Oxygen Assessment in Tumors In Vivo Using Phosphorescence Lifetime Imaging Microscopy.

The oxygen level in a tumor is a crucial factor for its development and response to therapies. Phosphorescence lifetime imaging (PLIM) with the use of phosphorescent oxygen probes is a highly sensitive, noninvasive optical technique for the assessment of molecular oxygen in living cells and tissues. Here, we present a protocol for microscopic mapping of oxygen distribution in a mouse tumor model in vivo. We demonstrate that PLIM microscopy, in combination with an Ir(III)-based probe, enables visualization of cellular-level heterogeneity of tumor oxygenation.

Dosis de radiación por radiografías y factores asociados en neonatos de la Unidad de Recién Nacidos del Hospital Universitario San Ignacio, Bogotá, Colombia / X-ray radiation dose and associated factors in neonates from the newborn unit of Hospital Universitario San Ignacio, Bogotá, Colombia

Introducción. Las radiografías continúan usándose ampliamente, subestimando los riesgos. Esto sucede, especialmente, en las unidades de cuidado neonatal, lo que implica que los neonatos reciben una dosis de radiación ionizante mayor que los adultos. Objetivo. Cuantificar las dosis de radiación recibidas al tomar radiografías y evaluar los posibles factores asociados con el aumento de la dosis. Materiales y métodos. Se llevó a cabo un estudio observacional de 160 neonatos de la Unidad de Recién Nacidos del Hospital Universitario San Ignacio, Bogotá, Colombia. Se consideró como variable dependiente la dosis de entrada en piel por cada radiografía. Se hizo la caracterización de los pacientes, seguida de un análisis multivariado con regresión lineal múltiple para identificar factores asociados. Resultados. Se analizaron 160 pacientes y 492 radiografías en total. Entre los hallazgos más frecuentes, se encuentran: pacientes de sexo masculino (n=87; 54,4 %), nacimiento por cesárea (n=122; 76,3 %) e indicación de toma de radiografías por dificultad respiratoria (n=123; 24,9 %). El 1,8 % (n=9) de los pacientes no tenían una indicación para la toma de la radiografía. La radiografía más frecuente fue la de tórax (n=322; 65,4 %). La mayoría de las radiografías se tomaron con el equipo computarizado (n=352; 71,5 %) y no con el digital (n=140, 28,4 %). La mediana de la dosis de entrada en piel con el equipo computarizado fue de 0,112 mGy (0,022; 0,134 mGy) y, con el equipo digital, de 0,020 mGy (0,019, 0,022 mGy). Conclusiones. Se cuantificaron las dosis de radiación absorbida en neonatos, general y específica, con el equipo computarizado y el digital. Se identificaron mayores dosis con el equipo computarizado. Se reconoció la interacción entre el equipo computarizado con menores edades gestacionales corregidas como principal factor para el aumento de la dosis. Además, se reconoció la relación entre el equipo computarizado y una menor edad gestacional corregida, como principal factor para una mayor dosis.

Introduction. Radiographs are still widely used, underestimating the risks. This situation is frequent in neonatal care units, generating radiation doses than in adults. Objective. To quantify the received radiation doses when performing radiographs on neonates and the possible factors associated with higher doses. Materials and methods. We performed an observational study of 160 neonates from the newborn unit of the Hospital Universitario San Ignacio, Bogotá, Colombia. We considered the input dose of each radiograph as the dependent variable. Patients were characterized and a multivariate analysis with multiple linear regression was performed to identify associated factors. Results. We analyzed 160 newborns and 492 radiographs. The most frequent findings were male patients (n=87, 54.4%), cesarean delivery (n=122, 76.3%), and radiograph indication for respiratory distress (n=123, 24.9%). One-point eight percent of the patients (n=9) did not have radiograph indication. The most frequently taken radiograph was chest (322, 65.4%). Most radiographs were taken with a computerized equipment (n=352, 71.5%), compared to a digital one (n=140, 28.4%). The median input dose with computerized equipment was 0.112 mGy (0.022, 0.134 mGy), and with the digital equipment was 0.020 mGy (0.019, 0.022 mGy). Conclusions. The general and specific absorbed radiation doses were measured in neonates with a computerized and a digital equipment. We identified higher doses with the computerized equipment. In addition, it was recognized the correlation between computerized radiography equipment with lower corrected gestational ages as the main factor for dose increase.

