Population structure and genetic diversity of Polish Arabian horses based on pedigree data.

With a history tracing back to at least the 18th century and a substantial global influence on various breeds, Polish Arabian horse population is of paramount importance for both breeders and conservationists. However, its genetic makeup and the population dynamics are still not well understood. This study presents an analysis of the modern Polish Arabian horse population using pedigree data, focusing on the breed's genetic diversity and population structure. Our analysis encompassed 1 498 individuals defined as the reference population (RP) and their 11 065 ancestors, which resulted in the dataset of 12 254 individuals (total population). We traced their genealogy to assess inbreeding coefficients (F), founder effects, and genetic variability measures such as the effective number of founders (fe), ancestors (fa), or founder genome equivalents (fge). The results indicated a good pedigree quality with an average of 28.1 maximum traced generations, revealing high pedigree completeness for initial generations with a decline beyond the seventh generation. The genetic diversity parameters showed a considerable bottleneck effect, with an effective number of founders at 73, which reflects a substantial loss of genetic diversity over time. Despite the vast total number of founders (852), only a few have had a lasting impact on the current population, signaling the need for revised breeding strategies to maintain diversity. The study identified a slight but consistent rise in inbreeding over the last century, with a marginal recent decline, and a significant difference in the contribution of various founders. The average F was 5.8%, with 99.6% of the reference population being inbred. The analysis of effective population size (Ne) highlighted potential risks for genetic diversity, urging for revision of breeding goals to consider a wider array of founder lineages. The study indicated that stallions belonging to RP can be attributed to 15 distinct sirelines, whereas mares to 45 unique damlines, more than considered in the current breeding program (8 and 15, respectively). Conclusively, the study underlines the need for ongoing monitoring and strategic breeding to maintain and enhance the genetic diversity of Polish Arabians, considering the breed's historical significance and contemporary genetic challenges.

Effect of obesity and hypothyroidism on hepcidin concentration in pregnancy - a pilot study using maternal and umbilical cord blood at delivery day.

Hepcidin is a primary regulator of iron metabolism in the human body. By promoting ferroportin degradation, hepcidin reduces intestinal iron absorption and its release from intracellular stores. In the course of pregnancy, gradually declining hepcidin concentrations encourage placental iron transfer, thereby providing the appropriate amount of iron for fetal development. Hence, we aimed to investigate changes in maternal and cord blood hepcidin and iron metabolism parameters in normal-weight (n=17) and obese (n=17) gestating women, as well as gravid women with a history of hypothyroidism following the restoration of euthyroidism (n=17). All blood samples were taken on the day of delivery, and ELISA kits were used for measurements. A significant increase in maternal hepcidin concentration was observed in obese pregnant women, compared to normal-weight controls (29.53±4.20 ng/mL vs. 25.69±5.70 ng/mL; P<0.05). However, only a slight, insignificant tendency for lower hepcidin was noted in the hypothyroid group, compared to the healthy controls (23.10±6.00 ng/mL vs. 25.69±5.70 ng/mL; P=NS). Moreover, decreased maternal free triiodothyronine, triiodothyronine, free thyroxine, and ferritin levels were revealed in the hypothyroid group, compared to the normal-weight individuals (P<0.05). Furthermore, positive correlations between maternal hepcidin and the majority of maternal thyroid hormones were found, with a most potent relation to FT3 (r=0.40; P<0.01). Interestingly, no alterations of thyroid hormones and iron metabolism parameters were noticed in cord blood in any of the subgroups. In summary, pre-pregnancy obesity is associated with elevated maternal hepcidin, albeit no signs of lowered cord blood iron status were shown. Medical history of hypothyroidism following the restoration of euthyroidism does not substantially influence maternal nor cord blood hepcidin concentration, as well as fetal iron homeostasis, even though free thyroid hormone levels correlate with maternal hepcidin.

Obesity is associated with increased level of kisspeptin in mothers' blood and umbilical cord blood - a pilot study.

