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The globalization of markets has diversified the food supply, but it has also made the distribution chain more difficult, increasing the risk of microbial contamination. One strategy to obtain safer food and extend its shelf life is to develop active packaging with antimicrobial properties that prevent the growth of pathogenic microorganisms or spoilage in food products. In this context, and in line with the growing social awareness about the environmental impact generated by plastic waste, this work evaluated the effectiveness of polylactic acid (PLA) films loaded with different concentrations of copper (II) hydroxynitrate nanoparticles (CuHS) against the microbiota of fresh foods (chicken, fish and cheese). The results showed that the developed films containing 1, 3 and 5% w/w of CuHS in the polymeric matrix caused a decrease in the microbial abundance equal to or higher than 3 logarithmic units in all foods tested. Moreover, the mechanical and thermal properties of the formulated composites showed that the added CuHS concentrations did not substantially modify these properties compared to the PLA films. Taking into account the results obtained for antimicrobial activity, Cu (II) migration levels and the cytotoxicity of the films formulated, the PLA composite loaded with 1% CuHS (w/w) was the most suitable for its potential use as food packaging material. In addition, the biodegradation of this composite film was studied under conditions simulating intensive aerobic composting, demonstrating that almost 100% disintegration after 14 days of testing was achieved. Therefore, the innovative PLA-based films developed represent a promising strategy for the fabrication of packaging and active surfaces to increase food shelf life while maintaining food safety. Moreover, their biodegradable character will contribute to efficient waste management, turning plastic residues into a valuable resource.
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Several scientific themes are reviewed in the context of the 75-year period relevant to this special platinum issue of Radiation Research. Two criteria have been considered in selecting the scientific themes. One is the exposure of the associated research activity in the annual meetings of the Radiation Research Society (RRS) and in the publications of the Society's Journal, thus reflecting the interest of members of RRS. The second criteria is a focus on contributions from Australian members of RRS. The first theme is the contribution of radiobiology to radiation oncology, featuring two prominent Australian radiation oncologists, the late Rod Withers and his younger colleague, Lester Peters. Two other themes are also linked to radiation oncology; preclinical research aimed at developing experimental radiotherapy modalities, namely microbeam radiotherapy (MRT) and Auger endoradiotherapy. The latter has a long history, in contrast to MRT, especially in Australia, given that the associated medical beamline at the Australian Synchrotron in Melbourne only opened in 2011. Another theme is DNA repair, which has a trajectory parallel to the 75-year period of interest, given the birth of molecular biology in the 1950s. The low-dose radiobiology theme has a similar timeline, predominantly prompted by the nuclear era, which is also connected to the radioprotector theme, although radioprotectors also have a long-established potential utility in cancer radiotherapy. Finally, two themes are associated with biodosimetry. One is the micronucleus assay, highlighting the pioneering contribution from Michael Fenech in Adelaide, South Australia, and the other is the γ-H2AX assay and its widespread clinical applications.
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Radioterapia (Especialidade) , Radiobiologia , Austrália , Humanos , História do Século XX , Radioterapia (Especialidade)/história , Radiobiologia/história , História do Século XXI , Reparo do DNA , Radioterapia/históriaRESUMO
We present a case report of a five-year-old male with acute ischemic stroke who underwent successful mechanical endovascular thrombectomy and early surgical resection of left atrial myxoma two days after onset of stroke symptoms without additional neurological sequelae.
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Neoplasias Cardíacas , AVC Isquêmico , Mixoma , Acidente Vascular Cerebral , Masculino , Humanos , Pré-Escolar , AVC Isquêmico/complicações , Átrios do Coração , Acidente Vascular Cerebral/etiologia , Neoplasias Cardíacas/cirurgia , Mixoma/cirurgiaRESUMO
Resumen Introducción El empleo es uno de los principales determinantes del estado general de salud. Para las personas que padecen un trastorno mental grave obtener un empleo supone un punto crucial en su recuperación por lo que la búsqueda, adquisición y mantenimiento de un empleo son objetivos fundamentales para las intervenciones de terapia ocupacional en esta población. Objetivos Conocer los resultados de las intervenciones de terapia ocupacional basadas en el modelo Individual Placement and Support sobre la inserción laboral y la calidad de vida de personas con trastorno mental grave. Método Se empleó la declaración PRISMA según los criterios establecidos por Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Las búsquedas se realizaron en las bases de datos: PubMed, Web of Science, Scopus y Cochrane. El riesgo de sesgo se evaluó con la herramienta Review Manager Web. El protocolo de revisión se registró en PROSPERO: CRD42023418778. Resultados Se incluyeron 12 estudios. El rango de edad de los participantes oscila entre los 18 y 53 años, predominando el género masculino. Los resultados vocacionales demuestran que la tasa de empleo fue al menos un 20% mayor en el grupo de apoyo individualizado al empleo que en el grupo control. No se encontraron hallazgos concluyentes para los resultados no vocacionales. Conclusión Los resultados sugieren que este modelo es efectivo en la inserción laboral de las personas con trastorno mental grave. Son necesarios futuros estudios con mayor rigor metodológico para confirmar la eficacia de este modelo en las variables no vocacionales.
