Plenary Session Friday April 5, 2013
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Інститут молекулярної біології і генетики НАН України
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Plenary Session Friday April 5, 2013 / Вiopolymers and Cell. — 2013. — Т. 29, № 2, доп. — С. 18-29.— англ. |
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18
Abstracts
Plenary Session
Friday April 5, 2013
19
New approaches and expertise in technology transfer to fund
translational research
Levy S. D.1 and Laur J. D.2
1 Nixon Peabody,
LLP, 555 West Fifth Street, 46th Floor, Los Angeles, CA 90013 USA
2 Cedars-Sinai Medical Center,
8700 Beverly Blvd., TSB-290, Los Angeles, CA 90048 USA
The funding of translational research, particularly in the life sciences, is currently faced
with significant challenges. This is especially true for the stages of research that reside
between basic academic research, on the one hand, and later stage commercial research
and development, on the other. Basic academic research is often funded through
government or philanthropic support. Much later, once it has already been demonstrated
that an innovation is likely to achieve commercial success, and thus, the risk of failure
has been substantially reduced, large companies, venture capital investors or other
funding partners are likely to support the research. In between, however, it can be very
difficult to find funding support. The challenge, therefore, is how to bridge the co-called
“valley of death” in research funding between the academic laboratory and the
commercial sector. Doing so requires new approaches and different types of expertise for
academic institutions to bring their technologies from the laboratory to the marketplace.
There is a need for new, creative sources of funding, which at times requires investment
by the academic institution itself. Coordinating the process of identifying innovations that
are worthy of funding and then managing the investments once they are made are often
not within the skill set of academic technology transfer office personnel. Even if the
personnel possess these skills, utilizing those skills might consume so much time and
effort that it would be unreasonable for the office to undertake those tasks on a regular
basis for what could become a significant portfolio of projects and investments. This
session will describe several new programs that Cedars-Sinai Medical Center has
established to meet these challenges – bridging the research funding valley of death and
deploying a staffing model, including specific outside expertise that supports these
activities without overburdening the technology transfer office. The session will also
include a case study featuring a technology developed in South America that Cedars-
Sinai is bringing to the global marketplace through use of this enhanced, modern
approach to technology transfer.
20
Update of research and perspectives of collaboration of Institute of
Cell Biology (ICB) within RECOOP association
Stoika R. S.
Institute of Cell Biology, NAS of Ukraine,
Drahomanov Str. 14/16, Lviv, 79005, Ukraine,
stoika@cellbiol.lviv.ua
There are several basic research approaches which are presently developed in the Department of
Regulation of Cell Proliferation and Apoptosis at the ICB (NAS of Ukraine) and are perspective
for conducting closer collaboration within the RECOOP Association:
1) NanoBioTech. Project: Development of novel magnetic and polymeric nanoscale materials for
medical treatment and diagnostics (ex. bio-imaging of apoptotic cells and macrophages).
RECOOP partners: Institute of Macromolecular Chemistry (Prague, Czech Republic), Wroclaw
Technical University (Wroclaw, Poland), Institute of Biochemistry (Kyiv, Ukraine). None-
RECOOP partner: Lviv National Polytechnic University (Lviv, Ukraine).
2) Cancer. Project: Pre-clinical study (in vitro and in vivo) of novel anticancer drugs of natural
(Landomycins) and synthetic (4-thiazolidone derivatives) origin. RECOOP partners: Lviv
National Medical University (actual partner), Pecz University (potential partner under the
Visegrad fellowship support). None-RECOOP partner: Institute for Cancer Research at Vienna
Medical University, Austria). See posters of Panchuk et al. and Chumak et al.
3) Stress (Immunity and Autoimmunity). Project: Immunoglobulin glycosylation as a diagnostic
instrument at autoimmune diseases. RECOOP partner: University of Osijek, Croatia (planned).
None-RECOOP partner: Medical University in Erlangen, Germany. See poster of Bilyy et al.
