Resting‐state glutamatergic neurotransmission is related to the peak latency of the auditory mismatch negativity (MMN) for duration deviants: An 1H‐MRS‐EEG study

Mismatch negativity (MMN), an ERP elicited by a deviant stimulus in a train of standard stimuli, has been suggested to be associated to glutamatergic neurotransmission, mediated by glutamatergic NMDA receptors. In this study, we examined the relationship between interindividual variation of ¹H‐MRS‐measured glutamate+glutamine (Glx) in the superior temporal gyrus and MMN for duration and frequency deviants in 19 healthy young adults (9 male). We found a significant relationship between the peak latency of the duration‐MMN peak and creatine‐scaled Glx (p = .0003, η² = .43), with increased Glx level being associated to earlier peak of the duration‐MMN (r = ?.63). In contrast, the amplitude of the duration‐MMN was not related to Glx. There was no significant relationship between Glx and the frequency‐MMN. The present study is the first to demonstrate that interindividual variation in the glutamatergic neurotransmission affects the MMN response in healthy individuals.     

Y‐Chromosomal Lineages of Latvians in the Context of the Genetic Variation of the Eastern‐Baltic Region

Variations of the nonrecombining Y‐chromosomal region were investigated in 159 unrelated Baltic‐speaking ethnic Latvians from four different geographic regions, using 28 biallelic markers and 12 short tandem repeats. Eleven different haplogroups (hgs) were detected in a regionally homogeneous Latvian population, among which N1c, R1a, and I1 cover more than 85% of its paternal lineages. When compared its closest geographic neighbors, the composition of the Latvian Y‐chromosomal gene pool was found to be very similar to those of Lithuanians and Estonians. Despite the comparable frequency distribution of hg N1c in Latvians and Lithuanians with the Finno‐Ugric‐speaking populations from the Eastern coast of the Baltic Sea, the observed differences in allelic variances of N1c haplotypes between these two groups are in concordance with the previously stated hypothesis of different dispersal ways of this lineage in the region. More than a third of Latvian paternal lineages belong specifically to a recently defined R1a‐M558 hg, indicating an influence from a common source within Eastern Slavic populations on the formation of the present‐day Latvian Y‐chromosome gene pool.     

Cytogenetic abnormalities in childhood acute myeloid leukaemia: a Nordic series comprising all children enrolled in the NOPHO-93-AML trial between 1993 and 2001

Between 1993 and 2001, 318 children were diagnosed with acute myeloid leukaemia (AML) in the Nordic countries. The patient group comprised 237 children < 15 years of age with de novo AML, 42 children < 15 years with Down syndrome (DS) and de novo AML, 18 adolescents 15-18 years of age with de novo AML, and 21 children < 15 years with treatment-related AML (t-AML). The first group was all-inclusive, yielding an annual childhood de novo AML incidence of 0.7/100 000. Cytogenetic analyses were successful in 288 cases (91%), and clonal chromosomal abnormalities were detected in 211 (73%). The distribution of ploidy levels were pseudodiploidy (55%), hyperdiploidy (34%) and hypodiploidy (11%). The most common aberrations (> 2%) were + 8 (23%) (as a sole change in 6.2%), 11q23-translocations, including cryptic MLL rearrangements (22%) [t(9;11)(p21-22;q23) in 11%], t(8;21)(q22;q22) (9.0%), inv(16)(p13q22) (6.2%), -7/7q- (5.2%), and t(15;17)(q22;q12) (3.8%). Except for +8, these abnormalities were rare in group 2; only one DS patient had a t(8;21) and none had 11q23-translocations, t(15;17) or inv(16). In the t-AML group, three cases displayed 11q23-rearrangements, all t(9;11); and there were no t(8;21), t(15;17) or inv(16). Overall, the observed frequencies of t(8;21) and t(15;17) were lower, and frequencies of trisomy 8 and 11q23-translocations higher, than in previous studies. Furthermore, seven abnormalities that were previously reported as only single AML cases were also seen, meaning that der(4)t(4;11)(q26-27;q23), der(6)t(1;6)(q24-25;q27), der(7)t(7;11)(p22;q13), inv(8)(p23q11-12), t(11;17)(p15;q21), der(16)t(10;16)(q22;p13) and der(22)t(1;22)(q21;q13) are now classified as recurrent abnormalities in AML. In addition, 37 novel aberrations were observed, 11 of which were sole anomalies.     

