Priority areas for scientific research
Slovak Health for 2008 - 2011:
List of assisted areas 2008

The draft material was adopted at the regular plenary session of the Scientific Council of the Ministry of Health of the Slovak Republic on 07 February 2008, published in accordance with MZ SR Directive No 15854/2007 between 22 February 2008 and 20 March 2008 for public consultation on the website of the Slovak Republic. After receiving the proposals and discussion comments, these were analysed in the relevant expert commissions of the CoR of the Slovak Republic and in the chair of the Scientific Council of the Slovak Republic.

Following the discussion and cooperation with the presidents of the relevant expert commissions of the CoR of the Slovak Republic, the Council, in accordance with the directive of the Slovak Republic No 15854/2007 of 28 May 2007, presents this proposal for the negotiation of a german meeting of the Minister of Health of the Slovak Republic.

It also notes that, in line with the above-mentioned Directive, it is a list of priority areas for 2008 and, in the context of the foreseen call for the 4th round of project submission, a list of areas for project submission for 2008-2011.

I. DISEASES OF THE HEART, PLOY AND CIVE

Cardiovascular Epidemiologicals

Cardiovascular and cerebrovascular diseases are the most common cause of mortality in the Slovak Republic. More than 50% of Slovak citizens die from complications of atherosclerosis. Research into causes, pathogenesis, clinical manifestations and complications of cardio and cerebrovascular diseases is therefore a fundamental priority in the field of biomedical research.

Type 2 diabetes affects almost 7% and metabolic syndrome more than 20% of the Slovak population. Both diseases are associated with a 2-4-fold increased risk of cardiovascular disease development and diabetes is also associated with the risk of severe microvascular complications.

Epidemiology of respiratory diseases

In economically developed countries chronic obstructive pulmonary disease (hereinafter referred to as "COPD') is the fourth most common cause of mortality, with COPD expected to be the third most common cause of death worldwide by 2020. Bronchial asthma and chronic cough are also significantly involved in morbidity in all European countries. The statistics of the European Respiratory Society report the presence of night cough in 30%, productive cough in 10% and non-productive cough in 10% of the population.

Sleep apnoea affects 4-6 percent of the adult population, with an independent risk factor for serious cardiovascular diseases such as arterial hypertension, stroke, coronary artery disease and heart failure. At the same time, sleep apnoea is associated with a high risk of insulin resistance, with the presence of metabolic syndrome and type 2 diabetes.

Research orientation on cardiovascular diseases

Atherosclerosis is the most important pathological-anatomic substrate of heart and vascular diseases. Analyses of pilot epidemiological studies carried out so far in Slovakia showed an alarmingly high incidence of serious risk factors for atherosclerosis. Risk factors for atherosclerosis often clump together in high risk conditions such as metabolic syndrome, type 2 diabetes mellitus, sleep apnoea, certain endocrine diseases (hypothyroidism, growth hormone deficiency, hypercorticism) and chronic renal disease. Research in recent years suggests that chronic subclinical inflammation plays an important role in the development of atherosclerosis. It is believed that subclinical inflammation may be involved in the development of cardiovascular diseases in metabolic syndrome, type 2 diabetes, COPD, sleep apnoea as well as systemic connective tissue disorders.

It is therefore proposed to support research projects aimed at: (a) the monitoring of genetic and environmental factors involved in the development of atherosclerosis, (b) the monitoring of genetic, humoral and environmental factors involved in the development of pathomechanisms in the development and development of obesity, metabolic syndrome and type 2 diabetes, (c) the conduct of a prospective randomised intervention study to monitor the pharmacological impact of risk factors on atherosclerosis; at the same time evaluate the pharmacoeconomic parameters of intensive and conventional care for patients with defined risk factors of atherosclerosis, (d) the monitoring of early myocardial injury markers.

Research direction on respiratory diseases

In the field of pneumology, it is necessary to focus research on obstructive pulmonary diseases It becomes a priority: a) epidemiologically map the occurrence of chronic obstructive pulmonary diseases in Slovakia, b) monitor interactions between genetic factors and the environment in the progression of obstructive ventilation disorder and/or chronic cough, c) identify pathogenicity mechanisms that contribute to the development of COPD and bronchial asthma. The incidence of atherosclerosis and its complications as well as the occurrence of metabolic disorders is higher in COPD patients than in the non-obstructive ventilation disorder population. At the same time, the frequent co-incidence of COPD with respiratory disorders in sleep is - obstructive sleep apnoea, which is often associated with arterial hypertension and metabolic syndrome. It is therefore necessary to focus research also on the monitoring of diseases associated with COPD and the so-called systemic manifestations of this disease.

