scholarly journals Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Valentina Barrera ◽  
Ian James Callum MacCormick ◽  
Gabriela Czanner ◽  
Paul Stephenson Hiscott ◽  
Valerie Ann White ◽  
...  
Keyword(s):  
Image Analysis ◽  
Severe Disease ◽  
Retinal Vessel ◽  
Tissue Response ◽  
Blood Retinal Barrier ◽  
Distinctive Features ◽  
Malarial Retinopathy ◽  
Eye Examination ◽  
Underlying Mechanisms ◽  
Angiographic Image

Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with P. falciparum cerebral malaria. We investigated their clinical significance and underlying mechanisms through linked clinical, clinicopathological and image analysis studies. Orange vessels and severe foveal whitening (clinical examination, n = 817, OR, 95% CI: 2.90, 1.96–4.30; 3.4, 1.8–6.3, both p<0.001), and arteriolar involvement by intravascular filling defects (angiographic image analysis, n = 260, 2.81, 1.17–6.72, p<0.02) were strongly associated with death. Orange vessels had dense sequestration of late stage parasitised red cells (histopathology, n = 29; sensitivity 0.97, specificity 0.89) involving 360° of the lumen circumference, with altered protein expression in blood-retinal barrier cells and marked loss/disruption of pericytes. Retinal whitening was topographically associated with tissue response to hypoxia. Severe neurovascular sequestration is visible at the bedside, and is a marker of severe disease useful for diagnosis and management.

scholarly journals IgM autoantibodies recognizing ACE2 are associated with severe COVID-19

2020 ◽  
Author(s):  
Livia Casciola-Rosen ◽  
David R. Thiemann ◽  
Felipe Andrade ◽  
Maria Isabel Trejo Zambrano ◽  
Jody E. Hooper ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Severe Disease ◽  
Vascular Endothelial ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Therapeutic Implications ◽  
Pathological Analysis ◽  
Cell Staining ◽  
Underlying Mechanisms ◽  
Pathogenic Effects

AbstractSARS-CoV-2 infection induces severe disease in a subpopulation of patients, but the underlying mechanisms remain unclear. We demonstrate robust IgM autoantibodies that recognize angiotensin converting enzyme-2 (ACE2) in 18/66 (27%) patients with severe COVID-19, which are rare (2/52; 3.8%) in hospitalized patients who are not ventilated. The antibodies do not undergo class-switching to IgG, suggesting a T-independent antibody response. Purified IgM from anti-ACE2 patients activates complement. Pathological analysis of lung obtained at autopsy shows endothelial cell staining for IgM in blood vessels in some patients. We propose that vascular endothelial ACE2 expression focuses the pathogenic effects of these autoantibodies on blood vessels, and contributes to the angiocentric pathology observed in some severe COVID-19 patients. These findings may have predictive and therapeutic implications.One-sentence summaryACE2 autoantibodies in severe COVID-19 have features of a T-independent immune response, and may mediate vascular damage.

scholarly journals A Review of Nasal Polyps

2019 ◽  
Vol 4 (11) ◽  
Keyword(s):  
Nasal Polyps ◽  
Severe Disease ◽  
Treatment Options ◽  
Primary Treatment ◽  
Good Evidence ◽  
Sinus Surgery ◽  
Molecular Alterations ◽  
The Past ◽  
Postoperative Prophylaxis ◽  
Underlying Mechanisms

Nasal polyps (NP) are one of the most common inflammatory lesions of the nose, affecting up to 4% of the population. Their etiology remains unclear, but they are known to have associations with allergy, asthma, infection, cystic fibrosis, and aspirin sensitivity. However, the underlying mechanisms interlinking these pathologic conditions to NP formation remain unclear. Also strong genetic factors are implicated in the pathogenesis of NP, but genetic and molecular alterations required for its development and progression are still unclear. They present with nasal obstruction, anosmia, rhinorrhea, post nasal drip, and less commonly facial pain. Management of polyposis involves a combination of medical therapy and surgery. There is good evidence for the use of corticosteroids (systemic and topical) both as primary treatment and as postoperative prophylaxis against recurrence. Surgical treatment has been refined significantly over the past twenty years with the advent of endoscopic sinus surgery and, in general, is reserved for cases refractory to medical treatment. Recurrence of the polyposis is common with severe disease recurring in up to ten percent of patients. In this talk I will present the newer treatment options available for better control and possibly cure of the disease.