Abstract Introduction Employment is one of the main determinants of general health status. For people suffering from serious mental disorders, obtaining a job is a crucial point in their recovery, which is why finding, acquiring, and maintaining a job are fundamental objectives for occupational therapy interventions with this population. Objective Find out the results of occupational therapy interventions based on the Individual Placement and Support model in the labor market insertion and quality of life of people with severe mental disorders. Method A review was conducted according to the criteria established by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Searches were carried out in the following databases: PubMed, Web of Science, Scopus, and Cochrane. Risk of bias was assessed using the Review Manager Web tool. The review protocol was registered at PROSPERO: CRD42023418778. Results Twelve studies were included. Participants ranged in age from 18 to 53 years, with predominance of males. Vocational results show that the employment rate was at least 20% higher in the individualized employment support group than in the control group. No conclusive findings were found for non-vocational outcomes. Conclusion The results suggest that this model is effective in the employability of people with severe mental disorders. Future studies with greater methodological rigor are needed to confirm the effectiveness of this model in non-professional variables.
Resumo Introdução O trabalho é um dos principais determinantes do estado geral de saúde. Para pessoas que sofrem de transtorno mental grave, conseguir um emprego é um ponto crucial em sua recuperação, razão pela qual encontrar, adquirir e manter um emprego são objetivos fundamentais para intervenções de terapia ocupacional nessa população. Objetivo Conhecer os resultados das intervenções de terapia ocupacional baseadas no modelo Individual Placement and Support sobre a inserção no mercado de trabalho e a qualidade de vida de pessoas com transtorno mental grave. Método Uma revisão foi conduzida de acordo com os critérios estabelecidos pelo Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). As buscas foram realizadas nos seguintes bancos de dados: PubMed, Web of Science, Scopus e Cochrane. O risco de viés foi avaliado usando a ferramenta Review Manager Web. O protocolo de revisão foi registrado no PROSPERO: CRD42023418778. Resultados Doze estudos foram incluídos. A idade dos participantes variou de 18 a 53 anos, com predominância do sexo masculino. Os resultados vocacionais demostram que a taxa de emprego foi pelo menos 20% maior no grupo de apoio individualizado ao emprego do que no grupo controle. Não foram encontrados achados conclusivos para os resultados não vocacionais. Conclusão : Os resultados sugerem que esse modelo é eficaz na integração ocupacional de pessoas com transtorno mental grave. São necessários estudos futuros com maior rigor metodológico para confirmar a eficácia desse modelo em variáveis não profissionais.
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BACKGROUND: Surgery is essential for curative treatment of solid tumors. Evidence from recent retrospective clinical analyses suggests that use of propofol-based total intravenous anesthesia during cancer resection surgery is associated with improved overall survival compared to inhaled volatile anesthesia. Evaluating these findings in prospective clinical studies is required to inform definitive clinical guidelines but will take many years and requires biomarkers to monitor treatment effect. Therefore, we examined the effect of different anesthetic agents on cancer recurrence in mouse models of breast cancer with the overarching goal of evaluating plausible mechanisms that could be used as biomarkers of treatment response. METHODS: To test the hypothesis that volatile anesthesia accelerates breast cancer recurrence after surgical resection of the primary tumor, we used three mouse models of breast cancer. We compared volatile sevoflurane anesthesia with intravenous propofol anesthesia and used serial non-invasive bioluminescent imaging to track primary tumor recurrence and metastatic recurrence. To determine short-term perioperative effects, we evaluated the effect of anesthesia on vascular integrity and immune cell changes after surgery in animal models. RESULTS: Survival analyses found that the kinetics of cancer recurrence and impact on survival were similar regardless of the anesthetic agent used during cancer surgery. Vascular permeability, immune cell infiltration and cytokine profiles showed no statistical difference after resection with inhaled sevoflurane or intravenous propofol anesthesia. CONCLUSIONS: These preclinical studies found no evidence that choice of anesthetic agent used during cancer resection surgery affected either short-term perioperative events or long-term cancer outcomes in mouse models of breast cancer. These findings raise the possibility that mouse models do not recapitulate perioperative events in cancer patients. Nonetheless, the findings suggest that future evaluation of effects of anesthesia on cancer outcomes should focus on cancer types other than breast cancer.
