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The anemia of critical illness (ACI) is a nearly universal pathophysiological consequence of burn injury and a primary reason burn patients require massive quantities of transfused blood. Inflammatory processes are expected to drive postburn ACI and prevent meaningful erythropoietic stimulation through iron or erythropoietin supplementation, but to this day no specific inflammatory pathways have been identified as a critical mechanism. In this study, we examined whether secretion of G-CSF and IL-6 mediates distinct features of postburn ACI and interrogated inflammatory mechanisms that could be responsible for their secretion. Our analysis of mouse and human skin samples identified the burn wound as a primary source of G-CSF and IL-6 secretion. We show that G-CSF and IL-6 are secreted independently through an IL-1/MyD88–dependent mechanism, and we ruled out TLR2 and TLR4 as critical receptors. Our results indicate that IL-1/MyD88–dependent G-CSF secretion plays a key role in impairing medullary erythropoiesis and IL-6 secretion plays a key role in limiting the access of erythroid cells to iron. Importantly, we found that IL-1α/β neutralizing Abs broadly attenuated features of postburn ACI that could be attributed to G-CSF or IL-6 secretion and rescued deficits of circulating RBC counts, hemoglobin, and hematocrit caused by burn injury. We conclude that wound-based IL-1/MyD88 signaling mediates postburn ACI through induction of G-CSF and IL-6 secretion.

Viewing alcohol-related cues (e.g., advertisements) is known to promote expressions of racial bias and aggression through the temporary promotion of reflexive or impulsive responding. However, this increased automaticity may be inhibited by thoughtful control of behavior. We examined the role of controlled processes in the suppression of racial bias following alcohol cue exposure across two experiments. Experiment 1 (N = 125) indicated reduced control of behavior promoted greater expressions of racial bias after viewing alcohol-related cues. Experiment 2 (N = 71) replicated these effects, suggesting individuals with lower neural indices of control, indexed by reduced amplitudes of the error-related negativity (ERN), similarly express greater racial bias after viewing alcohol-related cues. These findings replicate previous work suggesting alcohol-related cues promote impulsivity and application of negative racial stereotypes. Yet, whether this automaticity manifests into behavioral expressions of racial bias depends on the availability to engage self-control to inhibit these socially undesirable responses.

Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activation in a receptor activator of nuclear factor-κB ligand and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease.

Since the discovery of conspicuously spatially tuned neurons in the hippocampal formation over 50 years ago, characterizing which, where, and how neurons encode navigationally relevant variables has been a major thrust of navigational neuroscience. While much of this effort has centered on the hippocampal formation and functionally-adjacent structures, recent work suggests that spatial codes, in some form or another, can be found throughout the brain, even in areas traditionally associated with sensation, movement, and executive function. In this review, we highlight these unexpected results, draw insights from comparison of these codes across contexts, regions, and species, and finally suggest an avenue for future work to make sense of these diverse and dynamic navigational codes.

Stereotactic radiotherapy has become a standard in the management of patients with brain metastases; its main interest is to differ whole brain radiotherapy, provider of neurocognitive toxicity and to increase the rate of local control. The repetition of radiotherapy sessions under stereotactic conditions is not codified, neither on the number of technically and clinically possible sessions, nor on the maximum total number or volume of metastases to be treated. The purpose of this review is to analyse the data in the literature concerning repeated irradiations under stereotactic conditions. The second reirradiation in stereotactic condition shows satisfactory results in terms of overall survival, local control, and toxicity. However, we lack data for patients receiving more than two sessions of SRS as well as to define dose constraints to reirradiated healthy tissues. Prospective trials are still needed to validate the management of recurrent brain metastases after initial SRS.

Substance use among pregnant and postpartum women (PPW) is a serious public health concern. The COVID-19 pandemic has exacerbated substance use among the general population including pregnant women, and disrupted operations for substance use treatment centers. Little is known about the outcomes of substance use treatment for PPW before and during the COVID-19 pandemic.Data from a longitudinal program evaluation were analyzed to examine outcomes among 136 PPW participating in a residential SUD treatment program, and to explore differences in treatment outcomes for women who enrolled in services before versus during the COVID-19 pandemic. Analyses were used to test the significance of change from treatment intake to 6-month post-intake on assessments of substance use, mental health symptoms, and functioning collected to evaluate the Healthy Families Program (HFP), a comprehensive program for PPW located within a gender-specific SUD treatment facility in the United States.Results indicated that from treatment intake to follow-up assessment, clients self-reported statistically significant improvements in family functioning and daily functioning as well as reduced days of substance use. Notably, the rate of treatment intakes declined during the COVID-19 pandemic. In separate analyses by subgroup, mental health indicators showed improvements only for clients engaged in treatment before the COVID-19 pandemic and not for clients served during the COVID-19 pandemic, but substance use decreased significantly for both pre-pandemic and pandemic enrollees.Specialized treatment considerations and implications for PPW are discussed, including a need for added emphasis on co-occurring mental health symptoms and family system stress during a pandemic, and the role of nurses in identifying and addressing these concerns. Additionally, potential relapse prevention efforts during COVID-19 for PPW with substance use disorders are examined.The present research continues to highlight the importance of specialized treatment programming for PPW with SUDs as well as the potential need for additional recovery support mechanisms to be utilized during the COVID-19 pandemic.