5) Cardiovascular Diseases. Project: Identification of novel genes capable of protecting against
massive cell death (via apoptosis and necroptosis) after ischaemia-reperfusion, as well as after
tumor-induced cachexia and neurodegenerative processes. Potential RECOOP partners: Institute
of Cardiology, Debrecen, Hungary, Clinic for Internal Medicine, Osijek, Croatia. None-
RECOOP partner: Percuros BV & Leiden University Medical Center, The Netherlands). See
poster of Korchynskyi et al.
5) Preterm Birth. Project: Identification of novel auto-antigens and specific gene polymorphism
involved in pathogenesis of the recurrent pregnancy loss (RPL). Potential RECOOP partner:
Department of Obstetrics and Gynaecology, Charles University in Prague, Faculty of Medicine
Hradec Kralove, University Hospital Hradec Kralove, Czech Republic, School of Medicine,
Osijek, Croatia. None-RECOOP Partner: Institute of the Hereditary Pathology, Lviv, Ukraine).
See poster of Zastavna & Kit et al.
6) Infection in Reproductive Biology. Project: Targeting glycocalyx for identification and
isolation of specific (ex. apoptotic) cells at infection by the uropathogenic strains of E. coli in
women. Interested RECOOP partners are welcome to joint the project. None-RECOOP partner:
University of Lille, France. See poster of Dumych et al.
21
Infantile hemangiomas and retinopathy of prematurity: common
mechanisms of pathogenesis?
R M Hyland,1 K Komlósi,2 BW Alleman,1 M Tolnai,3 LM Wood,1 EF. Bell,1 T Ertl3
1Department of Pediatrics, University of Iowa,
200 Hawkins Drive, Iowa City, IA 52242, USA;
2 Department of Medical Genetics,
3 Department of Neonatology, School of Medicine, University of Pécs,
Szigeti út 12, Pécs, Hungary, H-7624
Aims: Retinopathy of prematurity (ROP) is an eye disease that affects the retina of the
preterm infant and can cause impairment of vision. Infantile hemangiomas (IHs) are
benign vascular tumors that develop in infancy. Studying IH and ROP may further
increase our understanding of the mechanisms of normal or abnormal vasculogenesis.
Methods: We undertook the present study to examine the concordance between IH and
ROP in populations of preterm infants in the U.S. and Hungary. Clinically collected data
from infants with gestational ages less than 32 weeks born between May 1, 2007 and
December 31, 2010 were analyzed. A total of 897 infants with gestational ages less than
32 weeks were admitted to the NICUs at Iowa and Pécs, 684 subjects were eligible for
the study (236 from Pécs and 448 from Iowa). Their data were entered into a study
database and were analyzed by center and then combined through meta-analysis.
Results: There were no significant demographic differences between populations. After
univariate analysis of potential covariates in Iowa and Pécs populations, hyperglycemia,
transfusion, infection, breast feeding, postnatal corticosteroids, gestational age, birth
weight, highest bilirubin, and days on oxygen were all related significantly to IH or ROP
and entered into a logistic regression model. After stepwise regression, hemangioma
remained in the logistic regression model in each population but showed only a trend
toward significant relation to ROP. When the corrected associations from the two
populations were combined through random effects meta-analysis, a significant
relationship between IH and ROP was detected (OR=1.84, 95 % CI 1.08-3.12).
Conclusions: These combined results suggest that IH and ROP do not occur
independently in preterm infants. Further study of these conditions and their association
may shed new light on the role of abnormal vasculogenesis in these disorders and on
common mechanisms of pathogenesis in IH and ROP.
Key Words: Angiogenesis · Hemangioma · Preterm infants · Retinopathy of prematurity
22
Markers to diagnose infection in PPROM
Marian Kacerovsky, MD, PhD
University Hospital Hradec Kralove, Czech Republic
Spontaneous preterm birth is an enduring and principal cause of perinatal morbidity and
mortality worldwide. Approximately 30 % of all preterm births are preceded by preterm
prelabor rupture of membranes (PPROM). Besides requiring acute intensive care, the
newborns are often threatened by lifelong adverse sequelae (e.g. cerebral palsy).