Retinal Microvascular Signs: A Key to Understanding the Underlying Pathophysiology of Different Stroke Subtypes?

2008 ◽  
Vol 3 (4) ◽  
pp. 297-305 ◽  
Author(s):  
Richard I. Lindley ◽  
Keyword(s):  
Acute Stroke ◽  
Small Vessel Disease ◽  
New Technology ◽  
Retinal Vessel ◽  
Small Vessel ◽  
Stroke Subtype ◽  
Vessel Disease ◽  
Underlying Mechanisms ◽  
New Treatments ◽  
Retinal Microvascular Signs

Background The heterogeneity of the pathology of stroke has been a major difficulty in assessing new treatments for acute stroke, and contributes to the complexity of stroke medicine. Some underlying mechanisms are poorly understood, such as small vessel (lacunar) disease. New technology such as advanced brain imaging has transformed our knowledge of large vessel disease and we suggest that other new technology such as detailed analysis of retinal vessels may provide new insights into the pathology of small vessel (lacunar) stroke disease. We hypothesise that retinal microvascular signs differ by pathological stroke subtype, and we plan to test this hypothesis in over 1000 acute stroke patients. Summary Eligible patients undergo a standardised neurological assessment followed by digital retinal photography. At a consensus meeting, an anatomical and aetiological classification is determined. Retinal photographs will be assessed qualitatively (e.g. retinal emboli, arteriovenous nicking) and quantitatively (arteriolar/venule ratio). Six-month vascular event rates together with disability and vital status are collected. Conclusion Retinal vessel appearances may provide a ‘window’ to the brain and help determine the important underlying pathophysiological mechanisms of small vessel disease stroke.

Organization of matter into one-dimensional units on designed media

Open Physics ◽  
2011 ◽  
Vol 9 (2) ◽  
Author(s):  
Karen Paul
Keyword(s):  
Building Blocks ◽  
Parent Material ◽  
Distinctive Features ◽  
Patterned Media ◽  
One Dimensional ◽  
Perpendicular Magnetization ◽  
Micro Particles ◽  
Tube Reactor ◽  
Underlying Mechanisms

AbstractThe organization of magnetic materials into one-dimensional micro- and nanowires on designed media is discussed, exemplified by two experiments on the microscale and nanoscale, with regard to particles as basic building blocks for the growth and development of matter.In the first organizational experiments, cobalt (Co) micro-particles are assembled on patterned media with perpendicular magnetization by acoustic vibrations onto designed shapes reflecting macroscopically the parent material. In the second experiments, semiconductor Germanium-Dysprosium (Ge98Dy2) matter is assembled on gold (Au) catalytic nuclei in a tube reactor by physical vapor transport as clusters of nanowires.The underlying mechanisms of organization are described, and similarities and distinctive features in the processes are discussed. The role of the energy-input in the form of mechanical vibrations and heat is outlined with its similar impact on the assembly and growth of matter on surfaces. The description of these experiments in view of organization allows more control over the processes of planned arrangement on designed media. Routes for further progress in this direction are briefly outlined.

scholarly journals Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients

2021 ◽  
Vol 6 (56) ◽  
pp. eabf6692
Author(s):  
Yu Zhao ◽  
Christoph Kilian ◽  
Jan-Eric Turner ◽  
Lidia Bosurgi ◽  
Kevin Roedl ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Severe Disease ◽  
Lavage Fluid ◽  
Lung Damage ◽  
Lung Pathology ◽  
Gm Csf ◽  
Protein Levels ◽  
Cytokine Expression Profile ◽  
Cell Clones ◽  
Underlying Mechanisms

Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome (ARDS) with high mortality in patients with severe coronavirus disease 2019 (COVID-19). To understand the underlying mechanisms involved in lung pathology, we investigated the role of the lung-specific immune response. We profiled immune cells in bronchoalveolar lavage fluid and blood collected from COVID-19 patients with severe disease and bacterial pneumonia patients not associated with viral infection. By tracking T cell clones across tissues, we identified clonally expanded tissue-resident memory-like Th17 cells (Trm17 cells) in the lungs even after viral clearance. These Trm17 cells were characterized by a a potentially pathogenic cytokine expression profile of IL17A and CSF2 (GM-CSF). Interactome analysis suggests that Trm17 cells can interact with lung macrophages and cytotoxic CD8+ T cells, which have been associated with disease severity and lung damage. High IL-17A and GM-CSF protein levels in the serum of COVID-19 patients were associated with a more severe clinical course. Collectively, our study suggests that pulmonary Trm17 cells are one potential orchestrator of the hyperinflammation in severe COVID-19.

scholarly journals BacStalk: a comprehensive and interactive image analysis software tool for bacterial cell biology

2018 ◽  
Author(s):  
Raimo Hartmann ◽  
Muriel C.F. van Teeseling ◽  
Martin Thanbichler ◽  
Knut Drescher
Keyword(s):  
Image Analysis ◽  
Data Analysis ◽  
Cell Biology ◽  
Software Tool ◽  
Model Organisms ◽  
Analysis Software ◽  
Prokaryotic Cell ◽  
Image Analysis Software ◽  
Spatial Dimensions ◽  
Underlying Mechanisms

ABSTRACTProkaryotes display a remarkable spatiotemporal organization of processes within individual cells. Investigations of the underlying mechanisms rely extensively on the analysis of microscopy images. Advanced image analysis software has revolutionized the cell-biological studies of established model organisms with largely symmetric rod-like cell shapes. However’ algorithms suitable for analyzing features of morphologically more complex model species are lacking’ although such unusually shaped organisms have emerged as treasure-troves of new molecular mechanisms and diversity in prokaryotic cell biology. To address this problem’ we developed BacStalk’ a simple’ interactive’ and easy-to-use MatLab-based software tool for quantitatively analyzing images of commonly and uncommonly shaped bacteria’ including stalked (budding) bacteria. BacStalk automatically detects the separate parts of the cells (cell body’ stalk’ bud’ or appendage) as well as their connections’ thereby allowing in-depth analyses of the organization of morphologically complex bacteria over time. BacStalk features the generation and visualization of concatenated fluorescence profiles along cells’ stalks’ appendages’ and buds to trace the spatiotemporal dynamics of fluorescent markers. Cells are interactively linked to demographs’ kymographs’ cell lineage analyses’ and scatterplots’ which enables intuitive and fast data exploration and’ thus’ significantly speeds up the image analysis process. Furthermore’ BacStalk introduces a 2D representation of demo- and kymographs’ enabling data representations in which the two spatial dimensions of the cell are preserved. The software was developed to handle large data sets and to generate publication-grade figures that can be easily edited. BacStalk therefore provides an advanced image analysis platform that extends the spectrum of model organisms for prokaryotic cell biology to bacteria with multiple morphologies and life cycles.IMPORTANCEProkaryotic cells show a striking degree of subcellular organization. Studies of the underlying mechanisms and their variation among different species greatly enhance our understanding of prokaryotic cell biology. The image analysis software tool BacStalk extracts an unprecedented amount of information from images of stalked bacteria, by generating interactive demographs, kymographs, cell lineages, and scatter plots that aid fast and thorough data analysis and representation. Notably, BacStalk can preserve the two spatial dimensions of cells when generating demographs and kymographs to accurately and intuitively reflect the intracellular organization. BacStalk also performs well on established, non-stalked model organisms with common or uncommon shapes. BacStalk therefore contributes to the advancement of prokaryotic cell biology, as it widens the spectrum of easily accessible model organisms and enables a more intuitive and interactive data analysis and visualization.