Pelvic bone marrow is the site of nearly 50% of total hematopoiesis. Radiation therapy of pelvic lymph node areas, and cancers located near the bony structures of the pelvis, exposes to hematological toxicity in the range of 30 to 70%. This toxicity depends on many factors, including the presence or absence of concomitant chemotherapy and its type, the volume of irradiated bone, the received doses, or the initial hematopoietic reserve. Intensity modulated radiation therapy allows the optimisation of dose deposit on at risk organs while providing optimal coverage of target volumes. However, this suggests that dose constraints should be known precisely to limit the incidence of radiation side effects. This literature review focuses firstly on pelvic lymph node areas and bony volumes nearby, then on the effects of irradiation on bone marrow and the current dosimetric constraints resulting from it, and finally on hematological toxicities by carcinologic location and progress in reducing these toxicities.

The performance of deformable medical image registration (DIR) algorithms has become a major concern.We aimed to obtain updated information on DIR algorithm performance quantification through a literature review of articles published between 2010 and 2022. We focused only on studies using operator-based methods to treat real patients. The PubMed, Google Scholar and Embase databases were searched following PRISMA guidelines.One hundred and seven articles were identified. The mean number of patients and registrations per publication was 20 and 63, respectively. We found 23 different geometric metrics appearing at least twice, and the dosimetric impact of DIR was quantified in 32 articles. Forty-eight different at-risk organs were described, and target volumes were studied in 43 publications. Prostate, head-and-neck and thoracic locations represented more than ¾ of the studied locations. We summarized the type of DIR and the images used, and other key elements. Intra/interobserver variability, threshold values and the correlation between metrics were also discussed.This literature review covers the past decade and should facilitate the implementation of DIR algorithms in clinical practice by providing practical and pertinent information to quantify their performance on real patients.

Purpose Brain metastases (BMs) are the leading cause of intracranial malignant neoplasms in adults. WHO, Karnofsky performance status (KPS), age, number of BMs, extracerebral progression (ECP), recursive partitioning analysis (RPA), diagnosis-specific graded prognostic assessment (Ds-GPA) are validated prognostic tools to help clinicians decide on treatment. No consensus exists for repeat stereotactic radiotherapy (SRT) for BMs. The aim of this study was to review the changes in patient characteristics treated with repeated SRTs. Methods and materials The data of patients treated between 2010 and 2020 with at least two courses of SRT without previous whole brain radiotherapy (WBRT) were reviewed. Age, WHO, KPS, ECP, type of systemic treatment, number of BMs were recorded. RPA, Ds-GPA and brain metastasis velocity (BMV) were calculated. Results 184 patients were treated for 915 BMs and received two to six SRTs for local or distant brain recurrence. The median number of BMs treated per SRT was 1 (range: 1–6), for a median of 4 BMs treated during all sessions (range: 2–19). WHO, Ds-GPA and RPA were stable between each session of SRT, whereas KPS was significantly better in SRT1 than in the following SRT. The number of BMs was not significantly different between each SRT, but there was a tendency for more BM at SRT1 (p = 0.06). At SRT1, patients had largest BM and undergo more surgery than during the following SRT (p p Conclusion Repeated SRT doesn't lead to a marked alteration in the general condition, KPS was maintained at over 70% for more than 95% of patients during all SRTs. Long survival can be expected, especially in low-grade BMV patients. WBRT shouldn't be aborted, especially for patients developing more than twelve BMs annually.

