News

12. 4. 2021 |

Non-alcoholic fatty liver disease (NAFLD) is a disease in which fat accumulates in the liver without excessive alcohol consumption. It is related, among other things, to the development of diabetes II. type, obesity and also genetic predisposition and is therefore an increasingly common diagnosis. It is estimated that more than a quarter of the world's population suffers from NAFLD.

An international research team, whose members were also scientists from The International Clinical Research Center of St. Anne's University Hospital Brno (FNUSA-ICRC), focused in its work on how NAFLD is affected by genetic variations. Their article entitled "Pediatric Non-Alcoholic Fatty Liver Disease is Affected by Genetic Variants Involved in Lifespan / Healthspan" was published in the Journal of Pediatric Gastroenterology and Nutrition.

"We investigated the impact of single nucleotide polymorphisms (SNPs), which are related to lifespan," said Manlio Vinciguerra, Ph.D. MSc, Principal Investigatorof Epigenetics, Metabolism and Aging research team of FNUSA-ICRC. Single nucleotide polymorphisms are variations in a single nucleotide in the human genome and are the basis of differences in our susceptibility to various diseases.

The research was performed on a sample of 177 patients with this diagnosis with an average age of 13.7 years. As a control, there were 146 healthy individuals. 10 single nucleotide polymorphism were selected, which are demonstrably related to metabolism and also to liver function. "We used multidimensional reduction analysis and control of SNP-SNP interactions on the obtained samples in order to identify the effect of the examined SNPs in the prediction of NAFLD and related complications," described Dr. Vinciguerra.

The results showed that all examined SNPs are related to individual metabolic features of NAFLD, however, none was significantly associated with its diagnosis. Subsequent testing of potential synergies revealed that the combination of IL-6 rs1800795 and ANRIL rs1556516 could be used to diagnose NAFLD and to estimate their life expectancy. "To confirm whether the genetic interaction between the two genes affects the development of this disease in children, another, larger, study will be needed," added Dr. Vinciguerra.

You can find the article here:

1. 4. 2021 |

At the beginning of March, the University of Cape Town organized a workshop called CCP4 Crystallographic School in South Africa. Due to the current situation, it was of course in the online environment and Ing. Andrea Schenkmayerová Ph.D. from Loschmidt laboratories of Faculty of Science MU and the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) achieved great success. The researcher of the Protein Engineering reserach team won the award for the best poster entitled Structural analysis of a haloalkane dehalogenase from subfamily HLD-III.

In general, crystallography is a scientific discipline that deals primarily with the study of the arrangement and bonding of atoms in crystals and the study of the geometric structure of crystal lattices. Although most of us imagine a crystal such as a grain of salt, the modern concept of a crystal is based directly on the characteristics of the internal structure at the level of atoms and not on its external shape. The crystalline state of matter is more energetically advantageous and at present we can get not only minerals but also metal alloys or organic molecules into this state. The importance of crystallography is also underlined by the fact that 32 Nobel Prizes have so far been awarded for research and related results.

Macromolecular crystallography deals with the study of the structure and spatial arrangement of biological macromolecules (eg proteins, DNA) and their complexes, which is key to understanding their function in organisms. A detailed understanding of the structure and function of biological macromolecules is then key to understanding complex cellular processes, their homeostasis but also their pathological manifestations.

Crystallography is also used to research new proteins and their inhibitors, which could be used, for example, as drugs. The therapeutic effect is influenced, inter alia, by the shape of the molecules of the therapeutic component, so that crystallography functions here as a tool for obtaining information about the shape of the molecules. However, we would not find a classic optical microscope in this area, the light has too long wavelength - for microscopy at the molecular level devices using for example, X-rays. In general, the best drug is one whose molecule fits into a suitable binding site in the macromolecule and thus affects its biological activity.

Ing. Andrea Schenkmayerová Ph.D. in her work focused on hitherto structurally unexplored enzymes from the haloalkane dehalogenase family. These enzymes have an interesting property - they catalyze the cleavage of carbon-halogen bonds to form the corresponding alcohol, halogen anion and proton. Due to these properties, these enzymes are used in various biotechnological applications. In addition to haloalkane dehalogenase activity, lactone decarboxylase activity has been found in some of these enzymes in recent years, prompting a broad scientific discussion of the natural biological function of these enzymes and how they evolved during evolution.