Intervenções psicológicas necessárias: a prática como residente no serviço de medicina fetal / Necessary psychological interventions: the practice as a resident in the fetal medicine service / Intervenciones psicológicas necesarias: la práctica como residente en el servicio de medicina fetal

Com os avanços tecnológicos e o aprimoramento da prática médica via ultrassonografia, já é possível detectar possíveis problemas no feto desde a gestação. O objetivo deste estudo foi analisar a prática do psicólogo no contexto de gestações que envolvem riscos fetais. Trata-se de um estudo qualitativo sob formato de relato de experiência como psicólogo residente no Serviço de Medicina Fetal da Maternidade Escola da Universidade Federal do Rio de Janeiro (UFRJ). Os registros, feitos por observação participante e diário de campo, foram analisados em dois eixos temáticos: 1) intervenções psicológicas no trabalho em equipe em consulta de pré-natal, exame de ultrassonografia e procedimento de amniocentese; e 2) intervenções psicológicas em casos de bebês incompatíveis com a vida. Os resultados indicaram que o psicólogo nesse serviço é essencial para atuar de forma multiprofissional na assistência pré-natal para gravidezes de alto risco fetal. Ademais, a preceptoria do residente é relevante para sua formação e treinamento para atuação profissional no campo da psicologia perinatal.(AU)

Face to the technological advances and the improvement of medical practice via ultrasound, it is already possible to detect possible problems in the fetus since pregnancy. The objective of this study was to analyze the psychologist's practice in the context of pregnancies which involve fetal risks. It is a qualitative study based on an experience report as a psychologist trainee at the Fetal Medicine Service of the Maternity School of UFRJ. The records, based on the participant observation and field diary, were analyzed in two thematic axes: 1) psychological interventions in the teamwork in the prenatal attendance, ultrasound examination and amniocentesis procedure; and 2) psychological interventions in cases of babies incompatible to the life. The results indicated that the psychologist in this service is essential to work in a multidisciplinary way at the prenatal care for high fetal risk pregnancies. Furthermore, the resident's preceptorship is relevant to their education and training for professional performance in the field of Perinatal Psychology.(AU)

Con los avances tecnológicos y la mejora de la práctica médica a través de la ecografía, ya se puede detectar posibles problemas en el feto desde el embarazo. El objetivo de este estudio fue analizar la práctica del psicólogo en el contexto de embarazos de riesgos fetal. Es un estudio cualitativo basado en un relato de experiencia como residente de psicología en el Servicio de Medicina Fetal de la Escuela de Maternidad de la Universidade Federal do Rio de Janeiro (UFRJ). Los registros, realizados en la observación participante y el diario de campo, se analizaron en dos ejes temáticos: 1) intervenciones psicológicas en el trabajo en equipo, en la consulta prenatal, ecografía y los procedimientos de amniocentesis; y 2) intervenciones psicológicas en casos de bebés incompatibles con la vida. Los resultados señalaron como fundamental la presencia del psicólogo en este servicio trabajando de forma multidisciplinar en la atención prenatal en el contexto de embarazos de alto riesgo fetal. Además, la tutela del residente es relevante para su educación y formación para el desempeño profesional en el campo de la Psicología Perinatal.(AU)

Impact of photoinitiator quality on chemical-mechanical properties of dental adhesives under different light intensities / Impacto da qualidade de fotoiniciadores nas propriedades químico mecânicas de adesivos dentais sob diferentes intensidades de luz

Objective: Evaluate the mechanical properties of experimental adhesive models with different photoinitiators (PI) polymerized by LED units of different power densities. Material and Methods: Three groups of adhesive models based on HEMA/BisGMA (45/55) were prepared in association with different PI combinations: G2 (control) ­ 2 PI: 0.5% CQ, 0.5% EDMAB; G3 - 3 PI: 0.5% CQ; 0.5% DMAEMA, 0.5% DPIHP; G4 - 4 PI: 0.5% CQ; 0.5% EDMAB; 0.5% DMAEMA; 0.5% DPIHP. The three formulations were polymerized at two different LED power densities: 550 mW/cm2 and 1200 mW/cm2. The degree of conversion (DC) of adhesive monomers was monitored in situ through the FTIR for 600 s. Specimens were prepared for each formulation for analysis mong adhesive systems (G2

