Online Mindfulness Experience for Emotional Support to Healthcare staff in times of Covid-19.

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).

Microbeam Radiotherapy-A Novel Therapeutic Approach to Overcome Radioresistance and Enhance Anti-Tumour Response in Melanoma.

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.

Potential strategies to ameliorate risk of radiotherapy-induced second malignant neoplasms.

This review is aimed at the issue of radiation-induced second malignant neoplasms (SMN), which has become an important problem with the increasing success of modern cancer radiotherapy (RT). It is imperative to avoid compromising the therapeutic ratio while addressing the challenge of SMN. The dilemma is illustrated by the role of reactive oxygen species in both the mechanisms of tumor cell kill and of radiation-induced carcinogenesis. We explore the literature focusing on three potential routes of amelioration to address this challenge. An obvious approach to avoiding compromise of the tumor response is the use of radioprotectors or mitigators that are selective for normal tissues. We also explore the opportunities to avoid protection of the tumor by topical/regional radioprotection of normal tissues, although this strategy limits the scope of protection. Finally, we explore the role of the bystander/abscopal phenomenon in radiation carcinogenesis, in association with the inflammatory response. Targeted and non-targeted effects of radiation are both linked to SMN through induction of DNA damage, genome instability and mutagenesis, but differences in the mechanisms and kinetics between targeted and non-targeted effects may provide opportunities to lessen SMN. The agents that could be employed to pursue each of these strategies are briefly reviewed. In many cases, the same agent has potential utility for more than one strategy. Although the parallel problem of chemotherapy-induced SMN shares common features, this review focuses on RT associated SMN. Also, we avoid the burgeoning literature on the endeavor to suppress cancer incidence by use of antioxidants and vitamins either as dietary strategies or supplementation.

Cadherin 13: human cis-regulation and selectively-altered addiction phenotypes and cerebral cortical dopamine in knockout mice.

The cadherin 13 (CDH13) gene encodes a cell adhesion molecule likely to influence development and connections of brain circuits that modulate addiction, locomotion and cognition, including those that involve midbrain dopamine neurons. Human CDH13 mRNA expression differs by more than 80% in postmortem cerebral cortical samples from individuals with different CDH13 genotypes, supporting examination of mice with altered Cdh13 expression as models for common human variation at this locus. Constitutive cdh13 knockout mice display evidence for changed cocaine reward: shifted dose response relationship in tests of cocaine-conditioned place preference using doses that do not alter cocaine conditioned taste aversion. Reduced adult Cdh13 expression in conditional knockouts also alters cocaine reward in ways that correlate with individual differences in cortical Cdh13 mRNA levels. In control and comparison behavioral assessments, knockout mice display modestly-quicker acquisition of rotarod and water maze tasks, with a trend toward faster acquisition of 5 choice serial reaction time tasks that otherwise displayed no genotype-related differences. They display significant differences in locomotion in some settings, with larger effects in males. In assessments of brain changes that might contribute to these behavioral differences, there are selective alterations of dopamine levels, dopamine/metabolite ratios, dopaminergic fiber densities and mRNA encoding the activity dependent transcription factor npas4 in cerebral cortex of knockout mice. These novel data and previously reported human associations of CDH13 variants with addiction, individual differences in responses to stimulant administration and attention deficit hyperactivity disorder (ADHD) phenotypes suggest that levels of CDH13 expression, through mechanisms likely to include effects on mesocortical dopamine, influence stimulant reward and may contribute modestly to cognitive and locomotor phenotypes relevant to ADHD.

[Ability to detect psychiatric disorders by the family physician]. / Capacidad de detección de patología psiquiátrica por el médico de familia.

OBJECTIVE: To determine the ability of family physicians to detect psychiatric disorders, comparing the presence of psychiatric disorders detected using validated tests and referrals by family physicians. DESIGN: Cross-sectional, two-phase study. LOCATION: Primary healthcare centres in an urban area of Madrid. PARTICIPANTS: Patients between 18 and 65years attending primary healthcare centres for non-administrative purposes. MAIN MEASUREMENTS: To detect psychiatric disorders in the waiting room, an interview was performed using GHQ-28 and MULTICAGE CAD-4 in the screening phase (considered positive: score of 6 or higher on the GHQ-28 or a score 2 or higher on MULTICAGE CAD-4). Patients with a positive score and 20% with negative were recruited for the second phase (case identification) using MINI interview. During family physician consultation, the patient gave his doctor a card with an identification number to record the presence of psychiatric illness in his/her opinion and whether there was treatment with psychotropic drugs. RESULTS: A total of 628 subjects participated. The prevalence of psychiatric disorders corrected by two phase methodology was 31.7% (95%CI: 27.9 to 35.5). Of the 185 patients with a psychiatric disorder detected, 44.2% (95%CI: 36.7 to 51.7) were identified as patients with psychiatric disorders by their family physician. Disorders best detected were: hypomania, dysthymic disorder, depressive episode with melancholic symptoms, and panic disorder. CONCLUSIONS: A significant percentage of patients with possible psychiatric disorders detected with validated test have not been identified by their family physician.