Summary of preferred areas:

Pharmacovigilance assessment of intensive and conventional care for patients with defined risk factors for atherosclerosis.

Molecular-biological aspects of obesity development with emphasis on the role of hormones.

Markers early diagnosis and quality of early myocardial injury therapy and chronic heart failure.

Molecular-biological aspects of metabolic disorders in patients with respiratory disorders.

II. ONOLOGICAL DISEASES

Tumour diseases are among the main causes of morbidity and death in the population of industrialized countries, including the population of Slovakia. In recent years, there has been an explosion in the knowledge of cancers, which are concentrated in the following areas:

It is therefore desirable to direct the research capacity of Slovak health in the above mentioned areas, focusing in particular on the following main core programmes:

The output of the solution of each submitted and approved scientific-research project in the field of -Oncology- should be the effort to improve diagnostic algorithms, innovation of therapeutic protocols, increasing individualisation of therapy and achieving improved quality of life and survival of the cancer patient.

III. Diseases associated with the Motherhood and the Childhood Age

III.1.a. Birthplace

In recent years, the absence of a national peri-natal programme for mother, fetus and newborns has produced negative results. In addition to the significant, almost 50% decline in birth rates, we achieved almost twice as bad results in perinatal mortality and morbidity in 15 years after the split of Czechoslovakia compared to the Czech Republic.

National Children's Care and Adolescence Programme in Slovakia adopted for 2008-2015, as well as the current National Programme for the Protection of Sexual and Reproductive Health in Slovakia, including attention focused mainly on prenatal diagnosis and in utero treatment of the fetus, should bring improvements in the quality of statistical indicators of perinatal mortality and morbidity by improving the prenatal diagnosis of intrauterine threat to healthy foetuses by hypoxia and at the same time increasing the quality of the gene pool of the population by early diagnosis and treatment of genetically-related and congenital and metabolic fetal diseases.

An important part of the above-mentioned national programmes is also the economic benefit in the form of reduced costs in health and social care of the physically or mentally affected individual, early prenatal diagnosis and effective intrauterine treatment of the endangered or affected foetus. An important component is to complete National Center of Maternal Fetal Medicine in Bratislava as a top professional facility for research, diagnosis and treatment of fetal and neonatal diseases.

III.1.b. Gynaecology

Mini-invasive surgery is an operating technique that saves the patient while maintaining the full extent of surgery. Such a procedure allows intimate contact with the surgical field, selective access to lymphatic system-sparing tissues and vegetative nerves. The result is early recovery, return to full life in the postoperative period and after radical surgery of patients with cancer and endometriosis.

The focus of the proposed scientific activity is:

III. 2. Children age

Baseline:

The incidence of congenital developmental defects, genetic and immune-related diseases is increasing in Slovakia, but the prevention and extent of diagnosis is still lagging behind developed countries.

Objectives of the programme:

The aim of the scientific programme is to stimulate activities aimed at promoting health and healthy lifestyles, reducing negative environmental impacts and increasing the efficiency and quality of health care provided in order to reduce the negative consequences of diseases. Academic research activities based on university institutions and applying newer biomedical knowledge, as well as multidisciplinary research networks in paediatric practice, are supported to study the health status of larger newborns, children and adolescents. An important tool to identify the impact of environmental, genetic, nutritional, social and other factors on children's health, as well as to know the relationships between prenatal parameters and chronic childhood and adult age diseases is long-term monitoring of cohort parents - children.

Programme Scientific Headings
The programme shall concentrate on:

Specific scientific areas of the project include:

Characteristics of the expected outcome of the solution:

IV. MOVEMENT SYSTEM DISEASES

1. Monitoring of autoimmune syndromes in chromosome aberrants.

This is an interesting clinical problem from a rheumatological point of view. Pooled autoimmune diseases such as juvenile idiopathic arthritis, rheumatoid arthritis and systemic lupus erythematosus, or dermatomyositis/polymyositis, especially in Klinefelter syndrome, are common in these diseases. In Turner syndrome, juvenile idiopathic arthritis or rheumatoid arthritis-like arthritis may occur. As part of the forthcoming research in the coming years, it is desirable to try to monitor gene mutations in diffuse diseases in an effort to detect in our population suffering from autoimmune diseases, the mutation of genes involved in the development of autoimmune diseases, especially in juvenile idiopathic arthritis.

