[Comparison of Health-related Behavior Patterns of Boys and Girls in Germany: Results of the MoMo Study]. / Vergleich gesundheitsrelevanter Verhaltensmuster von Jungen und Mädchen in Deutschland: Ergebnisse der MoMo Studie.

AIM OF THE STUDY: For optimal health promotion in adolescents, it is important to know their typical behavior patterns. The aims of this study were to identify and compare sex-specific health-related behavior patterns of adolescents in Germany. METHODS: The KiGGS Survey and the MoMo Study assessed the health behavior of 832 boys and 811 girls by means of a questionnaire. The indices physical activity, diet quality and media use were included in cluster analyses for boys and girls separately. RESULTS: For each sex, 4 clusters with similar characteristics on the three included indices were identified. However, cluster size, level of the characteristics and correlates were different in boys and girls: fewer girls showed high activity levels. Overall, physical activity and media use were less pronounced in the behavior pattern of girls. There was a stronger association of behavior patterns with socio-economic status in girls. In boys, behavior patterns were significantly associated with prevalence of overweight. CONCLUSIONS: The similar cluster solutions for boys and girls support the assumption that there are typical health-related behavior patterns among German adolescents. This finding might facilitate the precise definition of homogeneous target groups for health promotion programs. Furthermore, it seems that sex-specific foci should be set.

Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder.

BACKGROUND: Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses. METHOD: During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately. RESULTS: BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation. CONCLUSIONS: This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders.

[Social Differences in Physical Activity among Adolescents in Germany: Analyses Based on Information Concerning the Metabolic Equivalent of Task (MET)]. / Soziale Unterschiede in der körperlich-sportlichen Aktivität bei Jugendlichen: Analyse der MoMo-Daten mithilfe der metabolischen Äquivalente (MET).

Introduction: Energy consumption, i. e., the metabolic equivalent of task (MET), provides a precise assessment of physical activity (PA). Studies on social inequalities of PA have hardly used this possibility, however. Methods: The analyses are based on the 'Motorik-Modul (MoMo) of the KiGGS study (German Health Interview and Examination Survey for Children and Adolescents) conducted between 2003 and 2006 (n=1 757; age group 11-17 years). PA has been assessed in 3 settings (sport club in school, other sport club, leisure time). 3 dependent variables were distinguished by combining the following criteria: at least 21 MET-hours per week, intensity between 3 and 6 METs, at least 7 hours a week. The main independent variables are: type of school and socioeconomic status (SES) of the parents. 'Two part models' have been used to assess social difference in PA among those who are physically active. Results: PA is much more common in the higher SES groups. Looking at the MET-hours, though, there are just little differences among those who are physically active (regressions coefficient for low vs. high SES: 1.15; 95% conf. interv. 0.99-1.33). Conclusion: Social differences can be seen mainly for the proportion of adolescents being physically active, not for the extent of PA among those who are physically active. Therefore, the central request should be to increase the proportion of adolescents performing any PA in the low SES group.

Twenty-one years to the right diagnosis - clinical overlap of Simpson-Golabi-Behmel and Beckwith-Wiedemann syndrome.

Clinical overlap makes the diagnosis of overgrowth syndromes challenging. Clinical overlap exists between Simpson-Golabi-Behmel syndrome (SGBS) and Beckwith-Wiedemann syndrome (BWS) which share pre- and postnatal overgrowth, macroglossia, umbilical hernia, organomegaly, ear lobe creases, and occurrence of embryonal tumors as characteristic features. Based on the clinical history of a patient, who was diagnosed with BWS shortly after birth and reassessed and rediagnosed with SGBS at age 21 years, particular attention should be paid to developing facial dysmorphia. In addition, we delineate further clinical findings that may allow differentiation between both conditions.

Silver-Russell patients showing a broad range of ICR1 and ICR2 hypomethylation in different tissues.

