GM-CSF in glomerulonephritisDespite glomerulonephritis being an immune-mediated disease, the contributions of individual immune cell types are not clear. To address this gap in knowledge, Paust
. ...characterized pathological immune cells in samples from patients with glomerulonephritis and in samples from mice with the disease. The authors found that CD4+ T cells producing granulocyte-macrophage colony-stimulating factor (GM-CSF) licensed monocytes to promote disease by producing matrix metalloproteinase 12 and disrupting the glomerular basement membrane. Targeting GM-CSF to inhibit this axis reduced disease severity in mice, implicating this cytokine as a potential therapeutic target for patients with glomerulonephritis. -CM.
Objective
Acute pancreatitis (AP) is an inflammatory disorder, the severe form of which is burdened with multi-organ dysfunction and high mortality. The pathogenesis of life –threatening organ ...complications, such as respiratory and renal failure, is unknown.
Design
Organ dysfunction was investigated in a mouse model of AP. The influence of monocytes and neutrophils on multi organ dysfunction syndrome (MODS) was investigated
in vivo
by antibody depletion. Using real-time-fluorescence and deformability-cytometry (RT-DC) analysis we determined the mechanical properties of neutrophils and monocytes during AP. Furthermore, blood samples of pancreatitis patients were used to characterize severity-dependent chemokine profiles according to the revised Atlanta classification.
Results
Similar to AP in humans, severe disease in the mouse model associates with organ dysfunction mainly of lung and kidney, which is triggered by a mobilisation of Ly6g
-
/CD11b
+
/Ly6c
hi
monocytes, but not of Ly6g
+
/CD11b
+
neutrophils. Monocyte depletion by anti-CCR2 antibody treatment ameliorated lung function (oxygen consumption) without interfering with the systemic immune response. RT-DC analysis of circulation monocytes showed a significant increase in cell size during SAP, but without a compensatory increase in elasticity. Patient chemokine profiles show a correlation of AP severity with monocyte attracting chemokines like MCP-1 or MIG and with leukocyte mobilisation.
Conclusion
In AP, the physical properties of mobilized monocytes, especially their large size, result in an obstruction of the fine capillary systems of the lung and of the kidney glomeruli. A selective depletion of monocytes may represent a treatment strategy for pancreatitis as well as for other inflammation-related disorders.
Purpose
In patients with newly diagnosed glioblastoma that harbors a nonmethylated O
6
-methylguanine–DNA methyltransferase promotor, standard temozolomide (TMZ) has, at best, limited efficacy. The ...GLARIUS trial thus explored bevacizumab plus irinotecan (BEV+IRI) as an alternative to TMZ.
Patients and Methods
In this phase II, unblinded trial 182 patients in 22 centers were randomly assigned 2:1 to BEV (10 mg/kg every 2 weeks) during radiotherapy (RT) followed by maintenance BEV (10 mg/kg every 2 weeks) plus IRI(125 mg/m
2
every 2 weeks) or to daily TMZ (75 mg/m
2
) during RT followed by six courses of TMZ (150-200 mg/m
2
/d for 5 days every 4 weeks). The primary end point was the progression-free survival rate after 6 months (PFS-6).
Results
In the modified intention-to-treat (ITT) population, PFS-6 was increased from 42.6% with TMZ (95% CI, 29.4% to 55.8%) to 79.3% with BEV+IRI (95% CI, 71.9% to 86.7%; P <.001). PFS was prolonged from a median of 5.99 months (95% CI, 2.7 to 7.3 months) to 9.7 months (95% CI, 8.7 to 10.8 months; P < .001). At progression, crossover BEV therapy was given to 81.8% of all patients who received any sort of second-line therapy in the TMZ arm. Overall survival (OS) was not different in the two arms: the median OS was 16.6 months (95% CI, 15.4 to 18.4 months) with BEV+IRI and was 17.5 months (95% CI, 15.1 to 20.5 months) with TMZ. The time course of quality of life (QOL) in six selected domains of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ) –C30 and QLQ-BN20 (which included cognitive functioning), of the Karnofsky performance score, and of the Mini Mental State Examination score was not different between the treatment arms.