Objetivo: Avaliar as propriedades mecânicas de modelos adesivos experimentais com diferentes fotoiniciadores (PI) polimerizados por unidades de LED de diferentes densidades de energia. Material e Métodos: Três grupos de modelos adesivos baseados em HEMA/BisGMA (45/55) foram preparados em associação com diferentes combinações de PI: G2 (controle) ­ 2 PI: 0,5% CQ, 0,5% EDMAB; G3 - 3PI: 0,5% CQ; 0,5% DMAEMA, 0,5% DPIHP; G4 - 4 PI: 0,5% CQ; 0,5% EDMAB; 0,5% DMAEMA; 0,5% DPIHP. As três formulações foram polimerizadas em duas densidades de potência de LED: 550 mW/cm2 e 1200 mW/cm2. O grau de conversão (DC) dos monômeros adesivos foi monitorado in situ através do FTIR durante 600 s. Amostras foram preparadas para cada formulação para análise de resistência à flexão (FS), módulo de elasticidade (ME), sorção (SOR) e solubilidade (SOL). Os dados foram submetidos aos testes ANOVA 2-fatores e Tukey (5%). Resultados: DC: houve diferença significativa entre os sistemas adesivos (G2

Radiación y medios de contraste en embarazo y lactancia: lo que el clínico necesita saber / Radiation and contrast media in pregnancy and lactation: what the clinician needs to know

Introducción: el uso de técnicas de imagenología es habitual e incluso indispensable en algunos procesos diagnósticos. Sin embargo, su indicación en mujeres embarazadas y en período de lactancia es controvertida. Objetivo: presentar una revisión narrativa sobre los riesgos asociados al uso de imágenes con radiación y medio de contraste en embarazo y periodo de lactancia, con énfasis en las recomendaciones y aplicaciones clínicas que el médico tratante debe tener presente al momento de su indicación. Métodos: se realizó una revisión bibliográfica de la literatura relevante sobre los riesgos y consideraciones especiales del uso de medios de contraste en el embarazo y lactancia. Resultados: los riesgos de la radiación ionizante sobre el feto varían de acuerdo al estadio del embarazo, por lo que la indicación del estudio debe ponderar los riesgos y beneficios. En las dosis clínicas en embarazo y lactancia, el uso de contraste yodado como basados en gadolinio no tienen efectos deletéreos en la salud de la madre ni la del feto. Sin embargo, las sociedades internacionales recomiendan limitar su uso. Conclusión: si bien la indicación de estudios de imagen que utilizan radiación ionizante en el embarazo y lactancia es seguro, el médico clínico debe conocer los posibles riesgos de la radiación ionizante en este grupo de pacientes. Respecto a los medios de contraste, el único efecto adverso reportado es la disfunción tiroidea transitoria en hijos de madres que recibieron medios de contraste yodado.

Introduction: the use of imaging techniques is essential in some diagnostic processes. However, its indication in pregnant and lac-tating women is controversial. Objective: To present a narrative review of the risks associated with using images with radiation and contrast media in pregnancy and lactation. Emphasis will be put on the recommendations and clinical applications that the physician must consider before its indication. Methods: a bibliographic review of the relevant literature on the risks and special considerations of contrast media in pregnancy and lactation was performed. Results: the risks of ionising radiation on the fetus vary according to the stage of pregnancy, so the indication of the study must balance the risks and benefits. The use of iodinated and gadolinium-based con-trast agents in clinical doses in pregnancy and lactation has no effects on the health of the mother or the fetus. However, international societies recommend limiting its use. Conclusion: Although the indication for imaging studies using ionising radiation in pregnancy and lactation is safe, the clinician must be aware of the possible risks of ionising radiation in this group of patients. The only adverse effect reported is transient thyroid dysfunction in children of mothers who received iodinated contrast media.

The Global Experiment: How the International Atomic Energy Agency Proved Dosimetry to Be a Techno-Diplomatic Issue.

