The association of children's mathematic abilities with both adults' cognitive abilities and intrinsic fronto-parietal networks is altered in preterm-born individuals.

Mathematic abilities in childhood are highly predictive for long-term neurocognitive outcomes. Preterm-born individuals have an increased risk for both persistent cognitive impairments and long-term changes in macroscopic brain organization. We hypothesized that the association of childhood mathematic abilities with both adulthood general cognitive abilities and associated fronto-parietal intrinsic networks is altered after preterm delivery. 72 preterm- and 71 term-born individuals underwent standardized mathematic and IQ testing at 8 years and resting-state fMRI and full-scale IQ testing at 26 years of age. Outcome measure for intrinsic networks was intrinsic functional connectivity (iFC). Controlling for IQ at age eight, mathematic abilities in childhood were significantly stronger positively associated with adults' IQ in preterm compared with term-born individuals. In preterm-born individuals, the association of children's mathematic abilities and adults' fronto-parietal iFC was altered. Likewise, fronto-parietal iFC was distinctively linked with preterm- and term-born adults' IQ. Results provide evidence that preterm birth alters the link of mathematic abilities in childhood and general cognitive abilities and fronto-parietal intrinsic networks in adulthood. Data suggest a distinct functional role of intrinsic fronto-parietal networks for preterm individuals with respect to mathematic abilities and that these networks together with associated children's mathematic abilities may represent potential neurocognitive targets for early intervention.

Extensive and interrelated subcortical white and gray matter alterations in preterm-born adults.

Preterm birth is a leading cause for impaired neurocognitive development with an increased risk for persistent cognitive deficits in adulthood. In newborns, preterm birth is associated with interrelated white matter (WM) alterations and deep gray matter (GM) loss; however, little is known about the persistence and relevance of these subcortical brain changes. We tested the hypothesis that the pattern of correspondent subcortical WM and GM changes is present in preterm-born adults and has a brain-injury-like nature, i.e., it predicts lowered general cognitive performance. Eighty-five preterm-born and 69 matched term-born adults were assessed by diffusion- and T1-weighted MRI and cognitive testing. Main outcome measures were fractional anisotropy of water diffusion for WM property, GM volume for GM property, and full-scale IQ for cognitive performance. In preterm-born adults, reduced fractional anisotropy was widely distributed ranging from cerebellum to brainstem to hemispheres. GM volume was reduced in the thalamus, striatum, temporal cortices, and increased in the cingulate cortices. Fractional anisotropy reductions were specifically associated with GM loss in thalamus and striatum, with correlation patterns for both regions extensively overlapping in the WM of brainstem and hemispheres. For overlap regions, fractional anisotropy was positively related with both gestational age and full-scale IQ. Results provide evidence for extensive, interrelated, and adverse WM and GM subcortical changes in preterm-born adults. Data suggest persistent brain-injury-like changes of subcortical-cortical connectivity after preterm delivery.

Smoking ban in public areas is associated with a reduced incidence of hospital admissions due to ST-elevation myocardial infarctions in non-smokers. Results from the Bremen STEMI Registry.

INTRODUCTION: Laws banning tobacco smoking from public areas have been passed in several countries, including the region of Bremen, Germany at the end of 2007. The present study analyses the incidence of hospital admissions due to ST-elevation myocardial infarctions (STEMIs) before and after such a smoking ban was implemented, focusing on differences between smokers and non-smokers. In this respect, data of the Bremen STEMI Registry (BSR) give a complete epidemiological overview of a region in northwest Germany with approximately 800,000 inhabitants since all STEMIs are admitted to one central heart centre. METHODS AND RESULTS: Between January 2006 and December 2010, data from the BSR was analysed focusing on date of admission, age, gender, and prior nicotine consumption. A total of 3545 patients with STEMI were admitted in the Bremen Heart Centre during this time period. Comparing 2006-2007 vs. 2008-2010, hence before and after the smoking ban, a 16% decrease of the number of STEMIs was observed: from a mean of 65 STEMI/month in 2006-2007 to 55/month in 2008-2010 (p < 0.01). The group of smokers showed a constant number of STEMIs: 25/month in 2006-2007 to 26/month in 2008-2010 (+4%, p = 0.8). However, in non-smokers, a significant reduction of STEMIs over time was found: 39/month in 2006-2007 to 29/month in 2008-2010 (-26%, p < 0.01). The decline of STEMIs in non-smokers was consistently observed in all age groups and both sexes. Adjusting for potentially confounding factors like hypertension, obesity, and diabetes mellitus did not explain the observed decline. CONCLUSIONS: In the BSR, a significant decline of hospital admissions due to STEMIs in non-smokers was observed after the smoking ban in public areas came into force. No reduction of STEMI-related admissions was found in smokers. These results may be explained by the protection of non-smokers from passive smoking and the absence of such an effect in smokers by the dominant effect of active smoking.