OBJECTIVE: Kisspeptin (KP) is a major regulator of reproductive functions. It has also been shown to be involved in the metabolic changes associated with obesity. According to the well-established concept of prenatal programming, environmental factors can influence physiological and behavioral systems at the early stages of development. Thus, we hypothesized that in pregnant women, obesity can be associated with alterations in the levels of KP. We also assumed that the observed changes in obese mothers' blood (MB) would be reflected in the umbilical cord blood (CB). MATERIALS AND METHODS: We collected MB and CB from obese and nonobese women and analyzed the differences in metabolic and hormonal profiles, including KP concentration, using commercially available assays. RESULTS: We found that the level of KP was increased in the MB and CB of obese patients compared to nonobese subjects (p<0.05). A strong correlation was observed between the concentration of KP in MB and CB (r=0.8343; p<0.01). Moreover, we detected that the differences in the adipokine profile observed in the MB were not reflected in CB. CONCLUSIONS: Our results indicate that blood KP concentration can serve as a valuable marker in pregnant women. However, further studies are needed to understand the alterations of this peptide in obese pregnant woman and their potential effects on offspring.

Role of hepcidin in physiology and pathophysiology. Emerging experimental and clinical evidence.

Normal iron metabolism is an inherent feature of maintaining homeostasis. There is a wide range of iron disorders, which arise from iron deficiency or overload. In addition, disturbances in iron metabolism are observed in the course of numerous chronic diseases. Since iron is an essential constituent of hemoglobin, different types of anemia are clinical manifestations of both iron deficit or excess. This seemingly contradictory statement may be elucidated by the presence of hepcidin. Hepcidin is a primary regulator of iron metabolism in the human body. By promoting ferroportin degradation, hepcidin decreases the amount of iron in the circulation due to iron sequestration in the tissues and reduced intestinal absorption. Altered hepcidin concentration is a compensatory mechanism aimed at restoring iron homeostasis in various physiologic states, including pregnancy. However, hepcidin may also participate in the pathophysiologic background of hereditary hemochromatosis, anemia of chronic disease, myelodysplastic syndromes or ß-thalassemia. Moreover, hepcidin is an acute-phase protein involved in innate immunity reactions. In our paper, we provide a comprehensive review of the physiologic and pathophysiologic functions of hepcidin. We present current knowledge on the structure, physiologic role and its expression control, as well as demonstrate the contribution of hepcidin in a state of illness. We also summarize the significance of hepcidin in normal and complicated pregnancy. Emphasizing the alterations in hepcidin upon treatment of specific diseases and their position in certain pathomechanisms, we support clinicians with practical aspects related to hepcidin.

Effects of a nine-strain bacterial synbiotic compared to simethicone in colicky babies - an open-label randomised study.

The aim of the study was to determine effects of administration of simethicone and a multi-strain synbiotic on the crying behaviour of colicky babies. The study design consisted of an open-label, two parallel treatment group study involving 87 infants aged 3-6 weeks with infantile colic (defined as crying episodes lasting 3 or more hours per day and occurring at least 3 days per week within 3 weeks prior to enrolment) randomly, unequally [1:1.5] assigned to receive simethicone (n=33) or a multi-strain synbiotic (n=54) orally for 4 weeks. The multi-strain synbiotic contained Lactobacillus acidophilus LA-14, Lacticaseibacillus casei R0215, Lacticaseibacillus paracasei Lp-115, Lacticaseibacillus rhamnosus GG, Ligilactobacillus salivarius Ls-33, Bifidobacterium lactis Bl-04, Bifidobacterium bifidum R0071, Bifidobacterium longum R0175 and fructooligosaccharides). Primary outcome measures were the responder rates (effect ≥50% reduction from baseline) of the measures 'crying days last 3 weeks', 'average evening crying duration last 3 weeks' and 'reduction of average number of crying phases per day last three weeks' at the end of treatment. The study is registered at ClinicalTrials.gov under NCT04487834. Significantly higher responder rates (effect ≥50% reduction from baseline) of the multi-strain synbiotic compared to simethicone were found for the measures 'crying days last 3 weeks' (72% vs 18%, P<0.0001) and 'average evening crying duration last 3 weeks' (85% vs 39%, P=0.0001). No significant difference was found for the measure 'reduction of average number of crying phases per day last three weeks' (50% vs 42%, P=0.4852). No adverse effects were reported for the two treatment groups. Based on these results, the multi-strain synbiotic can be considered as an interesting therapeutic possibility for the treatment of infantile colic, worthwhile to be investigated further in non-clinical and clinical studies.