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Anestésicos Inalatórios , Anestésicos , Neoplasias da Mama , Propofol , Animais , Camundongos , Humanos , Feminino , Neoplasias da Mama/patologia , Propofol/farmacologia , Sevoflurano/farmacologia , Estudos Prospectivos , Estudos Retrospectivos , Recidiva Local de Neoplasia , Anestesia Intravenosa/métodos , Anestesia Geral , Biomarcadores , Anestésicos Intravenosos/farmacologia , Anestésicos Inalatórios/farmacologiaRESUMO
Background: The kinetics of circulating tumor DNA (ctDNA) release following commencement of radiotherapy or chemoradiotherapy may reflect early tumour cell killing. We hypothesised that an increase in ctDNA may be observed after the first fraction of radiotherapy and that this could have clinical significance. Materials and methods: ctDNA analysis was performed as part of a prospective, observational clinical biomarker study of non-small cell lung cancer (NSCLC) patients, treated with curative-intent radiotherapy or chemoradiotherapy. Blood was collected at predefined intervals before, during (including 24 h after fraction 1 of radiotherapy) and after radiotherapy/chemoradiotherapy. Mutation-specific droplet digital PCR assays used to track ctDNA levels during and after treatment. Results: Sequential ctDNA results are available for 14 patients with known tumor-based mutations, including in EGFR, KRAS and TP53, with a median follow-up of 723 days (range 152 to 1110). Treatments delivered were fractionated radiotherapy/chemoradiotherapy, in 2-2.75 Gy fractions (n = 12), or stereotactic ablative body radiotherapy (SABR, n = 2). An increase in ctDNA was observed after fraction 1 in 3/12 patients treated with fractionated radiotherapy with a complete set of results, including in 2 cases where ctDNA was initially undetectable. Neither SABR patient had detectable ctDNA immediately before or after radiotherapy, but one of these later relapsed systemically with a high detected ctDNA concentration. Conclusions: A rapid increase in ctDNA levels was observed after one fraction of fractionated radiotherapy in three cases. Further molecular characterization will be required to understand if a "spike" in ctDNA levels could represent rapid initial tumor cell destruction and could have clinical value as a surrogate for early treatment response and/or as a means of enriching ctDNA for mutational profiling.
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The globalization of the market, as well as the increasing world population, which require a higher demand for food products, pose a great challenge to ensure food safety and prevent food loss and waste. In this sense, active materials with antibacterial properties are an important alternative in the prolongation of shelf life and ensuring food safety. In this work, the ability of copper(II) hydroxy nitrate (CuHS) to obtain antibacterial films based on low density polyethylene (LDPE) and polylactic acid (PLA), was evaluated. The thermal properties of the composites, evaluated using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), showed that the concentrations of added CuHS do not particularly change these characteristics with respect to the neat polymer matrix films. The mechanical properties, determined using dynamic mechanical analysis (DMTA), indicate a small increase in the brittleness of the material in PLA-based composites. The antibacterial properties against Listeria monocytogenes and Salmonella enterica were evaluated using a surface contact test, and a bacterial reduction of at least 8 to 9 logarithmic units for the composites with 0.3% CuHS, both in LDPE and PLA and against both bacteria, were achieved. The reusability of the composite films after their first use demonstrated a higher stability against Listeria monocytogenes. The migration and cytotoxicity of the composites loaded with 0.3% CuHS was evaluated, demonstrating the safety of these materials, which reinforces their potential use in food packaging applications.