International audience; Background: To describe the characteristics of the largest European study of MEC of salivary glands and to determine the prognostic factors for overall and disease free survival.Patients and methods: Patients with MEC were prospectively included in the Réseau d'Expertise Français sur les Cancers ORL Rares (REFCOR, French Network of Rare Head and Neck Tumors) database between 2009 and 2015.Results: A total of 292 patients were included. Tumors were classified as low grade in 175 cases (60%), intermediate in 39 (13%) and high grade in 78 (27%). Median follow-up was 26 months. The 5-year OS and DFS rates were respectively 83% and 69%. In multivariate analysis, age (p = 0.004), diabetes (p = 0.02) and advanced stage (p = 0.03) were found to have a significant negative impact on OS. Diabetes (p = 0.001), alcohol consumption (p = 0.003) and advanced stage (p = 0.001) were found to have a significant negative impact on DFS. Compare to low grade, high grade tended to have a negative impact on OS (p = 0.05) and had a significant effect on DFS (0.002) while intermediate grade had no significant influence on survival. The surgical treatment had a positive impact on both OS (p = 0.00005) and DFS (p = 0.0005). Postoperative radiotherapy had no impact in multivariate analysis.Conclusion: Advanced clinical stage, high grade tumor, high age, the impossibility of carrying out a complete surgical resection, and diabetes are the main prognostic factors in this prospective series of patients with MEC. Such findings open new research perspectives on the influence of these components on initial patient care.

Although some genetic alterations in glioblastoma (GBM) have been characterized, the prognostic value of these gene mutations is not yet established in patients treated with standard therapy.40 patients with newly diagnosed GBM, treated between July 2017 and December 2019, and who had genomic analysis were analyzed. Next-generation sequencing techniques (NGS) were used with a panel of 26 genes. Patients were grouped according to MGMT status, the presence or absence of at least one mutated gene on the panel, and p53 expression by immunohistochemistry.the median follow-up was 11.5 months (1.0-37). For all patients, the median duration of progression-free survival was 8 months (95% CI, 5.3-10.7) and the median overall survival (OS) was 17 months (95% CI, 7.5-26.5). Progression-free and overall survival were significantly different according to MGMT status but not according to NGS and p53 status. Three groups of patients according to different combined status could be distinguished due to significant differences in overall survival.we have shown that the presence of MGMT promoter methylation is a good prognostic factor. By grouping the patients according to their MGMT, NGS and p53 status, three groups of patients could be separated according to their overall survival. However, these results must be confirmed on a larger number of patients.

Glucosinolates in mustard leaves (Brassica juncea L.) and seeds (Brassica nigra L.) were investigated via chemical analysis of their major components and the activity of their hydrolysis products. High-performance liquid chromatography (HPLC) revealed that raw seeds have the highest amount of glucosinolates among the samples tested. Boiling of mustard leaves for 15 minutes significantly reduced the total glucosinolate content (10.94 mmol/g) to up to ~80% in comparison with the raw sample (54.31 mmol/g) which is attributed to thermal degradation of glucosinolates or leaching out to the boiling medium. Similarly, roasting of mustard seeds resulted in a marked decline in total glucosinolate content to 33.70 µmol/g compared with that of raw seed samples (86.18 µmol/g) due to thermal degradation. Liquid chromatography-mass spectrometry (LC-MS) revealed that sinigrin (allyl glucosinolate) is the major glucosinolate in mustard leaves, while the seeds contain sinigrin and gluconapin. Allyl isothiocyanate was identified as the major hydrolytic product using gas chromatography-mass spectrometry (GC-MS). The amount of isothiocyanates were quantified via cyclocondensation reaction and HPLC analysis. Boiling of leaves and roasting of seeds have no significant effect on the total isothiocyanate in comparison with the raw samples. However, the amount of isothiocyanates increases upon hydrolysis in the presence of exogenous myrosinase. Lastly, mustard leaf extracts were found to possess antioxidant properties due to its ability to scavenge free radicals as evidenced by the DPPH assay, which could be attributed to bioactive isothiocyanates inherent in the plant samples.

