Excited state intramolecular proton transfer (ESIPT) and subsequent intramolecular charge transfer (ICT) dynamics of a 2-(2'-hydroxyphenyl)benzoxazole derivative conjugated with an electron withdrawing group (HBOCE) in solutions and a polymer film has been investigated by femtosecond time-resolved fluorescence (TRF) and TRF spectra measurements without the conventional spectral reconstruction method. TRF with high enough resolution (<100 fs) reveals that the ESIPT dynamics of HBOCE in liquids proceeds by at least two time constants of approximately 250 fs and approximately 1.2 ps. The relative amplitude of the slower picosecond component is smaller in the polymer film than that in solution. Conformational heterogeneity in the ground state originating from the dispersion of the dihedral angle between the phenolic and benzoxazole groups is invoked to account for the dispersive ESIPT dynamics in liquids. From the TRF spectra of both the enol and keto isomers, we have identified the ICT reaction of the keto isomer occurring subsequent to the ESIPT. The ICT proceeds also by two time constants of near instantaneous and 2.7 ps. Since the ICT dynamics of HBOCE is rather close to the polar solvation dynamics, we argue that the ICT is barrierless and determined mostly by the solvent fluctuation.

OBJECTIVE

Tocotrienols and tocopherols are members of the vitamin E family, with similar structures; however, only tocotrienols have been reported to achieve potent anti-cancer effects. The study described here has evaluated anti-cancer activity of vitamin E to elucidate mechanisms of cell death, using human breast cancer cells.

METHODS

Anti-cancer activity of a tocotrienol-rich fraction (TRF) and a tocotrienol-enriched fraction (TEF) isolated from palm oil, as well as pure vitamin E analogues (α-tocopherol, α-, δ- and γ-tocotrienols) were studied using highly aggressive triple negative MDA-MB-231 cells and oestrogen-dependent MCF-7 cells, both of human breast cancer cell lines. Cell population growth was evaluated using a Coulter particle counter. Cell death mechanism, poly(ADP-ribose) polymerase cleavage and levels of NF-κB were determined using commercial ELISA kits.

RESULTS

Tocotrienols exerted potent anti-proliferative effects on both types of cell by inducing apoptosis, the underlying mechanism of cell death being ascertained using respective IC50 concentrations of all test compounds. There was marked induction of apoptosis in both cell lines by tocotrienols compared to treatment with Paclitaxel, which was used as positive control. This activity was found to be associated with cleavage of poly(ADP-ribose) polymerase (a DNA repair protein), demonstrating involvement of the apoptotic cell death signalling pathway. Tocotrienols also inhibited expression of nuclear factor kappa-B (NF-κB), which in turn can increase sensitivity of cancer cells to apoptosis.

CONCLUSIONS

Tocotrienols induced anti-proliferative and apoptotic effects in association with DNA fragmentation, poly(ADP-ribose) polymerase cleavage and NF-κB inhibition in the two human breast cancer cell lines.

We previously presented the YM500 database, which contains >8000 small RNA sequencing (smRNA-seq) data sets and integrated analysis results for various cancer miRNome studies. In the updated YM500v3 database (http://ngs.ym.edu.tw/ym500/) presented herein, we not only focus on miRNAs but also on other functional small non-coding RNAs (sncRNAs), such as PIWI-interacting RNAs (piRNAs), tRNA-derived fragments (tRFs), small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs). There is growing knowledge of the role of sncRNAs in gene regulation and tumorigenesis. We have also incorporated >10 000 cancer-related RNA-seq and >3000 more smRNA-seq data sets into the YM500v3 database. Furthermore, there are two main new sections, 'Survival' and 'Cancer', in this updated version. The 'Survival' section provides the survival analysis results in all cancer types or in a user-defined group of samples for a specific sncRNA. The 'Cancer' section provides the results of differential expression analyses, miRNA-gene interactions and cancer miRNA-related pathways. In the 'Expression' section, sncRNA expression profiles across cancer and sample types are newly provided. Cancer-related sncRNAs hold potential for both biotech applications and basic research.

