that these NK cells might exhibit immunoregulatory functions. In vitro, PD-L1 expression was induced on NK cells from healthy donors (HD) upon direct tumor cell recognition through NKG2D and was further up-regulated by monocyte-derived IL-18. Moreover, in vitro generated PD-L1hi NK cells displayed an activated phenotype and enhanced effector functions compared to PD-L1- NK cells, but simultaneously, they directly inhibited CD8+ T cell proliferation in a PD-L1-dependent manner. Our results suggest that tumors might drive the development of PD-L1-expressing NK cells that acquire immunoregulatory functions in humans. Hence, rational manipulation of these regulatory cells emerges as a possibility that may lead to improved anti-tumor immunity in cancer patients.

[A functional platform to monitor SARS-CoV-2-specific T cell responses in vaccinated individuals and COVID-19 recovered patients]. / COVID-T: Una plataforma funcional para monitorear la respuesta de linfocitos T específicos de SARS-CoV-2 en individuos vacunados y recuperados de COVID-19.

The rapid spread of the SARS-CoV-2, the causative agent of the emergent pandemic disease COVID-19, requires the urgent commitment of the immunology community to understand the adaptive immune response developed by COVID-19 convalescent patients and individuals vaccinated with different strategies and schemes, with the ultimate goal of implementing and optimizing health care and prevention policies. Currently, assessment of SARS-CoV-2-specific immunity is mainly focused on the measurement of the antibody titers and analysis of their neutralizing capacity. However, a considerable proportion of individuals lack humoral responses or show a progressive decline of SARS-CoV-2-specific neutralizing antibodies. In order to study the cellular response of convalescent patients and vaccinated individuals, we have developed the "COVID-T Platform", an optimized strategy to study SARS-CoV-2-specific T cell responses. This platform allows assessment of the nature, magnitude and persistence of antigen-specific T-cell immunity in COVID-19-convalescent patients and vaccinated individuals. Moreover, it gives the opportunity to study cellular responses against emerging coronavirus variants and to identify individuals with cross-reactive immunity against seasonal coronaviruses.

La rápida propagación del coronavirus SARS-CoV-2, agente causal de la enfermedad pandémica emergente COVID-19 y sus nuevas variantes, requiere del compromiso de la comunidad inmunológica para comprender la magnitud y naturaleza de la respuesta inmunológica adaptativa desarrollada por pacientes recuperados de COVID-19 e individuos vacunados con diferentes estrategias y protocolos, a los fines de implementar nuevas políticas sanitarias. En la actualidad, la determinación de la inmunidad contra SARS-CoV-2 se basa principalmente en la detección de anticuerpos específicos y la determinación de su actividad neutralizante. Sin embargo, a pesar de la alta sensibilidad de estos ensayos, un número considerable de pacientes e individuos vacunados carecen de respuesta humoral detectable, o evidencian una disminución rápida de la misma en el tiempo. Con el objetivo de estudiar la respuesta inmune celular desencadenada frente a SARS-CoV-2, en nuestro laboratorio desarrollamos la "Plataforma COVID-T" estrategia integral optimizada dirigida a caracterizar y monitorear la respuesta de linfocitos T específicos de SARS-CoV-2 a partir de muestras de sangre de individuos vacunados y/o recuperados de COVID-19. Esta plataforma permite evaluar la naturaleza, magnitud y persistencia de la inmunidad celular T generada tanto por la infección con SARS-CoV-2, como por distintos esquemas y protocolos de vacunación en diferentes poblaciones de individuos. Asimismo, permite evaluar la respuesta inmunológica T generada frente a nuevas variantes del virus e identificar individuos sanos resistentes a SARS-CoV-2 con inmunidad pre-existente hacia coronavirus estacionales.

COVID-T: una plataforma funcional para monitorear la respuesta de linfocitos t específicos de SARS-COV-2 en individuos vacunados y recuperados de COVID-19 / COVID-T: A functional platform to monitor SARS-CoV-2-specific T cell responses in vaccinated individuals and COVID-19 recovered patients

Resumen La rápida propagación del coronavirus SARS-CoV-2, agente causal de la enfermedad pandémica emergente COVID-19 y sus nuevas variantes, requiere del compromiso de la comunidad inmunológica para comprender la magnitud y naturaleza de la respuesta inmunológica adaptativa desarrollada por pacientes recuperados de COVID-19 e individuos vacunados con diferentes estrategias y protocolos, a los fines de imple mentar nuevas políticas sanitarias. En la actualidad, la determinación de la inmunidad contra SARS-CoV-2 se basa principalmente en la detección de anticuerpos específicos y la determinación de su actividad neutralizante. Sin embargo, a pesar de la alta sensibilidad de estos ensayos, un número considerable de pacientes e indivi duos vacunados carecen de respuesta humoral detectable, o evidencian una disminución rápida de la misma en el tiempo. Con el objetivo de estudiar la respuesta inmune celular desencadenada frente a SARS-CoV-2, en nuestro laboratorio desarrollamos la "Plataforma COVID-T" estrategia integral optimizada dirigida a caracte rizar y monitorear la respuesta de linfocitos T específicos de SARS-CoV-2 a partir de muestras de sangre de individuos vacunados y/o recuperados de COVID-19. Esta plataforma permite evaluar la naturaleza, magnitud y persistencia de la inmunidad celular T generada tanto por la infección con SARS-CoV-2, como por distintos esquemas y protocolos de vacunación en diferentes poblaciones de individuos. Asimismo, permite evaluar la respuesta inmunológica T generada frente a nuevas variantes del virus e identificar individuos sanos resistentes a SARS-CoV-2 con inmunidad pre-existente hacia coronavirus estacionales.

Abstract The rapid spread of the SARS-CoV-2, the caus ative agent of the emergent pandemic disease COVID-19, requires the urgent commitment of the immunology community to understand the adaptive immune response developed by COVID-19 convalescent patients and individuals vaccinated with different strategies and schemes, with the ultimate goal of implementing and optimizing health care and prevention policies. Currently, assessment of SARS-CoV-2-specific immunity is mainly focused on the measurement of the antibody titers and analysis of their neutralizing capacity. However, a considerable proportion of individuals lack humoral responses or show a progressive decline of SARS-CoV-2-specific neutral izing antibodies. In order to study the cellular response of convalescent patients and vaccinated individuals, we have developed the 'COVID-T Platform', an optimized strategy to study SARS-CoV-2-specific T cell responses. This platform allows assessment of the nature, magnitude and persistence of antigen-specific T-cell immunity in COVID-19-convalescent patients and vaccinated individuals. Moreover, it gives the opportunity to study cellular responses against emerging coronavirus variants and to identify individuals with cross-reactive immunity against seasonal coronaviruses.

Explicit and implicit markers of fairness preeminence in criminal judges.

Achieving justice could be considered a complex social decision-making scenario. Despite the relevance of social decisions for legal contexts, these processes have still not been explored for individuals who work as criminal judges dispensing justice. To bridge the gap, we used a complex social decision-making task (Ultimatum game) and tracked a heart rate variability measurement: the square root of the mean squared differences of successive NN intervals (RMSSD) at their baseline (as an implicit measurement that tracks emotion regulation behavior) for criminal judges (n = 24) and a control group (n = 27). Our results revealed that, compared to controls, judges were slower and rejected a bigger proportion of unfair offers. Moreover, the rate of rejections and the reaction times were predicted by higher RMSSD scores for the judges. This study provides evidence about the impact of legal background and expertise in complex social decision-making. Our results contribute to understanding how expertise can shape criminal judges' social behaviors and pave the way for promising new research into the cognitive and physiological factors associated with social decision-making.