Digital Image Analysis for Morphometric Evaluation of Tissue Response after Implanting Alloplastic Vascular Prostheses

2006 ◽  
Vol 12 (5) ◽  
pp. 366-375 ◽  
Author(s):  
Roland Zippel ◽  
Andreas Hoene ◽  
Uwe Walschus ◽  
Raymond Jarchow ◽  
Torsten Ueberrueck ◽  
...  
Keyword(s):  
Image Analysis ◽  
Digital Image ◽  
Digital Image Analysis ◽  
Tissue Response ◽  
Proliferation Rate ◽  
Ki 67 ◽  
Vascular Prostheses ◽  
Beta 1 Integrin ◽  
Reproducible Method ◽  
Morphometric Evaluation

The aim of this study was to examine the suitability of digital image analysis, using the KS400 software system, for the morphometric evaluation of the tissue response after prosthesis implantation in an animal model. Twenty-four female pigs aged 10 weeks were implanted with infrarenal Dacron® prostheses for 14, 21, 28, and 116 days. Following the explantation and investigation of the neointima region, the expression of beta-1-integrin, the proliferation rate by means of Ki-67 positive cells, and the intima thickness were evaluated as exemplary parameters of the tissue response after implantation. Frozen tissue sections were immunohistochemically stained and subsequently examined using computer-aided image analysis. A maximum expression of 32.9% was observed for beta-1-integrin 14 days after implantation, gradually declining over time to 9.8% after 116 days. The proliferation rate was found to be 19% on day 14, increasing to 39% on day 21 with a subsequent gradual decline to 5% after 116 days. The intima thickness increased from 189.9 μm on day 14 to 1228.0 μm on day 116. In conclusion, digital image analysis was found to be an efficient and reproducible method for the morphometric evaluation of a peri-prosthetic tissue response.

scholarly journals Update on intensive motor training in spinocerebellar ataxia: time to move a step forward?

2019 ◽  
Vol 48 (2) ◽  
pp. 030006051985462 ◽  
Author(s):  
Giuseppe Lanza ◽  
Jacopo Antonino Casabona ◽  
Maria Bellomo ◽  
Mariagiovanna Cantone ◽  
Francesco Fisicaro ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
High Intensity ◽  
Severe Disease ◽  
Whole Body ◽  
Motor Training ◽  
Spinocerebellar Ataxias ◽  
Intensive Training ◽  
Underlying Mechanisms ◽  
Training Programmes ◽  
Training Success

Some evidence suggests that high-intensity motor training slows down the severity of spinocerebellar ataxia. However, whether all patients might benefit from these activities, and by which activity, and the underlying mechanisms remain unclear. We provide an update on the effect and limitations of different training programmes in patients with spinocerebellar ataxias. Overall, data converge of the finding that intensive training is still based either on conventional rehabilitation protocols or whole-body controlled videogames (“exergames”). Notwithstanding the limitations, short-term improvement is observed, which tends to be lost once the training is stopped. Exergames and virtual reality can ameliorate balance, coordination, and walking abilities, whereas the efficacy of adapted physical activity, gym, and postural exercises depends on the disease duration and severity. In conclusion, although a disease-modifying effect has not been demonstrated, constant, individually tailored, high-intensity motor training might be effective in patients with degenerative ataxia, even in those with severe disease. These approaches may enhance the remaining cerebellar circuitries or plastically induce compensatory networks. Further research is required to identify predictors of training success, such as the type and severity of ataxia and the level of residual functioning.

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