Hepatocytes coordinate immune evasion in cancer via release of serum amyloid A proteins.

T cell infiltration into tumors is a favorable prognostic feature, but most solid tumors lack productive T cell responses. Mechanisms that coordinate T cell exclusion are incompletely understood. Here we identify hepatocyte activation via interleukin-6/STAT3 and secretion of serum amyloid A (SAA) proteins 1 and 2 as important regulators of T cell surveillance of extrahepatic tumors. Loss of STAT3 in hepatocytes or SAA remodeled the tumor microenvironment with infiltration by CD8+ T cells, while interleukin-6 overexpression in hepatocytes and SAA signaling via Toll-like receptor 2 reduced the number of intratumoral dendritic cells and, in doing so, inhibited T cell tumor infiltration. Genetic ablation of SAA enhanced survival after tumor resection in a T cell-dependent manner. Likewise, in individuals with pancreatic ductal adenocarcinoma, long-term survivors after surgery demonstrated lower serum SAA levels than short-term survivors. Taken together, these data define a fundamental link between liver and tumor immunobiology wherein hepatocytes govern productive T cell surveillance in cancer.

Menarcheal experience, beliefs about and attitudes toward menstruation in Mexico: Changes in the last 20 years.

We explored how menarcheal experiences and attitudes toward menstruation of Mexican adolescents have changed in the last 20 years. Two questionnaires were applied to female adolescent students, and the results were compared with those obtained in 2002-3 when adolescents of the same ages were surveyed using the same questionnaires. Although some aspects of menstrual education have not changed, the secrecy surrounding menstruation has diminished. In contrast, the belief that menstruation is disabling and keeps women from their normal activities has increased. It is important that adolescents receive adequate preparation about psychosocial and physical aspects of the menstrual cycle.

Multimodal immune phenotyping reveals microbial-T cell interactions that shape pancreatic cancer.

Microbes are an integral component of the tumor microenvironment. However, determinants of microbial presence remain ill-defined. Here, using spatial-profiling technologies, we show that bacterial and immune cell heterogeneity are spatially coupled. Mouse models of pancreatic cancer recapitulate the immune-microbial spatial coupling seen in humans. Distinct intra-tumoral niches are defined by T cells, with T cell-enriched and T cell-poor regions displaying unique bacterial communities that are associated with immunologically active and quiescent phenotypes, respectively, but are independent of the gut microbiome. Depletion of intra-tumoral bacteria slows tumor growth in T cell-poor tumors and alters the phenotype and presence of myeloid and B cells in T cell-enriched tumors but does not affect T cell infiltration. In contrast, T cell depletion disrupts the immunological state of tumors and reduces intra-tumoral bacteria. Our results establish a coupling between microbes and T cells in cancer wherein spatially defined immune-microbial communities differentially influence tumor biology.

Printability of Nixtamalized Corn Dough during Screw-Based Three-Dimensional Food Printing.

This study aimed to analyze the printability of corn-based dough during screw-based three-dimensional (3D) food printing (3DFP) by relating its rheological and mechanical properties to its screw-based 3DFP performance, with the objective of providing insights into the utilization of corn-based dough to produce 3D-printed foods. Screw-based 3DFP was performed using seven corn-based doughs with different nixtamalized corn flour (NCF) and water contents. Afterward, their rheological and mechanical properties were analyzed and associated with their screw-based 3DFP performance. The results showed that stable printability was obtained within a specific range of NCF content in the dough (30-32.5 wt%). Below this range, the 3D-printed foods flattened, while above it, the extrudability of the dough was affected. The printability of the dough was influenced by different rheological and mechanical properties, depending on the stage of the screw-based 3DFP process. During the extrusion stage, the loss tangent at nozzle strain, yield stress, apparent viscosity, and adhesiveness mainly affected the extrudability of the dough. In contrast, the loss tangent at minimum strain, elastic modulus, Young's modulus, and hardness influenced the self-supporting stage. Therefore, it is important to find a balance between all of these properties, where stable extrudability and self-supporting of the 3D structure are achieved.

Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1.

Myeloid cells facilitate T cell immune evasion in cancer yet are pliable and have antitumor potential. Here, by cotargeting myeloid activation molecules, we leveraged the myeloid compartment as a therapeutic vulnerability in mouse models of pancreatic cancer. Myeloid cells in solid tumors expressed activation receptors including the pattern recognition receptor Dectin-1 and the TNF receptor superfamily member CD40. In mouse models of checkpoint inhibitor-resistant pancreatic cancer, coactivation of Dectin-1, via systemic ß-glucan therapy, and CD40, with agonist antibody treatment, eradicated established tumors and induced immunological memory. Antitumor activity was dependent on cDC1s and T cells but did not require classical T cell-mediated cytotoxicity or blockade of checkpoint molecules. Rather, targeting CD40 drove T cell-mediated IFN-γ signaling, which converged with Dectin-1 activation to program distinct macrophage subsets to facilitate tumor responses. Thus, productive cancer immune surveillance in pancreatic tumors resistant to checkpoint inhibition can be invoked by coactivation of complementary myeloid signaling pathways.