"It was started by my colleague Ing. Klaudia Chmelová and after she left for maternity, I started doing it, "said Schenkmayerová. "It was a real challenge, because so far no one in the world has been able to determine the structure of the enzyme from the HLD-III subgroup, because it forms heterogeneous oligomeric structures, which makes their structural analysis very impossible. In our laboratory, systematic work has succeeded in developing a method by which we are able to prepare relatively homogeneous enzyme preparations, which opened the way for their structural analysis using cryo-electron microscopy and X-ray crystallography. Although we eventually managed to prepare crystals of this enzyme and collect quality crystallographic data, we still had trouble solving the structure due to the atypical internal arrangement of the crystal and the lower resolution of the obtained crystallographic data."

She signed up for the workshop with work that still needed to be completed, and with the help of lecturers, she finally succeeded. It was a truly international collaboration, on the result contributed for example, professor Kay Diederichs from the University of Konstanz or professor Randy J. Read and Dr. Tristan Croll from the University of Cambridge. Important data were obtained in CEITEC laboratories and measurements were also performed on a Swiss Light Source synchotron device in Switzerland.

"This is a perfect example of an integrated approach in structural biology, which combines several experimental approaches at the same time so that it is possible to solve the structure of biomolecules when one technique is not enough. The original, say, wild-type protein formed various types of oligomers and we failed to crystallize for a long time. Using protein engineering methods, we prepared a stabilized form of the enzyme that did not produce so many different types of oligomers, and we were able to crystallize it. Despite all the difficulties, the workshop managed to solve the crystal structure of this unexplored enzyme, which will help us understand the biological function of these very interesting biocatalysts, "described Schenkmayerová.
A manuscript of the publication is currently being prepared, we will inform you as soon as it is ready.

Fig. 1: Ing. Andrea Schenkmayerová PhD. with her leader RNDr. Ing. Martin Marek Ph.D.
Fig. 2: Photo of protein crystal

30. 3. 2021 |

The international journal Frontiers in Psychiatry published the work of the Translational Neuroscience and Aging Program Research Group in collaboration with the research group Kardiovize led by Dr. Juan Pablo Gonzalez Rivas – both from the International Clinical Research Center of St. Anne's University Hospital Brno – and the Mayo Clinic in the United States.

A multidisciplinary team led by dr. Stokin focused on the analysis of the impact of the COVID-19 pandemic and related anti-epidemic measures in the spring of 2020 on the mental health of the Kardiovize study population and on the role of selected risk factors on mental health changes.

 "The results showed that the prevalence of increased stress and the presence of depressive symptoms increased 1.4-fold to 5.5-fold compared to the period before the COVID-19 pandemic," said the first author of the study, Dr. Novotný. This deterioration was seen in all age groups and was more pronounced in women. The main risk factors associated with this increased prevalence have been feelings of loneliness, perceptions of COVID-19 as threatening, and some negative lifestyle effects (sleep quality, exercise, financial implications). On the contrary, a higher level of resilience proved to be a protective factor.

The results of this study support previous findings about the significant impact of the COVID-19 pandemic not only on the physical health of the population (or its economic and social functionality), but also on mental health and point to the need to respond to this threat in a timely and targeted manner. to reduce the risk of a subsequent pandemic of mental disorders in the population. The study's research team continues this study in an effort to capture long-term changes in mental health as the COVID-19 pandemic continues to grow.

The article can be found here: 


16. 3. 2021 |

With the increasing power of supercomputers, artificial intelligence is penetrating more and more areas of scientific life and helping to solve the problem that scientific leaders have been struggling with for decades. A necessary prerequisite for successfully finding a solution is the availability of a sufficient amount of quality source data, based on which the algorithm analyzes the problem. Without data, finding the right solution is much more difficult or impossible. Many scientific communities have not dealt with historically systematic data collection and management, and their current acquisition from thousands of published studies is very time consuming and laborious.

One of the attractive areas for the application of artificial intelligence is the analysis of the effect of mutations on the thermal stability of a protein, as this mechanism is not well understood. This area also suffers from a lack of quality data, and therefore data analysts and programmers from the Loschmidt Laboratories of the Faculty of Science, Masaryk University and the International Clinical Research Center of St. Anne's University Hospital Brno (FNUSA-ICRC) under the guidance of molecular biologist Mgr. David Bednář Ph.D. and Mathematics Stanislav Mazurenko Ph.D. from the FNUSA-ICRC Protein Engineering research team decided to create a new database FireProtDB, which would systematically collect and maintain this data for a long time.