Reperfusion injury as a target for diminishing infarct size.

Therapies for preventing reperfusion injury (RI) have been widely studied. However, the attempts to transfer cardioprotective therapies for reducing RI from experiments into clinical practice have been so far unsuccessful. Pathophysiological mechanisms of RI are complicated and compose of many pathways e.g. hypercontracture-mediated sarcolemma rupture, mitochondrial permeability transition pore persistent opening, reactive oxygen species formation, inflammation and no-reflow phenomenon. Based on research, it cannot be determined which mechanism dominates, probably they cooperate with a domination of one or another in different clinical circumstances. Our hypothesis is, that only intervention that at the same time interferes with different (all?) pathways of RI may turn out to be effective in decreasing the final area of infarction.

Transcriptomic population markers for human population discrimination.

BACKGROUND: Numerous studies have demonstrated significant differences in the expression level across continental human populations. Most of published results were performed on B-cell lines materials examined under specific laboratory conditions, without further validation in a primary biological material. The goal of our study was to identify mRNA markers characterized by a significant and stable difference in the gene expression profile in Caucasian and Chinese populations, both in the commercially available B-lymphocyte cell lines and in the primary samples of the peripheral blood. RESULTS: The preliminary selection of population-differentiating transcripts was based on Illumina expression microarray analysis of the representative group of ethnically-specified B-lymphocyte cell lines. Twenty genes with the inter-population difference in the mean expression characterized by the at least 1.5-fold change and FDR <  0.05 were identified. Subsequently, a two-step validation procedure was carried out. In the first step, a subset of selected population- differentiating transcripts was tested in the independent set of B-lymphocyte cell lines, using TLDA cards. Based on TLDA analysis, three transcripts representing Fch > 2 were chosen for validation. The differentiating status was confirmed for all of them: UTS2, UGT2B17 and SLC7A7. The mean expression of UTS2 was higher in CHB (25.8-fold change compared to CEU), while the expression of UGT2B17 and SLC7A7 was higher in CEU (3.2- and 2.2-fold change, respectively). In the next validation step, two transcripts were verified in the primary biological material. As an ultimate result of our study, two mRNA markers (UTS2 and UGT2B17) exhibiting population differences in the expression level in both B-cell line and in the blood were identified. Further statistical analysis confirmed the discriminatory potential of these two markers. CONCLUSIONS: An inter-population differences on the level of gene expression were identified in both B-cell lines and peripheral blood samples. These findings may have a practical application in the field of forensic science. In particular, these transcripts, targeted by specific probes, may be used as population-specific targets in the efforts aiming to separate mixture of blood from individuals of different populations. Notwithstanding, these results have to be confirmed on extended population group.

Dynamics of solid alanine by means of nuclear magnetic resonance relaxometry.

1H nuclear magnetic resonance relaxometry was applied to investigate the dynamics of l-alanine in the solid phase (powder). The experimental studies were carried out in a very broad frequency range, covering four orders of magnitude-from 4 kHz to 40 MHz (referring to the 1H resonance frequency) in order to probe motional processes of much different time scales by a single experiment. To get access to the dynamics of different proton groups of alanine, the 1H spin-lattice relaxation measurements were performed for non-deuterated and partially deuterated alanine. The experiments were carried out in the temperature range of 293 K-370 K (non-deuterated alanine) and 318 K-370 K (partially deuterated alanine). As a result of a thorough theoretical analysis of the extensive set of experimental results, three motional processes occurring on different time scales are identified and quantitatively described. The slowest process occurs on a time scale of µs and it is attributed to the collective dynamics of a 3D hydrogen bond network of alanine, while the intermediate, attributed to the dynamics of the NH3 group, corresponds to the range of tenths of ns. The fast process describes the rotation of the CH3 group.

Structure and dynamics of [NH2(CH3)2]3Sb2Cl9 by means of 1H NMR relaxometry - quadrupolar relaxation enhancement effects.