First, do no harm: why anti-immigrant policies in the United States are a public health concern.

It can be argued that anti-immigrant policies, such as the 287(g) program, can have a direct impact on the health and well-being of the immigrant community in general, particularly undocumented immigrants in the United States. While there is yet to be a comprehensive and conclusive empirical assessment of this issue, what is known is that the immigrant community faces many stress factors and structural barriers that negatively impact health. We argue that it is urgent that public health responds to the unique experiences and challenges of the undocumented and wider immigrant community. In doing so, we propose three recommendations for addressing this issue: (1) Assess the causal relationship between anti-immigration policies and immigrant health, (2) Increase funding and access to health care services for immigrant communities in jurisdictions implementing anti-immigrant policies, and (3) For public health to engage in a conscious effort to service the undocumented immigrant community. Even though we focus specifically on the United States, our recommendations are applicable on a global scale since anti-immigration policies are prevalent across nations and are a pervasive human rights issue around the world.

Risk and protective factors related to alcohol and drug use amongst American Indian youth: An application of the social development model.

The goal of this study is to assess the relevance of the Social Development Model (SDM) in predicting substance use across American Indian (AI) youth. We rely on self-reported data collected as part of the 2004 Arizona Youth Survey (AYS). The final sample included 2,912 AI students from 169 schools in 15 counties. Results indicate relatively high levels of alcohol and drug use amongst AI youth. Overall, we find the SDM as a promising framework for identifying risk factors associated with the increased likelihood of alcohol and drug use amongst AI youth.

TNF blockade uncouples toxicity from antitumor efficacy induced with CD40 chemoimmunotherapy.

Agonist CD40 antibodies are under clinical development in combination with chemotherapy as an approach to prime for antitumor T cell immunity. However, treatment with anti-CD40 is commonly accompanied by both systemic cytokine release and liver transaminase elevations, which together account for the most common dose-limiting toxicities. Moreover, anti-CD40 treatment increases the potential for chemotherapy-induced hepatotoxicity. Here, we report a mechanistic link between cytokine release and hepatotoxicity induced by anti-CD40 when combined with chemotherapy and show that toxicity can be suppressed without impairing therapeutic efficacy. We demonstrate in mice and humans that anti-CD40 triggers transient hepatotoxicity marked by increased serum transaminase levels. In doing so, anti-CD40 sensitizes the liver to drug-induced toxicity. Unexpectedly, this biology is not blocked by the depletion of multiple myeloid cell subsets, including macrophages, inflammatory monocytes, and granulocytes. Transcriptional profiling of the liver after anti-CD40 revealed activation of multiple cytokine pathways including TNF and IL-6. Neutralization of TNF, but not IL-6, prevented sensitization of the liver to hepatotoxicity induced with anti-CD40 in combination with chemotherapy without impacting antitumor efficacy. Our findings reveal a clinically feasible approach to mitigate toxicity without impairing efficacy in the use of agonist CD40 antibodies for cancer immunotherapy.

Systemic inflammation is a determinant of outcomes of CD40 agonist-based therapy in pancreatic cancer patients.

Agonistic anti-CD40 monoclonal antibody (mAb) therapy in combination with chemotherapy (chemoimmunotherapy) shows promise for the treatment of pancreatic ductal adenocarcinoma (PDA). To gain insight into immunological mechanisms of response and resistance to chemoimmunotherapy, we analyzed blood samples from patients (n = 22) with advanced PDA treated with an anti-CD40 mAb (CP-870,893) in combination with gemcitabine. We found a stereotyped cellular response to chemoimmunotherapy characterized by transient B cell, CD56+CD11c+HLA-DR+CD141+ cell, and monocyte depletion and CD4+ T cell activation. However, these cellular pharmacodynamics did not associate with outcomes. In contrast, we identified an inflammatory network in the peripheral blood consisting of neutrophils, cytokines (IL-6 and IL-8), and acute phase reactants (C-reactive protein and serum amyloid A) that was associated with outcomes. Furthermore, monocytes from patients with elevated plasma IL-6 and IL-8 showed distinct transcriptional profiles, including upregulation of CCR2 and GAS6, genes associated with regulation of leukocyte chemotaxis and response to inflammation. Patients with systemic inflammation, defined by neutrophil/lymphocyte ratio (NLR) greater than 3.1, had a shorter median overall survival (5.8 vs. 12.3 months) as compared with patients with NLR less than 3.1. Taken together, our findings identify systemic inflammation as a potential resistance mechanism to a CD40-based chemoimmunotherapy and suggest biomarkers for future studies.