This paper draws attention to the role of the IAEA in shaping radiation dosimetry practices, instrumentation, and standards in the late 1950s and 1960s. It traces the beginnings of the IAEA's radiation dose intercomparison program which targeted all member states and involved the WHO so as to standardize dosimetry on a global level. To standardize dosimetric measurement methods, techniques, and instruments, however, one had to devise a method of comparing absorbed dose measurements in one laboratory with those performed in others with a high degree of accuracy. In 1964 the IAEA thus started to build up what I call the "global experiment," an intercomparison of radiation doses with participating laboratories from many of its member states. To carry out the process of worldwide standardization in radiation dosimetry, I argue, an organization with the diplomatic power and global reach of the IAEA was absolutely necessary. Thus, "global experiment" indicates a novel understanding of the experimental process. What counts as an experiment became governed by a process that was designed and strictly regulated by an international organization; it took place simultaneously in several laboratories across the globe, while experimental data became centrally owned and alienated from those that produced it.

Ultrawide-range radiation detection based on dynamic identification and analysis of the response of a monolithic active pixel sensor.

In this paper, we present an ultrawide-range radiation detection method based on dynamic recognition and analysis of the response signal of a monolithic active pixel sensor (MAPS). Our analysis of the MAPS response mechanism determined that adaptive adjustment of the sensor's integral time is key to quantification of ionizing radiation in an ultrawide range. We also determined that different data processing methods are required for accurate quantification of high and low radiation dose rates. The results of experiments conducted after calibration demonstrate that our technique is capable of radiation detection across five orders of magnitude (ranging from milligrays per hour to hundreds of grays per hour), with errors of less than 5%. Chip-based nuclear radiation detection can be realized using our technique, enabling MAPS to be used as a supplement to traditional detectors in characterization of unknown and complex radiation environments.

Nucleus Near-Infrared (nNIR) Irradiation of Single A549 Cells Induces DNA Damage and Activates EGFR Leading to Mitochondrial Fission.

There has been great interest in identifying the biological substrate for light-cell interaction and their relations to cancer treatment. In this study, a near-infrared (NIR) laser is focused into the nucleus (nNIR) or cytoplasm (cNIR) of a single living cell by a high numerical aperture condenser to dissect the novel role of cell nucleus in mediating NIR effects on mitochondrial dynamics of A549 non-small cell lung cancer cells. Our analysis showed that nNIR, but not cNIR, triggered mitochondrial fission in 10 min. In contrast, the fission/fusion balance of mitochondria directly exposed to cNIR does not change. While the same phenomenon is also triggered by single molecular interactions between epidermal growth factor (EGF) and its receptor EGFR, pharmacological studies with cetuximab, PD153035, and caffeine suggest EGF signaling crosstalk to DNA damaging response to mediate rapid mitochondrial fission as a result of nNIR irradiation. These results suggest that nuclear DNA integrity is a novel biological target for cellular response to NIR.

Biological and internal dosimetry for radiation medicine: current status and future perspectives.

The International Atomic Energy Agency (IAEA) and Hiroshima International Council for Health Care of the Radiation-Exposed (HICARE) jointly organized two relevant workshops in Hiroshima, Japan, i.e. a Training Meeting 'Biodosimetry in the 21st century' (BIODOSE-21) on 10-14 June 2013 and a Workshop on 'Biological and internal dosimetry: recent advance and clinical applications' which took place between 17 and 21 February 2020. The main objective of the first meeting was to develop the ability of biodosimetry laboratories to use mature and novel techniques in biological dosimetry for the estimation of radiation doses received by individuals and populations. This meeting had a special focus on the Asia-Pacific region and was connected with the then on-going IAEA Coordinated Research Project (CRP) E35008 'Strengthening of "Biological dosimetry" in IAEA Member States: Improvement of current techniques and intensification of collaboration and networking among the different institutes' (2012-17). The meeting was attended by 25 participants, which included 11 lecturers. The 14 trainees for this meeting came from India, Indonesia, Japan, Malaysia, Philippines, Republic of Korea, Singapore, Thailand and Vietnam. During the meeting 13 lectures by HICARE and IAEA invited lecturers were delivered besides eight research reports presented by the IAEA CRP E35008 network centers from the Asia-Pacific region. Two laboratory exercises were also undertaken, one each at Hiroshima University and the Radiation Effects Research Foundation (RERF). The second training workshop aimed to discuss with the participants the use of mature and novel techniques in biological and internal dosimetry for the estimation of radiation effects by accidental, environmental and medical exposures. The workshop was attended by 19 participants from Indonesia, Jordan, Oman, Philippines, Singapore, Syrian Arab Republic, Thailand, UAE, USA and Yemen. The main outcome of both meetings was a review of the state-of-the-art of biodosimetry and internal dosimetry and their future perspectives in medical management. This report highlights the learning outcome of two meetings for the benefit of all stake-holders in the field of biological and internal dosimetry.

