scholarly journals Preservation of cellular nano-architecture by the process of chemical fixation for nanopathology

2018 ◽  
Author(s):  
Xiang Zhou ◽  
Luay Almassalha ◽  
Yue Li ◽  
Adam Eshein ◽  
Lusik Cherkezyan ◽  
...  

AbstractTransformation in chromatin organization is one of the most universal markers of carcinogenesis. Microscale chromatin alterations have been a staple of histopathological diagnosis of neoplasia, and nanoscale alterations have emerged as a promising marker for cancer prognostication and the detection of predysplastic changes. While numerous methods have been developed to detect these alterations, most methods for sample preparation remain largely validated via conventional microscopy, and have not been examined with nanoscale sensitive imaging techniques. For these nanoscale sensitive techniques to become standard of care screening tools, new histological protocols must be developed that preserve nanoscale information. Partial Wave Spectroscopic (PWS) microscopy has recently emerged as a novel imaging technique sensitive to length scales ranging between 20 and 200 nanometers. As a label-free, high-throughput, and non-invasive imaging technique, PWS microscopy offers many advantages for risk stratification of early cancer, and is an ideal tool to quantify structural information during sample preparation. Therefore, in this work we applied PWS microscopy to systematically evaluate the effects of cytological preparation on the nanoscales changes of chromatin using two cell line models: Hela cells differentially treated with daunorubicin and TP53 differentially mutated ovarian carcinoma cells. Notably, we show that existing cytological preparation can be modified in order to maintain clinically relevant nanoscopic differences, paving the way for the emerging field of nanopathology.

2021 ◽  
Vol 10 (5) ◽  
pp. 903
Author(s):  
Zeno Sparchez ◽  
Rares Craciun ◽  
Cosmin Caraiani ◽  
Adelina Horhat ◽  
Iuliana Nenu ◽  
...  

Hepatocellular carcinoma (HCC) is probably the epitome of a screening target, with a well-defined high-risk population, accessible screening methods, and multiple curative-intent treatments available for early disease. Per major societies guideline consensus, biannual ultrasound (US) surveillance of the at-risk patients is the current standard of care worldwide. Yet, despite its documented success in the past decades, this standard is far from perfect. While the whole community is working to further tighten the knots, a worrying number of cases still slip through this safety net. Consequently, these patients lose their chance to a curative solution which leads to a high disease burden with disproportionate mortality. While US will probably remain the fundamental staple in the screening strategy, key questions are seeking better answers. How can its caveats be addressed, and the technique be improved? When are further steps needed? How to increase accuracy without giving up on accessibility? This narrative review discusses the place of US surveillance in the bigger HCC picture, trying to navigate through its strengths and limits based on the most recent available evidence.


Author(s):  
Weiping Liu ◽  
Jennifer Fung ◽  
W.J. de Ruijter ◽  
Hans Chen ◽  
John W. Sedat ◽  
...  

Electron tomography is a technique where many projections of an object are collected from the transmission electron microscope (TEM), and are then used to reconstruct the object in its entirety, allowing internal structure to be viewed. As vital as is the 3-D structural information and with no other 3-D imaging technique to compete in its resolution range, electron tomography of amorphous structures has been exercised only sporadically over the last ten years. Its general lack of popularity can be attributed to the tediousness of the entire process starting from the data collection, image processing for reconstruction, and extending to the 3-D image analysis. We have been investing effort to automate all aspects of electron tomography. Our systems of data collection and tomographic image processing will be briefly described.To date, we have developed a second generation automated data collection system based on an SGI workstation (Fig. 1) (The previous version used a micro VAX). The computer takes full control of the microscope operations with its graphical menu driven environment. This is made possible by the direct digital recording of images using the CCD camera.