A prospective observational study of Gallium-68 ventilation and perfusion PET/CT during and after radiotherapy in patients with non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancers, and is the leading cause of cancer deaths. Radiation therapy (RT), alone or in combination with chemotherapy, is the standard of care for curative intent treatment of patients with locally advanced or inoperable NSCLC. The ability to intensify treatment to achieve a better chance for cure is limited by the risk of injury to the surrounding lung. METHODS/DESIGN: This is a prospective observational study of 60 patients with NSCLC receiving curative intent RT. Independent human ethics board approval was received from the Peter MacCallum Cancer Centre ethics committee. In this research, Galligas and Gallium-68 macroaggregated albumin (MAA) positron emission tomography (PET) imaging will be used to measure ventilation (V) and perfusion (Q) in the lungs. This is combined with computed tomography (CT) and both performed with a four dimensional (4D) technique that tracks respiratory motion. This state-of-the-art scan has superior resolution, accuracy and quantitative ability than previous techniques. The primary objective of this research is to observe changes in ventilation and perfusion secondary to RT as measured by 4D V/Q PET/CT. Additionally, we plan to model personalised RT plans based on an individual's lung capacity. Increasing radiation delivery through areas of poorly functioning lung may enable delivery of larger, more effective doses to tumours without increasing toxicity. By performing a second 4D V/Q PET/CT scan during treatment, we plan to simulate biologically adapted RT depending on the individual's accumulated radiation injury. Tertiary aims of the study are assess the prognostic significance of a novel combination of clinical, imaging and serum biomarkers in predicting for the risk of lung toxicity. These biomarkers include spirometry, (18)F-Fluorodeoxyglucose PET/CT, gamma-H2AX signals in hair and lymphocytes, as well as assessment of blood cytokines. DISCUSSION: By correlating these biomarkers to toxicity outcomes, we aim to identify those patients early who will not tolerate RT intensification during treatment. This research is an essential step leading towards the design of future biologically adapted radiotherapy strategies to mitigate the risk of lung injury during dose escalation for patients with locally advanced lung cancer. TRIALS REGISTRATION: Universal Trial Number (UTN) U1111-1138-4421.

Susceptibility to bystander DNA damage is influenced by replication and transcriptional activity.

Direct cellular DNA damage may lead to genome destabilization in unexposed, bystander, cells sharing the same milieu with directly damaged cells by means of the bystander effect. One proposed mechanism involves double strand break (DSB) formation in S phase cells at sites of single strand lesions in the DNA of replication complexes, which has a more open structure compared with neighboring DNA. The DNA in transcription complexes also has a more open structure, and hence may be susceptible to bystander DSB formation from single strand lesions. To examine whether transcription predisposes non-replicating cells to bystander effect-induced DNA DSBs, we examined two types of primary cells that exhibit high levels of transcription in the absence of replication, rat neurons and human lymphocytes. We found that non-replicating bystander cells with high transcription rates exhibited substantial levels of DNA DSBs, as monitored by γ-H2AX foci formation. Additionally, as reported in proliferating cells, TGF-ß and NO were found to mimic bystander effects in cell populations lacking DNA synthesis. These results indicate that cell vulnerability to bystander DSB damage may result from transcription as well as replication. The findings offer insights into which tissues may be vulnerable to bystander genomic destabilization in vivo.

Early Surgical Resection of Left Atrial Myxoma After Thromboembolic Stroke.

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.

What's Changed in 75 Years of RadRes? - An Australian Perspective on Selected Topics.

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.

Evaluation of PLA-Based Composite Films Filled with Cu2(OH)3NO3 Nanoparticles as an Active Material for the Food Industry: Biocidal Properties and Environmental Sustainability.

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.

Imaging evaluation of developmental hip dysplasia in the young adult.

OBJECTIVE: The purpose of this article is to review the clinical and imaging features as well as the potential complications of hip dysplasia in the young adult. Hip dysplasia is an important cause of secondary osteoarthrosis, which accounts for a significant proportion of patients requiring total hip arthroplasty. The radiographic diagnosis of mild hip dysplasia in the young adult may be subtle and is primarily based on the detection of deficient coverage of the femoral head by the acetabulum. CONCLUSION: Cross-sectional imaging, including CT and MRI, afford improved detection and characterization by providing morphologic information about acetabular deficiency. MRI also allows evaluation of potential associated injuries to the articular cartilage, the labrum, and the ligamentum teres. Familiarity with the radiographic and cross-sectional imaging findings of mild hip dysplasia in the young adult may allow a timely diagnosis and implementation of treatment strategies, which may prevent or delay the development of early osteoarthritis.