Exerting self-control depletes capacity for future self-control, which can promote greater alcohol use. However, certain populations may be more susceptible to these effects of depleted self-control capacity. For example, individuals with lower alcohol sensitivity (i.e., requiring more drinks to experience the effects of alcohol) are a high-risk group who are likely to engage in hazardous alcohol use and develop an alcohol use disorder. Those lower in alcohol sensitivity also exhibit heightened motivational reactivity in response to alcohol-related cues, which may be enhanced following exertion of self-control. However, whether drinkers lower in alcohol sensitivity are at higher risk for exhibiting greater motivations toward alcohol-related cues after exerting self-control is unclear. The current research examined the role of alcohol sensitivity in predicting approach motivation following exertion of self-control. It was expected drinkers exerting self-control would exhibit greater orientation toward rewarding cues, particularly after viewing alcohol-related cues. However, we predicted this pattern would be most prominent among drinkers lower in alcohol sensitivity. Experiment 1 supported these hypotheses, with lower alcohol sensitivity predicting greater approach motivation among drinkers required to exert self-control prior to viewing alcohol-related compared to neutral cues. Experiment 2 aimed to replicate these findings by assessing asymmetrical frontal cortical activation, an index of approach motivation. Drinkers with lower alcohol sensitivity exhibited greater relative left frontal cortical activation, consistent with approach motivation, while viewing alcohol-related cues following exertion of self-control. Results have implications for interventions aimed at identifying those at risk for greater alcohol motivations during states of mental exhaustion. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Risky alcohol use is prevalent among college students. Pre-intervention research has established methods of influencing alcohol cognition and reducing short-term alcohol consumption among students using evaluative conditioning (EC), repeatedly pairing alcohol with emotionally valenced images. Specifically, negative EC promotes negative attitudes toward alcohol, but additional research is needed to understand the range of EC effects and conditions under which it is or is not effective. For example, whether pairing alcohol with positive images promotes positive alcohol attitudes has not been tested. Further, drinking motives may influence the effectiveness of conditioning alcohol attitudes, since these motives are strongly associated with emotional stimuli like those presented in EC. The current experiment tested the interaction of drinking motives (coping and enhancement) and EC valence (negative or positive) on implicit alcohol avoidance. Participants (N = 95) were undergraduate students reporting active alcohol use. Results indicated no main effect of EC condition on implicit alcohol avoidance. However, drinking motives interacted with EC procedures assigned to participants. Those reporting greater coping motives exhibited less implicit alcohol avoidance following negative EC, whereas those reporting greater enhancement motives exhibited less alcohol avoidance following positive EC. Findings indicate drinking motives may influence the effectiveness of EC for altering alcohol attitudes. Negative EC did not promote alcohol avoidance among college students reporting higher coping motives, and positive EC only reduced avoidance among students reporting higher enhancement motives. These results indicate drinking motives interact with situational cues to impact both positive and negative responses to alcohol.

Between 10 and 40% of patients with cancer will develop one or more brain metastases (BMs). Stereotactic radiotherapy (SRT) is part of the therapeutic arsenal for the treatment of de novo or recurrent BM. Its main interest is to delay whole brain radiation therapy (WBRT), which may cause cognitive toxicity. However, SRT is not exempt from long-term toxicity, and the most widely known SRT is radionecrosis (RN). The objective of this study was to analyze the occurrence of RN per BM and per patient.Between 2010 and 2020, data from 184 patients treated for 915 BMs by two to six SRT sessions for local or distant brain recurrence without previous or intercurrent WBRT were retrospectively reviewed. RN was examined on trimestral follow-up MRI and potentially confirmed by surgery or nuclear medicine. For each BM and SRT session plan, summation VAt the end of follow-up, 23.0% of patients presented RN, and 6.3% of BM presented RN. Median follow-up of BM was 13.3 months (95%CI 18.3-20.8). The median interval between BM irradiation and RN was 8.7 months (95% CI 9.2-14.7). Six-, 12- and 24-month RN-free survival rates per BM were 75%, 54% and 29%, respectively. The median RN-free survival per patient was 15.3 months (95% CI 13.6-18.1). In multivariate analysis, the occurrence of RN per BM was statistically associated with local reirradiation (P0.001) and the number of SRTs (P0.001). In univariate analysis, the occurrence of RN per patient was statistically associated with the sum of all VBased on these results, a small number of BMs show RN during repeated SRT for local or distant recurrent BMs. Local reirradiation was the most predictive factor of brain RN. A V

Glioblastoma invariably recurs after primary Stupp tumor therapy and portends a poor prognosis. Cryoablation is a well-established treatment strategy for extra-cranial tumors. The safety and efficacy of interventional MR-guided cryoablation (iMRgC) has not been explored in recurrent glioblastoma.A retrospective analysis of data collected over a period of 24 months was performed. The inclusion criteria were: (I) recurrent glioblastoma despite Stupp protocol; (II) MRI followed by histological confirmation of recurrent glioblastoma; (III) location allowing iMRgC followed by microsurgical resection; and (IV) patient's consent. The primary objective was to assess feasibility in terms of complications. The secondary objective was to analyze progression-free survival (PFS), post-iMRgC survival and overall survival (OS).The study included 6 patients, with a mean age of 67±7.6 years [range, 54-70 years]. No major complications were observed. Median PFS was 7.5 months [IQR 3.75-9.75] and 6-month PFS was 50%. Median post-iMRgC survival was 9 months [IQR 7.5-15.25] and 6-month post-iMRgC survival was 80%. Median OS was 22.5 months [IQR 21.75-30].iMRgC for recurrent glioblastoma demonstrated a good safety profile, with no major complications. Our data suggest improved PFS and OS.No. IRB00011687 retrospectively registred on July 7th 2021.

Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a PAM lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes suggested a role for osteoclast-like cells in the defense against microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activity in a receptor activator of nuclear factor-κB ligand (RANKL) and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease.

The crystal structure of an unprecedented silver complex of O-acetylsinigrin has shown chelating bonds of the sulfated thiohydroximate and an η2-bond of the ethylene moiety with Ag(i). Mechanistic studies on the formation and decomposition of the complex by the 1H NMR measurements and theoretical calculations with the DFT method indicated relevance to the glucosinolate degradation in biological systems.

A highly sensitive bismuth/silver nanoparticles/Nafion-modified screen-printed graphene electrode was fabricated and was utilized for the detection of trace lead (Pb) concentrations in river water samples prior to and after remediation using calamansi (Citrofortunella Microcarpa) rinds in different forms viz., ground sun-dried, dry-ashed, food-grade pectin, fractionated pectin, and alcohol insoluble solids—extracted pectin. All these forms of pectin remediated Pb in the water samples. Hence, this novel method of using calamansi rinds in different forms is an effective method for the removal of lead in water. The electrode was characterized using scanning electron microscopy and energy dispersive x-ray spectrometry which confirmed the presence of the modifiers on the electrode surface. The limit of detection of 267.6 ppt and the strong linear relationship between the Pb concentration and the anodic current response (R2 = 0.999) were obtained under optimized experimental conditions and parameters.

Studies have shown different effects of Raphanus sativus L. (RS) extract on different cancer cell types. However, the dynamics of gene regulation between RS and cancer is still unknown. In this study, a mathematical model was incorporated to link cell cycle regulation pathways associated with the pharmacognosy of radish extracts towards breast cancer (BC), chronic myelogenous leukemia (CML), and colorectal cancer (CC). The cell cycle regulation pathways considered were MAPK/ERK and PI3K/Akt signaling pathways. A model created using ordinary differential equations was used to simulate the steady state concentrations of the proteins in both pathways, before and after exposure to radish extracts. Among the proteins ubiquitous in these pathways, Cyclin D1-CDK complex and p53 were found to be predominantly dysregulated in most cancers. The expression of these proteins was used as the benchmark of the pharmacognosy of radish extracts. Our simulation showed a decreasing trend in the binding specificities (\(K_M\)) of RS with Cyclin D1-CDK complex and p53 respectively from CML \(\left[ 5\,\upmu \mathrm{M}, 100 \,\upmu \mathrm{M}\right] \), CC \([2.5 \times 10^{-2}\,\upmu \mathrm{M}, 10\,\upmu \mathrm{M}]\) up to BC \([10^{-6}\,\upmu \mathrm{M}, 10^{-3}\,\upmu \mathrm{M}]\) which led to a decrease in Cyclin D1-CDK complex (90.74% for BC, 73.42% for CC, 1.10% for CML) and an increase in p53 (83.47% for BC, 62.75% for CC, 5.69% for CML). This suggests that the anticancer activity of RS was through the moderation of cell proliferation and induction of apoptosis in malignant neoplasms. Hence, the model proposed that RS had high chemotherapeutic activity on BC while having moderate efficacy on CC and insignificant efficacy on CML as substantiated by cytotoxicity assays on MCF-7 and HT-29 which both exhibited \(IC_{50} 100\,\upmu \)g/mL.

The present experiment assessed implicit alcohol motivations and explicit alcohol expectancies following the interaction between alcohol-congruent (i.e. social drinking) versus incongruent (i.e. driving safety) goal primes and recent drinking habits among college students ( n = 176). Heavy drinkers exhibited greater implicit alcohol approach and explicit tension reduction expectancies following social goal primes, while displaying greater implicit alcohol avoidance and explicit cognitive and behavioural impairment expectancies after driving safety goal primes. These findings indicate recent drinking habits interact with goal salience to influence explicit and implicit responses to alcohol, which has implications for the development of interventions to reduce college drinking.

