Biomedical Experiments Research Articles

Dispersion of Single-Walled Carbon Nanotubes in Biocompatible Environments

The unique physical and chemical properties of carbon nanotubes (CNTs), including SWCNTs (single-walled carbon nanotubes), allow their applications in many fields, including biomedicine. The optical properties of SWCNTs are attractive for application in the field of nanobiotechnology compared to MWCNTs (multi-walled carbon nanotubes). An important objective of SWCNT application for biomedical purposes is obtaining homogenous dispersions characterized by bioavailability and biocompatibility. The possibility of obtaining homogenous dispersions of different types of SWCNTs in biocompatible media for further use in different biomedical experiments and applications has been investigated. The sizes of SWCNT agglomerates in prepared dispersions were measured by the method of dynamic light scattering; bioavailability was studied by dark field microscopy in BEAS-2B bronchial epithelium cells. The dispersions were analyzed for the presence of bacterial contamination. Biocompatible and bioavailable dispersions have been obtained on the basis of cell culture media and 1% bovine serum albumin, which can be used in experiments on assessing the safety of SWCNTs at biological objects but have a number of limitations in the field of biomedicine. Dispergents based on lung surfactant components, which could be used in biomedical applications (DPPC and Survanta®), did not show efficency.

Mission Beyond: The Acoustic Diagnostics Experiment on Board the International Space Station

Acoustic Diagnostics is an Italian Space Agency (ASI) biomedical experiment exploiting the diagnostic potential of otoacoustic emissions (OAEs) to monitor the astronauts’ hearing health on board the International Space Station (ISS). It is being performed (July 2019–April 2020) on the ISS, in the framework of the BEYOND mission, sponsored by European Space Agency (ESA). A dedicated instrument for measuring distortion product OAE (DPOAE) in a noisy environment was designed by University of Rome Tor Vergata and INAIL. Aerospace Logistics Technology Engineering Company (ALTEC) took care of the payload development, mechanical, thermal and electromagnetic tests, verification, and acceptance. Two astronauts were subjected, before leaving for their mission on the ISS, to the DPOAE test, along with a full set of audiological tests (Baseline Data Collection, BDC), especially designed at University of Roma La Sapienza and Campus Bio-Medico. An identical DPOAE apparatus was used five times on board the ISS to test the two astronauts. Finally, a post-flight BDC was performed, few days after return to Earth. Preliminary analysis demonstrated that the payload was able to record DPOAEs on board the ISS with very low instrumental noise level, despite the high noise level of the ISS environment. ASI, in the frame of its national mission of promoting and fostering the culture of space across the Country, provides access to the ISS as a laboratory in space. The utilization support services are provided, thanks to a contract, awarded by ASI, to ARGOTEC/Telespazio (UTISS Team).

The Nutriss Study: A New Approach to Calibrate Diet and Exercise in Long-Term Space Missions to Maintain Body Fat, Muscle and Fluid Homeostasis

Energy balance maintenance is crucial to preserve astronaut’s wellness and quality of life during long-duration spaceflight and nutritional intervention can effectively counteract the detrimental effect of microgravity on skeletal muscle mass and metabolism. NutrISS (Nutrition monitoring for the International Space Station) is an Italian Space Agency (ASI) biomedical experiment investigating the changes in body composition during long-term spaceflight. The goal of this proof-of-concept study is to monitor the body composition of astronauts and, if needed, to provide nutritional advice during the mission. It has been executed on the ISS, from July 2019 till January 2020 and sponsored by ESA. The payloads selected for the mission “BEYOND” result from a public-call funded and coordinated by ASI, in the frame of its national mission of promoting and fostering the culture of space across the Country and providing access to the ISS as a laboratory in space to the Italian research community. The utilization support services is ensured by Argotec/Telespazio (UTISS Team). An astronaut underwent to baseline data collections, i.e. body composition, anthropometric evaluation and energy and metabolic assessment carried out by the scientific team. Body composition, estimated through resistance/reactance to a low-intensity current has been assessed with a Bio-Impedance Analyser (BIA) device manufactured by Akern and modified by Kayser Italia. To maintain the participant in near-neutral energy balance, the science team monitored monthly the astronaut body mass during the entire space flight period. Advice on energy intake was given to the astronaut when needed.