Infection-induced myelopoiesis during intracellular bacterial infection is critically dependent upon IFN-γ signaling.

Although microbial infections can alter steady-state hematopoiesis, the mechanisms that drive such changes are not well understood. We addressed a role for IFN-γ signaling in infection-induced bone marrow suppression and anemia in a murine model of human monocytic ehrlichiosis, an emerging tick-borne disease. Within the bone marrow of Ehrlichia muris-infected C57BL/6 mice, we observed a reduction in myeloid progenitor cells, as defined both phenotypically and functionally. Infected mice exhibited a concomitant increase in developing myeloid cells within the bone marrow, an increase in the frequency of circulating monocytes, and an increase in splenic myeloid cells. The infection-induced changes in progenitor cell phenotype were critically dependent on IFN-γ, but not IFN-α, signaling. In mice deficient in the IFN-γ signaling pathway, we observed an increase in myeloid progenitor cells and CDllb(lo)Gr1(lo) promyelocytic cells within the bone marrow, as well as reduced frequencies of mature granulocytes and monocytes. Furthermore, E. muris-infected IFN-γR-deficient mice did not exhibit anemia or an increase in circulating monocytes, and they succumbed to infection. Gene transcription studies revealed that IFN-γR-deficient CDllb(lo)Gr1(lo) promyelocytes from E. muris-infected mice exhibited significantly reduced expression of irf-1 and irf-8, both key transcription factors that regulate the differentiation of granulocytes and monocytes. Finally, using mixed bone marrow chimeric mice, we show that IFN-γ-dependent infection-induced myelopoiesis occurs via the direct effect of the cytokine on developing myeloid cells. We propose that, in addition to its many other known roles, IFN-γ acts to control infection by directly promoting the differentiation of myeloid cells that contribute to host defense.

Capability of Copper Hydroxy Nitrate (Cu2(OH)3NO3) as an Additive to Develop Antibacterial Polymer Contact Surfaces: Potential for Food Packaging Applications.

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.

Type of anesthesia for cancer resection surgery: No differential impact on cancer recurrence in mouse models of breast cancer.

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.

Early circulating tumor DNA dynamics at the commencement of curative-intent radiotherapy or chemoradiotherapy for NSCLC.

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.

Fovea alta on MR images: is it a marker of hip dysplasia in young adults?

OBJECTIVE: The objective of our study was to investigate the association between high fovea capitis (fovea alta) and hip dysplasia in young adults. MATERIALS AND METHODS: In a retrospective study, blinded observers reviewed 82 pelvic radiographic and hip MRI studies of three groups of patients: those with developmental dysplasia of the hip (DDH) (center-edge angle, ≤20°), those with borderline DDH (center-edge angle, 21°-25°), and control patients (center-edge angle, >25°). The center-edge angle and coxa valga (femoral neck-shaft angle, >135°) were assessed on pelvic radiographs, and fovea alta was assessed on MR images (delta angle, ≤10°). The Mann-Whitney and Fisher exact tests were used to correlate fovea alta with DDH and with coxa valga, respectively. Interobserver agreement for center-edge and delta angles and the diagnostic performance of fovea alta as a marker of DDH were calculated. RESULTS: Thirty-one patients with DDH, 23 with borderline DDH, and 28 without DDH were included. Excellent interobserver agreement was found for center-edge angle (concordance correlation coefficient, 0.94) and for delta angle (concordance correlation coefficient, 0.91). Fovea alta had a significant association with DDH (p<0.001) but no association with coxa valga (p>0.57). A significant difference (p<0.001) was found between patients with DDH (3.4°) and those without DDH (21.7°) with respect to mean delta angle measurements. Fovea alta had 69.4% sensitivity, 82.1% specificity, 67.2% positive predictive value, 81.0% negative predictive value, and 75.6% overall accuracy as an indicator of DDH. CONCLUSION: Fovea alta shows promise as a strong MRI marker of DDH.

Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner.

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.

Combining FLASH and spatially fractionated radiation therapy: The best of both worlds.

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.

Antibacterial Capability of MXene (Ti3C2Tx) to Produce PLA Active Contact Surfaces for Food Packaging Applications.

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.

Microbeam Radiation Therapy Controls Local Growth of Radioresistant Melanoma and Treats Out-of-Field Locoregional Metastasis.

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.