1H spin-lattice relaxation experiments have been performed for [NH2(CH3)2]3Sb2Cl9 (tris(dimethylammonium)nonachlorodiantimonate(iii)) in the temperature range of 253-313 K and a broad range of frequencies - from 4 kHz to 40 MHz. From the analysis of quadrupolar relaxation enhancement effects (quadrupolar peaks) associated with 14N nuclei, two lattice sites characterized by different electric field gradient tensors have been revealed. The 14N quadrupolar couplings and asymmetry parameters at these sites differ by a factor of about two. Three motional processes have been identified and attributed to the overall dynamics of the NH2(CH3)2 cations (slow motion), dynamics of the NH2 groups (intermediate motion) and methyl group rotation (fast motion). It has been shown that the slow dynamics is only weakly temperature dependent, while the intermediate and fast motional processes are characterized by activation energies of 2.92 kJ mol-1 and 0.41 kJ mol-1, respectively. The correlation time of the slow dynamics is of the order of µs, while the intermediate dynamics is faster by 2-3 orders of magnitude (depending on temperature). All correlation times have turned out to be independent of the position of the cations in the lattice (they are the same for both lattice sites). The analysis presented in this work is an example of the potential of the quadrupolar relaxation enhancement effects as a method revealing information on the dynamics and structure of solids.

Verification of the authenticity of drugs by means of NMR relaxometry-Viagra® as an example.

1H spin-lattice Nuclear Magnetic Resonance (NMR) relaxometry, vibrational spectroscopy and Atomic Force Microscopy (AFM) have been applied to differentiate between original and counterfeit Viagra®. The relaxation studies have been performed in a frequency range covering four orders of magnitude, from 4kHz to 40MHz. It has been shown that for the counterfeit product the relaxation is bi-exponential in the whole frequency range, while for the original Viagra® the relaxation process is always single exponential. Thus, even a qualitative analysis of the relaxation data makes it possible to identify the falsified medicine. Moreover, it has been demonstrated that vibrational spectroscopy does not allow for differentiating between the products, while AFM studies are likely to lead one to deceptive conclusions regarding the originality of the medicine. Furthermore, a quantitative analysis of the relaxation data has been performed to describe in detail the relaxation properties of the original and falsified products.

(1)H NMR relaxometry and quadrupole relaxation enhancement as a sensitive probe of dynamical properties of solids--[C(NH2)3]3Bi2I9 as an example.

(1)H nuclear magnetic resonance relaxometry has been applied to reveal information on dynamics and structure of Gu3Bi2I9 ([Gu = C(NH2)3] denotes guanidinium cation). The data have been analyzed in terms of a theory of quadrupole relaxation enhancement, which has been extended here by including effects associated with quadrupole ((14)N) spin relaxation caused by a fast fluctuating component of the electric field gradient tensor. Two motional processes have been identified: a slow one occurring on a timescale of about 8 × 10(-6) s which has turned out to be (almost) temperature independent, and a fast process in the range of 10(-9) s. From the (1)H-(14)N relaxation contribution (that shows "quadrupole peaks") the quadrupole parameters, which are a fingerprint of the arrangement of the anionic network, have been determined. It has been demonstrated that the magnitude of the quadrupole coupling considerably changes with temperature and the changes are not caused by phase transitions. At the same time, it has been shown that there is no evidence of abrupt changes in the cationic dynamics and the anionic substructure upon the phase transitions.

A method of water-soluble solid fraction saturation concentration evaluation in dry thalli of Antarctic lichenized fungi, in vivo.