Author(s):  
C. Barry Carter

This paper will review the current state of understanding of interface structure and highlight some of the future needs and problems which must be overcome. The study of this subject can be separated into three different topics: 1) the fundamental electron microscopy aspects, 2) material-specific features of the study and 3) the characteristics of the particular interfaces. The two topics which are relevant to most studies are the choice of imaging techniques and sample preparation. The techniques used to study interfaces in the TEM include high-resolution imaging, conventional diffraction-contrast imaging, and phase-contrast imaging (Fresnel fringe images, diffuse scattering). The material studied affects not only the characteristics of the interfaces (through changes in bonding, etc.) but also the method used for sample preparation which may in turn have a significant affect on the resulting image. Finally, the actual nature and geometry of the interface must be considered. For example, it has become increasingly clear that the plane of the interface is particularly important whenever at least one of the adjoining grains is crystalline.A particularly productive approach to the study of interfaces is to combine different imaging techniques as illustrated in the study of grain boundaries in alumina. In this case, the conventional imaging approach showed that most grain boundaries in ion-thinned samples are grooved at the grain boundary although the extent of this grooving clearly depends on the crystallography of the surface. The use of diffuse scattering (from amorphous regions) gives invaluable information here since it can be used to confirm directly that surface grooving does occur and that the grooves can fill with amorphous material during sample preparation (see Fig. 1). Extensive use of image simulation has shown that, although information concerning the interface can be obtained from Fresnel-fringe images, the introduction of artifacts through sample preparation cannot be lightly ignored. The Fresnel-fringe simulation has been carried out using a commercial multislice program (TEMPAS) which was intended for simulation of high-resolution images.


Author(s):  
Weiping Liu ◽  
John W. Sedat ◽  
David A. Agard

Any real world object is three-dimensional. The principle of tomography, which reconstructs the 3-D structure of an object from its 2-D projections of different view angles has found application in many disciplines. Electron Microscopic (EM) tomography on non-ordered structures (e.g., subcellular structures in biology and non-crystalline structures in material science) has been exercised sporadically in the last twenty years or so. As vital as is the 3-D structural information and with no existing alternative 3-D imaging technique to compete in its high resolution range, the technique to date remains the kingdom of a brave few. Its tedious tasks have been preventing it from being a routine tool. One keyword in promoting its popularity is automation: The data collection has been automated in our lab, which can routinely yield a data set of over 100 projections in the matter of a few hours. Now the image processing part is also automated. Such automations finish the job easier, faster and better.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 382
Author(s):  
Barbara Pacholczyk-Sienicka ◽  
Grzegorz Ciepielowski ◽  
Łukasz Albrecht

Spices and herbs are among the most commonly adulterated food types. This is because spices are widely used to process food. Spices not only enhance the flavor and taste of food, but they are also sources of numerous bioactive compounds that are significantly beneficial for health. The healing effects of spices are connected with their antimicrobial, anti-inflammatory and carminative properties. However, regular consumption of adulterated spices may cause fatal damage to our system because adulterants in most cases are unhealthy. For that reason, the appropriate analytical methods are necessary for quality assurance and to ensure the authenticity of spices. Spectroscopic methods are gaining interest as they are fast, require little or no sample preparation, and provide rich structural information. This review provides an overview of the application of NMR spectroscopy combined with chemometric analysis to determine the quality and adulteration of spices.


Author(s):  
Alessandra Ley ◽  
Marcel Kamp ◽  
Christiane von Sass ◽  
Daniel Hänggi ◽  
Michael Sabel ◽  
...  

Summary Background Patients diagnosed with low-grade glioma (LGG) must live with constant knowledge of an upcoming malignant tumor transformation which may lead to increased anxiety and reduced quality of life. Here, we (1) analyzed the prevalence and risk factors for distress in LGG patients using (2) different screening tools to subsequently (3) evaluate their need for psychological support. Method Patients with LGG-suspicious findings in MRI studies as well as patients with histopathological confirmed LGG were screened using three established self-assessment instruments (Hospital Anxiety and Depression Scale, Distress Thermometer, EORTC-QLQ-C30-BN20). Screening results were correlated with sociodemographic factors. Results One hundred forty-nine patients (74 men and 75 women) were prospectively included. Patients were further divided into different subgroups regarding the time of screening and diagnosis. An increased level of distress was observed in 20.8% (mean score 1.21, 95% CI 1.15–1.28) of all patients screened by HADS. Significant associated factors were pre-existing psychiatric disorders (p = 0.003) and psychotropic medication (p = 0.029). HRQoL (p = 0.022) and global health item (p = 0.015), as well as future uncertainty (p = 0.047), assessed by the EORTC-QLQ-C30-BN20 were significantly higher in those patients without histopathological diagnosis. Increased distress was significantly correlated with results in chosen sub-items of the HRQoL questionnaire (p < 0.001). Conclusions Our results demonstrate the need for frequent distress screening. If specific tools are not available, HRQoL questionnaires can also be used. Patients with pre-existing psychological stress should be offered additional psychooncological support, irrespectively of the time of screening or tumor diagnosis. Clinical trial registration number: 4087


Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 354
Author(s):  
Walid Mnasri ◽  
Mahsa Parvizian ◽  
Souad Ammar-Merah

Current biomedical imaging techniques are crucial for the diagnosis of various diseases. Each imaging technique uses specific probes that, although each one has its own merits, do not encompass all the functionalities required for comprehensive imaging (sensitivity, non-invasiveness, etc.). Bimodal imaging methods are therefore rapidly becoming an important topic in advanced healthcare. This bimodality can be achieved by successive image acquisitions involving different and independent probes, one for each mode, with the risk of artifacts. It can be also achieved simultaneously by using a single probe combining a complete set of physical and chemical characteristics, in order to record complementary views of the same biological object at the same time. In this scenario, and focusing on bimodal magnetic resonance imaging (MRI) and optical imaging (OI), probes can be engineered by the attachment, more or less covalently, of a contrast agent (CA) to an organic or inorganic dye, or by designing single objects containing both the optical emitter and MRI-active dipole. If in the first type of system, there is frequent concern that at some point the dye may dissociate from the magnetic dipole, it may not in the second type. This review aims to present a summary of current activity relating to this kind of dual probes, with a special emphasis on lanthanide-based luminescent nano-objects.


2021 ◽  
Vol 22 (2) ◽  
pp. 880
Author(s):  
Thomas Schmitz ◽  
Ajay Abisheck Paul George ◽  
Britta Nubbemeyer ◽  
Charlotte A. Bäuml ◽  
Torsten Steinmetzer ◽  
...  

The saliva of blood-sucking leeches contains a plethora of anticoagulant substances. One of these compounds derived from Haementeria ghilianii, the 66mer three-disulfide-bonded peptide tridegin, specifically inhibits the blood coagulation factor FXIIIa. Tridegin represents a potential tool for antithrombotic and thrombolytic therapy. We recently synthesized two-disulfide-bonded tridegin variants, which retained their inhibitory potential. For further lead optimization, however, structure information is required. We thus analyzed the structure of a two-disulfide-bonded tridegin isomer by solution 2D NMR spectroscopy in a combinatory approach with subsequent MD simulations. The isomer was studied using two fragments, i.e., the disulfide-bonded N-terminal (Lys1–Cys37) and the flexible C-terminal part (Arg38–Glu66), which allowed for a simplified, label-free NMR-structure elucidation of the 66mer peptide. The structural information was subsequently used in molecular modeling and docking studies to provide insights into the structure–activity relationships. The present study will prospectively support the development of anticoagulant-therapy-relevant compounds targeting FXIIIa.


2003 ◽  
Vol 2 (4) ◽  
pp. 289-302 ◽  
Author(s):  
Louis-Michel Wong Kee Song ◽  
Kenneth K. Wang

Dysplastic Barrett's esophagus is a condition that offers multiple diagnostic and therapeutic challenges. The diagnosis of dysplasia within Barrett's esophagus currently relies on periodic endoscopic surveillance with multiple biopsies, a methodology limited by random sampling error, inconsistent histopathologic interpretation and delay in diagnosis. Optical spectroscopic and imaging techniques have the potential to identify dysplastic or early neoplastic lesions in real-time. These diagnostic modalities are needed to enhance the endoscopic surveillance of Barrett's esophagus in the future as well as help to define lesions for endoscopic therapy. Esophagectomy has been the standard of care for Barrett's esophagus with high-grade dysplasia although it is a procedure associated with significant morbidity and mortality. Minimally invasive endoscopic ablative therapies are attractive and less morbid alternatives to esophagectomy, with promising results obtained from the use of light-activated drugs (i.e., photodynamic therapy). The combination of novel optical diagnostic techniques and therapies will provide the endoscopist with much needed tools that can considerably enhance the management of patients with Barrett's esophagus. This article reviews the current status and future prospects of optical-based modalities for diagnosis and therapy of dysplastic Barrett's esophagus.


Sign in / Sign up

Export Citation Format

Share Document