Ionizing Radiation Exposure in Children with Vesicoureteral Reflux: Should We Be Alarmed? / Exposición a radiacion ionizante en niños con reflujo vesicoureteral: Debemos preocuparnos?

Objectives Ionizing radiation imaging is commonly used for diagnosis and follow up in children with vesicoureteral reflux (VUR). We aim to measure the effective dose (mSv) in patients with VUR. Methods We reviewed our electronic database of patients under 8-years-old with VUR. Primary endpoint was to calculate the effective radiation dose (ED). Absolute frequencies and percentages were reported for global qualitative variables. This study conducted a logistic regression model to calculate the odds ratio for radiation exposure. Analysis was performed using STATA version 14.0 (StataCorp LLC, College Station, TX, EEUU). Results A total of 140 patients were found, 97 were assessed for eligibility. We included 59 patients in the final analysis. Mean age was 20 ± 17.9 months, 66% were females. Most cases of VUR were bilateral (44%) and high grade (93.4%). The lowest number of studies per patient was two, with a minimum radiation of 5.7 mSv. The highest radiation was estimated at 20.7 mSv corresponding to a total of five studies. Logistic regression showed that highest grades of VUR and age of first UTI episode were associated with higher ED (OR, 1.7; 95% CI, 0.87-3.31), (OR 1.02; 95% CI 0.97-1.07) respectively. A mean ED for children with VUR was estimated of 5.5 ± 3 mSv/year. Conclusion In our study, the children with VUR were exposed to 5.5 mSv/year without counting the natural background radiation, which is alarming, and we believe should raise awareness worldwide in how we are unnecessarily diagnosing indolent VUR cases and following patients.

Objetivos La imagenología por radiación ionizante es una herramienta usada frecuentemente para el diagnóstico y seguimiento de pacientes con reflujo vesicoureteral (RVU). El objetivo del presente trabajo es calcular la dosis estimada en milisieverts (mSv) de pacientes con RVU. Métodos Se realizó una revisión retrospectiva de todos los pacientes menores de 8 años con RVU. El objetivo principal fue calcular la dosis de radiación efectiva recibida por los pacientes con base en los estudios imagenológicos realizados hasta el momento de la revisión de la base de datos. Las frecuencias y porcentajes fueron reportados para las variables cualitativas. Se realizó una regresión logística para calcular la asociación de factores de riesgo con la exposición a radiación. El análisis estadístico fue realizado con el programa STATA versión 14.0 (StataCorp LLC, College Station, TX, EEUU). Resultados Se identificaron 140 patientes, de los cuales 97 fueron evaluados para coprobar su elegibilidad. En total, 59 pacientes fueron incluidos para el análisis final. La edad promedio de los pacientes fue de 20 ± 1,.9 meses, y 66% eran mujeres. La mayoría de casos fueron bilaterales (44%) y de alto grado (93,4%). El menor número de estudios realizados por paciente fue 2, con una dosis mínima de radiación acumulada de 5,7 mSv. La máxima radiación acumulada fue de 20,7 mSv, correspondiente a un total de 5 estudios. La regresión logística demostró que altos grados de reflujo y la edad a la cual tuvieron la primera infección se asociaban con mayores dosis de radiación efectiva (razón de probabilidades [RP]: 1.7; intervalo de confianza del 95% [IC95%]: 0,87­3,31), (RP: 1,02; IC95%: 0,97­1,07), respectivamente. Estimamos una dosis efectiva de radiación de 5,5 ± 3 mSv/año en nuestra población. Conclusión Nuestro estudio demuestra que pacientes con reflujo son expuestos a un promedio de 5,5 mSv/año sin contar la radiación de base a la que se exponen todos los humanos anualmente, lo cual resulta alarmante. Esto debe generar introspección al momento de evaluar pacientes con reflujo y evitar efectos a largo y mediano plazos.