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The globalization of the market and the increase of the global population that requires a higher demand of food products superimposes a big challenge to ensure food safety. In this sense, a common strategy to extend the shelf life and save life of food products is by avoiding bacterial contamination. For this, the development of antibacterial contact surfaces is an urgent need to fulfil the above-mentioned strategy. In this work, the role of MXene (Ti3C2Tx) in providing antibacterial contact surfaces was studied through the creation of composite films from polylactic acid (PLA), as the chosen polymeric matrix. The developed PLA/MXene films maintained the thermal and mechanical properties of PLA and also presented the attractive antibacterial properties of MXene. The composites' behaviour against two representative foodborne bacteria was studied: Listeria mono-cytogenes and Salmonella enterica (representing Gram-positive and Gram-negative bacteria, respectively). The composites prevented bacterial growth, and in the case of Listeria only 0.5 wt.% of MXene was necessary to reach 99.9999% bactericidal activity (six log reductions), while against Salmonella, 5 wt.% was necessary to achieve 99.999% bactericidal activity (five log reductions). Cy-totoxicity tests with fHDF/TER166 cell line showed that none of the obtained materials were cytotoxic. These results make MXene particles promising candidates for their use as additives into a polymeric matrix, useful to fabricate antibacterial contact surfaces that could prove useful for the food packaging industry.
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FLASH radiotherapy (FLASH-RT) and spatially fractionated radiation therapy (SFRT) are two new therapeutical strategies that use non-standard dose delivery methods to reduce normal tissue toxicity and increase the therapeutic index. Although likely based on different mechanisms, both FLASH-RT and SFRT have shown to elicit radiobiological effects that significantly differ from those induced by conventional radiotherapy. With the therapeutic potential having been established separately for each technique, the combination of FLASH-RT and SFRT could therefore represent a winning alliance. In this review, we discuss the state of the art, advantages and current limitations, potential synergies, and where a combination of these two techniques could be implemented today or in the near future.
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Fracionamento da Dose de Radiação , Humanos , Dosagem RadioterapêuticaRESUMO
PURPOSE: Synchrotron-generated microbeam radiation therapy (MRT) represents an innovative preclinical type of cancer radiation therapy with an excellent therapeutic ratio. Beyond local control, metastatic spread is another important endpoint to assess the effectiveness of radiation therapy treatment. Currently, no data exist on an association between MRT and metastasis. Here, we evaluated the ability of MRT to delay B16F10 murine melanoma progression and locoregional metastatic spread. METHODS AND MATERIALS: We assessed the primary tumor response and the extent of metastasis in sentinel lymph nodes in 2 cohorts of C57BL/6J mice, one receiving a single MRT and another receiving 2 MRT treatments delivered with a 10-day interval. We compared these 2 cohorts with synchrotron broad beam-irradiated and nonirradiated mice. In addition, using multiplex quantitative platforms, we measured plasma concentrations of 34 pro- and anti-inflammatory cytokines and frequencies of immune cell subsets infiltrating primary tumors that received either 1 or 2 MRT treatments. RESULTS: Two MRT treatments were significantly more effective for local control than a single MRT. Remarkably, the second MRT also triggered a pronounced regression of out-of-radiation field locoregional metastasis. Augmentation of CXCL5, CXCL12, and CCL22 levels after the second MRT indicated that inhibition of melanoma progression could be associated with increased activity of antitumor neutrophils and T-cells. Indeed, we demonstrated elevated infiltration of neutrophils and activated T-cells in the tumors after the second MRT. CONCLUSIONS: Our study highlights the importance of monitoring metastasis after MRT and provides the first MRT fractionation schedule that promotes local and locoregional control with the potential to manage distant metastasis.
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Melanoma , Síncrotrons , Animais , Citocinas , Melanoma/radioterapia , Camundongos , Camundongos Endogâmicos C57BL , Síndrome , Linfócitos TRESUMO
Radiation therapy (RT) is a vital component of multimodal cancer treatment, and its immunomodulatory effects are a major focus of current therapeutic strategies. Macrophages are some of the first cells recruited to sites of radiation-induced injury where they can aid in tissue repair, propagate radiation-induced fibrogenesis and influence tumour dynamics. Microbeam radiation therapy (MRT) is a unique, spatially fractionated radiation modality that has demonstrated exceptional tumour control and reduction in normal tissue toxicity, including fibrosis. We conducted a morphological analysis of MRT-irradiated normal liver, lung and skin tissues as well as lung and melanoma tumours. MRT induced distinct patterns of DNA damage, reflecting the geometry of the microbeam array. Macrophages infiltrated these regions of peak dose deposition at variable timepoints post-irradiation depending on the tissue type. In normal liver and lung tissue, macrophages clearly demarcated the beam path by 48 h and 7 days post-irradiation, respectively. This was not reflected, however, in normal skin tissue, despite clear DNA damage marking the beam path. Persistent DNA damage was observed in MRT-irradiated lung carcinoma, with an accompanying geometry-specific influx of mixed M1/M2-like macrophage populations. These data indicate the unique potential of MRT as a tool to induce a remarkable accumulation of macrophages in an organ/tissue-specific manner. Further characterization of these macrophage populations is warranted to identify their organ-specific roles in normal tissue sparing and anti-tumour responses.