BACKGROUND

Telomere signaling plays a role in regulating cardiomyocyte apoptosis during cardiac dysfunction. In this study, we investigated the effects of epigallocatechin gallate (EGCG), the major component of polyphenols in green tea, on telomere dependent apoptotic signal in pressure overload cardiac hypertrophy.

RESULTS

Cardiac hypertrophy in rats was established by abdominal aortic constriction (AC). EGCG 50, 100 mg/kg, quercetin (Que) 100mg/kg, captopril (Cap) 50mg/kg, losartan (Los) 30 mg/kg and carvedilol (Carv) 30 mg/kg was intragastrically administered for 6 weeks. Three, five and 7 weeks after aortic constriction, the heart weight indices increased progressively. Malondialdehyde (MDA) contents progressively increased, while superoxide dismutase (SOD) activities decreased. Progressive cardiomyocyte apoptosis and telomere attrition were also found. Although no significant alteration of telomerase reverse transcriptase (TERT) mRNA was found till 7 weeks after aortic constriction, progressive upregulation of p53, c-myc and downregulation of bcl-2, telomere repeat-binding factor 2(TRF(2)) were seen. EGCG, quercetin, captopril, losartan and carvedilol markedly reduced heart weight indices and apoptotic cardiomyocyte in hypertrophic myocardium, but they had different effects on apoptotic related proteins bcl-2, p53 and c-myc. EGCG, quercetin and carvedilol, have potent antioxidant effects as evidenced by reduction of MDA contents and resumption of SOD activities. EGCG, quercetin and carvedilol could prevent telomere attrition and telomere repeat-binding factor 2 (TRF(2)) loss remarkably, whereas captopril and losartan had no effect on oxidative stress and telomere signal.

CONCLUSIONS

Pressure overload induced cardiac hypertrophy initiates oxidative stress, induces telomere repeat-binding factor 2 loss and accelerates telomere shortening in hypertrophic myocardium. EGCG, quercetin and carvedilol with potent antioxidant effect, may inhibit cardiac myocyte apoptosis by preventing telomere shortening and telomere repeat-binding factor 2 (TRF(2)) loss.

BACKGROUND

Diagonal earlobe crease (ELC) have been proposed as a marker of generalized atherosclerosis, so in the present study it was investigated whether individuals with ELC have a shortened telomere, which correlates with an accelerated cell turnover and premature aging, leading to atherosclerosis.

RESULTS

The mean terminal restriction fragment (TRF) was determined by Southern blot hybridization in the peripheral blood cells of 34 male Japanese patients with metabolic syndrome (MetS) who were under 70 years of age with (n=17) and without (n=17) bilateral ELC, and assessed the relationship of ELC to atherosclerotic cardiovascular disease (AVD). The results showed that the TRF was shorter in the MetS patients with ELC in comparison to age- and risk-factor-matched MetS patients without ELC (7.6+/-1.1 kbp vs 8.6+/-1.2 kbp; P<0.05). ELC were present in 13 patients in the AVD group (n=18), but only 4 patients in the non-AVD group (n=16) had ELC (72.2% and 25% respectively; P<0.05).

CONCLUSIONS

These findings suggest that ELC is a useful dermatological indicator of an accelerated aging process, as suggested by excessive telomere loss, and might be a useful indirect marker of high-risk patients.

OBJECTIVE

To assess psychological and social functioning and health related quality of life and its early determinants in children born with congenital diaphragmatic hernia (CDH).

METHODS

Cross-sectional follow-up study.

METHODS

Outpatient clinic of a tertiary care hospital.

METHODS

33 CDH survivors aged 6-16 years.

METHODS

Patients who developed CDH associated respiratory distress within 24 h after birth.

METHODS

Psychological and social functioning assessed with the Wechsler Intelligence Scale for Children (WISC-R), Bourdon-Vos test, Beery Developmental Test of Visual Motor Integration, Child Behavior Checklist (CBCL) and Teacher Report Form (TRF), and health related quality of life assessed with the Child Health Questionnaire (CHQ) and Health Utilities Index (HUI).

