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Tumor-associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs is controlled by long-chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en-route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAMs and tumor growth in vivo. In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate-induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro-tumoral myeloid cells on a metabolic level.
While the consequences of cyberbullying victimization have received some attention in the literature, to date, little is known about the multiple types of strains in adolescents’ lives, such as whether cyberbullying victimization and peer rejection increase their vulnerability to depression and anxiety. Even though some research found that adolescents with disabilities show higher risk for cyberbullying victimization, most research has focused on typically developing adolescents. Thus, the present study focused on examining the moderating effect of peer rejection in the relationships between cyberbullying victimization, depression, and anxiety among adolescents with autism spectrum disorder. There were 128 participants (89% male; ages ranging from 11–16 years old) with autism spectrum disorder in the sixth, seventh, or eighth grade at 16 middle schools in the United States. Participants completed questionnaires on cyberbullying victimization, peer rejection, depression, and anxiety. Results revealed that cyberbullying victimization was associated positively with peer rejection, anxiety, and depression among adolescents with autism spectrum disorder. Further, peer rejection was linked positively with depression and anxiety. Peer rejection moderated the positive relationship between cyberbullying victimization and depression, but not anxiety. Implications for prevention programs and future research are discussed.
While the consequences of cyberbullying victimization have received some attention in the literature, to date, little is known about the multiple types of strains in adolescents’ lives, such as whether cyberbullying victimization and peer rejection increase their vulnerability to depression and anxiety. Even though some research found that adolescents with disabilities show higher risk for cyberbullying victimization, most research has focused on typically developing adolescents. Thus, the present study focused on examining the moderating effect of peer rejection in the relationships between cyberbullying victimization, depression, and anxiety among adolescents with autism spectrum disorder. There were 128 participants (89% male; ages ranging from 11–16 years old) with autism spectrum disorder in the sixth, seventh, or eighth grade at 16 middle schools in the United States. Participants completed questionnaires on cyberbullying victimization, peer rejection, depression, and anxiety. Results revealed that cyberbullying victimization was associated positively with peer rejection, anxiety, and depression among adolescents with autism spectrum disorder. Further, peer rejection was linked positively with depression and anxiety. Peer rejection moderated the positive relationship between cyberbullying victimization and depression, but not anxiety. Implications for prevention programs and future research are discussed.
Research question: The purpose of this study was to evaluate the test-retest reliability of lower extremity kinematics during squat, hip abduction and lunge exercises captured by the Kinect and to evaluate the agreement to a reference 3D camera-based motion system. Methods: Twenty-one healthy individuals performed five repetitions of each lower limb exercise on two different days. Movements were simultaneously assessed by the Kinect and the reference 3D motion system. Joint angles and positions of the lower limb were calculated for sagittal and frontal plane. For the inter-session reliability and the agreement between the two systems standard error of measurement (SEM), bias with limits of agreement (LoA) and Pearson Correlation Coefficient (r) were calculated. Results: Parameters indicated varying reliability for the assessed joint angles and positions and decreasing reliability with increasing task complexity. Across all exercises, measurement deviations were shown especially for small movement amplitudes. Variability was acceptable for joint angles and positions during the squat, partially acceptable during the hip abduction and predominately inacceptable during the lunge. The agreement between systems was characterized by systematic errors. Overestimations by the Kinect were apparent for hip flexion during the squat and hip abduction/adduction during the hip abduction exercise as well as for the knee positions during the lunge. Knee and hip flexion during hip abduction and lunge were underestimated by the Kinect. Significance: The Kinect system can reliably assess lower limb joint angles and positions during simple exercises. The validity of the system is however restricted. An application in the field of early orthopedic rehabilitation without further development of post-processing techniques seems so far limited.
Background: Chronic kidney disease (CKD) is a frequent comorbidity among elderly patients and those with cardiovascular disease. CKD carries prognostic relevance. We aimed to describe patient characteristics, risk factor management and control status of patients in cardiac rehabilitation (CR), differentiated by presence or absence of CKD.
Design and methods: Data from 92,071 inpatients with adequate information to calculate glomerular filtration rate (GFR) based on the Cockcroft-Gault formula were analyzed at the beginning and the end of a 3-week CR stay. CKD was defined as estimated GFR <60 ml/min/1.73 m(2).