Development of a novel method to characterize mean surface peak curvature as a signature of tribological performance of dental implant surfaces

The integrity of dental implant surfaces might be compromised during surgical insertion. Wear and topographical modifications can occur during implant insertion, which can potentially have clinical implications. Accordingly, the analysis and prediction of the wear behaviour of dental implant surfaces is fundamental. Surface mean curvature is a key topographical parameter in contact mechanics, related to wear and plastic deformation; however, there is not a consensus on its characterization. In this paper, a critical analysis of the feature parameter Spc from ISO 25178-2 is carried out, which addresses its limited ability to characterize dental implant surfaces. A novel alternative parameter (named ‘relative mean peak curvature’ ΔSdq) is presented and evaluated in representative dental implant treatments. The obtained results suggest a positive correlation between the surface peak curvature and its tribological signature in biomedical implants. Although biomedical experiments are needed to validate this correlation, the novel method is presented as a tool for future studies.

Systematic review of guidelines for internal validity in the design, conduct and analysis of preclinical biomedical experiments involving laboratory animals

Over the last two decades, awareness of the negative repercussions of flaws in the planning, conduct and reporting of preclinical research involving experimental animals has been growing. Several initiatives have...

A simple method for short-term maintenance of neonatal mice without foster mothers.

Mice are typically weaned from their mother between 21 and 28 days of age, or at 10 grams of body weight. However, some biochemical experiments need to be done before the weaning days, and the mother might cannibalize or ignore those manipulated pups. Here, we provide a detailed protocol for maintenance of neonatal mice without the presence of their mothers for biomedical research. The basic instinct of neonate mice to hide under covers is harnessed for their survival in a mother-free environment. When covers are soaked with milk and the only targets for hiding, the neonates would acquire their nutrients at least in an involuntary fashion. The protocol is simple and can be used for neonatal rodent studies for short periods of times, and assures the accuracy of the biomedical experiments if survival rate of neonates is critical.

Biomedical data analysis using neuro-fuzzy model with post-feature reduction

Now-a-days, a large volume of biomedical data are continuously generated from various biomedical devices and experiments due to the rapid technological advancement in medical science. The effective analysis of these biomedical data such as extracting the significant features biologically and diagnostically is really a challenging task. This paper proposes a Neuro-Fuzzy model with post-feature reduction to analyze these complex biomedical data. The proposed Neuro-Fuzzy approach uses class belongingness fuzzification of input patterns to handle uncertainty issues. However, the complexity of the model increases due to this fuzzy expansion of input patterns. On the other hand, all the expanded fuzzified patterns may not always be significant for model identification. To address this issue, post-feature reduction has been employed on fuzzified patterns to filter out the irrelevant, redundant and noisy features. Unlike pre-feature reduction, this allows all the features to be participated in the fuzzification process and then identify irrelevant features from the fuzzified patterns. Further, this approach allows exploring potential fuzzified features from the strong as well as weak feature set. The effectiveness of this proposed model has been tested and validated with a variety of benchmark biomedical data collected from various domains.

Methods for preprocessing time and distance series data from personal monitoring devices

There is a need to develop more advanced tools to improve guidance on physical exercise to reduce risk of adverse events and improve benefits of exercise. Vast amounts of data are generated continuously by Personal Monitoring Devices (PMDs) from sports events, biomedical experiments, and fitness self-monitoring that may be used to guide physical exercise. Most of these data are sampled as time- or distance-series. However, the inherent high-dimensionality of exercise data is a challenge during processing. As a result, current data analysis from PMDs seldomly extends beyond aggregates.Common challanges are:•alterations in data density comparing the time- and the distance domain;•large intra and interindividual variations in the relationship between numerical data and physiological properties;•alterations in temporal statistical properties of data derived from exercise of different exercise durations.These challenges are currently unresolved leading to suboptimal analytic models. In this paper, we present algorithms and approaches to address these problems, allowing the analysis of complete PMD datasets, rather than having to rely on cumulative statistics. Our suggested approaches permit effective application of established Symbolic Aggregate Approximation modeling and newer deep learning models, such as LSTM.

