New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant ...therapy with the arginine-depleting agent ADI-PEG20 in a non-arginine-auxotrophic cellular background (argininosuccinate synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response, with extended disease-free survival in an orthotopic immune-competent model of GBM, with no significant toxicity. ADI-PEG20 not only enhanced the cellular sensitivity of argininosuccinate synthetase 1-positive GBM to ionizing radiation by elevated production of nitric oxide (˙NO) and hence generation of cytotoxic peroxynitrites, but also promoted glioma-associated macrophage/microglial infiltration into tumors and turned their classical antiinflammatory (protumor) phenotype into a proinflammatory (antitumor) phenotype. Our results provide an effective, well-tolerated, and simple strategy to improve GBM treatment that merits consideration for early evaluation in clinical trials.
This paper addresses the differential impacts on decisions towards collective action in the context of payments for ecosystem services (PES) where individual and collective rewards are conditional on ...a minimum collective conservation level being achieved. Interactions between the different reward types, farmers' social preferences, social ties and communication are identified. A field game experiment is conducted with Andean farmers in Peru and framed around their decisions to conserve agrobiodiversity as an impure public good. The main results are that PES schemes could be effective in motivating collective action for agrobiodiversity conservation and that individual rewards are likely to be more effective and less sensitive to social factors than collective rewards. The latter might have a positive effect on conservation when they are shared within socially closely-related groups or in situations where communication and deliberation about collective action are possible.
•We study the impact of PES in the context of agricultural biodiversity conservation.•A framed field experiment was conducted with Peruvian farmers in the Andes.•Results show that generally individual rewards outperform collective rewards.•Collective rewards perform best when communication is allowed for or in socially close groups.
Lynch syndrome (LS) is a hereditary condition that increases the risk for endometrial and other cancers. The identification of endometrial cancer (EC) patients with LS has the potential to influence ...life-saving interventions. We aimed to study the prevalence of LS among EC patients in our population.
Universal screening for LS was applied for a consecutive series EC. Tumor testing using microsatellite instability (MSI), immunohistochemistry (IHC) for mismatch-repair (MMR) protein expression and MLH1-methylation analysis, when required, was used to select LS-suspicious cases. Sequencing of corresponding MMR genes was performed.
One hundred and seventy-three EC (average age, 63 years) were screened. Sixty-one patients (35%) had abnormal IHC or MSI results. After MLH1 methylation analysis, 27 cases were considered suspicious of LS. From these, 22 were contacted and referred for genetic counseling. Nineteen pursued genetic testing and eight were diagnosed of LS. Mutations were more frequent in younger patients (<50 yrs). Three cases had either intact IHC or MSS and reinforce the need of implement the EC screening with both techniques.
The prevalence of LS among EC patients was 4.6% (8/173); with a predictive frequency of 6.6% in the Spanish population. Universal screening of EC for LS is recommended.
Alterations in DNA methylation patterns have been found to correlate with several diseases including osteoarthritis (OA). The aim of this study was to identify, for the first time, the genome-wide ...DNA methylation profiles of human articular chondrocytes from OA cartilage and healthy control cartilage samples.
DNA methylation profiling was performed using Illumina Infinium HumanMethylation27 in 25 patients with OA and 20 healthy controls. Subsequent validation was performed by genome-wide expression analysis using the Affymetrix Human Gene 1.1 ST array in an independent cohort of 24 patients with OA. Finally, the most consistent genes in both assays were amplified by quantitative reverse transcriptase PCR in a validation cohort of 48 patients using microfluidic real-time quantitative PCR. Appropriate bioinformatics analyses were carried out using R bioconductor software packages and qBase plus software from Biogazelle.
We found 91 differentially methylated (DM) probes, which permitted us to separate patients with OA from healthy controls. Among the patients with OA, we detected 1357 DM probes that identified a tight cluster of seven patients who were different from the rest. This cluster was also identified by genome-wide expression in which 450 genes were differentially expressed. Further validation of the most consistent genes in an independent cohort of patients with OA permitted us to identify this cluster, which was characterised by increased inflammatory processes.
We were able to identify a tight subgroup of patients with OA, characterised by an increased inflammatory response that could be regulated by epigenetics. The identification and isolation of this subgroup may be critical for the development of effective treatment and disease prevention.
Data acquisition is a crucial stage in the execution of condition monitoring (CM) of rotating machinery, by means of vibration analysis. However, the major challenge in the execution of this ...technique lies in the features of the recording equipment (accuracy, resolution, sampling frequency and number of channels) and the cost they represent. The present work proposes a low-cost data acquisition system, based on Raspberry-Pi, with a high sampling frequency capacity in the recording of up to three channels. To demonstrate the effectiveness of the proposed data acquisition system, a case study is presented in which the vibrations registered in a bearing are analyzed for four degrees of failure.