In all known congenital imprinting disorders an association with aberrant methylation or mutations at specific loci was well established. However, several patients with transient neonatal diabetes mellitus (TNDM), Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS) exhibiting multilocus hypomethylation (MLH) have meanwhile been described. Whereas TNDM patients with MLH show clinical symptoms different from carriers with isolated 6q24 aberrations, MLH carriers diagnosed as BWS or SRS present only the syndrome-specific features. Interestingly, SRS and BWS patients with nearly identical MLH patterns in leukocytes have been identified. We now report on the molecular findings in DNA in three SRS patients with hypomethylation of both 11p15 imprinted control regions (ICRs) in leukocytes. One patient was a monozygotic (MZ) twin, another was a triplet. While the hypomethylation affected both oppositely imprinted 11p15 ICRs in leukocytes, in buccal swab DNA only the ICR1 hypomethylation was visible in two of our patients. In the non-affected MZ twin of one of these patients, aberrant methylation was also present in leukocytes but neither in buccal swab DNA nor in skin fibroblasts. Despite mutation screening of several factors involved in establishment and maintenance of methylation marks including ZFP57, MBD3, DNMT1 and DNMT3L the molecular clue for the ICR1/ICR2 hypomethylation in our patients remained unclear. Furthermore, the reason for the development of the specific SRS phenotype is not obvious. In conclusion, our data reflect the broad range of epimutations in SRS and illustrate that an extensive molecular and clinical characterization of patients is necessary.

Submicroscopic chromosomal imbalances in idiopathic Silver-Russell syndrome (SRS): the SRS phenotype overlaps with the 12q14 microdeletion syndrome.

Silver-Russell syndrome (SRS) is a heterogeneous disorder associated with intrauterine and postnatal growth restriction, body asymmetry, a relative macrocephaly, a characteristic triangular face and further dysmorphisms. In about 50% of patients, genetic/epigenetic alterations can be detected: >38% of patients show a hypomethylation of the IGF2/H19 imprinting region in 11p15, whereas the additional 10% carry a maternal uniparental disomy of chromosome 7. In single cases, cytogenetic aberrations can be detected. Nevertheless, there still remain 50% of SRS patients without known genetic/epigenetic alterations. To find out whether submicroscopic imbalances contribute to the aetiology of SRS, 20 idiopathic SRS patients were screened with the Affymetrix GeneChip Human Mapping 500 K array set. Apart from known apathogenic copy number variations, we identified one patient with a 12q14 microdeletion. The 12q14 microdeletion syndrome is characterised by dwarfism but it additionally includes mental retardation and osteopoikilosis. The deletion in our patient is smaller than those in the 12q14 microdeletion carriers but it also affects the LEMD3 and the HMGA2 genes. LEMD3 haploinsufficiency and point mutations have been previously associated with osteopoikilosis but radiographs of our patient at the age of 16 years did not reveal any hint for osteopoikilosis lesions. Haploinsufficiency of HMGA2 is probably responsible for aberrant growth in 12q14 microdeletion syndrome. However, in this study, a general role of HMGA2 mutations for SRS was excluded by sequencing of 20 idiopathic patients. In conclusion, our results exclude a common cryptic chromosomal imbalance in idiopathic SRS patients but show that chromosomal aberrations are relevant in this disease. Thus, molecular karyotyping is indicated in SRS and should be included in the diagnostic algorithm.

Computational analysis of candidate intron regulatory elements for tissue-specific alternative pre-mRNA splicing.

Alternative pre-mRNA splicing is a major cellular process by which functionally diverse proteins can be generated from the primary transcript of a single gene, often in tissue-specific patterns. The current study investigates the hypothesis that splicing of tissue-specific alternative exons is regulated in part by control sequences in adjacent introns and that such elements may be recognized via computational analysis of exons sharing a highly specific expression pattern. We have identified 25 brain-specific alternative cassette exons, compiled a dataset of genomic sequences encompassing these exons and their adjacent introns and used word contrast algorithms to analyze key features of these nucleotide sequences. By comparison to a control group of constitutive exons, brain-specific exons were often found to possess the following: divergent 5' splice sites; highly pyrimidine-rich upstream introns; a paucity of GGG motifs in the downstream intron; a highly statistically significant over-representation of the hexanucleotide UGCAUG in the proximal downstream intron. UGCAUG was also found at a high frequency downstream of a smaller group of muscle-specific exons. Intriguingly, UGCAUG has been identified previously in a few intron splicing enhancers. Our results indicate that this element plays a much wider role than previously appreciated in the regulated tissue-specific splicing of many alternative exons.

Formation of interstrand cross-links in chloroacetaldehyde-treated DNA demonstrated by ethidium bromide fluorescence.

