Visualization of Lipid Droplets in the Alveolar Macrophage Cell Line MH-S with Live-cell Imaging by 3D Holotomographic Microscopy (Nanolive)

Lipid droplets (LD), triglycerides and sterol esters among them, are well known for their capacity as lipid storage organelles. Recently, they have emerged as critical cytoplasmic structures involved in numerous biological functions. LD storage is generated de novo by the cell and provides an energy reserve, lipid precursors, and cell protection. Moreover, LD accumulation can be observed in some pathologies as obesity, atherosclerosis, or lung diseases. Fluorescence imaging techniques are the most widely used techniques to visualize cellular compartments in live cells, including LD. Nevertheless, presence of fluorophores can damage subcellular components and induce cytotoxicity, or even alter the dynamics of the organelles. As an alternative to fluorescence microscopy, label-free techniques such as stimulated Raman scattering and coherent anti-stokes Raman scattering microscopy offer a solution to avoid the undesirable effects caused by dyes and fluorescent proteins, but are expensive and complex. Here, we describe a label-free method using live-cell imaging by 3D holotomographic microscopy (Nanolive) to visualize LD accumulation in the MH-S alveolar macrophage cell line after treatment with oleic acid, a monounsaturated fatty acid that promotes lipid accumulation.We are grateful to Instituto de Salud Carlos III for financial support to S.H.(PI20CIII/00018). A. Pérez-Montero is supported by Comunidad de Madrid (PEJ-2020-AI/BMD-17651).S

La oncología radioterápica moderna: situación actual

En los últimos años, en España, se ha incrementado tanto la incidencia del cáncer como su mortalidad, hasta ocupar el segundo lugar tras las enfermedades cardiovasculares, a pesar de que con los métodos terapéuticos actuales pueden curarse la mitad de los pacientes con esta enfermedad. La Oncología Radioterápica es una especialidad médica dedicada a los aspectos diagnósticos, cuidados clínicos y terapéuticos del enfermo oncológico. Desde el descubrimiento de los rayos X y la radiactividad natural a finales del siglo XIX hasta la actualidad, esta especialidad ha experimentado un gran desarrollo tanto a nivel de avances tecnológicos como de incremento del índice terapéutico. A esto ha contribuido, en los últimos años, el mejor conocimiento de las bases moleculares del cáncer así como los progresos radiobiológicos. La radioterapia es un arma terapéutica fundamental en la curación de los tumores y que puede ser utilizada de forma exclusiva o asociada a otros tratamientos.In this article we present how to include a psychologist specialist on Oncology in a Service or cancer centre. We begin by describing Psycho-Oncology historical introduction in the United States and in Spain. Afterwards we trace the oncologist and psycho-oncologist point of view facing the multiple requests due the special characteristics of the illness. We continue defining the current model of inclusion of a Psycho-Oncologist on Oncology, called the Consultation Model. We describe our proposed model called Foundational Model, born in the MSKCC, New York. To conclude we explain the integration experience of a Psycho-Oncologist in an Oncology Unit that we have carried out in the Hospital Universitario Marqués de Valdecilla. According to our experience, the integration of the Psycho-Oncologist on Oncology medical teams is not only possible but also necessary and beneficent

Recovering and harmonizing research cruises information

The IEO has maintained since late 60s, a local database with basic information on oceanographic campaigns, formerly known as ROSCOF reports, which were established in the framework of IODE initiatives, as a low-level inventory for future access to data. Technological advances in recent decades and different coordination activities between NODCs have favored the implementation of these reports in standardized digital formats (Cruise Summary Reports, CSR) that allow their integration in international repositories as SeaDataNet or POGO. However, this inventory and cataloging activity has suffered ups and downs over 40 years of activity, changes in storage criteria and periods of less activity. In the search for a unique criterion that can last over time and that unifies this information as much as possible with the data generated in these campaigns, an exhaustive review of the existing information has been carried out

Recovering and harmonizing research cruises information

The IEO has maintained since late 60s, a local database with basic information on oceanographic campaigns, formerly known as ROSCOF reports, which were established in the framework of IODE initiatives, as a low-level inventory for future access to data. Technological advances in recent decades and different coordination activities between NODCs have favored the implementation of these reports in standardized digital formats (Cruise Summary Reports, CSR) that allow their integration in international repositories as SeaDataNet or POGO. However, this inventory and cataloging activity has suffered ups and downs over 40 years of activity, changes in storage criteria and periods of less activity. In the search for a unique criterion that can last over time and that unifies this information as much as possible with the data generated in these campaigns, an exhaustive review of the existing information has been carried out. The result has been the retrieval of information from short-term campaigns carried out on smaller vessels with great coastal activity, as well as updating information regarding old campaigns performed on the first half of the 20th century onboard of decommissioned vessels. All this is completed with the systematic campaigns carried out by INTECMAR in the Galician rias, research vessels operated by the national Fisheries Administration, and information on research surveys carried out by foreign ships in national waters, forming a catalog of more than 4000 entries. This approach is also followed by the UTM-CSIC, on its own-managed vessels and campaigns carried out since 1991. The common approach allows a unified response to the governmental needs for the planning of future campaigns, and in successive improvements in data recovering, archiving and accessing at NODC/CEDO

Impact of Early Interferon-β Treatment on the Prognosis of Patients with COVID-19 in the First Wave: A Post Hoc Analysis from a Multicenter Cohort