Intra-droplet particle enrichment in a focused acoustic field.

Particle enrichment is an important preparation or collection process in biomedical and biochemical experiments, but the enrichment process in droplets is harder to realize than in continuous fluid. Here we demonstrate an on-chip, label-free and controllable intra-droplet particle enrichment realized in a focused acoustic field. In this process, droplets containing microparticles are trapped, merged together and split off in the focused acoustic region, resulting in droplets with particles of high concentration. By changing the experimental conditions, the degree of enrichment of this method can be tuned up to 26 times, which enables it to meet requirements for sample preparation in various applications.

Enhanced detection using stable isotope enriched 65Cu doped ferrite nanoparticles for tracing studies

65Copper stable isotope doped ferrite nanoparticles with two dopant concentrations were prepared by a co-precipitation method for conducting biomedical experiments at environmentally relevant concentrations. The synthesized (65CuxFe1-xFe2O4) nanoparticles were of 30 ± 7 nm in size and the VSM measurements showed a magnetic moment of 30 emu/g of un-doped ferrite particles at 310 K. The amount of 65Cu doped in the ferrite nanoparticles were calculated using ICP-MS. Cytocompatibility studies were performed through cellular toxicity assays on WRL68 liver cell line. MTT and ROS assay demonstrated cell viability in an order of Fe3O4>65Cu0.088Fe2.085O4>65Cu0.143Fe3.31O4. The cytocompatibility and magnetic measurement data set indicate that by doping a small amount of copper, the ferrite nanoparticles can retain their magnetic properties and the cytocompatibility is not severely compromised. 65Cu0.088Fe2.085O4 (d1-Fe3O4) and 65CuO nanoparticles were used for tracing experiments, wherein, even at a lower exposure concentration of 0.5 μg/mL, 65Cu can be detected in the media even when the copper background concentration is high. The results indicate the ability to perform biological studies at low exposure concentrations with enhanced detection ability. The proposed technique shows that isotope enriched copper doped ferrite can serve the purpose of quantifiable traceable nanocarriers.

Legal Aspects of Biomedical Experiments on Humans in Russia

The relevance of the study is determined by the fact that it is often a question of diversification of possible restrictions that become the basis of antagonism between the scientific progress and the desire of human beings to preserve themselves. Therefore, such fragments are often unpredictable, since the question of the admissibility of conducting research on humans has always been part of the general social and philosophical system that determines the development of society. The novelty of the study is that for the first time in the legal and philosophical literature the question of the conformity of what is called biological and medical ethics is raised in accordance with the national culture and national identity. The authors of the article clearly identify the inseparability of the connection between the cultural and statistical approach to the expediency of regulating biomedical experiments and their legal regulation. The structure of international legislation and its regional adaptation in Russian legislation are revealed. The practical significance of the study is determined by the possibility of forming a stable position regarding the possibilities of expanding the subject of legal regulation of biomedical ethics. Results: ‎The authors of the article determine that this is necessary for the complete improvement of the processes of socio-economic development, structural coordination of efforts aimed at achieving certain parameters and formation of a general picture regarding the holistic development of the ethical complex of a human being.

Reducing the primate pet trade: Actions for primatologists.

This commentary emerged from a panel presentation at the International Primatological Society Congress in Nairobi, Kenya, 2018. The goal was to provide regional updates on the status of primate removal from habitat countries, especially for the pet trade, and develop guidelines that could help primatologists address this critical problem. The trade in live primates includes those used as pets, in entertainment, and as subjects of biomedical experimentation, but here we focus on those primates destined for the pet trade. Such transactions are a hugely lucrative business, impacting hundreds of thousands of individuals annually and affecting the survival of wild populations. Being intimately familiar with primate social behavior, life history and biology, primatologists, whether they work with captive or wild primates, are in a unique position to understand the nature of the trade and attempt to counter its effects. In addition to updating the status of the primate pet trade, we provide recommendations that may help primatologists formulate a plan to deal, locally and regionally, with illegal trafficking in live primates. General guidelines include increasing awareness of local customs, policies and laws; developing collaborative research opportunities for local people; engaging in training/informational opportunities; and instructing on how to take action when encountering illegally‐trafficked primates.