RESULTS

Normal mean (SD) total IQ (100.0 (13.2)) and normal visual-motor integration, but significantly lower results for sustained attention (Bourdon-Vos test, 38.8 (11.2) points) were found. Learning difficulties were reported by 30% of parents. Eight children had scores in the clinical range on the CBCL and/or TRF, indicating clinically significant behavioural problems. Except for the CHQ scale General Health, health status was not different from the reference population. No significant correlations between test results and severity of CDH were found, except for an association of general health and physical functioning with length of hospital stay.

CONCLUSIONS

CDH patients are at risk for subtle cognitive and behavioural problems, probably not related to CDH severity. Perception of general health is reduced compared to the reference population, indicating that CDH survivors and their parents believe their health is poor and likely to get worse.

Dissolved inorganic nitrogen (DIN) uptake by marine heterotrophic bacteria has important implications for the global nitrogen (N) and carbon (C) cycles. Bacterial nitrate utilization is more prevalent in the marine environment than traditionally thought, but the taxonomic identity of bacteria that utilize nitrate is difficult to determine using traditional methodologies. (15) N-based DNA stable isotope probing was applied to document direct use of nitrate by heterotrophic bacteria on the West Florida Shelf. Seawater was incubated in the presence of 2 μM (15) N ammonium or (15) N nitrate. DNA was extracted, fractionated via CsCl ultracentrifugation, and each fraction was analyzed by terminal restriction fragment length polymorphism (TRFLP) analysis. TRFs that exhibited density shifts when compared to controls that had not received (15) N amendments were identified by comparison with 16S rRNA gene sequence libraries. Relevant marine proteobacterial lineages, notably Thalassobacter and Alteromonadales, displayed evidence of (15) N incorporation. RT-PCR and functional gene microarray analysis could not demonstrate the expression of the assimilatory nitrate reductase gene, nasA, but mRNA for dissimilatory pathways, i.e. nirS, nirK, narG, nosZ, napA, and nrfA was detected. These data directly implicate several bacterial populations in nitrate uptake, but suggest a more complex pattern for N flow than traditionally implied.

Chronic myeloid leukemia (CML) is triggered by the BCR-ABL oncogene. Imatinib is the first-line treatment of CML; however imatinib resistance and intolerance have been detected in many patients. Therefore, new therapeutic approaches are required. The present work aimed at the development and application of transferrin receptor (TrfR) targeted liposomes co-encapsulating anti-BCR-ABL siRNA and imatinib at different molar ratios. The encapsulation yields and drug loading of each molecule was evaluated. Anti-leukemia activity of the developed formulations co-encapsulating siRNA and imatinib and of the combination of Trf-liposomes carrying siRNA and free imatinib under two different treatment schedules of pre-sensitization was assessed. The results obtained demonstrate that the presence of imatinib significantly decreases the encapsulation yields of siRNA, whereas imatinib encapsulation yields are increased by the presence of siRNA. Cytotoxicity assays demonstrate that the formulations co-encapsulating siRNA and imatinib promote a 3.84-fold reduction on the imatinib IC(50) (from 3.49 to 0.91 µM), whereas a 8.71-fold reduction was observed for the pre-sensitization protocols (from 42.7 to 4.9 nM). It was also observed that the formulations with higher siRNA to imatinib molar ratios promote higher cell toxicity. Thus, the present work describes a novel triple targeting strategy with one single system: cellular targeting (through the targeting ligand, transferrin) and molecular targeting at the BCR-ABL mRNA and Bcr-Abl protein level.

OBJECTIVE

To describe behavioural and emotional symptoms among Icelandic preschool children with cerebral palsy (CP).