Conclusion
BEV+IRI resulted in a superior PFS-6 rate and median PFS compared with TMZ. However, BEV+IRI did not improve OS, potentially because of the high crossover rate. BEV+IRI did not alter QOL compared with TMZ.
We compare homogeneous and selective emitters on monocrystalline silicon solar cells with passivated surfaces and present an analysis of the saturation current densities influencing the open-circuit ...voltage V OC and the fill factor FF . The cells' surfaces are passivated by a thin thermal oxide. Selective emitters are fabricated by laser doping from phosphosilicate glass. On both Czochralski-grown silicon (Cz-Si) as well as float zone silicon (FZ-Si), we find higher conversion efficiencies for the cells featuring a selective emitter. An efficiency up to 20.0% is reported on FZ-Si with an area of 148.4 cm 2 . For the selective emitter cells, 8 mV higher open-circuit voltages are found compared with the baseline. A saturation current analysis reveals that these cells exhibit a lower diode saturation current density of ideality 2 ( J 02 ), as well as improved shielding of the minorities in the emitter from the front contact. The selective emitter cells show a minor loss in short-circuit current density J SC of 0.5 % rel due to the presence of highly doped, illuminated areas. Front contact quality of the cells featuring a selective emitter is found to be superior compared with the cells with a homogeneously doped emitter.
Wearable technology is a leading fitness trend in the growing commercial industry and an established method for collecting 24-hour physical behavior data in research studies. High-quality free-living ...validation studies are required to enable both researchers and consumers to make guided decisions on which study to rely on and which device to use. However, reviews focusing on the quality of free-living validation studies in adults are lacking.
This study aimed to raise researchers' and consumers' attention to the quality of published validation protocols while aiming to identify and compare specific consistencies or inconsistencies between protocols. We aimed to provide a comprehensive and historical overview of which wearable devices have been validated for which purpose and whether they show promise for use in further studies.
Peer-reviewed validation studies from electronic databases, as well as backward and forward citation searches (1970 to July 2021), with the following, required indicators were included: protocol must include real-life conditions, outcome must belong to one dimension of the 24-hour physical behavior construct (intensity, posture or activity type, and biological state), the protocol must include a criterion measure, and study results must be published in English-language journals. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool with 9 questions separated into 4 domains (patient selection or study design, index measure, criterion measure, and flow and time).
Of the 13,285 unique search results, 222 (1.67%) articles were included. Most studies (153/237, 64.6%) validated an intensity measure outcome such as energy expenditure. However, only 19.8% (47/237) validated biological state and 15.6% (37/237) validated posture or activity-type outcomes. Across all studies, 163 different wearables were identified. Of these, 58.9% (96/163) were validated only once. ActiGraph GT3X/GT3X+ (36/163, 22.1%), Fitbit Flex (20/163, 12.3%), and ActivPAL (12/163, 7.4%) were used most often in the included studies. The percentage of participants meeting the quality criteria ranged from 38.8% (92/237) to 92.4% (219/237). On the basis of our classification tree to evaluate the overall study quality, 4.6% (11/237) of studies were classified as low risk. Furthermore, 16% (38/237) of studies were classified as having some concerns, and 72.9% (173/237) of studies were classified as high risk.
Overall, free-living validation studies of wearables are characterized by low methodological quality, large variability in design, and focus on intensity. Future research should strongly aim at biological state and posture or activity outcomes and strive for standardized protocols embedded in a validation framework. Standardized protocols for free-living validation embedded in a framework are urgently needed to inform and guide stakeholders (eg, manufacturers, scientists, and consumers) in selecting wearables for self-tracking purposes, applying wearables in health studies, and fostering innovation to achieve improved validity.