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During the first confinement in Spain, between the months of March to June 2020, Information and Communication Technologies strategies were implemented in order to support health workers in the Wellbeing of Mental Health. Faced with so much uncertainty about the pandemic, an Online Mindfulness course. The objective of the course was to support healthcare professionals in Castilla y León in managing stress, anxiety and other emotional disturbances generated by coping with a situation as uncertain and unexpected as a pandemic, in order to manage emotions and thoughts that can lead to suicidal ideation. The motivations for the demand, reasons or motivations in which the health professionals of Castilla y León decided to participate in the mindfulness course in the first wave of Covid-19 in Spain are described. The descriptive and inferential statistical analysis of the customer satisfaction survey applied at the end of the mindfulness course, to the health professionals who participated in a satisfaction survey (CSQ-8: Client Satisfaction Questionnaire). Professional were asked to complete a survey based on (CSQ-8: Client Satisfaction Questionnaire) whose Cronbach's alpha = 0.917 is why the instrument used with N = 130 participants has high reliability. The 66% answered with a highly satisfied that they would return to the mindfulness online course. The 93% of the people who answered the satisfaction survey were women, of which they are professionals in the nursing area, with a participation of around 62%. In relation to the online system used in the Mindfulness intervention, 74% expressed that they fully agreed that it has been easy to use the online system for the mindfulness intervention. Health Professionals responded with 58% high satisfaction and 36% satisfaction, making a total of 94% on the help received in the online mindfulness courses to solve their problems. There is no difference between the age groups of the professionals who have preferred the Mindfulness online course (p = 0.672).
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COVID-19 , Atenção Plena , Feminino , Humanos , Satisfação do Paciente , Reprodutibilidade dos Testes , SARS-CoV-2RESUMO
Melanoma is the deadliest type of skin cancer, due to its invasiveness and limited treatment efficacy. The main therapy for primary melanoma and solitary organ metastases is wide excision. Adjuvant therapy, such as chemotherapy and targeted therapies are mainly used for disseminated disease. Radiotherapy (RT) is a powerful treatment option used in more than 50% of cancer patients, however, conventional RT alone is unable to eradicate melanoma. Its general radioresistance is attributed to overexpression of repair genes in combination with cascades of biochemical repair mechanisms. A novel sophisticated technique based on synchrotron-generated, spatially fractionated RT, called Microbeam Radiation Therapy (MRT), has been shown to overcome these treatment limitations by allowing increased dose delivery. With MRT, a collimator subdivides the homogeneous radiation field into an array of co-planar, high-dose microbeams that are tens of micrometres wide and spaced a few hundred micrometres apart. Different preclinical models demonstrated that MRT has the potential to completely ablate tumours, or significantly improve tumour control while dramatically reducing normal tissue toxicity. Here, we discuss the role of conventional RT-induced immunity and the potential for MRT to enhance local and systemic anti-tumour immune responses. Comparative gene expression analysis from preclinical tumour models indicated a specific gene signature for an 'MRT-induced immune effect'. This focused review highlights the potential of MRT to overcome the inherent radioresistance of melanoma which could be further enhanced for future clinical use with combined treatment strategies, in particular, immunotherapy.