METHODS

Children with congenital CP, assessed with the Child Behavior Checklist/1½-5 (CBCL/1½-5) and Caregiver-Teacher Report Form (C-TRF), were enrolled in the study. A comparison group was recruited from the general population. Thirty-six children (53% males) with CP were assessed at a mean age of 4 years 11 months (SD 5 mo, range 4-6 y); 26 (72%) had bilateral distribution of symptoms and 32 (89%) had spastic CP. Thirty (83%) were at Gross Motor Function Classification System levels I or II and six at levels III or IV. For comparison, 110 (43% males) and 120 (48% males) children were assessed with the CBCL/1½-5 and the C-TRF respectively, at a mean age of 4 years 6 months (SD 6 mo, range 4-6 y).

RESULTS

Sixteen children (48%) with CP had high scores on total problems scale of the CBCL/1½-5 and 20 (65%) on the C-TRF compared with 18% of the comparison group, both on the CBCL/1½-5 and the C-TRF (p<0.001). Children with CP had higher scores on all subscales of the CBCL/1½-5 and the C-TRF, except somatic complaints. Attention difficulties, withdrawn, aggressive behaviour, and anxious/depressed symptoms were most pronounced among children with CP.

CONCLUSIONS

A large proportion of preschool children with CP have substantial behavioural and emotional difficulties, which need to be addressed in their treatment.

OBJECTIVE

To investigate whether telomere shortening may play a role in senescence of the placenta.

METHODS

Villous tissue was collected from single, random sites of full-term placentas (39-41 weeks of gestation; n=10) as well as multiple, specific sites of the same placenta (39-41 weeks of gestation; n=5). For the latter group of placentas, samples were taken near the umbilical cord and at the periphery on both the maternal and fetal sides (a total of 4 samples per placenta). Cord blood samples were also obtained from all placental donors. Telomerase activity was assessed by the TRAP assay, and telomere length measured by Southern analysis of mean terminal restriction fragment (TRF) length.

RESULTS

We show for the first time that telomeres are longer ( approximately 25% longer; P<0.001) in placenta tissue than in cord blood from the same donor.

CONCLUSIONS

Telomere shortening is unlikely to have a significant role in senescence or terminal maturation of the placenta.

Global spread and evolutionary links of an epidemic Clostridium difficile strain (PCR-ribotype 027) have been noted in recent decades. However, in Japan, no outbreaks caused by type 027 have been reported to date. A total of 120 C. difficile isolates from patients at 15 hospitals during non-outbreak seasons between 2011 and 2013 as well as 18 and 21 isolates collected from two hospitals in 2010 and 2009, respectively, in outbreak periods in Japan, were examined. Among these 120 isolates, Japan-ribotypes smz and ysmz (subtype variant of smz) were the most predominant (39.2 %) followed by Japan-ribotype trf (15.8 %). Types smz/ysmz and trf were also concurrently predominant at two hospitals in the outbreak settings. Out of the five binary toxin-positive isolates observed, only one was PCR-ribotype 027 and another PCR-ribotype 078. Type smz was later found to correspond to PCR-ribotype 018. High rates of resistance against gatifloxacin, moxifloxacin, erythromycin and clindamycin were observed in the PCR-ribotype 018 isolates. Interestingly, all trf isolates were toxin A-negative, toxin B-positive, but they did not correspond to PCR-ribotype 017, thus being assigned a new ribotype (PCR-ribotype 369). In conclusion, PCR-ribotypes 018 (smz) and 369 (trf) were identified as major circulating strains in both outbreak and non-outbreak settings in Japan. Given their epidemiological relevance, molecular investigations are warranted to clarify potential evolutionary links with related strains found elsewhere, such as PCR-ribotypes 018 and 017 from Europe and North America.