BACKGROUND: At initial steps of rehydration from cryptobiosis of anhydrobiotic organisms or at rehydration of dry tissues the liquid 1H NMR signal increased anomaly. The surplus in liquid signal may appear if some solid constituents dissolved, or if they were decomposed by enzymatic action. METHODS: Hydration kinetics, sorption isotherm, 1H NMR spectra and high power relaxometry were applied to monitor gaseous phase rehydration of Antarctic lichen Cetraria aculeata. Tightly and loosely bound water signal were distinguished, and the upper hydration limit for dissolution of water soluble solid fraction was not observed. A simple theoretical model was proposed. RESULTS: The hydration courses showed a very tightly bound water fraction, a tightly bound water, and a loosely bound water fraction. Sigmoidal in form sorption isotherm was fitted well by multilayer sorption model. 1H NMR showed one Gaussian signal component from solid matrix of thallus and one or two Lorentzian line components from tightly bound, and from loosely bound water. The hydration dependency of liquid signal was fitted by rational function. CONCLUSIONS: Although in dehydrated C.aculeata the level of carbohydrates and polyols was low, the lichenase action during rehydration process increased it; the averaged saturation concentration cs =(57.3±12.0)%, which resembled that for sucrose. GENERAL SIGNIFICANCE: The proposed method of water soluble solid fraction saturation concentration, cs , calculation from 1H NMR data may be applied for other organisms experiencing extreme dehydration or for dry tissues. We recalculated the published elsewhere data for horse chestnut (Aesculus hippocastanum) bast [water-soluble solid fraction recognized as sucrose, cs =(74.5±5.1)%]; and for Usnea antarctica, where cs =0.81±0.04.

Decreased effectiveness of ischemic heart preconditioning in the state of chronic inflammation.

There is growing evidence, that beneficial effects of ischemic heart preconditioning (IPC) may be lost or limited due to diabetes, hyperlipidemia, hypertension, atherosclerosis, heart failure and senility. It is plausible, that these conditions interfere with the biochemical pathways underlying the IPC response, but the detailed explanation is not clear. Pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α), monocyte chemotactic protein-1 (MCP-1), histamine and many other agents used in a single dose before prolonged ischemia mimic IPC. However prolonged exposure to preconditioning mimetics leads to tolerance (tachyphylaxis). In the state of such tolerance ischemic preconditioning is no longer protective. Studies suggest that diabetes, hyperlipidemia, hypertension, atherosclerosis, heart failure and older age are accompanied by increased plasma levels of pro-inflammatory cytokines, MCP-1 and other inflammatory mediators. Therefore, we raised the hypothesis, that the reported lack of benefits of IPC in the listed states may be due to tolerance to IPC developed during prolonged exposure of the myocardium to preconditioning mimetics.

Dynamics of [C3H5N2]6[Bi4Br18] by means of (1)H NMR relaxometry and quadrupole relaxation enhancement.

(1)H spin-lattice field cycling relaxation dispersion experiments in the intermediate phase II of the solid [C3H5N2]6[Bi4Br18] are presented. Two motional processes have been identified from the (1)H spin-lattice relaxation dispersion profiles and quantitatively described. It has been concluded that these processes are associated with anisotropic reorientations of the imidazolium ring, characterized by correlation times of the order of 10(-8) s-10(-9) s and of about 10(-5) s. Moreover, quadrupole relaxation enhancement (QRE) effects originating from slowly fluctuating (1)H-(14)N dipolar interactions have been observed. From the positions of the relaxation maxima, the quadrupole coupling parameters for the (14)N nuclei in [C3H5N2]6[Bi4Br18] have been determined. The (1)H-(14)N relaxation contribution associated with the slow dynamics has been described in terms of a theory of QRE [Kruk et al., Solid State Nucl. Magn. Reson. 40, 114 (2011)] based on the stochastic Liouville equation. The shape of the QRE maxima (often referred to as "quadrupole peaks") has been consistently reproduced for the correlation time describing the slow dynamics and the determined quadrupole coupling parameters.

Comparison of the cryoprotective solutions based on human albumin vs. autologous plasma: its effect on cell recovery, clonogenic potential of peripheral blood hematopoietic progenitor cells and engraftment after autologous transplantation.