Docking Study to Predict the Efficacy of Phosphatidylinositol 3-Kinase α Inhibitors

The phosphatidylinositol 3-kinase (PI3K) family comprises lipid kinases that cross-link signals between living cells and their surroundings. PI3Ks are classified into several groups and isoforms with specific characteristics and functions. Genes encoding PI3Ks are mutated in several types of cancer, and their isoforms have varying capacity in promoting cell signaling and cancer progression. Many compounds have been introduced as PI3Kα inhibitors, but not all of them have the same inhibitory effects. For successful PI3K-related biomedical experiments, it is vital to select the most specific and potent compounds with the highest inhibitory effects for targeting this kinase. In this study, we investigate 28 well-recognized PI3Kα inhibitors through predicting their specificity and potency using the docking software AutoDock Vina. Our data showed that PF 05212384 had the highest docking score (−9.2 kcal/mol), and 3-methyladenine had the lowest docking score (−4.8 kcal/mol). Our data also showed different types of interactions and bonds formed between the inhibitors and protein residues. In conclusion, PF 05212384 and AZD 6482 compounds are the best candidates for targeting PI3Kα. In addition to hydrophobic interactions in the PI3Kα binding pocket, the formation of hydrogen bonds between these inhibitors and binding pocket residues was confirmed.

THE PROTESTING SELF OF BIOETHICS AND THE PATIENT

The article considers the history of bioethics formation as a human rights movement aimed at establishing patient autonomy and limiting the practice of uncontrolled medical manipulation of human body, biomedical experimentation on people in the name of science, “public good” and other values. It is shown that the forms of expression and content of the statements of the protesting bioethical expert and the content turned out to be extremely diverse and based on conflicting ethical principles, actually demonstrating total rejection and confrontation of various conceptual arguments and often not contributing to the development of a universal, acceptable to all stakeholders ethical position. The article considers the peculiarities of bioethical protest and philosophical reasoning in connection with the emergence in the field of modern medicine of the diagnosis of brain death and gives a general idea of the intense public perception of this diagnosis.

Семиотический подход в биоэтике: от морального кодекса читателя к этике чистого листа

<p>Целью статьи является исследование возможностей использования эвристических ресурсов семиотики в современном биоэтическом дискурсе. Опираясь на идеи классиков семиотики Ч. С. Пирса, В. леди Уэлби, У. Эко автор обращает внимание на концепт знака как этически релевантного объекта. В процессе исследования демонстрируется необходимость поиска «семантических универсалий» (понятие У. Эко), которые должны были бы обеспечить универсальные соматические (телесные) права человека. По мнению автора, данные универсалии являются фундирующими для биоэтического дискурса и, в целом, являются необходимыми для перевода динамики науки «в интеллектуальное и моральное русло» (В. Уэлби).</p><p>На основе использования результатов исследований отечественных философов (Б. Г. Юдина, П. Д. Тищенко, И. В. Мелик-Гайказян и др.) артикулирован ряд проблем биоэтики, позволяющих оценить релевантность семантического подхода для формирования биоэтического знания. Показано, что языковые игры с именованием и манипулированием знаками, представляющие реализацию лингвистического модуса конструирования человека, зачастую направлены на осуществление тех или иных прагматических биомедицинских целей, которые соответствуют познавательным интенциям ученого, например, связанным с проведением успешного биомедицинского эксперимента. При переходе в рассуждениях о человеке от персонально ориентированного дискурса к дискурсам о «вещах», «артефактах», «объектах опыта» и т. д. дискурсивное пространство может использоваться как инструмент легитимации каких-либо действий по отношению к человеческому существу.</p><p>Сделан вывод о том, что среди существующих стратегий толкования человеческого существования (в контексте распространяющихся тенденций генетического и нейронаучного редукционизма) необходимо отстаивать нередукционистскую герменевтику человека и сопряженную с нею «этику чистого листа» (понятие О. В. Поповой).</p>

MHC class I allele diversity in cynomolgus macaques of Vietnamese origin.