Uma reflexão sobre o uso da tomografia computadorizada em Endodontia / Considerations on the use of computed tomography in Endodontics

Será o exame de tomografia computadorizada realmente de alto custo para o paciente, ou existe uma resistência por grande parte dos profissionais em indicá-lo? Paradigmas já foram quebrados com relação à dose de radiação. Ela é tão pequena que, em muitas universidades nos EUA, o paciente não utiliza avental de chumbo durante o exame. Isso se dá porque o exame usado para Endodontia tem algumas diferenças em relação à tomografia médica (AU).

Is the CT scan really a high cost for the patient, or is there a resistance on the part of most professionals to indicate it? Paradigms have already been broken with regard to the radiation dose. In many universities in the USA, the patient does not wear a lead apron during the exam because the dose is so small. The reason for this is that the exam used for Endodontics has some differences in relation to medical tomography (AU).

Comparative analysis of the immune responses in cancer cells irradiated with X-ray, proton and carbon-ion beams.

Radiotherapy (RT) is an effective treatment option for cancer; however, its efficacy remains less than optimal in locally advanced cancer. Immune checkpoint inhibitor-based therapy, including the administration of anti-PD-L1 antibodies, is a promising approach that works synergistically with RT. Proton beam therapy and carbon-ion therapy are common options for patients with cancer. Proton and carbon ions are reported to induce an immune reaction in cancer cells; however, the underlying mechanisms remain unclear. Here, we aimed to compare the immune responses after irradiation (IR) with X-ray, protons, and carbon ions in an oesophageal cancer cell line and the underlying mechanisms. An oesophageal cancer cell line, KYSE450, was irradiated with 1 fraction/15 GyE (Gy equivalent) of X-ray, proton, or carbon-ion beams, and then, the cells were harvested for RNA sequencing and gene enrichment analysis. We also knocked out STING and STAT1 in the quest for mechanistic insights. RNA sequencing data revealed that gene expression signatures and biological processes were different in KYSE450 irradiated with X-ray, proton, and carbon-ion beams 6-24 h after IR. However, after 3 days, a common gene expression signature was detected, associated with biological pathways involved in innate immune responses. Gene knock-out experiments revealed that the STING-STAT1 axis underlies the immune reactions after IR. X-Ray, proton, and carbon-ion IRs induced similar immune responses, regulated by the STING-STAT1 axis.

Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B.

Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n = 23) and ALL (n = 9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrent PDGFRA amplification and loss of CDKN2A/B and an absence of somatic hotspot mutations in genes encoding histone 3 variants or IDH1/2, uncovering diagnostic markers and potentially actionable targets.

Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma.

Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.

Expansion of monocytic myeloid-derived suppressor cells ameliorated intestinal inflammatory response by radiation through SOCS3 expression.

Radiation-induced colitis is a common clinical problem after radiation therapy and accidental radiation exposure. Myeloid-derived suppressor cells (MDSCs) have immunosuppressive functions that use a variety of mechanisms to alter both the innate and the adaptive immune systems. Here, we demonstrated that radiation exposure in mice promoted the expansion of splenic and intestinal MDSCs and caused intestinal inflammation due to the increased secretion of cytokines. Depletion of monocytic MDSCs using anti-Ly6C exacerbated radiation-induced colitis and altered the expression of inflammatory cytokine IL10. Adoptive transfers of 0.5 Gy-derived MDSCs ameliorated this radiation-induced colitis through the production IL10 and activation of both STAT3 and SOCS3 signaling. Intestinal-inflammation recovery using 0.5 Gy-induced MDSCs was assessed using histological grading of colitis, colon length, body weight, and survival rate. Using in vitro co-cultures, we found that 0.5 Gy-induced MDSCs had higher expression levels of IL10 and SOCS3 compared with 5 Gy-induced MDSCs. In addition, IL10 expression was not enhanced in SOCS3-depleted cells, even in the presence of 0.5 Gy-induced monocytic MDSCs. Collectively, the results indicate that 0.5 Gy-induced MDSCs play an important immunoregulatory role in this radiation-induced colitis mouse model by releasing anti-inflammatory cytokines and suggest that IL10-overexpressing mMDSCs may be potential immune-therapy targets for treating colitis.