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Melanoma/radioterapia , Animais , Terapia Combinada/métodos , Humanos , Imunidade/imunologia , Imunoterapia/métodos , Melanoma/imunologia , Melanoma/terapia , Radioterapia/métodos , SíncrotronsRESUMO
Synchrotron radiation, especially microbeam radiotherapy (MRT), has a great potential to improve cancer radiotherapy, but non-targeted effects of synchrotron radiation have not yet been sufficiently explored. We have previously demonstrated that scattered synchrotron radiation induces measurable γ-H2AX foci, a biomarker of DNA double-strand breaks, at biologically relevant distances from the irradiated field that could contribute to the apparent accumulation of bystander DNA damage detected in cells and tissues outside of the irradiated area. Here, we quantified an impact of scattered radiation to DNA damage response in "naïve" cells sharing the medium with the cells that were exposed to synchrotron radiation. To understand the effect of genetic alterations in naïve cells, we utilised p53-null and p53-wild-type human colon cancer cells HCT116. The cells were grown in two-well chamber slides, with only one of nine zones (of equal area) of one well irradiated with broad beam or MRT. γ-H2AX foci per cell values induced by scattered radiation in selected zones of the unirradiated well were compared to the commensurate values from selected zones in the irradiated well, with matching distances from the irradiated zone. Scattered radiation highly impacted the DNA damage response in both wells and a pronounced distance-independent bystander DNA damage was generated by broad-beam irradiations, while MRT-generated bystander response was negligible. For p53-null cells, a trend for a reduced response to scattered irradiation was observed, but not to bystander signalling. These results will be taken into account for the assessment of genotoxic effects in surrounding non-targeted tissues in preclinical experiments designed to optimise conditions for clinical MRT and for cancer treatment in patients.
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Introduction: Resilience is a multidimensional and dynamic construct associated with positive growth and the capacity to transform stressful and negative factors into opportunities of personal development and self-improvement when faced with difficult experiences. The resilience process of each individual integrates multiple analysis levels, which range from genetic-environmental interactions to a complex process of adaptation between the individual and his/her family, friends, co-workers, society, and culture. Objective: To determine whether resilience improves in students of occupational therapy when exposed for the first time to practice placement education. Methodology: Quasi-experimental, prospective, observational, multi-center study with a sample composed of students from the Degree of Occupational Therapy of the public universities of Málaga (UMA) and Castilla-La Mancha (UCLM) (Spain). Two weeks prior to the beginning of the practice education period, the participants completed a questionnaire that included sociodemographic data and the area of their internships. They were also given the Spanish version of the Connor-Davidson's resilience scale (CD-RISC). All these instruments were also completed 1 week after the end of the clinical practice. Results: There were statistically significant differences between the variables that make up resilience and the different internship areas. On the other hand, there was a significant improvement of global resilience after the clinical practice period, in both women (13.85 points; p < 0.001) and men (7.72 points; p < 0.035), when the internship area was not considered. Conclusions: The results show that resilient students are more optimistic and work to improve a situation beyond doing simply what is expected of them, knowing how to control their feelings. This is beneficial for students in practice education, since, during these, they face difficult situations that require a resilient pattern, which helps reduce stress and the burnout syndrome.
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Ionizing radiation interacts with the immune system in many ways with a multiplicity that mirrors the complexity of the immune system itself: namely the need to maintain a delicate balance between different compartments, cells and soluble factors that work collectively to protect, maintain, and restore tissue function in the face of severe challenges including radiation damage. The cytotoxic effects of high dose radiation are less relevant after low dose exposure, where subtle quantitative and functional effects predominate that may go unnoticed until late after exposure or after a second challenge reveals or exacerbates the effects. For example, low doses may permanently alter immune fitness and therefore accelerate immune senescence and pave the way for a wide spectrum of possible pathophysiological events, including early-onset of age-related degenerative disorders and cancer. By contrast, the so called low dose radiation therapy displays beneficial, anti-inflammatory and pain relieving properties in chronic inflammatory and degenerative diseases. In this review, epidemiological, clinical and experimental data regarding the effects of low-dose radiation on the homeostasis and functional integrity of immune cells will be discussed, as will be the role of immune-mediated mechanisms in the systemic manifestation of localized exposures such as inflammatory reactions. The central conclusion is that ionizing radiation fundamentally and durably reshapes the immune system. Further, the importance of discovery of immunological pathways for modifying radiation resilience amongst other research directions in this field is implied.