Chloroacetaldehyde, the stable metabolite of the human carcinogen vinyl chloride, forms interstrand cross-links in vitro in salmon sperm DNA and in the alternating copolymer, poly(deoxyadenylate-deoxythymidylate) [poly(dA-dT)]. Formation of the cross-link was a function of both time of reaction and concentration of chloroacetaldehyde. Cross-linking in chloroacetaldehyde-treated poly(dA-dT) was detected initially by changes in renaturation hysteresis [Singer et al., Carcinogenesis (Lond.), 5: 1165-1171, 1984]. This has been confirmed and quantitated using the relative fluorescence of ethidium bromide after denaturation and reannealing at 40 degrees C. Three percent cross-linking was detected after 10 min reaction with 20 mM chloroacetaldehyde at 24 degrees C. In DNA the relative fluorescence of ethidium bromide after denaturation and rapid cooling was used to estimate the number of cross-links formed. Three times as much cross-linking occurs in DNA compared to poly(dA-dT) under identical reaction conditions. The postulated structure for an interstrand cross-link in poly(dA-dT) is a hydroxyethyl bridge across the strands between the N6-amino groups of alternate adenine residues. In DNA, other amino groups in the proper configuration can be involved.

Fibers of RecA protein and complexes of RecA protein and single-stranded phi X174 DNA as visualized by negative-stain electron microscopy.

Monomers of purified RecA protein polymerize into helical fibers whose pitch is 7.2 nm to 7.5 nm and whose diameter is 11 nm. Either short (approximately 0.2 micron), single fibers, or bundles of aligned, longer fibers, can be formed preferentially, by varying the Mg2+ concentration. When RecA protein is bound to circular, single-stranded phi X174 DNA it forms helical fibers of different classes of contour lengths, ranging from 0.98 micron, depending upon the conditions of assembly. Two different helical pitches are found, one of 9.3 nm when the incubation buffer contains, besides the obligatory Mg2+, either ATP gamma S or ATP accompanied by single-strand binding protein, and one of 5.5 nm when the latter additives are omitted. Preformed fibers of the compact type can be converted to open ones of 9.3 nm pitch upon addition of ATP gamma S, even after the removal of unbound RecA. All signs of helicity are obliterated upon glutaraldehyde cross-linking except in those fibers whose assembly has been mediated by ATP gamma S. RecA protein and single-strand binding protein are competitively bound to single-stranded DNA. Composite complexes, however, are not encountered unless ATP gamma S is present. Otherwise, segments of DNA that are coated by one or the other protein are seen as separate regions. When the assembly of complexes of single-stranded DNA and RecA is mediated by single-strand binding protein and ATP, the axial separation between successive bases is 0 X 42 nm, somewhat greater than the axial distance between bases in one strand of duplex DNA in the B form. It is proposed that the bases of the single-stranded DNA in the complex are located near its inner surface, and that base-pairing with double-stranded DNA takes place following invasion of the central cavity of the complex.

Corporate travel medicine: benefit analysis of on-site services.

BACKGROUND: Corporations with employees who travel internationally address their travel-related medical needs in a variety of ways. Options utilized include corporate medical departments, local health departments, and local clinics, both contracted and independent. METHODS: A travel clinic at a university medical center routinely provided preventive travel medicine services for many of the local companies. Two of these companies had on-site medical clinics which routinely saw patients for occupational and personal health reasons. At these companies , the university travel clinic assisted in moving employee travel medicine services to the on-site clinic. Direct and indirect costs for new, predeparture employee travel care at each company were compared before, and after, the move on-site. RESULTS: When measured per patient, total cost savings associated with the on-site travel clinic were greater than 15% at both companies (17%, 25%), primarily due to the value of the employees' time saved with decreased travel. Utilization increased at one company by 24% over the first 8 months and lead to higher overall cost, but this cost increase was only 4%. Informal assessments of the value of the on-site service at both companies was uniformly positive. CONCLUSION: For certain corporate settings, on-site clinics may be effective ways of providing travel medicine services.

Emerging technologies from the Human Genome Project for understanding susceptibility and risk.

The new technologies from the Human Genome Program provide exceptional opportunities for surveying and measuring human exposure, as well as determining susceptibility on an individual-by-individual basis. These new technologies will soon enable rapid screening of populations at risk, as well as the broader public, for a variety of genes known to be associated with increased risk. These include specific oncogenes, tumor suppressor genes and DNA repair enzymes. Use of these technologies also presents a number of ethical issues, both in screening and in use of the information about individuals. Overall, the use of rapid genotyping technologies will introduce a specificity and possible group identifiers that will present new challenges to the determination of risk within the EPA mandate.