It is also recommended to monitor the genetic variation in the autoimmune gene PTPN22 to differentiate T lymphocytes in rheumatoid arthritis patients and their first-stage relatives. Rheumatoid arthritis is the most common systemic disease affecting approximately 1% of the world population. While the aetiology of RA remains unclear, it is now clear that genetic predisposition plays an important role in the development of the disease.

Recent single-nucleotide polymorphism (C-on-T-position 1858) of the PTPN22 gene coding for lymphoid tyrosine phosphatase (LYP) is the second most common genetic variant associated with RA and other autoimmune diseases, such as type 1 diabetes, juvenile idiopathic arthritis, or systemic lupus erythematosus, following specific HLA variants in the major histocompatible complex. It is relatively well known that ancillary CD4+ T lymphocytes play a primary role in the development of inflammation in RA. RA is traditionally considered a disease led by Th 1 auxiliary lymphocytes. However, the latest data points to the key role of Th 17 subpopulations in RA development. Some interleukins (IL) such as IL-2 produce CD4+ lymphocytes necessary for the activation of cytotoxic CD8+ T lymphocytes involved in the destruction of tissue affected by the inflammatory process. Antigenic receptor T lymphocytes (TCR) is a significant mediator regulating CD4+ T lymphocytes. The PTPN22 T1858 allele leads to the substitution of arginine amino acid for tryptophan at 620 in LYP protein. The function of this protein is relatively little known and practically limited to interaction with signal kinases in CD4 lymphocytes. LYP is a negative kinase regulator that mediates signal transmission from the TCR complex (TCRζ/CD3) in CD4+ lymphocytes. TCR results in the transactivation of the IL-2 gene. Interestingly, the phosphatase activity of the LYP-encoded gene-associated variant RA (T1858) is higher than the normal variant. Paradoxically, there is a stronger inhibition of the signal from the TCR. What mechanism is therefore the T1858 variant involved in the development of an autoimmune process is not yet clear. Research aims to help clarify the LYP function in CD4+ lymphocytes.

The working hypothesis is that the LYP variant, encoded by the T1858 allele gene, is involved in different naive CD4 cell graduations to individual stem types of ancillary lymphocytes (Th1, Th2 or Th17) compared to the normal 1858 allele in PTPN22. In the future, research will contribute greatly to understanding the impact of PTPN22 variation on differentiation of T lymphocytes, which is one of the key pathogenicity processes in the development of chronic inflammation in RA.

The third part of the research intention is to monitor musculoskeletal disorders in Down syndrome, focusing on skeletal changes, atlanto-axial dislocation, early development of degenerative joint changes, in particular coxarthritis, or arthropathy, which are very similar to the clinical picture of juvenile idiopathic arthritis. Early diagnosis and treatment of musculoskeletal disorders with the chromosome and picks listed above will help to reduce the progression and improve the prognosis of patients with Down syndrome, especially in terms of improving quality of life. It is desirable to work with the endocrinologist of adults and children, the SZU Down Syndrome Center, to select patients. Patients should be clinically evaluated, the autoantibodies profile, hormonal analysis shall be determined and the presence of inflammatory rheumatic diseases, or congenital or familial arthropathy, juvenile idiopathic arthritis or other locomopathic disorders such as hypermobile syndrome, premature coxarthritis and atlanto-axial dislocation shall be confirmed or excluded according to valid diagnostic criteria. It will also be important to monitor therapeutic practices from the basis of basal treatment for the occurrence of autoimmune diseases in chromosomes as well as special rehabilitation procedures.

Another part of potential research is the monitoring of genetic mutation in 18 chromosomes during chronic multifocal osteomyelitis in children and other autoimmune diseases such as familial hypertrophic synovitis in children. These nosological units are rare autoimmune diseases and their nosographic boundaries need to be developed further knowledge.

2. Monitoring of the relationship between osteoporosis and cardiovascular disease

Osteoporosis and atherosclerosis have long been considered as two independent diseases, the common feature of which is an increasing incidence with age. Osteoporosis and atherosclerosis are chronic degenerative diseases and are currently among the most serious health problems worldwide. As the population grows older, their numbers increase. According to WHO, the percentage of people over 60 in developed countries should increase by about 9 times by 2050.

Both diseases are associated with high morbidity and mortality. Cardiovascular diseases are the leading cause of death in the world. Atherosclerosis is characterized by the formation of fat plates in the arterial wall due to autoimmune or inflammatory processes. More than 90% of these sheets are calcified. There is sufficient evidence in the literature of a direct relationship between the degree of calcification of the atherosclerotic plate and mortality in patients with cardiovascular disease. Morbidity and mortality of osteoporosis mainly refer to the occurrence of fractures.