Introduction Au cours de ces dernieres annees, l’evaluation de la qualite de vie liee a la sante est devenue un objectif majeur dans la prise en charge des patients en cancerologie. La qualite de vie comme facteur pronostique a ete etudiee dans plusieurs etudes. Toutefois, dans ces differentes etudes, le role pronostique de la qualite de vie semble limite a la prediction de la survie. L’objectif de ce travail est de demontrer le role pronostique de la qualite de vie dans la survie des toxicites majeures chez les patients atteints d’un cancer de la tete et du cou. Methodes Cette etude a ete realisee a partir des donnees d’un essai randomise phase III ( NCT01210872 ) portant sur l’impact de l’evaluation en routine de la qualite de vie de 200 patients atteints d’un cancer de la tete et du cou non-metastatique et qui recevaient la radiotherapie comme traitement premier traitement initial dans l’un des quatre centres de cancerologie du grand EST. La qualite de vie a l’inclusion a ete evaluee a l’aide du questionnaire EORTC QLQ-C30 et d’un module specifique au cancer de la tete et du cou EORTC-QLQ-HN 82,7 (24) ; 73 (22,9) ; 89,1 (17,6) ; 83,8 (23,8), respectivement pour le fonctionnement physique, les activites courantes, le fonctionnement emotionnel, le fonctionnement cognitif et le fonctionnement social. Le suivi median etait de 24 mois et 41 patients (20,5 %) ont presente une toxicite majeure. En analyses multivariables ajustees, seule la dimension etat de sante global etait statistiquement associee a la survenue de toxicite majeure. Le HR associe a une augmentation de 10 points de l’etat de sante global etait 0,77 (IC99 %= [0,60-0,93], p = 0,0073). Les dimensions fonctionnelles n’etaient pas statistiquement associees a la toxicite majeure (p > 0,01). Conclusion L’etat de sante global s’est presente comme un facteur pronostique independant des toxicites majeures. L’implementation en pratique clinique de l’evaluation de la qualite de vie avant la radiotherapie devrait etre encouragee afin d’identifier les patients a risque de developper des toxicites chez les patients atteints d’un cancer de la tete et du cou.

Stereotactic radiotherapy has become a standard in the management of patients with brain metastases; its main interest is to differ whole brain radiotherapy, provider of neurocognitive toxicity and to increase the rate of local control. The repetition of radiotherapy sessions under stereotactic conditions is not codified, neither on the number of technically and clinically possible sessions, nor on the maximum total number or volume of metastases to be treated. The purpose of this review is to analyse the data in the literature concerning repeated irradiations under stereotactic conditions. The second reirradiation in stereotactic condition shows satisfactory results in terms of overall survival, local control, and toxicity. However, we lack data for patients receiving more than two sessions of SRS as well as to define dose constraints to reirradiated healthy tissues. Prospective trials are still needed to validate the management of recurrent brain metastases after initial SRS.

Alcohol attitudes predict unique variance in drinking behavior and have been the target of manipulations and interventions to reduce high-risk alcohol use among youth and adults. However, whether these manipulations create long-lasting changes in alcohol-related attitudes and drinking behavior is unclear. The current mini-review focuses on evaluative conditioning (EC), a manipulation which pairs alcohol-related stimuli repeatedly with affectively valanced stimuli to create new semantic associations in memory; such associations underlie reflexive or impulsive behaviors like high-risk alcohol use. Across experimental studies, EC has been shown to promote negative alcohol attitudes and reduce alcohol consumption. However, recent evidence suggests the effectiveness of EC may depend on the depth of learning facilitated during the task, which may strengthen the semantic associations through propositional learning. While researchers have experimentally promoted greater depth of learning through the manipulation of contextual factors, we review evidence that alcohol-related individual differences also impact the effectiveness of alcohol EC, particularly when these factors are explicitly linked to the stimuli used during the manipulation. This review provides future directions for researchers and practitioners aiming to shape alcohol-related attitudes and behaviors. Specifically, the malleability of alcohol-related attitudes may depend on propositional learning facilitated by contextual and individual factors. Researchers and practitioners should incorporate these factors into interventions like EC aiming to reduce high-risk alcohol consumption.

Pelvic bone marrow is the site of nearly 50% of total hematopoiesis. Radiation therapy of pelvic lymph node areas, and cancers located near the bony structures of the pelvis, exposes to hematological toxicity in the range of 30 to 70%. This toxicity depends on many factors, including the presence or absence of concomitant chemotherapy and its type, the volume of irradiated bone, the received doses, or the initial hematopoietic reserve. Intensity modulated radiation therapy allows the optimisation of dose deposit on at risk organs while providing optimal coverage of target volumes. However, this suggests that dose constraints should be known precisely to limit the incidence of radiation side effects. This literature review focuses firstly on pelvic lymph node areas and bony volumes nearby, then on the effects of irradiation on bone marrow and the current dosimetric constraints resulting from it, and finally on hematological toxicities by carcinologic location and progress in reducing these toxicities.