Functional expression of the human neonatal Fc-receptor, hFcRn, in isolated cultured human syncytiotrophoblasts.

Materno-fetal IgG transfer in the mature human placenta involves transport across the syncytiotrophoblast (STB) and fetal endothelial cell layer. The MHC class I-related Fc gamma-receptor (hFcRn) localized in STB as well as in endothelial cells is involved in overall IgG transfer from the maternal into the fetal circulation. Functional hFcRn is a heterodimer of a transmembrane alpha-chain and beta2-microglobulin. To establish the basis for future studies to unravel the mechanism of IgG transport in STB, we investigated hFcRn alpha-chain and beta2-microglobulin expression in cytotrophoblasts (CTB) isolated from human term placentae and cultured in vitro under conditions where differentiation into multinuclear STB takes place (>or=48 h). Northern blot analysis demonstrated up-regulation of alpha-chain mRNA after 48 h of in vitro cultivation. Likewise, hFcRn alpha-chain and beta2-microglobulin were at the limit of detection by immunofluorescence microscopy in CTB immediately after isolation, but their expression increased upon STB formation. hFcRn alpha-chain co-localized with beta2-microglobulin in multinuclear STB and formed a functional, i.e. low pH IgG binding, receptor as shown by affinity isolation. The in vitro differentiated STB exhibited specific, low pH-dependent IgG binding to the plasma membrane. In conclusion, these cultures can now be applied to study the role of hFcRn in IgG transport and trafficking in STB cultures in vitro.

[Official veterinary supervision of zoos--experiences in Brandenburg]. / Amtstierärztliche Uberwachung von Zoos--Erfahrungen im Land Brandenburg.

Based on the law of animal welfare and on the EU-rule about keeping of wild animals in zoological gardens 15 zoological gardens in Brandenburg were inspected by a temporary team consisting of one veterinarian from the state office of feeds and agriculture, the local authorized veterinarian and one director of the zoogardens. Data of every zoological garden at first were recorded by special lists of queries. So it was possible to estimate the keeping conditions and to realize deficiencies and the main problems. During the local inspection these data were controlled and the structure of keeping units as well as the conditions and behaviour of the animals were evaluated. Every unit was evaluated taking into consideration all points of view. If necessary proposals for improvements were made which were to enforce by the local authority. Furthermore the documentation and the economic areas were inspected. The number of kept species and animals was relatively low. Only two zoological gardens were to classify as mean ones. The majority of the fences and aviaries corresponded with the minimal demands of the today rules resp. was larger in the dimension and space. There were very nice keeping units, but also some deficiently in the structure or in the quality of the ground. By some photographs positive and negative examples are demonstrated. The feeding and also the veterinary service were on high level. The team found out that staffs of the zoogardens had a positive position to animal welfare. Step by step they improved the keeping conditions. The central inspection by a multi-professional team was estimated positively and should be repeated in certain intervals. The used lists of queries were suitable. The valid rules and guide lines should be revised in near future.

Degradation of desferrioxamines by Azospirillum irakense: assignment of metabolites by HPLC/electrospray mass spectrometry.