One of the most common complications of PPROM is microbial invasion of the amniotic
cavity (MIAC), which complicates PPROM in approximately 30 % of cases. Specific
motifs on the microbial surface, as well as endogenous molecules released from damaged
tissue and cells, are recognized by pattern recognition receptors.
Activation of these specific receptors lead to the development of intraamniotic
inflammation (elevated levels of inflammatory mediators in the amniotic fluid) followed
by the recruitment of neutrophils and other immune cells from the uterine wall to the
placenta and fetal membranes. The neutrophil infiltration of the placenta and fetal
membranes is then called histological chorioamnionitis (HCA). The presence of MIAC
leading to HCA, determining an infectious phenotype of PPROM, is responsible for
serious neonatal morbidity, including chronic pulmonary diseases and adverse
neurodevelopmental outcome, both of which have long-term consequences on quality of
life and health care costs.
This suggests that the identification of MIAC and HCA is crucial for improving neonatal
outcome and parental counselling of women at risk. Regrettably, there is no robust
diagnostic tool currently available for identifying these conditions. Nevertheless,
proteomic analyses of amniotic fluid and ultrasound evaluation of the fetus offer
alternative view on the protein composition and functional changes associated with these
pathological conditions.
23
Luminescent carbon materials in medicine
Alexander P. Demchenko
Paladin Institute of Biochemistry,
Leontovicha 9, Kiev 01030, Ukraine
The strong request for fluorescence materials for sensing, imaging, cell targeting,
physical destruction and drug delivery lead to nanoscale structures of carbon. They
include graphene G-dots, graphene oxide GO-dots, modified carbon nanotubes,
nanodiamonds and, essentially, the C-dots that combine simplicity of production and
absence of toxicity with high brightness. The properties of these new materials will be
analyzed with the focus on their presently realized and prospective applications as
scaffolds for constructing multifunctional nanocomposites.
In these applications, carbon nanomaterials feature essential advantages over
semiconductor Quantum Dots. Their production is easy, inexpensive and ‘green’. They
can be made of different sizes, and high surface areas and simple co-synthetic
incorporation of reactive groups allows assembling the structures of different
functionalities. The absence of toxicity and high drug-carrying ability offer additional
advantages. In contrast to organic dyes they do not bleach under strong visible or UV
light.
The in vitro and in vivo applications of these materials are on initial stage and their
success will be illustrated on several examples.
24
Pneumococcal conjugate vaccines
Prymula R.
University Hospital Hradec Kralove,
Sokolska 581, 500 05 Hradec Kralove, Czech Republic
Pneumococcal disease is a major cause of morbidity and mortality throughout the world
and Invasive pneumococcal disease (IPD) represents a significant burden to individuals
and to society. A highly effective pneumococcal conjugate vaccine (PCV), offering
protection against disease caused by seven virulent serotypes, was first licensed in the
USA in 2000 and has since been incorporated into the immunization programs of an
increasing number of developed countries for children up to 5 years of age. New vaccine
formulations containing more conjugated serotypes have been developed and licensed
afterwards. The incidence and mortality of IPD, including bacteremic pneumococcal
pneumonia, is especially elevated in older adults and risk of pneumococcal diseases
development is multiplied in chronic ill adults. This is the reason why originally pediatric
formulation of PCV13 was licensed for adults recently.
However still some questions remains: immunogenicity of pneumococcal vaccines
particularly in elderly and patients with chronic diseases impairing immunity,
immunosenescence, serotype coverage, hyporesponsiveness, herd effect, effect of
paracetamol on immunogenicity of vaccines, etc.