Pancreatin enhanced erosion of and macromolecule release from 2,2-bis(2-oxazoline)-linked poly(epsilon-caprolactone).

The degradation and erosion of solvent cast films and injection molded bars prepared from poly(epsilon-caprolactone) (PCL) and 2,2'-bis(2-oxazoline) linked poly(epsilon-caprolactone) (PCL-O) were evaluated in simulated gastric fluid (SGF) (pH 1.2, pepsin present) and in simulated intestinal fluid (SIF) (pH 7.5, pancreatin present). After incubation of the polymer films (10 mg) and bars (70 mg) in the medium, the resulting decrease in molecular weight (degradation) was determined by size exclusion chromatography and the weight loss of the preparations was measured. In addition, the effect of pancreatin on FITC-dextran (MW 4400) release from PCL and PCL-O microparticles, prepared by w/o/w double emulsion technique, was studied. No degradation or weight loss was observed for either PCL or PCL-O films in SGF (12 h incubation, 37 degrees C). When compared to PBS pH 7.4, pancreatin hardly enhanced the weight loss of PCL films and bars. In contrast, pancreatin enhanced substantially erosion of PCL-O films and bars. Unlike PCL preparations, the PCL-O preparations showed surface erosion in SIF. Pancreatin increased considerably FITC-dextran release from both PCL and PCL-O microparticles. In conclusion, the present results demonstrate the enzyme sensitivity of the novel PCL-O polymer. In addition, the results show that pancreatin present in intestinal fluid may substantially affect drug release from PCL based preparations.     

Screening for risk factors for chronic disease in children from fifteen countries

An international collaborative health screening project was undertaken to stimulate interest in child health education, to study feasibility of health screening in young children from diverse cultures, and to compare the distribution of chronic disease risk factors among 15 countries. Data for the 13-year-old participants showed that risk factors defined by cholesterol greater than 180 mg/dl, systolic blood pressure greater than 130 mm Hg, and daily or occasional smoking were present, to varying degrees, in children from each country. We found no relationship between obesity and cholesterol or blood pressure for these children. The acceptability of the screening, the children's enjoyment in participation, and the prevalence of risk factors at this young age lead to the conclusion that school-based health education programs should be initiated during childhood.     

Methylprednisolone esters of hyaluronic acid in ophthalmic drug delivery: in vitro and in vivo release studies

Films and microspheres were prepared from various esters of hyaluronic acid. A model drug, methylprednisolone, was either physically incorporated into the polymer matrix or chemically bound to the polymer backbone through an ester linkage. In vitro release from films with covalently bound drug was much slower (t_50% = 71 h) than that for physically dispersed drug (t_50% = 2.5−17 h). Methylprednisolone concentrations in the tear fluid of New Zealand rabbits were measured after ocular application of drug (approx. 420 μg) in different dosage forms. When methylprenisolone was physically dispersed in the polymer matrix, in vivo drug release from matrices was slower than that observed in vitro. Compared with a suspension control, peak methylprednisolone concentrations in tear fluid were 9–14 times lower after administration of drug in polymer films and AUC_{0–8 h} values were 4–7 times higher. These results imply that hyaluronic acid ester preparations can increase the residence time of methylprednisolone in the tear fluid of rabbits.     

Gait analysis by measuring ground reaction forces in children: changes to an adaptive gait pattern between the ages of one and five years

The aim of this study was to look at the maturational profile of gait parameters by measuring ground reaction forces during independent walking in children. Fifty-four normal children aged 1 to 5 years were examined. The children walked with eight force transducers under each sole. Gait velocity and step length increased with age, whereas step frequency remained relatively constant. Phases of double ground contact expressed as percentages of the total gait cycle decreased significantly from age 1 to 5 with the steepest decrease occuring in the first year of independent walking. No asymmetry between left and right could be detected for any of these parameters. The pattern of ground reaction forces with a significant heel strike and obvious enrollment process resembling that in adults was achieved between the age of 2 and 3 years. Measuring ground reaction forces is a fast and easily manageable method of analysing gait pattern in children and is also a promising tool for detection of gait abnormalities in children with neurological disease.