Publisher Correction: Science diplomacy for plant health.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Necrotizing cellulitis due to Rhizopus arrhizus in an extremely premature infant.

We report an extremely premature infant with necrotizing cellulitis. After minor trauma to the left arm when removing an adhesive sensor, patient developed rapidly progressive cellulitis, which evolved into a necrotic ulcer. Microbiological studies (mass spectroscopy and molecular assay) identified Rhizopus arrhizus as the responsible fungus.

Adherencia a las buenas prácticas de transfusión, observada en el personal de enfermería del Hospital Pediátrico Baca Ortiz / Adherence to good transfusion practices, observed in the nursing staff of the Baca Ortiz Pediatric Hospital

Contexto: el personal de enfermería cumple un rol fundamental en el proceso transfusional; el nivel de conocimientos debe ser periódicamente evaluado a fin de garantizar una buena práctica transfusional. Objetivo: evaluar el nivel de conocimientos que posee el personal de enfermería del Hospital Pediátrico Baca Ortiz (HPBO) previo y posterior a la intervención, frente a los procedimientos para solicitud, administración y monitoreo de los componentes sanguíneos. Sujetos y métodos: estudio no-experimental pre y post-evaluatorio en el personal de enfermería del Hospital Pediátrico Baca Ortiz de la ciudad de Quito. Se diseñó y aplicó una encuesta estructurada a los profesionales de enfermería del Hospital Pediátrico Baca Ortiz a través de la cual se evaluaron aspectos técnicos relativos a la práctica transfusional en lo relativo a solicitud, administración y monitoreo de los componentes sanguíneos. Resultados: la intervención se realizó en 176 profesionales, distribuidos en tres grupos de capacitación; se observó un incremento global del 14,27% en el puntaje post-intervención sobre 20 puntos, con una p<0,002, estadísticamente significativa. La pre-intervención demostró un menor porcentaje de respuestas correctas en lo referente a la toma y envío de muestras (45,2%). Al evaluar el impacto de la intervención se observó que en la etapa relativa a "recepción de hemocomponentes en el servicio hospitalario, verificación, condiciones de envío, validación del paciente y administración de la transfusión" paso del 67,7% al 79,06% de respuestas válidas con una diferencia porcentual de 11,3%. El área hospitalaria que mayor impacto tuvo fue consulta externa, desde un 22,2% de respuestas correctas en la etapa de pre-intervención y la de menor impacto fue el área quirúrgica con 14,15%. Conclusión: la pre-intervención evidenció debilidades y puntos de mejora en los conocimientos del personal de enfermería que fueron fortalecidos significativamente por la intervención realizada. La educación continua reviste utilidad y relevancia para mejorar percepciones y prácticas en medicina transfusional (AU)

Context: nurses play a fundamental role in the transfusion process; The level of knowledge should be periodically evaluated in order to guarantee good transfusion practice. Objective: to evaluate the level of knowledge held by the nursing staff of the Baca Ortiz Pediatric Hospital (HPBO) before and after the intervention, as opposed to the procedures for requesting, administering and monitoring the blood components. Subjects and methods: pre and post-evaluation non-experimental study in the nursing staff of the Baca Ortiz Pediatric Hospital in the city of Quito. A structured survey was designed and applied to the nursing professionals of the Baca Ortiz Pediatric Hospital through which technical aspects related to the transfusion practice regarding the application, administration and monitoring of the blood components were evaluated. Results: the intervention was carried out in 176 professionals, divided into three training groups; an overall increase of 14.27% was observed in the post-intervention score over 20 points, with p <0.002, statistically significant. The pre-intervention showed a lower percentage of correct answers regarding the taking and sending of samples (45.2%). When evaluating the impact of the intervention it was observed that in the stage relative to "reception of blood components in the hospital service, verification, delivery conditions, patient validation and administration of the transfusion" step from 67.7% to 79.06% of valid answers with a percentage difference of 11.3%. The hospital area that had the greatest impact was external consultation, from 22.2% of correct responses in the pre-intervention stage and the one with the least impact was the surgical area with 14.15%. Conclusion: the pre-intervention showed weaknesses and points of improvement in the knowledge of the nursing staff that were significantly strengthened by the intervention performed. Continuing education has utility and relevance to improve perceptions and practices in transfusion medicine. (AU)