Existing pneumococcal conjugate vaccines (PCVs) have significantly decreased the
incidence of pneumococcal disease, although a high disease burden still remains.
Widespread use of PCVs has also contributed to a shift in serotype epidemiology.
Therefore, there is still a need for new pneumococcal vaccines that offer broader serotype
coverage.
To meet this need, pneumococcal proteins that are highly conserved amongst
Streptococcus pneumoniae strains, which may then induce protection against all
pneumococcal serotypes are tested. The S. pneumoniae proteins, histidine triad protein D
(PhtD) and detoxified pneumolysin (dPly), either alone, or in combination with PCVs,
are potential candidates for such vaccines.
KEYWORDS: Immunization, S. pneumoniae, conjugate vaccines, Invasive
pneumococcal disease
25
Gender-related differences in coronary artery disease risk factors in
three Central European countries
Mlinarevic D1, Lukin A2, Borbély A3, Pitha J4, Papp Z3, Pék A3, Makarovic Z5,
Boban D5,Vari S6, Heffer M1, Steiner R5
1 Department of Medical Biology, School of Medicine, J.J.Strossmayer University, Osijek, Croatia
2 Department of Cardiology, University Hospital Centre Split, Split, Croatia
3 University of Debrecen, Medical and Health Science Center, Institute of Cardiology, Hungary
4 Laboratory for Atherosclerosis Research, Institute for Clinical and Experimental Medicine, Prague,
Czech Republic
5 Department of Cardiology, University Hospital Center Osijek, Osijek, Croatia
6 International Research and Innovation Management Program, Cedars - Sinai Medical Center, USA
Aims: The clinical characteristics of coronary artery disease (CAD) vary between populations
depending on various risk factors, and CAD has a different pattern in male and female patients.
To explore these differences, we analyzed clinical data from patients from three Central
European countries (Croatia, Czech Republic and Hungary) presenting with CAD, with a special
focus on gender-related differences. Since Split is a Mediterranean city, we expected to see
differences compared to the other three centers which are continental. Methods: Data was
obtained from patients hospitalized for CAD in 2007 in two centers in Croatia (Osijek and Split)
and one center in both Czech Republic (Prague) and Hungary (Debrecen) . This comparison
focuses on differences in traditional CAD risk factors– age and gender, body mass index (BMI),
cholesterol and HDL, LDL and triglyceride levels. The sample included 295 patients from
Osijek, 195 from Split, 247 from Debrecen and 400 from Prague. Results: Patients from Split
were the oldest on admission (68.8 ± 11.5 years; p < 0.001), followed by patients from Osijek,
Debrecen and Prague. The difference in age on admission is mostly due to the age of male
patients in Split. Also, female patients in Croatia were older than females in Debrecen and
Prague (p = 0.002). Patients from Split also had the lowest BMI (p < 0.001), with similar results
in other centers. Hypertension was most prevalent in Split (71.4 %), followed by Debrecen,
Osijek and Prague. The chi-square test for prevalence of diabetes was not significant in male
patients, but was significant in females, with Debrecen having the largest prevalence (38.1 %).
Cholesterol values were similarly high in Split, Osijek and Prague, with Debrecen having the
lowest values (p < 0.001). HDL was highest in Split and Debrecen, but the difference is again
due to values male patients’ values, in females the four-way comparison was not significant.
LDL was highest in Split and Prague, followed by Osijek and Debrecen. Triglycerides were
highest in Split and Osijek, followed by Debrecen and Prague. Again, Split had the highest
values due to male patients’ results, and Prague had the lowest due to female patients’ results.
Conclusions: We observed significant differences between the samples. Patients from Split were
the oldest, had the lowest BMI and highest HDL, but also had the highest cholesterol, LDL and
triglyceride values, which was surprising. This result is most likely due to the advanced age of
patients in Split and is mostly caused by high values in male patients, with females having values
similar to their counterparts in other Central European centers. Overall, the pattern between the
continental centers (Osijek, Debrecen, and Prague) was different to the one in Split which is a
Mediterranean city. We observed gender-related differences in every center were involved in
Central Europe. Delete: and in general the male patients' values contributed the most to the
overall results of the comparisons.