Actividad fotoprotectora de una crema con extracto acuoso liofilizado de Lepidium meyenii (MACA) frente a la irradiación ultravioleta en piel de ratones / Photoprotective activity of a cream containing lyophilized aqueous extract of Lepidium meyenii (MACA) against ultraviolet irradiation on mouse skin

RESUMEN Objetivos: Evaluar la actividad fotoprotectora de una crema con extracto acuoso liofilizado de maca (ELM) frente a la irradiación ultravioleta (UV) en la piel de ratones. Materiales y métodos: Se realizó un estudio experimental en 35ratones BALB/c. Los tratamientos fueron aplicados por vía tópica en el dorso de los animales y posteriormente irradiados con rayos ultravioleta B, para luego medir el grosor en micras (µm) de muestras histológicas de la piel de los ratones. Se asignaron siete grupos divididos en no irradiado: blanco (G1) e irradiados con luz UV: sin tratamiento (G2); con protector solar comercial con factor de protección solar (FPS) 30 (G3); crema (placebo) (G4); ELM al 15% en agua (G5); ELM al 5% en crema (G6); y ELM al 15% en crema (G7). Se determinó el FPS in vitro, mediante el método de Mansur. Se realizaron las lecturas de las absorbancias en un espectrofotómetro ultravioleta-visible (UV-VIS) y se determinaron los FPS para las siguientes formulaciones: ELM al 5% en crema, benzofenona-4 (BZF-4) y bloqueador solar comercial FPS 30. Resultados: El grosor de piel de ratón en micras (µm) fue de 27,28 en G2; 18,31 en G3; 27,33 en G4; 19,51 en G5 y 18,04 en G6; no hubo diferencia significativa entre el grupo no expuesto a la radiación (G1) y el grupo ELM al 15% en crema (G7), ambos presentaron los menores grosores (12,76 y 14,20 µm, respectivamente). El FPS de ELM al 15% en crema fue 5,480 ± 0,020. Conclusiones: La formulación con ELM en crema presentó actividad fotoprotectora frente a la irradiación UV, los alcaloides fueron los componentes fitoquímicos mayormente encontrados y la formulación fue compatible con el activo (ELM).

ABSTRACT Objectives: To evaluate the photoprotective activity of a cream with lyophilized aqueous extract of maca (LEM) against ultraviolet (UV) irradiation in the skin of mice. Materials and methods: An experimental study was carried out on 35 BALB/c mice. Treatment was applied topically on the dorsum of the animals, which were subsequently irradiated with ultraviolet B rays, and then we measured the thickness in microns (μm) of histological samples of the skin of the mice. Seven groups were assigned, divided into non-irradiated: Blank (G1) and irradiated with UV light: no treatment (G2); with commercial sunscreen with sun protection factor (SPF) 30 (G3); cream (placebo) (G4); LEM at 15% in water (G5); LEM cream at 5% (G6); and LEM cream at 15% (G7). In vitro SPF was determined using the Mansur method. Absorbance readings were taken in an ultraviolet- visible spectrophotometer (UV-VIS) and SPFs were determined for the following formulations: LEM cream at 5%, benzophenone-4 (BZF-4) and commercial sunscreen SPF 30. Results: Mouse skin thickness in microns (μm) was 27.28 in G2; 18.31 in G3; 27.33 in G4; 19.51 in G5 and 18.04 in G6. There was no significant difference between the group not exposed to radiation (G1) and the 15% LEM cream group (G7), both had the lowest thicknesses (12.76 and 14.20 μm, respectively). The SPF of LEM cream at 15% was 5.480 ± 0.020. Conclusions: The formulation with LEM cream showed photoprotective activity against UV irradiation, alkaloids were the phytochemical components mostly found and the formulation was compatible with the active principle (LEM).