Based on a recent finding that an Azospirillum isolate ASP-1 possessing high 16S rDNA similarity to Azospirillum irakense was able to degrade desferrioxamine type siderophores (Winkelmann et al. BioMetals 9, 78-83, 1996), various members of the genus Azospirillum were analyzed for their ability to degrade desferrioxamines. While the desferrioxamine-degrading activity was absent or scarcely detectable in strains of A. lipoferum, A. brasilense, A. amazonense, degradation activity seemed to be confined to the species A. irakense (KBC-1, KA3). Also the identity of strain ASP-1 as A. irakense could be confirmed by species-specific oligonucleotide hybridization, Inter-LINE PCR fingerprinting and carbon source utilization pattern (BIOLOG) analysis. Products of desferrioxamine B degradation were analyzed by analytical HPLC and HPLC/electrospray mass spectrometry. Using whole cells and purified enzyme it was shown that the trihydroxamate desferrioxamine B (561 amu) is split at the N-terminal amide bond yielding a monohydroxamate (MH1, 219 amu) and a dihydroxamate (DH1, 361 amu) metabolite. A second monohydroxamate (MH2, 319 amu) resulted from DH1 after splitting the acetylhydroxamate bond. Minor amounts of a further dihydroxamate (DH2, 419 amu) originated from splitting the second amide bond in desferrioxamine B. In addition to desferrioxamine B, several other linear and cyclic desferrioxamines and derivatives were degraded, whereas desferricoprogen and desferri-ferrichrome were not degraded, indicating high substrate specificity of the desferrioxamine hydrolase in A. irakense species. A simple microtiter plate assay was developed which can be used to phenotypically discriminate and identify species of A. irakense from other Azospirillum species by their characteristic feature of desferrioxamine degradation.

Health effects of sulfur-related environmental air pollution. I. Executive summary.

The motivation of simulating real-world environmental exposure in a number of long-term studies with dogs was to address the question of whether or not perpetual inhalation of air pollutants can initiate diseases in healthy lungs and can thus contribute to the increasing prevalence of respiratory diseases in industrialized countries. The major conclusion of this article is that this question has to be answered in the negative for the simultaneous inhalation of the major constituents of combustion-related air pollution, particle-associated sulfur(IV), and particle-associated hydrogen ions. Over 13 mo, 8 healthy beagle dogs were exposed in 2 whole-body chambers daily for 16.5 h to 1 microm neutral sulfite [sulfur(IV)] particles at a mass concentration of 1.5 mg m-3 and for 6 h to 1.1 microm acidic sulfate particles carrying 15 micromol m-3 hydrogen ions into the canine lungs. This longitudinal study was characterized by repeated observations of individual respiratory response patterns. To establish baseline data the dogs were repeatedly examined preexposure while the chambers were ventilated over 16 mo with clean air. Each individual served thus as its own control. Another eight dogs served as additional controls. They were housed in 2 chambers ventilated with clean air over the entire study period of 29 mo. To assess response patterns, respiratory lung function tests were performed pre- and postexposure, segmental lung lavages were repeatedly performed to obtain epithelial lining fluid from the lungs for analysis of cell content, cell function, and biochemical indicators of lung injury, and radiolabeled test particles were used to study pathways of intrapulmonary particle elimination. At the end of the study, the lungs of all animals were morphologically and morphometrically examined. Functional and structural responses were finally compared to those observed previously as a result of a sole exposure of canine lungs to neutral sulfite particles over 10 mo (Heyder et al., 1992). Interactions between responses induced by neutral sulfite and acidic sulfate particles occurred, but antagonism rather than synergism was observed. The responses induced by sulfur(IV) were less pronounced, not detectable, or even reversed when hydrogen ions were also delivered to the lungs. On the other hand, responses not induced by the sole exposure to sulfur(IV) were observed: The activity of alkaline phosphatase was elevated and type II pneumocytes proliferated. It can, however, be concluded that long-term exposure of healthy lungs to particle-associated neutral sulfur(IV) and hydrogen ions at concentration close to ambient levels causes subtle respiratory responses but does not initiate pathological processes in the lungs. In other words, the perpetual inhalation of sulfur(IV) and hydrogen ions from the atmospheric environment presents no health risk to the healthy lungs. It is thus also very unlikely that respiratory diseases can be initiated by the inhalation of these pollutants.

17 beta-estradiol reduces glycoxidative damage in the artery wall.