26
Central and Eastern Europe demography for risk factors in
preterm birth
Kinga Lancz1, Ladislava Wsólová2, Ľubica Palkovičová1, Tomáš Trnovec1,
Jaroslav Hinšt3, Igor Rusňák3
1Dept. of Environmental Medicine, Slovak Medical University, Bratislava, Slovakia
2Dept. of Biostatistics Analysis, Slovak Medical University, Bratislava, Slovakia
3Gyneacology and Obstetrics Clinic, University Hospital Bratislava, Slovakia
BACKGROUND: Retrospective studies, which look backward over a period of time and
normally attempt to compare the frequency of occurrence of a determinant in groups of
diseased and non- diseased individuals.
AIMS: To assess and compare demography risk factors leading to preterm birth in CEE.
The main advantage of retrospective studies is that they make use of data that have
already been collected like the RECOOP M&CH Research Network did.
METHODS: The demographic data on health indicators (birth and death rate, deliveries,
abortion, incidence of offspring), distribution of the population, food consumption,
employment and abuses by sex and countries (Romania, Czech Republic, Hungary,
Slovakia, Croatia) were collected retrospectively from statistical offices from years 2007
to 2010 by the RECOOP M&CH Research Network.
RESULTS: On the population we have data only from Czech Republic and Slovakia and
in both countries are more women than men. Marriages is in average 5 in Slovakia and
divorces 2.3 per 1000 inhabitants, in Czech Republic 3. We found live births around 58
000 in Slovakia, 22 000 in Czech Republic and 42 000 in Croatia from years 2007 to
2009. Stillborns were around 200 in Slovakia and Croatia also. The highest birth rate was
in Czech Republic 11.5, the next is Slovakia with 10.6 and with 9.9 Croatia in year 2008.
The death rate is closed to birth rate, 11.9 was in Romania and 9.5 in Slovakia also in
year 2008. The most preterm births were in Czech Republic 13 %, in Croatia 4% and
around 7% in Slovakia. Singleton pregnancy predominates in all observed countries but
the most deliveries were in Czech Republic (115 000). Twins are also common but
triplets and quadruplets occur not often. We gained data also on food consumption in
each country. From meat the biggest consumption was of pork in Czech Republic (10
kg), than Slovakia (32 kg) and Croatia (14 kg). After poultry the next often consumed
meat was beef. Sugar, cereal and soft drink consumption is big in all countries. In alcohol
usage is the winner Slovakia. Narcotics abuse is bigger at men than women in all CEE
countries. Some of the parameters were not available in all the countries.
CONCLUSIONS: There is no way of knowing the extent of the similarity between the
two different populations therefore it is necessary compare the available population
statistical data to the term and preterm birth retrospective data.
KEY WORDS: risk factors, term and preterm birth, CEE
27
Enteroviruses: a common cause of neonatal sepsis
Galama, J. M. D. MD, PhD.
Radboud University Medical Center,
Dept Medical Microbiology,
P.O. Box 9101, 6500HB
Nijmegen, the Netherlands.
Non-polio enteroviruses are the most common viral threats of neonates. Most infections
cause only fever but meningo-encephalitis and other -even more serious- afflictions may
occur. Neonatal enterovirus sepsis occurs 5–10x more often than Herpes of the neonate
and has equally bad consequences. The latter is not always appreciated.
Fever shortly before term leads frequently to a decision to treat the mother with
antibiotics and terminate the pregnancy. In case of a bacterial infection this decision is
justified, in case of a viral cause it is not: It may even worsen the condition for the child.
Neonatal enterovirus sepsis will be discussed in terms of incidence, diagnosis, prevention
and treatment.
Key Words: Enteroviruses, Neonatal sepsis syndrome, maternal infection, treatment,
prevention.