BACKGROUND AND OBJECTIVES: Cryopreservation of peripheral blood hematopoietic progenitor/stem cells (PBPCs) requires the addition of cryoprotectant such as DMSO, often prediluted using human serum albumin solution (HSAS). The goal of our study was to verify whether the HSAS may be replaced by autologous plasma (AP) without negative impact on PBPCs quality and engraftment. AP usage is less expensive and allows performing cell preparation in a 'closed system', and hence to reduce the risk of product contamination. MATERIALS AND METHODS: Peripheral blood progenitor cells from 18 patients were divided into two aliquots (500 µl) placed in separate vials, each containing 7·5% DMSO prediluted with 5% HSAS or AP. Post-thaw cell recovery and clonogenic potential was evaluated. During clinical part of the study, the impact of both cryoprotective solution on hematopoietic engraftment was evaluated in two cohorts (n = 26) matched for diagnosis, age and the number of transplanted CD34+ cells. RESULTS: The median recovery of nucleated cells and the number of colony-forming units did not differ between tested cryoprotective mixtures. For AP mixture, neither total protein nor albumin concentration of plasma correlated with cell recovery and clonogenic potential of the PBPCs after cryopreservation. In clinical evaluation, the median time to leucocyte recovery and reconstitution of neutrophils was comparable in both groups: 10 days. We did not observe either significant difference with regard to the time of platelet recovery (median: 15 days for AP vs. 16 for HSAS; P = 0·79). CONCLUSIONS: HSA in cryoprotective mixture may be replaced by AP without negative impact on cell recovery, clonogenic potential or engraftment.

Dynamics of ferroelectric bis(imidazolium) pentachloroantimonate(III) by means of nuclear magnetic resonance 1H relaxometry and dielectric spectroscopy.

Some of haloantimonates(III) and halobismuthates(III) are ferroelectric. Bis(imidazolium) pentachloroantimonate(III), (C3N2H5)2SbCl5 (abbreviation: ICA) is the first example of such compounds with a one-dimensional anionic chain which exhibits ferroelectric properties. The relation between the ionic dynamics and network structure and the ferroelectric features is not clear. Here Nuclear Magnetic Resonance (NMR) (1)H spin-lattice relaxation experiments at 25 MHz are reported for ICA in the temperature range of 80 K-360 K, covering ferroelectric-paraelectric and structural phase transitions of the compound occurring at 180 and 342 K, respectively. The relaxation process is biexponential in the whole temperature range indicating two dynamically nonequivalent types of imidazolium cations. Temperature dependences of both relaxation contributions allow for identifying three motional processes. Two of them are cation-specific - i.e. they are attributed to the two types of imidazolium cations, respectively. The third process involves both types of cations, and it is characterized by much lower activation energy. Moreover, the relaxation data (combined with (1)H second moment measurements) show that the ferroelectric-paraelectric phase transition mechanism is governed, to a large extent, by the anionic network arrangement. The NMR studies are complemented by dielectric spectroscopy experiments performed in the vicinity of the Curie temperature, TC = 180 K, to get insight into the mechanism of the ferroelectric-paraelectric phase transition. The dielectric dispersion data show critical slowing down of the macroscopic relaxation time, τ, in ICA when approaching TC from the paraelectric side, indicating an order-disorder type of ferroelectrics.

Intermediate-dose Ara-C plus G-CSF for stem cell mobilization in patients with lymphoid malignancies, including predicted poor mobilizers.

The optimal protocol for mobilization of hematopoietic stem cells in patients with lymphoid malignancies has not been determined so far. We retrospectively analyzed the efficacy and safety of Ara-C at a dose of 1.6 g/m(2) compared with CY at a dose of 4.0 g/m(2), both combined with filgrastim. Seventy and forty-five patients, respectively, were included, among whom 60% were defined as 'predicted poor mobilizers'. The use of Ara-C was associated with significantly higher peak number of circulating CD34(+) cells compared with CY (P<0.0001). In the Ara-C group, 95% of patients with multiple myeloma (MM) collected at least 5 × 10(6) CD34(+) cells/kg required for tandem transplantation, and 97% of lymphoma patients collected at least 2 × 10(6) CD34(+) cells/kg, needed for a single autologous hematopoietic SCT (autoHSCT), which was achieved with a single leukapheresis in 91% of cases. Results for the CY group were significantly inferior (P<0.0001). No patient mobilized with Ara-C experienced febrile neutropenia, whereas 35% required platelet transfusions. Among patients who proceeded to autoHSCT, the time of both neutrophil and platelet recovery was significantly shorter for those mobilized with Ara-C than CY. We conclude that intermediate-dose Ara-C+filgrastim is a very effective and relatively safe mobilization protocol for patients with lymphoid malignancies.