International audience; BACKGROUND:Head and neck mucosal melanoma (HNMM) is aggressive and rare, with a poor prognosis because of its high metastatic potential. The two main subtypes are sinonasal (sinonasal mucosal melanoma [SNMM]) and oral cavity (oral cavity mucosal melanoma [OCMM]). Consensual therapeutic guidelines considering the primary tumour site and tumour-node-metastasis (TNM) stage are not well established.MATERIAL & METHODS:Patients with HNMM from the prospective national French Rare Head and Neck Cancer Expert Network database between 2000 and 2017 were included. Clinical characteristics, treatment modalities, outcomes and prognostic factors were analysed.RESULTS:In total, 314 patients were included. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 49.4% and 24.7%, respectively, in the surgery group; no long-term survivors were observed when surgery was not feasible. Moreover, even after surgery, a high recurrence rate was reported with a median PFS of 22 months. In multivariate analysis, Union for International Cancer Control (UICC) stage and tumour site correlated with PFS and OS. Postoperative radiotherapy (PORT) improved the PFS but not OS in patients with small (T3) SNMM and OCMM tumours. Nodal involvement was more frequent in patients with OCMM (p < 10-4), although, as in SNMM, it was not a significant prognostic predictor.CONCLUSION:Even early HNMM was associated with poor oncologic outcomes due to distant metastases despite surgical resection with clear margins. Lymph node metastases had no impact on the prognosis, suggesting treatment de-escalation in cervical node management. PORT might be useful for local control.

International audience; Anaplastic oligodendroglioma (AO), IDH‐mutant and 1p/19q codeleted (IDHmut+/1p19qcodel), is a high‐grade glioma with only limited prognostic markers. The primary objective of this study was to evaluate, by immunohistochemistry, the prognostic value of two proliferation markers, MCM6 and Ki‐67, in a large series of IDHmut+/1p19qcodel AO included in the POLA (“Prise en charge des Oligodendrogliomes Anaplasiques”) French national multicenter network. We additionally examined the transcriptome obtained from this series to understand the functional pathways dysregulated with the mRNA overexpression of these two markers. The labelling indices (LI) of MCM6 and Ki‐67 were obtained via computer‐assisted color image analyses on immunostained AO tissues of the cohort (n=220). Furthermore, a subgroup of AO (n=68/220) was used to perform transcriptomic analyses. A high LI of either MCM6 (≥50%) or Ki‐67 (≥ 15%) correlated with shorter overall survival, both in univariate (P=0.013 and P=0.004, respectively) and multivariate analyses (P=0.027; multivariate Cox model including age, mitotic index, MCM6 and Ki‐67). MCM6 and Ki‐67 LI also correlated with overall survival in an additional retrospective cohort of 30 grade II IDHmut+/1p19qcodel oligodendrogliomas. The prognostic value of MCM6 mRNA level was confirmed in The Cancer Genome Atlas (TCGA) IDHmut+/1p19qcodel gliomas. The transcriptomic approach revealed that high transcriptional expressions of MCM6 and MKI67 were both linked positively with cell cycle progression, DNA replication, mitosis, pro‐neural phenotype as well as neurogenesis, and negatively with microglial cell activation, immune response, positive regulation of myelination, oligodendrocyte development, beta‐amyloid binding, and postsynaptic specialization.In conclusion, the overexpression of MCM6 and/or Ki‐67 is independently associated to shorter overall survival in IDHmut+/1p19qcodel AO. These two easy‐to‐use and cost‐effective markers could thus be used concurrently in routine pathology practice. Additionally, the transcriptomic analyses showed that AO with high proliferation index have down‐regulated immune response and lower microglial cells activation, and bears pro‐neural phenotype.

No recommandations have been established for reirradiation of brain metastases yet. The purpose of this review is to analyse the data of the five last years about the feasibility, efficacy and tolerance of reirradiation of brain metastases. Reirradiation can be 3D conformal or stereotactic. Whole brain irradiation seems appropriate for multiple brain metastases in order to obtain symptomatic relief, with or without supportive care. Stereotactic reirradiation has shown satisfying results in terms of overall survival, local control, without significant toxicity. Prospective trials are necessary in order to validate consensual recommandations.

Stereotactic radiation therapy of brain metastases is a treatment recognized as effective, well tolerated, applicable for therapeutic indications codified and validated by national and international guidelines. However, the effectiveness of this irradiation, the evolution of patient care and the technical improvements enabling its implementation make it possible to consider it in more complex situations: proximity of brain metastases to organs at risk; large, cystic, haemorrhagic or multiple brain metastases, combination with targeted therapies and immunotherapy, stereotactic radiotherapy in patients with a pacemaker. This article aims to put forward the arguments available to date in the literature and those resulting from clinical practice to provide decision support for the radiation oncologists.