"The database currently contains 16,000 experimental values obtained from own measurements, available scientific literature and no longer maintained databases, which have been thoroughly filtered and verified," said Mgr. Jan Štourač, who is one of the creators of the database. To access the data, it offers users a simple web interface, which has been visited by more than 500 scientists from around the world since its publication in October 2020. The data were also provided to the worldwide PDBe-KB database, which serves as a global repository of information for biological and biomedical research and is managed by the European Institute of Bioinformatics. The FireProtDB database was published in the prestigious scientific journal Nucleic Acids Research.

Link to the database here.
.

10. 3. 2021 |

... and it has awarded 20 stroke centers, 11 study nurses and coordinators and 5 academic studies.

More than 8 years ago, we started working on the idea of ​​creating a research network of clinical workplaces for the implementation of joint projects in the field of stroke. 4 years ago, we started trying to raise funds, and when we succeeded in cooperation with the CZECRIN research infrastructure, we were finally able to start building the network from last year. Today, after one year of solution, we can celebrate the first fruits of our efforts. To the network, which is initiated and led by prof. Robert Mikulík, head of the FNUSA-ICRC Cerebrovascular Research Program, involved 20 stroke centers, created a network of study coordinators and nurses at the participating hospitals, and began work on five academic studies. This with the support of the parent platform, the CZECRIN research infrastructure.

The idea of ​​the newly established STROCZECH network is to connect a well-functioning network of clinical stroke workplaces, which have patients, physicians and knowledge in the field of stroke research and care, with the CZECRIN research infrastructure, which brings know-how for academic clinical studies in the Czech Republic. The aim of the STROCZECH network is to raise the research of cerebrovascular diseases in the Czech Republic to the highest possible level with the possibility of conducting randomized clinical trials. At the same time, the National Research Stroke Network has become a model for other Disease Oriented Networks, which will continue to emerge within the CZECRIN research infrastructure (eg epilepsy or mental health).

To the STROCZECH network, which is coordinated by the Cerebrovascular Research Team of the St. Anne's University Hospital Brno, the following hospitals also participated: University Hospital Brno, Hospital Jihlava, Hospital České Budějovice, Hospital Písek, General University Hospital in Prague, Military University Hospital, Hospital Na Homolce, University Hospital in Motol, Thomayer University Hospital, University Hospital Královské Vinohrady, Regional Hospital Liberec, University Hospital Hradec Králové, Hospital Pardubice, Hospital Vyškov, University Hospital Olomouc, Tomas Bata´s Regional Hospital Zlín, Hospital Karviná, University Hospital Ostrava and Hospital Vítkovice.

Last year, the scientific council of the network was established, which consists of elected members of the Committee of the Cerebrovascular Section of the Czech Neurological Society of the Czech Medical Association JEP. It includes 13 experts in the field of stroke in the Czech Republic and also representatives of Czech stroke centers. The members of the Scientific Council prepare research protocols and plan the implementation of national academic studies as well as participation in international studies. However, ideas for scientific projects implemented within the network may also be submitted by other researchers, not only members of the Scientific Council.

The STROCZECH network has also become a member of the global alliance of stroke networks GAINS. Thanks to this, STROCZECH will have the opportunity to participate in international academic studies and also access to new knowledge.

However, not all centers of the network have been activated yet, for some partners we are in the contracting phase and in the phase of recruiting other research nurses. In particular, the legislative processes were a challenging point in the creation of the network, as was the pandemic, which, of course, paralyzed the network. So we still have a long way to go before we carry out our own multicenter academic studies throughout our network.

How do we prepare a generation of research coordinators and study nurses?


Last year, we also organized a workshop for research nurses and coordinators of our STROCZECH network. The two-day fully-fledged program was designed to present the workload of research nurses and their contribution to clinical research and patients, as well as the planned first academic clinical trials within the network.
The workshop program also involved experts from the CZECRIN research infrastructure, who presented work in the preparatory, evaluation and monitoring phases of clinical trials, ie start-up, project management, monitoring, pharmacovigilance, data management and statistics.
One of the blocks of the workshop was focused on increasing knowledge about strokes and the latest trends in their treatment. In the simulation center, participants could try out how to inform the patient together with the doctor about his possibility to participate in the clinical study and how to communicate with different types of patients. Professor Mikulík and MUDr. Ondřej Volný contributed their invaluable personal experience.

And how did our study nurses and coordinators like the workshop?

"Clinical trials are a completely new area for me, so the meeting was extremely interesting and beneficial for me from start to finish. I was most interested in the lecture on monitoring clinical trials and also the opportunity to participate in educational projects such as the HOBIT program implemented by the Cerebrovascular Research Team, "says Pavla, a research nurse from Liberec.