Impact of different dimethyl sulphoxide concentrations on cell recovery, viability and clonogenic potential of cryopreserved peripheral blood hematopoietic stem and progenitor cells.

BACKGROUND AND OBJECTIVES: The procedure of autologous hematopoietic stem/progenitor cell transplantation requires cryopreservation. Addition of DMSO is necessary to secure the viability of such cells, but this solvent is potentially toxic to stem cells' recipient. 10% DMSO solution is used by the majority of transplant centres. The aim of our study was to test if DMSO concentration might be reduced without negative impact on cell recovery and clonogenicity. MATERIALS AND METHODS: Samples were prospectively collected from 20 patients. Small volumes of leukapheresis products were frozen with different cryoprotective mixtures, containing 10%, 7·5%, 5% and 2·5% DMSO, respectively. The quality of cryoprotective mixtures was evaluated based on recovery, viability and clonogenic potential of hematopoietic stem cells after defreezing. RESULTS: Reduction in DMSO concentration to 7·5% or lower was associated with decreased recovery of nucleated cells. In contrast, the number of colonies was highest for 7·5% DMSO with significant differences when compared to 10% DMSO solution. CONCLUSION: Reduction in DMSO concentration from 10% to 7·5% may have favourable impact on hematopoietic recovery after autologous transplantation. The findings require confirmation in a clinical setting.

The impact of center experience on results of reduced intensity: allogeneic hematopoietic SCT for AML. An analysis from the Acute Leukemia Working Party of the EBMT.

Allogeneic hematopoietic SCT with reduced-intensity conditioning (RIC-HSCT) is increasingly adopted for the treatment of older adults with AML. Our goal was to verify for the first time, if center experience influences outcome of RIC-HSCT. Results of 1413 transplantations from HLA-matched related or unrelated donors for adult patients with AML in first CR were analyzed according to the level of center activity. Transplants were performed in 203 European centers between 2001 and 2007. The 2-year probability of leukemia-free survival (LFS) after RIC-HSCT performed in centers with the lowest activity (< or =15 procedures/7 years) was 43±3% compared with 55±2% in the remainder (P<0.001). The incidence of non-relapse mortality (NRM) was 24±3% and 15±1% (P=0.004), whilst relapse rate was 33±3% and 31±1% (P=0.33), respectively. In a multivariate model, adjusted for other prognostic factors, low RIC-HSCT activity was associated with decreased chance of LFS (hazard ratio (HR)=0.64; P<0.001) and increased risk of NRM (HR=1.47, P=0.04) and relapse (HR=1.41, P=0.01). Center experience is a very important predictor of outcome and should be considered in future analyses evaluating the results of RIC-HSCT. The reasons why centers with low RIC-HSCT activity have worse outcomes should be further investigated.

A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas.

BACKGROUND: Papillary thyroid cancer (PTC) incidence increased dramatically in children after the Chernobyl accident, providing a unique opportunity to investigate the molecular features of radiation-induced thyroid cancer. In contrast to the previous studies that included age-related confounding factors, we investigated mRNA expression in PTC and in the normal contralateral tissues of patients exposed and non-exposed to the Chernobyl fallout, using age- and ethnicity-matched non-irradiated cohorts. METHODS: Forty-five patients were analysed by full-genome mRNA microarrays. Twenty-two patients have been exposed to the Chernobyl fallout; 23 others were age-matched and resident in the same regions of Ukraine, but were born after 1 March 1987, that is, were not exposed to ¹³¹I. RESULTS: A gene expression signature of 793 probes corresponding to 403 genes that permitted differentiation between normal tissues from patients exposed and from those who were not exposed to radiation was identified. The differences were confirmed by quantitative RT-PCR. Many deregulated pathways in the exposed normal tissues are related to cell proliferation. CONCLUSION: Our results suggest that a higher proliferation rate in normal thyroid could be related to radiation-induced cancer either as a predisposition or as a consequence of radiation. The signature allows the identification of radiation-induced thyroid cancers.