Glycoxidative damage in the vasculature has been linked to atherosclerotic cardiovascular disease. Estrogens protect against the development and progression of atherosclerosis. Because estrogens are potent antioxidants that also effect glucose metabolism, part of their protection against atherosclerosis could be through attenuation of glycoxidative damage in the vascular wall. In this study, we tested the hypothesis that chronic estradiol administration is associated with decreased levels of glycoxidative damage in arterial walls. We harvested and examined iliac arteries from ovariectomized, 8-month-old rats that had been implanted for 6 months with 1 of the following subcutaneous hormone pellets: low estradiol (2.5 mg estradiol), high estradiol (25 mg estradiol), P4 (200 mg progesterone), low estradiol and P4, placebo (no hormone), or control (no implant). Using pentosidine as a biomarker of glycoxidative damage, we found that all vessels from rats receiving estradiol (low estradiol, high estradiol, and low estradiol+P4) exhibited a 50% reduction in glycoxidative damage compared with P4, placebo, and control vessels (P<0.05). Consistent with this finding, we observed that estradiol-treated rats had a 30% decrease in tissue levels of hydroperoxides, a marker of oxidative stress. Finally, estradiol-treated rats had a small, but significant, decrease in plasma glucose levels (P<0.01). In summary, we report the novel finding that chronic estrogen administration is associated with significant decreases in glycoxidative damage and oxidative stress in the arterial wall. It seems likely that these actions may constitute a mechanism by which estrogen attenuates the progression of atherosclerosis.

Predominately glucocorticoid agonist actions of RU-486 in young specific-pathogen-free Zucker rats.

Previous studies have demonstrated antiglucocorticoid actions for the progesterone receptor antagonist RU-486. In one study, daily administration of this drug for 2 wk decreased food intake (FI) and body weight gain (delta BW) in obese, but not lean, conventionally housed 5-wk-old female Zucker rats. We recently found that 2-wk administration of RU-486 attenuated delta BW in lean but not obese 12-wk-old male Zucker rats without affecting FI. To examine the actions of RU-486 and its effects on FI and delta BW in young (5 wk old) specific-pathogen-free (SPF) male and female Zucker rats, RU-486 was administered at 30 mg.kg-1.day-1 subcutaneously for 14 days. RU-486 did not affect FI in obese or lean male or female rats. RU-486 increased adrenal weight (P < 0.05) overall and in lean female rats and modestly decreased inguinal fat weight overall and in obese female rats (P < 0.01), suggesting some antiglucocorticoid activity in these animals. However, RU-486 also decreased thymus weight by 18-31% (P < 0.0001), increased plasma glucose by 10-16 mg/dl (P < 0.002), and increased plasma insulin by 47% in obese male rats (P < 0.028), demonstrating glucocorticoid agonist actions for the drug. Plasma corticosterone (B) and adrenocorticotropic hormone (ACTH) were elevated in vehicle-treated obese female and male rats by 150-360% (P < 0.0025) and 32-38% (P < 0.05), respectively, compared with lean rats. RU-486 treatment lowered the elevated plasma B and ACTH levels in obese female and male rats (both P < 0.02 vs. vehicle), a glucocorticoid agonist effect. We conclude that in young SPF Zucker rats 1) RU-486 administration does not alter FI or delta BW, 2) RU-486 has predominately glucocorticoid agonist actions in several tissues, 3) obese animals have increased hypothalamic-pituitary-adrenal (HPA) axis activity (plasma B and ACTH), and 4) RU-486 administration suppresses the HPA axis in obese rats.

[Preventative tail amputation in fattening bulls]. / Prophylaktische Schwanzamputation bei Mastbullen.

In 5 cattle fattening farms with 900 to 3000 bulls tail docking was practised prophylactically in consequence of losses due to tail necrosis. Following detailed consultations in the farms temporary exceptional permission of the ban of amputation according to article 6 of the German Animal Welfare Law was given to 4 of the 5 farms, associated with real instructions to improve the housing conditions. By that means communication between farmer and veterinary authority was intensified and the contrariety between legislation and practice was pointed out clearly. The farmers were concerned with consequences of the ban of tail docking intensively. A process of understanding began, resulting in renunciation of prophylactic tail docking in 4 of the 5 farms.

Characteristics of the obesity syndrome in Zucker-Brown Norway (ZBN) hybrid rats.