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Neoplasias , Radiação Ionizante , Relação Dose-Resposta à Radiação , Humanos , Sistema Imunitário , InflamaçãoRESUMO
BACKGROUND: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning systems, enabling conformal avoidance of highly functioning regions of lung, thereby facilitating increased doses to tumour while reducing normal tissue doses. METHODS AND ANALYSIS: This prospective interventional study will investigate the use of ventilation and perfusion PET/CT to identify highly functioning lung volumes and avoidance of these using VMAT planning. This single-arm trial will be conducted across two large public teaching hospitals in Australia. Twenty patients with stage III non-small cell lung cancer will be recruited. All patients enrolled will receive dose-escalated (69 Gy) functional avoidance radiation therapy. The primary endpoint is feasibility with this achieved if ≥15 out of 20 patients meet pre-defined feasibility criteria. Patients will be followed for 12 months post-treatment with serial imaging, biomarkers, toxicity assessment and quality of life assessment. DISCUSSION: Using advanced techniques such as VMAT functionally adapted radiation therapy may enable safe moderate dose escalation with an aim of improving local control and concurrently decreasing treatment related toxicity. If this technique is proven feasible, it will inform the design of a prospective randomised trial to assess the clinical benefits of functional lung avoidance radiation therapy. ETHICS AND DISSEMINATION: This study was approved by the Peter MacCallum Human Research Ethics Committee. All participants will provide written informed consent. Results will be disseminated via publications. TRIALS REGISTRATION NUMBER: NCT03569072; Pre-results.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Austrália , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Estudos de Viabilidade , Radioisótopos de Gálio , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Perfusão , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Qualidade de Vida , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada por Raios XRESUMO
Abscopal effects are an important aspect of targeted radiation therapy due to their implication in normal tissue toxicity from chronic inflammatory responses and mutagenesis. Gene expression can be used to determine abscopal effects at the molecular level. Synchrotron microbeam radiation therapy utilizing high-intensity X rays collimated into planar microbeams is a promising cancer treatment due to its reported ability to ablate tumors with less damage to normal tissues compared to conventional broadbeam radiation therapy techniques. The low scatter of synchrotron radiation enables microbeams to be delivered to tissue effectively, and is also advantageous for out-of-field studies because there is minimal interference from scatter. Mouse legs were irradiated at a dose rate of 49 Gy/s and skin samples in the out-of-field areas were collected. The out-of-field skin showed an increase in Tnf expression and a decrease in Mdm2 expression, genes associated with inflammation and DNA damage. These expression effects from microbeam exposure were similar to those found with broadbeam exposure. In immune-deficient Ccl2 knockout mice, we identified a different gene expression profile which showed an early increase in Mdm2, Tgfb1, Tnf and Ccl22 expression in out-of-field skin that was not observed in the immune-proficient mice. Our results suggest that the innate immune system is involved in out-of-field tissue responses and alterations in the immune response may not eliminate abscopal effects, but could change them.
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Dano ao DNA/genética , Expressão Gênica/efeitos da radiação , Imunidade Inata/efeitos da radiação , Síncrotrons , Animais , Quimiocina CCL2/genética , Perfilação da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Thoracic radiotherapy (RT) is required for the curative management of inoperable lung cancer, however, treatment delivery is limited by normal tissue toxicity. Prior studies suggest that using radiation-induced DNA damage response (DDR) in peripheral blood mononuclear cells (PBMC) has potential to predict RT-associated toxicities. We collected PBMC from 38 patients enrolled on a prospective clinical trial who received definitive fractionated RT for non-small cell lung cancer. DDR was measured by automated counting of nuclear γ-H2AX foci in immunofluorescence images. Analysis of samples collected before, during and after RT demonstrated the induction of DNA damage in PBMC collected shortly after RT commenced, however, this damage repaired later. Radiation dose to the tumour and lung contributed to the in vivo induction of γ-H2AX foci. Aliquots of PBMC collected before treatment were also irradiated ex vivo, and γ-H2AX kinetics were analyzed. A trend for increasing of fraction of irreparable DNA damage in patients with higher toxicity grades was revealed. Slow DNA repair in three patients was associated with a combined dysphagia/cough toxicity and was confirmed by elevated in vivo RT-generated irreparable DNA damage. These results warrant inclusion of an assessment of DDR in PBMC in a panel of predictive biomarkers that would identify patients at a higher risk of toxicity.