Background: Interferon-p is an attractive drug for repurposing and use in the treatment of COVID-19, based on its in vitro antiviral activity and the encouraging results from clinical trials. The aim of this study was to analyze the impact of early interferon-p treatment in patients admitted with COVID-19 during the first wave of the pandemic. Methods: This post hoc analysis of a COVID-19@Spain multicenter cohort included 3808 consecutive adult patients hospitalized with COVID-19 from 1 January to 17 March 2020. The primary endpoint was 30-day all-cause mortality, and the main exposure of interest was subcutaneous administration of interferon-beta, defined as early if started <= 3 days from admission. Multivariate logistic and Cox regression analyses were conducted to identify the associations of different variables with receiving early interferon-beta therapy and to assess its impact on 30-day mortality. A propensity score was calculated and used to both control for confounders and perform a matched cohort analysis. Results: Overall, 683 patients (17.9%) received early interferon-p therapy. These patients were more severely ill. Adjusted HR for mortality with early interferon-p was 1.03 (95% CI, 0.82-1.30) in the overall cohort, 0.96 (0.82-1.13) in the PS-matched subcohort, and 0.89 (0.60-1.32) when interferon-beta treatment was analyzed as a time-dependent variable. Conclusions: In this multicenter cohort of admitted COVID-19 patients, receiving early interferon-beta therapy after hospital admission did not show an association with lower mortality. Whether interferon-beta might be useful in the earlier stages of the disease or specific subgroups of patients requires further research

La sierra de Atapuerca durante el Holoceno: datos preliminares sobre las ocupaciones de la Edad del Bronce en la Cueva de El Mirador (Ibeas de Juarros, Burgos)

The paper presents data from the El Mirador cave, part of the Sierra de Atapuerca project. The data deriving from the first two stratigraphical excavation campaigns (1999 and 2000) are illustrated. A 2.5-m thick Holocene succession, containing Neolithic and Bronze Age occupations, was excavated and sampled using a multidisciplinary perspective. Preliminary data on the Bronze Age occupations indicate the utilization of the rock-shelter for various activities, among them animal stabling, habitation and burial. Animal stabling led to the accumulation of characteristic burnt layers, never seen before in the Meseta region or in wider European context. A Bronze Age collective burial showing evidence of pre-treatment of bodies before their deposition, and a stratified metal axe, were also found.Las excavaciones arqueológicas iniciadas en 1999 en la cueva de El Mirador de la sierra de Atapuerca han permitido documentar hasta el momento una sucesión estratigráfica holocena de unos 2,5 m de potencia, formada por niveles del Neolítico y de la Edad del Bronce. Los datos preliminares sobre las ocupaciones de la Edad del Bronce señalan el uso de la cueva como redil, zona de hábitat y espacio sepulcral. Durante su uso como redil se llevó a cabo la quema periódica del estiércol depositado en el interior del corral. Es la primera vez que dicha práctica se documenta en la Meseta y, en el ámbito europeo, en contexto geográfico continental. El uso como cueva sepulcral viene seña- lado por la presencia de una inhumación colectiva. Ésta presenta evidencias de un ritual relacionado con el tratamiento de los cadáveres previo a su enterramiento. Cabe subrayar también la presencia de una hacha de bronce de rebordes en contexto estratigráfico

IRE1α-XBP1 Activation Elicited by Viral Singled Stranded RNA via TLR8 May Modulate Lung Cytokine Induction in SARS-CoV-2 Pneumonia

Initial symptoms of COVID-19 infection depend on viral replication, while hyperinflammation is a hallmark of critical illness and may drive severe pneumonia and death. Among the mechanisms potentially involved in the hyperinflammatory state, we focused on the unfolded protein response, because the IRE1α-XBP1 branch can be activated as result of the endoplasmic reticulum stress produced by the overwhelming synthesis of viral components and synergizes with Toll-like receptor signaling to induce cytokine expression. Viral RNA may trigger the IRE1α-XBP1 branch via TLR7/8 activation and like TLR2 and TLR4 may underpin cytokine expression trough XBP1 splicing (sXBP1). The expression of IL1B, IL6, and TNF mRNA in bronchoalveolar aspirates (BAAs) were higher in COVID-19 patients under mechanical ventilation and intubation who showed sXBP1. The scrutiny of monocytic/macrophagic markers during active infection showed a reduction of those involved in antigen presentation and survival, as well as the IFN stimulated gene MX1. These changes reverted after infection tests turned negative. In contrast, the expression of the mRNA of the serine protease TMPRSS2 involved in S protein priming showed a high expression during active infection. TLR8 mRNA showed an overwhelming expression as compared to TLR7 mRNA, which suggests the presence of monocyte-derived dendritic cells (MDDCs). In vitro experiments in MDDCs activated with ssRNA40, a positive-sense, single-stranded RNA (+ssRNA) like SARS-CoV-2 RNA, induced sXBP1 and the expression of IL-1β, IL-6, and TNFα at mRNA and protein levels. These responses were blunted by the IRE1α ribonuclease inhibitor MKC8866. Given the analogies between the results observed in BAAs and the effects induced by +ssRNA in MDDCs, IRE1α ribonuclease inhibition might be a druggable target in severe COVID-19 disease.This study was funded by Fondo COVID-19 del Instituto de Salud Carlos III/Junta de Castilla y Leon (N.F.). European Commission-NextGenerationEU, through CSIC's Global Health Platform (PTI Salud Global) (project SGL2103016) (M.S.C.). Plan Nacional de Salud y Farmacia Grant SAF2017-83079-R and Grant PID2020-113751RB-I00 funded by MCIN/AEI/ 10.13039/501100011033 (M.S.C.). Junta de Castilla y Leon/Fondo Social Europeo Grants CSI035P17 (M.S.C.) and VA175P20 (N.F.). Proyecto SEAHORSE INFRARED: IR2020-1-UVA05 (JCyL).N

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Los restos faunísticos de El Pozuelo II (Miño de Medina, Soria)

Este capítulo está sujeto a una licencia CC BY-NC-ND 4.0.Peer reviewe