(1) Background: parenteral nutrition (PN) is indispensable for patients unable to receive oral or enteral feeding. However, the complexity of PN solutions presents challenges regarding stability and ...compatibility. Precipitation reactions may occur. The most frequent is the formation of calcium phosphate (Ca-P). The different factors influencing these reactions must be considered to ensure patient safety. (2) Methods: eight paediatric PN solutions were prepared, following standard protocols. Samples were stored at room temperature and in a refrigerator. Electron microscopy, coupled with energy dispersive X-ray spectroscopy (EDS), was employed. Precipitates were analysed for composition and morphology. (3) Results: precipitates were observed in all samples, even at day 0. Crystalline structures, predominantly composed of calcium or magnesium, sometimes associated with chlorine or phosphorus, were detected. Additionally, amorphous precipitates, contained heterogeneous compositions, including unexpected elements, were identified. (4) Conclusions: various precipitates, primarily calcium- or magnesium-based, can form in PN solutions, although it is not expected that they can form under the real conditions of use. Calcium oxalate precipitation has been characterised, but the use of organic calcium and phosphate salts appears to mitigate calcium phosphate precipitation. Electron microscopy provides interesting results on NP precipitation, but sample preparation may present technical limitations that affect the interpretation of the results.
In this research, we describe an actuation and control system designed for geared electromagnetic motors, which is characterized by its simple implementation, fast response to external input loads, ...reliable human-machine interaction features, no need for previous set-up or calibration from user to user and high portability due to the reduction of weight and space used. By the implementation of the proposed system, an electromagnetic motor can become a multitasking, wearable actuation system capable of: detecting the user's intentions regarding motion, tracking the limbs with minimal force interaction within a wide bandwidth and also providing controllable assistance and resistance forces to the user's movements, without the use of any biological signal. Validation of the proposed approach is shown by the construction of a powered orthosis for the knee, used to test the system's performance under real human motion conditions. The proposed system was tested on one healthy subject by measuring electromyographic levels both with and without the orthosis, under controlled flexion and extension cycles. Experimental results demonstrate the effectiveness of the proposed approach in detecting the user's intentions regarding motion, reducing and increasing muscular activity when configured for assistance and resistance, respectively, and also increasing the transparency of the actuation system when perfect tracking of the limbs is needed.
The importance of cardiometabolic factors in the inception and progression of atherosclerotic cardiovascular disease is increasingly being recognized. Beyond diabetes mellitus and metabolic syndrome, ...other factors may be responsible in patients with chronic kidney disease (CKD) for the high prevalence of cardiovascular disease, which is estimated to be 5- to 20-fold higher than in the general population. Although undefined uremic toxins are often blamed for part of the increased risk, visceral adipose tissue, and in particular epicardial adipose tissue (EAT), have been the focus of intense research in the past two decades. In fact, several lines of evidence suggest their involvement in atherosclerosis development and its complications. EAT may promote atherosclerosis through paracrine and endocrine pathways exerted via the secretion of adipocytokines such as adiponectin and leptin. In this article we review the current knowledge of the impact of EAT on cardiovascular outcomes in the general population and in patients with CKD. Special reference will be made to adiponectin and leptin as possible mediators of the increased cardiovascular risk linked with EAT.
This paper formulates the necessity of developing a new territorial culture, built from the complex and dynamic concept of landscape and geared towards the formulation of strategies for development ...and feasibility. This approach, based on the European Landscape Convention, requires a transdisciplinary perspective, and even though it's still novel, it's not only appropriate, but can be considered essential for some European rural cross-border territories marked by important economic and demographic problems, whose viability, in a globalization context, depends on the search for developmental alternatives and the creation of new territorial networks.
Few studies have focused on patients' emotional distress with end-stage chronic obstructive pulmonary disease (COPD) and their main family caregivers.
Cross-sectional data about emotional, ...functional, and burden-related variables were collected from 85 patients with end-stage COPD and their 85 respective main family caregivers to determine the variables that could predict their emotional well-being. Descriptive analyses, comparison of means, hierarchical regression models, and comparative quali-quantitative analyses were carried out.
Data show that the great majority of patients with COPD spend years with this diagnosis, and have been admitted to the hospital several times in advance stage of illness the previous year of the moment of end-of-life stage. Furthermore, only a tiny percentage of the patients were functionally independent in the advanced stage of illness.
The emotional distress and the burden of the family caregiver play an essential role in the distress of the patient, in conjunction with the patient's own functional independence and the time living with the disease, and comorbidity. On the other hand, variables of the patient, such as time since diagnosis, number of hospital admissions, comorbidity, functional dependence, and emotional distress, play an important role in the family caregiver's emotional distress and burden. Understanding how these variables are related is key to designing appropriate programs to reduce the emotional distress the patients with COPD at the end of life and their family caregivers.
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