"I was most impressed by the interactive training room, where we tried to get informed consent from the patient using a simulated situation, and I appreciated the great acting performance of all members of the simulation team," says David, a medical brother from Písek.

Kristýna, a research nurse for Prague hospitals, summed up the event as follows: “The workshop was fully loaded with information. I will draw from it on a daily basis in my research work. I consider the most useful information about the individual phases of the preparation of a clinical trial, about communication with regulatory authorities and about the monitoring of studies. "

We wish our network in the coming years to grow with new projects and other enthusiastic members and to gain in its importance, because its results will be beneficial both for the hospitals themselves and especially for patients.

Veronika Svobodová, Martina Sittová and Kristýna Znamenáčková
for the STROCZECH research network
Cerebrovascular research program FNUSA-ICRC

9. 3. 2021 |

The new head of the Biostatistics team is MUDr. Michal Šitina Ph.D. MSc. We talked in a short interview about his plans for the future, but also about the services that this department can offer not only to other research teams within the FNUSA-ICRC, but also to individual clinics of the hospital and external subjects.

A brief introduction at the beginning, what was your professional journey to the head of the Biostatistics department?
I used to hesitate to study medicine or physical chemistry or physics, because I was both very interested. I chose medicine and I still work as a doctor, internist with an interest in intensive care medicine. Later, I lived for about 8 years and worked as a doctor in Jena, Germany. In Jena because there is an extensive sepsis research program that I was going to get involved in. There is also  a large old university in Jena. Eventually, I succumbed to the urge to enroll in the Faculty of Mathematics and Computer Science, studying first bioinformatics and later a Master's degree in Computational and Data Science (basically Numerical Mathematics and Data Analysis), as well as a basic course in theoretical physics. After returning to the Czech Republic in 2019, I did not want to leave medicine, but also mathematical disciplines. FNUSA-ICRC made it possible to combine the two - I work for the most part at ARK (Department of Anaesthesiology and Resuscitation) as a doctor and a smaller one in the Biostatistics department. After Mrs. Mgr. Bělašková left FNUSA-ICRC, I became the head of the department. I have the slight advantage over others that I can be a mediator between statistics / mathematicians on the one hand and doctors / biologists on the other. The downside is that I can't do either properly.

You were actively involved in the fight against COVID-19 last spring, are you continuing to do so?
In the first wave of the pandemic, we helped the hospital monitor data on hospitalized patients and bed capacity. Because the hospital information system (NIS) does not easily provide all the necessary data, we have developed a new solution in the REDCap system. In the autumn, we adapted this solution for the needs of the entire South Moravian Region - every day the individual hospitals of the South Moravian Region update the condition of their beds of various types so that they can be available at any time, for example for the regional coordinator prof. Šrámek for managing patient routing and planning hospital capacity adjustments.

Biostatistics is a so-called Core Facility, what does it mean from your point of view?

A Core Facility is generally a central laboratory or unit that offers its expert services to other departments within a center, hospital, or external entity. It offers the services that most others need, such as statistics. I believe that we will be a sought-after and valuable partner for research teams. This year, we have hired three new colleagues, graduates of mathematical biology, so we can guarantee the delivery of serious results in a reasonably short time.

What services do you offer?
We offer several services. First of all data analysis. From easy analyzes that teams would probably be able to do without us, they just don't have the time to do so, through exploratory analyzes, which means searching for knowledge and context in data, to complex regression models, survival analysis, time series analysis, bioinformatics analysis, etc. We can also help with the preparation of projects or grants, such as estimating the required sample size of the study or consulting with its design. We will also help prepare professional charts for the needs of presentations or articles. Another important activity is the creation (fitted to a specific study) and management of a database in the REDCap system, which is easy to use. As a novelty, we offer support in the use of the OpenProject project application (https://project-icrc.fnusa.cz), which facilitates the planning and management of clinical trials or project management.
Why should research teams use the services of ours and not external suppliers? We offer an understanding of the problem - we are oriented not only in statistics, but also in medicine. We try to make the results not only statistically exact, but also give medical or biological meaning and answer the questions that the researcher asks.

So it's an IT job, how do you relax?
Unfortunately, I have a minimum time to relax. I still hope it gets better. But many are even more busy. I play piano. Classical music. I would like to actively improve my piano playing. Brno makes it possible, there is, for example, a conservatory and JAMU, unfortunately not a coronavirus situation at the moment.

Go to top