Cynomolgus macaques (Macaca fascicularis, Mafa) have been used as important experimental animal models for carrying out biomedical researches. The results of biomedical experiments strongly depend on the immunogenetic background of animals, especially on the diversity of major histocompatibility complex (MHC) alleles. However, there is much less information available on the polymorphism of MHC class I genes in cynomolgus macaques, than is currently available for humans. In this study, we have identified 40 Mafa-A and 60 Mafa-B exons 2 and 3 sequences from 30 unrelated cynomolgus macaques of Vietnamese origin. Among these alleles, 28 are novel. As for the remaining 72 known alleles, 15 alleles are shared with other cynomolgus macaque populations and 32 are identical to alleles previously reported in other macaque species. A potential recombination event was observed between Mafa-A1*091:02 and Mafa-A1*057:01. In addition, the Mafa-A1 genes were found to be more diverse than human HLA-A and the functional residues for peptide binding sites (PBS) or TCR binding sites (TBS) in Mafa-A1 have greater variability than that for non-PBS or non-TBS regions. Overall, this study provides important information on the diversity of Mafa-A and Mafa-B alleles from Vietnamese origin, which may help researchers to choose the most appropriate animals for their studies.

Distribution-free simultaneous tests for location-scale and Lehmann alternative in two-sample problem.

The paper deals with the classical two-sample testing problem for the equality of two populations, one of the most fundamental problems in biomedical experiments and case-control studies. The most familiar alternatives are the difference in location parameters or the difference in scale parameters or in both the parameters of the population density. All the tests designed for classical location or scale or location-scale alternatives assume that there is no change in the shape of the distribution. Some authors also consider the Lehmann-type alternative that addresses the change in shape. Two-sample tests under Lehmann alternative assume that the location and scale parameters are invariant. In real life, when a shift in the distribution occurs, one or more of the location, scale, and shape parameters may change simultaneously. We refer to change of one or more of the three parameters as a versatile alternative. Noting the dearth of literature for the equality two populations against such versatile alternative, we introduce two distribution-free tests based on the Euclidean and Mahalanobis distance. We obtain the asymptotic distributions of the two test statistics and study asymptotic power. We also discuss approximating p-values of the proposed tests in real applications with small samples. We compare the power performance of the two tests with several popular existing distribution-free tests against various fixed alternatives using Monte Carlo. We provide two illustrations based on biomedical experiments. Unlike existing tests which are suitable only in certain situations, proposed tests offer very good power in almost all types ofshifts.

Photolysis of dimethoxynitrobenzyl-\u201ccaged\u201d acids yields fluorescent products

Carboxylic acids conjugated with 4,5-dimethoxy-2-nitrobenzyl photoremovable protecting group are well known and widely used for biological studies. In this paper, we study the photolysis of likewise “caged” acetic, caprylic and arachidonic acids. Unexpectedly, we observed huge growth of fluorescence emission at ~430 nm during photolysis. Following further UV irradiation, a product with fluorescence at longer wavelength was formed (470 nm excitation / ~500–600 nm emission). While it may be used to monitor the “uncaging”, these fluorescent products may interfere with widespread dyes such as fluorescein in biomedical experiments. This effect might be negligible if the photolysis products dissolve in the medium. On the other hand, we observed that arachidonic and caprylic acids derivatives self-organize in emulsion droplets in water environment due to long lipophilic chains. Illumination of droplets by UV rapidly induces orange fluorescence excited by 488 nm light. This fluorescence turn-on was fast (~0.1 s) and apparently caused by the accumulation of water-insoluble fluorescent residuals inside droplets. These self-organized lipophilic structures with fluorescence turn-on capability may be of interest for biomedical and other application. We have identified and hypothesized some compounds which may be responsible for the observed fluorescense.