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Resumen Introducción La realización de prácticas en los contextos reales de trabajo supone uno de los aspectos clave en la organización, desarrollo y evaluación de los programas universitarios, tales como el Grado en Terapia Ocupacional. Además, permiten adquirir habilidades personales y profesionales, favoreciendo la integración de la teoría con la práctica, así como la identidad profesional. Método Estudio descriptivo transversal. 164 estudiantes de 2º, 3º y 4º curso del Grado en Terapia Ocupacional de la Universidad de Castilla-La Mancha fueron evaluados mediante un cuestionario online, tras el proceso de asignación de recursos. Se exploró la importancia que los estudiantes del Grado en Terapia Ocupacional atribuyen a su aprendizaje en recursos de prácticas y se identificaron los factores que determinan la elección de los dispositivos en los que realizarán su formación práctica. El reclutamiento de los estudiantes se llevó a cabo en el curso 2017-2018, siendo su participación voluntaria. Resultados Se obtuvieron diferencias estadísticamente significativas en función del curso académico (2º, 3º y 4º) entre las variables dependientes vinculadas con la valoración de las prácticas en el currículum académico: ayudan a solucionar problemas prácticos (p= 0,007) y enseñan habilidades interpersonales (p = 0,025). Más de la mitad de la muestra de estudiantes encuestados (51,2%) señaló la cercanía del centro de prácticas a su domicilio familiar como el factor más importante a la hora de seleccionar el dispositivo en el que realizará su formación práctica. Conclusiones Este trabajo contribuye a comprender el impacto de la toma de decisiones, así como a facilitar la mejora de dicho proceso por parte de los estudiantes, promoviendo experiencias en recursos de prácticas que resulten exitosas, así como un futuro desarrollo profesional satisfactorio.
Resumo Introdução A realização de ensino prático nos contextos reais de trabalho supõe um dos aspectos-chave na organização, desenvolvimento e avaliação dos programas universitários, como o Curso de Graduação em Terapia Ocupacional. Além disso, permite adquirir habilidades pessoais e profissionais, favorecendo a integração da teoria com a prática, assim como a identidade profissional. Método Estudo descritivo transversal. 164 alunos do 2º, 3º e 4º anos do Curso de Graduação em Terapia Ocupacional da Universidade de Castilla-La Mancha foram avaliados por meio de questionário on-line, após o processo de alocação de recursos. Foi explorada a importância que os alunos do curso de graduação em Terapia Ocupacional atribuem aos recursos de aprendizagem na prática e foram identificados os fatores que determinam a escolha dos dispositivos nos quais eles realizaram sua formação prática. O recrutamento dos alunos foi realizado no ano letivo 2017-2018, sendo sua participação voluntária. Resultados Foram obtidas diferenças estatisticamente significantes, dependendo do ano acadêmico (2º, 3º e 4º), entre as variáveis dependentes vinculadas à avaliação de práticas no currículo acadêmico: ajudam a resolver problemas práticos (p = 0,007) e ensinam habilidades interpessoais (p = 0,025). Mais da metade da amostra de estudantes pesquisados (51,2%) indicou a proximidade do centro de prática à casa da família como o fator mais importante na seleção do dispositivo no qual eles realizaram o estágio prático. Conclusão Este trabalho contribui para a compreensão do impacto da tomada de decisão, além de facilitar a melhoria do processo por parte dos alunos, promovendo experiências em recursos práticos bem-sucedidos, bem como o desenvolvimento profissional satisfatório futuro.
Abstract Introduction Carrying out internships within a real work context is one of the key aspects for the organisation, development and evaluation of university programmes such as the Degree in Occupational Therapy. In addition, it allows acquiring personal and professional skills, favouring this way the integration between theory and practice as well as the sense of a professional identity. Method This is a cross-sectional descriptive study. 164 students of 2nd, 3rd and 4th year of the Degree in Occupational Therapy of the University of Castilla-La Mancha were assessed by an online questionnaire after the process of allocation of resources. We explored the importance that students of the Occupational Therapy Degree attribute to their learning in practice resources and identified the factors that determine the choice of devices in which they will carry out their practical training. The selection of students was made during the 2017-2018 academic year and all of them participated voluntarily. Results Statistically significant differences were obtained depending on the academic year (2nd, 3rd and 4th) among the dependent variables linked to the assessment of the internship in the academic curriculum: it helps to solve practical problems (p = 0.007) and teach interpersonal skills (p = 0.025). More than half of the sample of students surveyed (51.2%) pointed out the proximity of the internship centre to their family home as the most important factor when selecting the device in which place where they would carry out their practical training. Conclusions This work helps to understand the impact of decision making as well as to facilitate the improvement of this process for students, promoting experiences in practical resources that are successful as well as a satisfactory future professional development.