Overcoming an autistic child's failure to acquire a tact repertoire.

A 6-year-old nonvocal autistic girl who had acquired over 30 signs as mands (requests), simple intraverbals (English-sign translations), and imitative responses repeatedly failed to acquire a tact (labeling) repertoire. It was speculated that the verbal stimulus "What is that?" blocked the establishment of stimulus control by nonverbal stimuli. When procedures to transfer stimulus control from verbal to nonverbal stimuli were implemented, the subject quickly learned to tact all 18 target stimuli.

Haploinsufficiency of ANKRD11 (16q24.3) Is Not Obligatorily Associated with Cognitive Impairment but Shows a Clinical Overlap with Silver-Russell Syndrome.

Microdeletions in 16q24.3 are associated with intellectual disability and a specific phenotype, e.g. short stature and a prominent forehead. The 16q24.3 microdeletion syndrome shows a broad phenotypic overlap with the KBG syndrome, which is caused by mutations within the ANKRD11 gene. Furthermore, both KBG and the 16q24.3 microdeletion syndromes show clinical findings reminiscent of Silver-Russell syndrome (SRS), an imprinting disorder characterized by severe primordial growth retardation. In a cohort of patients referred as SRS, we previously identified a 16q24.3 deletion, but at that time, only patients with larger imbalances in 16q24.3 and intellectual disability had been published. Considering the recent description of the ANKRD11 gene as the causative factor for the 2 16q24.3-associated disorders, we now classified our patient as a 16q24.3 microdeletion syndrome patient exhibiting some characteristic features but normal intelligence. Our case illustrates the broad clinical spectrum associated with microdeletions, and we confirm that the 16q24.3 microdeletion syndrome is a further microdeletion syndrome with very variable expressivity. Indeed, our case is the first 16q24.3 patient of normal intelligence, but we assume that this variant is present in further mentally healthy probands which have not yet been tested. In conclusion, the detection of the 16q24.3 deletion in a proband of unremarkable intellectual capacities once again illustrates the need to perform molecular karyotyping in dysmorphic patients with normal intelligence.

Transcriptional errors and ambiguity resulting from the presence of 1,N6-ethenoadenosine or 3,N4-ethenocytidine in polyribonucleotides.

1,N6-Ethenoadenosine (epsilon A) and 3,N4-Ethenocytidine (epsilon C) in copolymers with unmodified nucleosides were transcribed using DNA-dependent RNA polymerase in the presence of Mn2+. Nearest neighbor analysis of the products showed that epsilon A directed incorporation of A much greater than U greater than C while epsilon C directed the incorporation of U greater than or equal to A much greater than C Neither directed G into the complementary polymer. Such misincorporations resulting from epsilon A and epsilon C, compounds that are formed in vivo by the carcinogen vinyl chloride, may have a biological role as promutagens.

Effect of tautomeric shift on mutation: N4-methoxycytidine forms hydrogen bonds with adenosine in polymers.

N4-Methoxycytidine (mo4C), previously found to act only as uridine (U) in transcription [Singer, B., & Spengler, S. (1981) Biochemistry 20, 1127], was tested for its ability to base pair as U in copolymers of (U,mo4C) annealed with poly(A) or transcribed with ATP and DNA-dependent RNA polymerase. Mixing curves have now indicated that the derivative is retained in a poly(U,39% mo4C).poly(A) helix, unlike unmodified C in poly(U,35% C). The presence of 13-39% mo4C in U polymers lowered the melting temperature, Tm, observed in annealed complexes both with poly(A) and after transcription with ATP. However, complexes isolated after transcription had a large hyperchromicity and melted cooperatively, which indicated that they are hydrogen bonded. The decreased Tm for poly(U,mo4C).poly(A) compared to that for poly(U).poly(A) can be attributed to stacking changes and adjacent base-pair disruption by mo4C. The greater cooperative melting of transcribed poly(U,39% mo4C) as compared to the annealed complex may indicate that the methoxy substituent is normally a mixture of rotamers and that the syn rotamer is required for transcription. The interference of the methoxy substituent was also shown by the loss of helix formation by poly(C,mo4C) in acid solution. mo4C decreased the Tm much more than A, which stacks well in acid. U, which neither stacks nor participates in an acid structure, caused more distortion than either of the other bases. It is inferred that mo4C has the base-pairing ability of U but that the planarity of the substituent is lost.