Recent evidence of a closer relationship between osteoporosis and cardiovascular disease has been emerging with/without age. Osteoporosis and atherosclerosis share some pathophysiological mechanisms. Risk factors for vascular diseases such as dyslipidaemia, systemic arterial hypertension, diabetes mellitus and hyperhomocysteinaemia are associated with a high incidence of decreased bone density. There is also knowledge of the effect of anti-resorptive agents on the reduction of cardiovascular risk and the effect of statins, antihypertensives and insulin on bone growth. The mechanism of arterial calcification resembles the process of osteogenesis in which different cells, proteins and cytokines come together and which results in the mineralisation of tissue. The presence of ectopic bone tissue with osteoblasts transformed from endothelial cells has been confirmed in the calcified plates of the arterial walls.

The aim of the research is to monitor the relationship of patomechanisms of vascular calcification and bone metabolism. The lessons learned should help to clarify the potential impact on cardiovascular morbidity/mortality as well as the risk of osteoporosis development and fractures.

V. TRANSMISSION DISEASES AND IMMUNITY

The present state of knowledge.

Transmissible diseases are still a serious problem in the world's healthcare systems. The changing socio-economic conditions on the continents, together with the global development of trade, tourism, urbanisation, population migration, conditional economic, social, religious, ethnic and military conflicts, contribute to the rapid adaptability of infectious agents in new conditions and to their transfer between different ecosystems, as well as to the unprecedented overcoming of barriers between the animal kingdom and man. In this situation, the barrier between developed and developing countries is also being wiped out as regards the incidence of infectious diseases. Therefore, experts caution against reducing the attention of infectious diseases and the development of new therapeutic and preventive measures. New types of infectious diseases, caused by unknown or new agents, appear and emerge, as was the case with Lyme borreliosis, Legionnaire's disease, STSS, AIDS, SARS, avian influenza and others.

Current scientific knowledge provides evidence that infectious diseases and subsequent immune disorders are also involved in cardiovascular, endocrine and musculoskeletal disorders. Recent evidence from cancer also suggests that micro-organisms play a significant role in cancer development of up to 70%.

The effectiveness of the treatment of infectious aetiology diseases is undermined by increasing resistance of micro-organisms to antibiotics and biocides.

The incidence of allergic diseases is a significantly increasing trend. Skin and respiratory allergies are increasing in both adult and paediatric populations with a proportion of germ agents as triggers for these diseases. Immune system disorders based on both endogenous and exogenous factors are also on an increasing trend. It is important to realise that the diseases in question have an extremely serious impact on the economy of the Slovak Republic through losses caused by the loss of labour and the cost of health and social care. Moreover, the high incidence of these diseases hinders a faster increase in the life expectancy of our population.

Focus of research

It is therefore an absolute priority for every state, including our Republic, to enable the development of science and research activities which can make a fundamental contribution to:

New scientific knowledge acquired by creative research activities in the above mentioned

focussed is a real basis for strategic decision-making aimed at improving the diagnosis, prevention and treatment of diseases caused by infectious agents. In order to fulfil this objective, scientific research activities need to focus on the following areas:

VI. NEUROPOLOGICAL AND PSYCHIATRIC DISEASES

Cerebrovascular diseases are still a serious medical and socio-economic problem in Slovakia, as, unlike other developed states, mortality and morbidity have not only fallen, but have increased in some population groups. Although the main risk factors and underlying pathophysiological mechanisms of cerebrovascular disease are common to other cardiovascular diseases, there are demonstrably specifics that require special access to vascular strokes. Research projects should focus on:

In the context of the general ageing population, ensuring decent old age is one of the key tasks of modern society. Dementia is one of the diseases that particularly reduce the quality of life of both the elderly and the part of the working age population (due to care responsibilities). Research projects should focus on:

Neurodegenerative and demyelinating diseases are among the most common neurological diseases, which, due to the chronic course and the debilitating nature, affect the quality of life of patients in ways and represent a long-term social and economic burden for society as a whole. Research projects should focus on:

Intervertebral disc disease and its consequences, i.e. spinal cord compression, in the cervical and chest regions, or spinal cord roots in the lumbar region, affect the vast majority of the population to varying degrees, are also one of the most common causes of incapacity for work and often lead to disability. Research projects should focus on:

In order to improve comprehensive care for patients with brain tumours, research projects should focus on:

In Slovakia, patients with mental disorders account for 11 percent of all patients. It is necessary to ensure implementation of the principles of the National Programme for the Development of Mental Health and research projects should focus on:

VII. TRANSPLANTATION OF BODIES AND TANKS

Tissue and organ transplantations have now become relatively common and effective methods for treating numerous diseases. More than 20,000 new transplants are witnessing this, which are growing annually and whose success is increasing. The trend of transplant development has also been noted by Slovakia, which is mainly evidenced by kidney, bone marrow, heart transplants, which are performed in addition to Bratislava in Košice, Banská Bystrica and in Martin. The development of transplantation continues both in terms of research and practical and organisational. Slovakia cannot afford to lag behind in this dynamically developing medical area, especially now that it has already become a member of the European Union and is trying to get into its transplant companies. In particular, transplant research should focus on the following issues:

Of all these areas, the issue of establishing a reference laboratory for the determination of HLA-aliel and HLA-antigens and its accreditation by the European Immunogenicity Federation is most acute. Without this accreditation, international cooperation is not possible, especially recognition of the results of HLA-typing, organ exchange, creation of voluntary donor registers, participation in waiting lists for kidney transplantation, etc. In Slovakia, there are several HLA-laboratories, from which either the workplace at the Slovak Organ Transplant Centre or the laboratory of Hematology and Blood Transfusions FNsP Petržalka should undertake this task. Although professional activity is involved, it is closely related to research activity, because the field of transplant immunology, immunogenicity, immunotherapy, etc. is developing and its development needs to be kept in step and contribute to it by its own research activity.

VIII. GENOMICA AND PROTEOMICS

The development of molecular medicine, like in European Union countries, is one of the priorities of Slovak medical research. It remains an important task to build a strong infrastructure and to promote the application of molecular medicine knowledge to prevention, diagnosis and therapy for building the foundations of personnel medicine, including the creation of effective bioinformation tools for the processing and interpretation of ever-increasing amounts of genome data and making them available to professionals in usable form. Within this area, support will focus on application, interdisciplinary or internationally oriented quality teams and top-level projects to develop new or improve existing diagnostic and therapeutic practices. Priorityly supported areas of medical genomics in Slovakia include molecular biology and genetic factors in diagnostics, prognosis, prevention and treatment of serious multifactorial-related diseases (cardiovascular, cerebrovascular, respiratory, diabetes, tumor, neurological, psychological, etc.), building and supporting clinical and research bases in the field of prevention and intergenerational transmission of gene or genome anomalies, building and linking the information network of medical, molecular-biological and genetic workplaces, and harmonising existing databases as well as the use of gene manipulations in mammals in the study of pathogenesis of human diseases, and supporting research in the field of biotechnology and nanotechnology and risk assessment and benefits of the use of nanomaterials.

Specific themes 2008-2011

IX. PUBLIC HEALTH

According to the WHO, around a quarter of deaths and global disease burden can be attributed to living conditions, including working conditions. There is evidence that environmental factors play a role in more than 80% of the diseases regularly reported to the WHO.

In the period 2008 - 2011 we recommend focusing research on three main areas: environmental health, occupational health and epidemiology of infectious and non-infectious mass diseases. The general objective of environmental health research will be to clarify the relationship (and in particular their causality) between the exposure of the population and its selected sub-groups (e.g. children, pregnant women, workers and the elderly) to the factors of the environment and the working environment and the health status of the population.

Given the past inherited pollution of Slovakia's environment, the lifestyle of the Slovak population characterised by many unhealthy elements, changing working conditions and associated health risks and morbidity associated with a particular ethnic group, it is necessary to give priority to research in the field of environmental health based on the latest scientific knowledge on pathogenesis of a wide range of diseases, where one of the most important tasks is played by interaction between the genes of the individual concerned and environmental factors. Environmental factors are considered in the broadest sense, including chemical and physical components of the environment and lifestyles. According to this idea, which is increasingly supportive of scientific evidence, the interaction between individual genes and environmental factors leads to the emergence of most chronic degenerative diseases.

Scientific activities aimed at the knowledge of the mutagenic, carcinogenic and immunomodulatory properties of xenobiotics, their capacity to induce allergies and atopics and their properties as endocrine disruptors shall be encouraged to characterise these interactions.

Priority in this area will be given to programmes aimed at:

In particular, projects and topics in the following specific scientific fields will receive support:

Prof. MUDr. Luke Plank, CSc., v.r.
Chairman of the Scientific Council of the Slovak Republic