28
RECOOP HST Association’s Life Sciences Research (LFSR)
Platform
Dr. Sandor G. Vari, M.D.
International Research and Innovation Management Program, Cedars-Sinai Medical Center, Los
Angeles, CA, USA & President of the RECOOP HST Association
In 2006 Cedars–Sinai Medical Center (CSMC), Los Angeles, CA, USA with eleven CEE
universities and academic organizations from six countries formed the Regional
Cooperation for Health, Science and Technology (RECOOP HST) Consortium. The
Consortium is continuously growing and beside the 12 Founding Members additional 8
Associate Members are participating in the research and support networks from Croatia,
Czech Republic, Denmark, Hungary, Poland, Romania, Slovakia, Ukraine and USA.
In 2012 CSMC converted the Consortium into the Association for Regional Cooperation
in the Fields of Health, Science and Technology is registered by the Court of Debrecen in
Hungary under the registry number 4160 on May 10, 2012, TAX ID: 18299140-1-09.
Members of the Association from 9 countries (Croatia, Czech Republic, Denmark,
Hungary, Romania, Slovak Republic, Ukraine and USA) and 16 higher education or
research organizations are continuously implementing new research projects.
The RECOOP HST Association’s main goal is to enhance research collaboration and
provide platforms for scientific networking in life sciences within Europe and Cross –
Atlantic. The research priorities of the Association is the major public health problems
including women’s and children’s health, cardiovascular, metabolic, neurologic disorders
and cancer in the Visegrad Four European Macro-Region (Czech Republic, Hungary,
Poland and Slovakia) and the neighboring countries (Croatia, Romania, Ukraine). The
Association with the Mother and Child Health (M&CH) and the Women’s Health and
Cardiovascular Diseases (WH&CVD) and NanoBioTechnology Research Networks
paves the way toward GLOBAL Research Programs and supports the National Institutes
of Health, the World Health Organization and private funds (Gates, Clinton) goals to
improve the health of public Worldwide.
In the RECOOP Research Networks 147 scientists are working in 17 research projects –
basic, translational and clinical research studies. RECOOP scientists and clinicians are
investigating biological pathways leading to gender differences in cardiovascular
diseases, preterm birth, ovarian, breast and prostate cancer. The M&CH and the
WH&CVD Research Networks’ retro and prospective clinical research studies are using
web based electronic data entry forms (EDEF http://www.flexiform.hu/).
The Association’s activities compliment the U.S. Government’s commitment to the
Global Health Initiative – “is the next chapter in the way U.S. Government agencies
conduct global health activities, building on successful bipartisan leadership in global
health and expanding their impact for sustainable results around the world.” In the Global
Health Initiative the U.S. Department of Sate is already building public – private
29
partnership could be the frame for the regional network development and scientific
competitiveness.
All over the World the Health Research Consortiums and Networks should be founded on
local qualities and create a critical mass at the regional level in well defined geographical
regions have lingual, cultural, historical, economic and/or political common ground like
Central and Eastern Europe, Scandinavia, the Benelux Countries, the Mediterranean
Countries Arab League, Central and South America, South East Asia and the
Anglophone and Francophone Africa. After formation of regional research networks they
could compete at the global level as the RECOOP HST Association is doing.
Health Research Consortiums and Networks could provide platform also for the re-entry
grants for students and scholars from less developed or developing countries spent years
in the USA and in Europe. The G20 countries or the top 28 economies should provide co-
funding for re-entry grants.
A strong public – private partnership would be the fundament for the research networks
and for the regional young scientists’ life sciences conferences. Organizations should
solicit support from industry (Pharmaceuticals, Biotechnology & Life Sciences, Health
Care Equipment & Services; Food and Beverage, Information Technology, and Energy)
and from private founds (Bill & Melinda Gates Foundation, Warren Edward Buffett, the
William J. Clinton Foundation).
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