The existence of a restriction fragment length polymorphism (RFLP) closely linked to the fatty locus between the Zucker (Z) and Brown Norway (BN) rat strains allows evaluation of early effects of the fatty (fa) gene using offspring of back-crosses (N2) between F1 females and Zucker obese males. We examined several metabolic characteristics of N2 animals to determine if these hybrid animals exhibited similar characteristics of the obese syndrome to those of Zucker rats. Females from crosses of obese male Zucker (fa/fa) and lean female BN (+/+) rats were back-crossed to their sires, resulting in twelve N2 litters. At 9 weeks of age, liver, spleen, interscapular brown fat (IBAT), and gonadal, retroperitoneal (RP), and inguinal fat depots were removed and weighed. Samples of the RP depot were analyzed for cell size and number. Obese N2 rats were hyperphagic, with body weights in the range of those of obese Zucker rats. Obese N2 rats were also hyperinsulinemic [mean +/- SEM, microU/ml: females, 7.9 +/- 0.6 vs. 82.1 +/- 8.4 (lean vs. obese); males, 10.5 +/- 1.6 vs. 128.5 +/- 13.4 (lean vs. obese)] and mildly hyperglycemic [mean +/- SEM, mg/dl: females, 104.1 +/- 2.0 vs. 139.0 +/- 14.7 (lean vs. obese); males, 100.9 +/- 2.6 vs. 132.0 +/- 2.8 (lean vs. obese) p < or = 0.05]. White fat depots in obese rats were 3 to 7 times heavier than those in lean rats; adipocyte numbers in RP depots were 50% greater in obese than in lean rats; and cell size was more than 3 times larger. IBAT, liver, and spleen were also heavier in obese vs. lean rats, while tail lengths were shorter. Percent lean carcass mass and % carcass protein were about 30% greater in lean vs. obese rats, while % carcass fat in obese rats was 5 times greater than that of lean rats. Thus, phenotypic expression of the fa gene in ZBN hybrid animals, with approximately 25% of their genetic background coming from the BN strain, appears to be similar to that in Zucker rats. Given the similarity of phenotypic expression of the fa gene between the Zucker strain and ZBN hybrids, it is plausible to consider using ZBN hybrids for studies of early manifestations of fa gene action prior to onset of detectable obesity.

Early clinical trial of MDL 73.147 EF: a new 5-HT3-receptors antagonist for the prevention of chemotherapy-induced nausea and vomiting.

BACKGROUND: Like MDL 72.222, one of the first selective 5-hydroxytryptamine3 (5-HT3) receptors antagonist discovered, MDL 73.147 EF has been shown to possess antiemetic properties in the ferret model. We conducted a phase I study with MDL 73.147 EF in 31 patients, treated with emetogenic drugs over one to five days (cisplatin, cyclophosphamide, doxorubicin, dacarbazine). PATIENTS AND METHODS: 5 groups of at least 5 patients received rising unit doses of MDL 73.147 EF (10 to 50 mg) intravenously before chemotherapy, with two more doses per day if needed. Nausea was assessed by a patient-completed visual analogue scale and episodes of vomiting recorded by an independent observer. RESULTS: 51.6% of the patients were complete responders on day one and 40% on days two to five. One patient was given other rescue antiemetic therapy. Adverse events included constipation (25.8%), mildly elevated blood pressure (12.9%) and other minor events. No extrapyramidal effects have been reported. There was no suggestion of dose-dependent efficacy at the dose levels studied in this limited set of patients. CONCLUSIONS: We conclude that MDL 73.147 EF is a well tolerated and possibly effective antiemetic.

Attention deficits: current concepts, controversies, management, and approaches to classroom instruction.

This article reviews the current criteria for diagnosis of Attention-Deficit Hyperactivity Disorder and Undifferentiated Attention-Deficit Disorder, according to the American Psychiatric Association, and describes other typical presenting features of children with attentional disorders. The current theories of the biological basis of attentional disorders are reviewed. Treatments of attentional disorders are discussed, including medical treatments with stimulants and tricyclic antidepressants, and non-medical treatments, such as behavior modification, psychotherapy, diets, and specific educational modifications that are felt to be helpful. Finally, our current thinking about the long-term outlook for children with attentional disorders is summarized.