Live and Dead Cells Counting from Microscopic Trypan Blue Staining Images using Thresholding and Morphological Operation Techniques

<span lang="EN-US">Cell counting is a required procedure in biomedical experiments and drug testing</span><em><span lang="TH">. </span></em><span lang="EN-US">Manual cell counting performed with a hemocytometer is time consuming and individual dependence</span><em><span lang="TH">. </span></em><span lang="EN-US">This study reported</span><em></em><span lang="EN-US">the development of a computer</span><em><span lang="TH">-</span></em><span lang="EN-US">assisted program for trypan blue stained</span><em><span lang="TH">-</span></em><span lang="EN-US">cell counting using digital image analysis</span><em><span lang="TH">. </span></em><span lang="EN-US">Images of trypan blue</span><em><span lang="TH">-</span></em><span lang="EN-US">stained breast cancer cells line were obtained by a microscope with a digital camera</span><em><span lang="TH">. </span></em><span lang="EN-US">Undesired noise and debris were removed by applying a guided image filter</span><em><span lang="TH">. </span></em><span lang="EN-US">Color space HSV </span><span lang="EN-US">(</span><span lang="EN-US">Hue, Saturation and Value)</span><em></em><span lang="EN-US">conversion and grayscale conversion were performed for distinguishing between live and dead cells</span><em><span lang="TH">. </span></em><span lang="EN-US">Image thresholding and morphological operators were applied for image segmentation</span><em><span lang="TH">. </span></em><span lang="EN-US">Live and dead cells were counted after image segmentation and the results were compared with manual counting by three well</span><em><span lang="TH">-</span></em><span lang="EN-US">experienced counters</span><em><span lang="TH">. </span></em><span lang="EN-US">The computer</span><em><span lang="TH">-</span></em><span lang="EN-US">assisted cell counting from thirty</span><em><span lang="TH">-</span></em><span lang="EN-US">six trypan blue</span><em><span lang="TH">-</span></em><span lang="EN-US">stained microscopic images had a high correlation coefficient with the live cell results of the experts (r</span><em><span lang="TH">=</span></em><span lang="EN-US">0</span><em><span lang="TH">.</span></em><span lang="EN-US">99</span><span lang="EN-US">)</span><em><span lang="TH">. </span></em><span lang="EN-US">The correlation coefficient of the number of dead cells comparing the computer</span><em><span lang="TH">-</span></em><span lang="EN-US">assisted count and the experts</span><em><span lang="TH">’ </span></em><span lang="EN-US">count was 0</span><em><span lang="TH">.</span></em><span lang="EN-US">74</span><em><span lang="TH">. </span></em><span lang="EN-US">Our approach offers high accuracy (>85</span><em><span lang="TH">%</span></em><span lang="EN-US">)</span><em></em><span lang="EN-US">on counting live cells compared with the experts</span><em><span lang="TH">’ </span></em><span lang="EN-US">counting</span><em><span lang="TH">. </span></em><span lang="EN-US">This automated cell counting approach can assist biomedical researchers for both live and dead cells counting</span><em><span lang="TH">.</span></em>

CaosDB—Research Data Management for Complex, Changing, and Automated Research Workflows

We present CaosDB, a Research Data Management System (RDMS) designed to ensure seamless integration of inhomogeneous data sources and repositories of legacy data in a FAIR way. Its primary purpose is the management of data from biomedical sciences, both from simulations and experiments during the complete research data lifecycle. An RDMS for this domain faces particular challenges: research data arise in huge amounts, from a wide variety of sources, and traverse a highly branched path of further processing. To be accepted by its users, an RDMS must be built around workflows of the scientists and practices and thus support changes in workflow and data structure. Nevertheless, it should encourage and support the development and observation of standards and furthermore facilitate the automation of data acquisition and processing with specialized software. The storage data model of an RDMS must reflect these complexities with appropriate semantics and ontologies while offering simple methods for finding, retrieving, and understanding relevant data. We show how CaosDB responds to these challenges and give an overview of its data model, the CaosDB Server and its easy-to-learn CaosDB Query Language. We briefly discuss the status of the implementation, how we currently use CaosDB, and how we plan to use and extend it.