Heavy episodic drinking (HED) is a dangerous and pervasive problem in college populations. Two experiments examined the asymmetric effects of evaluative conditioning (EC) on cognitions underlying HED in a nonclinical, student sample. Based on the associative-propositional evaluation (APE) model, we predicted that negative EC would result in stronger implicit alcohol avoidance motivation compared to neutral EC but would not impact explicit alcohol expectancies; further, we hypothesized stronger negative EC effects among students reporting HED compared to light drinkers. Experiment 1 supported these hypotheses. In Experiment 2, participants were required to focus on either feelings or knowledge about alcohol following EC. Replicating Experiment 1, negative EC was effective in promoting implicit alcohol avoidance motivation among students reporting HED compared to neutral EC, whereas no differences in explicit alcohol expectations or urges emerged. However, greater implicit alcohol avoidance predicted lower explicit alcohol urges among participants instructed to focus on alcohol-related feelings, but not alcohol-related knowledge, regardless of condition. Findings suggest students reporting HED, but not light drinkers, may exhibit implicit alcohol avoidance following negative EC and that instructions to focus on alcohol-related feelings may align explicit and implicit responses. Results have implications for interventions aimed at retraining implicit alcohol cognitions among college students. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Off-site consultations by board-certified veterinary radiologists benefit residents and emergency clinicians by providing immediate feedback and potentially improving patient outcome. Smartphone devices and compressed images transmitted by email or text greatly facilitate availability of these off-site consultations. Criticism of a smartphone interface for off-site consultation is mostly directed at image degradation relative to the standard radiographic viewing room and monitors. The purpose of this retrospective, cross-sectional, methods comparison study was to compare the accuracy of abdominal radiographs in two imaging interfaces (Joint Photographic Experts Group, off-site, smartphone vs. Digital Imaging and Communications in Medicine, on-site, standard workstation) for the diagnosis of small intestinal mechanical obstruction in vomiting dogs and cats. Two board-certified radiologists graded randomized abdominal radiographs using a five-point Likert scale for the presence of mechanical obstruction in 100 dogs or cats presenting for vomiting. The area under the receiver operator characteristic curves for both imaging interfaces was high. The accuracy of the smartphone and traditional workstation was not statistically significantly different for either reviewer (P = 0.384 and P = 0.536). Correlation coefficients were 0.821 and 0.705 for each reviewer when the same radiographic study was viewed in different formats. Accuracy differences between radiologists were potentially related to years of experience. We conclude that off-site expert consultation with a smartphone provides an acceptable interface for accurate diagnosis of small intestinal mechanical obstruction in dogs and cat.

Researchers have developed many different computerized interventions designed to teach students about the dangers of substance use. Following in this tradition, we produced a series of video games called Bacon Brains. However, unlike many other programs, ours focused on the “Science of Addiction,” providing lessons on how alcohol and other drugs affect the brain. The purpose of this study was to evaluate the effectiveness of our games in teaching students our science-based curriculum. We enrolled over 200 students and randomly assigned them to play our games or a different series of NIDA-produced games. Of the students in the Bacon Brains conditions, half were instructed to play collaboratively and the other half was told to play competitively. Results indicate significantly greater knowledge gains among students in Bacon Brains compared to the existing games (5.01 mean knowledge score difference; [F(1,242)=9.588, p=.002]). Girls demonstrated knowledge gains in both collaborative and competitive conditions, but boys demonstrated similar gains only in the competitive condition. Based on our outcomes, we conclude that video games can serve as an effective method of science instruction. We further discuss the importance of considering gender differences in light of differential response to collaborative vs. competitive learning environments.

Since decades, stereotactic radiotherapy has spread out worldwide. Published results are very numerous. To clarify obviousness among all the publications, this recommendation review was written. Voluntarily, authors limited analysis of international best evidence literature on malignant tumors of lung, liver, prostate, head and neck, and metastasis of bone and brain. These data could be used to advance standardization and quality improvement of treatments performed in the nationwide radiotherapy departments and can provide useful guidance for centers worldwide.

Glioblastoma is the most frequent primary brain tumor, with more than half of all patients being at least 65 years old. The treatment of the elderly in this pathology represents therefore a considerable challenge for oncologists and radiation therapists. However, in most clinical trials, age is a non-eligible criterial. In the last ten years, geriatric therapeutic trials have been multiplied. The treatment of glioblastoma consists of adjuvant chemoradiotherapy. In elderly patients, the evaluation of performans status and the molecular characteristics of the tumor are important factors in order to propose the appropriate treatment in terms of efficacy and toxicity.