Results: Compared with non-CKD patients, CKD patients were significantly older (72.0 versus 58.0 years) and more often had diabetes mellitus, arterial hypertension, and atherothrombotic manifestations (previous stroke, peripheral arterial disease), but fewer were current or previous smokers had a CHD family history. Exercise capacity was much lower in CKD (59 vs. 92Watts). Fewer patients with CKD were treated with percutaneous coronary intervention (PCI), but more had coronary artery bypass graft (CABG) surgery. Patients with CKD compared with non-CKD less frequently received statins, acetylsalicylic acid (ASA), clopidogrel, beta blockers, and angiotensin converting enzyme (ACE) inhibitors, and more frequently received angiotensin receptor blockers, insulin and oral anticoagulants. In CKD, mean low density lipoprotein cholesterol (LDL-C), total cholesterol, and high density lipoprotein cholesterol (HDL-C) were slightly higher at baseline, while triglycerides were substantially lower. This lipid pattern did not change at the discharge visit, but overall control rates for all described parameters (with the exception of HDL-C) were improved substantially. At discharge, systolic blood pressure (BP) was higher in CKD (124 versus 121 mmHg) and diastolic BP was lower (72 versus 74 mmHg). At discharge, 68.7% of CKD versus 71.9% of non-CKD patients had LDL-C <100 mg/dl. Physical fitness on exercise testing improved substantially in both groups. When the Modification of Diet in Renal Disease (MDRD) formula was used for CKD classification, there was no clinically relevant change in these results.
Conclusion: Within a short period of 3-4 weeks, CR led to substantial improvements in key risk factors such as lipid profile, blood pressure, and physical fitness for all patients, even if CKD was present.
Understanding and quantifying total economic impacts of flood events is essential for flood risk management and adaptation planning. Yet, detailed estimations of joint direct and indirect flood-induced economic impacts are rare. In this study an innovative modeling procedure for the joint assessment of short-term direct and indirect economic flood impacts is introduced. The procedure is applied to 19 economic sectors in eight federal states of Germany after the flood events in 2013. The assessment of the direct economic impacts is object-based and considers uncertainties associated with the hazard, the exposed objects and their vulnerability. The direct economic impacts are then coupled to a supply-side Input-Output-Model to estimate the indirect economic impacts. The procedure provides distributions of direct and indirect economic impacts which capture the associated uncertainties. The distributions of the direct economic impacts in the federal states are plausible when compared to reported values. The ratio between indirect and direct economic impacts shows that the sectors Manufacturing, Financial and Insurance activities suffered the most from indirect economic impacts. These ratios also indicate that indirect economic impacts can be almost as high as direct economic impacts. They differ strongly between the economic sectors indicating that the application of a single factor as a proxy for the indirect impacts of all economic sectors is not appropriate.
Understanding and quantifying total economic impacts of flood events is essential for flood risk management and adaptation planning. Yet, detailed estimations of joint direct and indirect flood-induced economic impacts are rare. In this study an innovative modeling procedure for the joint assessment of short-term direct and indirect economic flood impacts is introduced. The procedure is applied to 19 economic sectors in eight federal states of Germany after the flood events in 2013. The assessment of the direct economic impacts is object-based and considers uncertainties associated with the hazard, the exposed objects and their vulnerability. The direct economic impacts are then coupled to a supply-side Input-Output-Model to estimate the indirect economic impacts. The procedure provides distributions of direct and indirect economic impacts which capture the associated uncertainties. The distributions of the direct economic impacts in the federal states are plausible when compared to reported values. The ratio between indirect and direct economic impacts shows that the sectors Manufacturing, Financial and Insurance activities suffered the most from indirect economic impacts. These ratios also indicate that indirect economic impacts can be almost as high as direct economic impacts. They differ strongly between the economic sectors indicating that the application of a single factor as a proxy for the indirect impacts of all economic sectors is not appropriate.
BACKGROUND: Pavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. METHODS: Recently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. RESULTS: When training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging-based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Delta = -24.4 +/- 6.0 g vs. -5.7 +/- 3.6 g; p = .019). CONCLUSIONS: These results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states.
Impact of self-assessment of return to work on employable discharge from multi-component cardiac rehabilitation. Retrospective unicentric analysis of routine data from cardiac rehabilitation in patients below 65 years of age. Presentation in the "Cardiovascular rehabilitation revisited" high impact abstract session during ESC Congress 2018.
Plants located adjacent to agricultural fields are important for maintaining biodiversity in semi-natural landscapes. To avoid undesired impacts on these plants due to herbicide application on the arable fields, regulatory risk assessments are conducted prior to registration to ensure proposed uses of plant protection products do not present an unacceptable risk. The current risk assessment approach for these non-target terrestrial plants (NTTPs) examines impacts at the individual-level as a surrogate approach for protecting the plant community due to the inherent difficulties of directly assessing population or community level impacts. However, modelling approaches are suitable higher tier tools to upscale individual-level effects to community level. IBC-grass is a sophisticated plant community model, which has already been applied in several studies. However, as it is a console application software, it was not deemed sufficiently user-friendly for risk managers and assessors to be conveniently operated without prior expertise in ecological models. Here, we present a user-friendly and open source graphical user interface (GUI) for the application of IBC-grass in regulatory herbicide risk assessment. It facilitates the use of the plant community model for predicting long-term impacts of herbicide applications on NTTP communities. The GUI offers two options to integrate herbicide impacts: (1) dose responses based on current standard experiments (acc. to testing guidelines) and (2) based on specific effect intensities. Both options represent suitable higher tier options for future risk assessments of NTTPs as well as for research on the ecological relevance of effects.