Coordinated neutrophil and monocyte recruitment is a characteristic feature of acute lung inflammatory responses. We investigated the role of monocyte chemotactic protein-1 (CCL2, JE) and the ...chemokine receptor CCR2 in regulating alveolar leukocyte traffic. Groups of wild-type (WT) mice, CCR2-deficient mice, lethally irradiated CCR2-deficient and WT mice that were reciprocally bone marrow transplanted (chimeric CCR2 deficient and WT, respectively), chimeric CCR2-deficient mice with an enriched CCR2(+) alveolar macrophage population, and CCR2-deficient mice transfused with CCR2(+) mononuclear cells were treated with intratracheal CCL2 and/or Escherichia coli endotoxin. Our data show that alveolar monocyte recruitment is strictly dependent on CCR2. LPS-induced neutrophil migration to the lungs is CCR2 independent. However, when CCR2-bearing blood monocytes are present, alveolar neutrophil accumulation is accelerated and drastically amplified. We suggest that this hitherto unrecognized cooperativity between monocytes and neutrophils contributes to the strong, coordinated leukocyte efflux in lung inflammation.
X-ray phase-contrast micro computed tomography using synchrotron radiation (SR PhC-µCT) offers unique 3D imaging capabilities for visualizing microstructure of the human brain. Its applicability for ...unstained soft tissue is an area of active research. Acquiring images from a tissue block without needing to section it into thin slices, as required in routine histology, allows for investigating the microstructure in its natural 3D space. This paper presents a detailed step-by-step guideline for imaging unstained human brain tissue at resolutions of a few micrometers with SR PhC-µCT implemented at SYRMEP, the hard X-ray imaging beamline of Elettra, the Italian synchrotron facility. We present examples of how blood vessels and neurons appear in the images acquired with isotropic 5 μm and 1 µm voxel sizes. Furthermore, the proposed protocol can be used to investigate important biological substrates such as neuromelanin or corpora amylacea. Their spatial distribution can be studied using specifically tailored segmentation tools that are validated by classical histology methods. In conclusion, SR PhC-µCT using the proposed protocols, including data acquisition and image processing, offers viable means of obtaining information about the anatomy of the human brain at the cellular level in 3D.
Technological and digital progress benefits physical activity (PA) research. Here we compiled expert knowledge on how Ambulatory Assessment (AA) is utilized to advance PA research, i.e., we present ...results of the 2nd International CAPA Workshop 2019 “Physical Activity Assessment – State of the Science, Best Practices, Future Directions” where invited researchers with experience in PA assessment, evaluation, technology and application participated. First, we provide readers with the state of the AA science, then we give best practice recommendations on how to measure PA via AA and shed light on methodological frontiers, and we furthermore discuss future directions. AA encompasses a class of methods that allows the study of PA and its behavioral, biological and physiological correlates as they unfold in everyday life. AA includes monitoring of movement (e.g., via accelerometry), physiological function (e.g., via mobile electrocardiogram), contextual information (e.g., via geolocation-tracking), and ecological momentary assessment (EMA; e.g., electronic diaries) to capture self-reported information. The strengths of AA are data assessments near real-time, which minimize retrospective biases in real-world settings, consequentially enabling ecological valid findings. Importantly, AA enables multiple assessments across time within subjects resulting in intensive longitudinal data (ILD), which allows unraveling within-person determinants of PA in everyday life. In this paper, we show how AA methods such as triggered e-diaries and geolocation-tracking can be used to measure PA and its correlates, and furthermore how these findings may translate into real-life interventions. In sum, AA provides numerous possibilities for PA research, especially the opportunity to tackle within-subject antecedents, concomitants, and consequences of PA as they unfold in everyday life. In-depth insights on determinants of PA could help us design and deliver impactful interventions in real-world contexts, thus enabling us to solve critical health issues in the 21st century such as insufficient PA and high levels of sedentary behavior.
•Study physical activity’s correlates (e.g., behavioral, biological) in REAL-LIFE.•assess data near REAL-TIME, WITHIN-PERSONS across multiple assessments.•Minimize retrospective biases for ECOLOGICAL VALID FINDINGS.•Unravel within-subject ANTECEDENTS, CONCOMITANTS, and CONSEQUENCES of PA.•Design and deliver impactful INTERVENTIONS in REAL-WORLD contexts.
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