[Comparison of 186Re to 662 keV photon radiation concerning biological radiation effect on the human B-cell line BV-173]. / Vergleich der biologischen Strahlenwirkung des ß--Emitters 186Re mit 662 keV Photonenstrahlung auf die humane B-Zelllinie BV-173.

ZIEL: Ziel der Untersuchung ist es, die Strahlenwirkung des ß--Emitters 186Re und von 662keV-Photonenstrahlung zu ermitteln, um die biologische Wirkung von Strahlung niedriger Dosisleistung (186Re) mit der hoher Dosisleistung zu vergleichen. MATERIAL UND METHODEN: Zellen der humanen Leukämie-Zelllinie BV-173 wurden mit 662keV-Photonenstrahlung respektive 186Re bestrahlt. In einem Inkubationszeitraum von 7 Tagen wurden Zahl und Vitalität der Zellen täglich bestimmt und als Dosiseffektkurven basierend auf der Vitalität dargestellt. Hierfür wurde der Zeitpunkt mit minimalem Überleben verwendet (72h 186Re und 24h Photonenstrahlung). ERGEBNISSE: Beide Strahlenarten zeigen am Auswertezeitpunkt (72h nach Versuchsbeginn für 186Re und 24h nach Versuchsbeginn für Photonenstrahlung) eine Überlebenskurve mit biexponentiellem Verlauf. Für Photonenstrahlung ist dies erklärbar durch eine Hypersensitivität im niedrigen Dosisbereich bis 1Gy, für die sich eine D0 von 3,3Gy ergibt, für Dosen über 1,0Gy liegt die D0 bei 10Gy. Für die 186Re-Inkubation ergibt sich eine D0 von 11,1Gy bei niedrigen Dosen verursacht durch die Reparatur subletaler Schäden, durch welche die biologische Wirkung abgeschwächt wird. Ab einer akkumulierten Dosis von etwa 1,6Gy zeichnet sich für 186Re ein wesentlich steilerer Kurvenverlauf mit einer D0 von 4,0Gy ab, der eine in diesem Bereich 2,5-fach stärkere biologische Wirkung als akute Photonenstrahlung wiedergibt (D0 4Gy für 186Re bzw. 10Gy für Photonen). SCHLUSSFOLGERUNG: Strahlung niedriger Dosisleistung zeigt eine geringere biologische Wirkung als eine akute Bestrahlung. Es existiert aber ein Grenzwert der akkumulierten Dosis, ab dem die biologische Wirkung von ß-Strahlung die der Photonenstrahlung sogar übertrifft.

Radiation-Induced Macrophage Senescence Impairs Resolution Programs and Drives Cardiovascular Inflammation.

Radiation is associated with tissue damage and increased risk of atherosclerosis, but there are currently no treatments and a very limited mechanistic understanding of how radiation impacts tissue repair mechanisms. We uncovered that radiation significantly delayed temporal resolution programs that were associated with decreased efferocytosis in vivo. Resolvin D1 (RvD1), a known proresolving ligand, promoted swift resolution and restored efferocytosis in sublethally irradiated mice. Irradiated macrophages exhibited several features of senescence, including increased expression of p16INK4A and p21, heightened levels of SA-ß-gal, COX-2, several proinflammatory cytokines/chemokines, and oxidative stress (OS) in vitro, and when transferred to mice, they exacerbated inflammation in vivo. Mechanistically, heightened OS in senescent macrophages led to impairment in their ability to carry out efficient efferocytosis, and treatment with RvD1 reduced OS and improved efferocytosis. Sublethally irradiated Ldlr -/- mice exhibited increased plaque necrosis, p16INK4A cells, and decreased lesional collagen compared with nonirradiated controls, and treatment with RvD1 significantly reduced necrosis and increased lesional collagen. Removal of p16INK4A hematopoietic cells during advanced atherosclerosis with p16-3MR mice reduced plaque necrosis and increased production of key intraplaque-resolving mediators. Our results demonstrate that sublethal radiation drives macrophage senescence and efferocytosis defects and suggest that RvD1 may be a new therapeutic strategy to limit radiation-induced tissue damage.