Bifidobacteria are intestinal anaerobes often associated with gut health. Specific bifidobacterial species are particularly common in the gastrointestinal tract of breast-fed infants. Current short read next-generation sequencing approaches to profile fecal microbial ecologies do not discriminate bifidobacteria to the species level. Here we describe a low-cost terminal restriction fragment length polymorphism (TRFLP) procedure to distinguish between the common infant-associated bifidobacterial species. An empirical database of TRF sizes was created from both common reference strains and well-identified isolates from infant feces. Species-specific quantitative PCR validated bifidobacterial-specific TRFLP profiles from infant feces. These results indicate that bifidobacterial-specific TRFLP is a useful method to monitor intestinal bifidobacterial populations from infant fecal samples. When used alongside next generation sequencing methods that detect broader population levels at lower resolution, this high-throughput, low-cost tool can help clarify the role of bifidobacteria in health and disease.

tRNA-derived fragments (tRF) are a class of potent regulatory RNAs. We mined the datasets from The Cancer Genome Atlas (TCGA) representing 32 cancer types with a deterministic and exhaustive pipeline for tRNA fragments. We found that mitochondrial tRNAs contribute disproportionally more tRFs than nuclear tRNAs. Through integrative analyses, we uncovered a multitude of statistically significant and context-dependent associations between the identified tRFs and mRNAs. In many of the 32 cancer types, these associations involve mRNAs from developmental processes, receptor tyrosine kinase signaling, the proteasome, and metabolic pathways that include glycolysis, oxidative phosphorylation, and ATP synthesis. Even though the pathways are common to multiple cancers, the association of specific mRNAs with tRFs depends on and differs from cancer to cancer. The associations between tRFs and mRNAs extend to genomic properties as well; specifically, tRFs are positively correlated with shorter genes that have a higher density in repeats, such as ALUs, MIRs, and ERVLs. Conversely, tRFs are negatively correlated with longer genes that have a lower repeat density, suggesting a possible dichotomy between cell proliferation and differentiation. Analyses of bladder, lung, and kidney cancer data indicate that the tRF-mRNA wiring can also depend on a patient's sex. Sex-dependent associations involve cyclin-dependent kinases in bladder cancer, the MAPK signaling pathway in lung cancer, and purine metabolism in kidney cancer. Taken together, these findings suggest diverse and wide-ranging roles for tRFs and highlight the extensive interconnections of tRFs with key cellular processes and human genomic architecture. SIGNIFICANCE: Across 32 TCGA cancer contexts, nuclear and mitochondrial tRNA fragments exhibit associations with mRNAs that belong to concrete pathways, encode proteins with particular destinations, have a biased repeat content, and are sex dependent.

It has been known that mature transfer RNAs (tRNAs) that are encoded in the nuclear genome give rise to short molecules, collectively known as tRNA fragments or tRFs. Recently, we reported that, in healthy individuals and in patients, tRFs are constitutive, arise from mitochondrial as well as from nuclear tRNAs, and have composition and abundances that depend on a person's sex, population origin and race as well as on tissue, disease and disease subtype. Our findings as well as similar work by other groups highlight the importance of tRFs and presage an increase in the community's interest in elucidating the roles of tRFs in health and disease.

We created MINTbase, a web-based framework that serves the dual-purpose of being a content repository for tRFs and a tool for the interactive exploration of these newly discovered molecules. A key feature of MINTbase is that it deterministically and exhaustively enumerates all possible genomic locations where a sequence fragment can be found and indicates which fragments are exclusive to tRNA space, and thus can be considered as tRFs: this is a very important consideration given that the genomes of higher organisms are riddled with partial tRNA sequences and with tRNA-lookalikes whose aberrant transcripts can be mistaken for tRFs. MINTbase is extremely flexible and integrates and presents tRF information from multiple yet interconnected vantage points ('vistas'). Vistas permit the user to interactively personalize the information that is returned and the manner in which it is displayed. MINTbase can report comparative information on how a tRF is distributed across all anticodon/amino acid combinations, provides alignments between a tRNA and multiple tRFs with which the user can interact, provides details on published studies that reported a tRF as expressed, etc. Importantly, we designed MINTbase to contain all possible tRFs that could ever be produced by mature tRNAs: this allows us to report on their genomic distributions, anticodon/amino acid properties, alignments, etc. while giving users the ability to at-will investigate candidate tRF molecules before embarking on focused experimental explorations. Lastly, we also introduce a new labeling scheme that is tRF-sequence-based and allows users to associate a tRF with a universally unique label ('tRF-license plate') that is independent of a genome assembly and does not require any brokering mechanism.

MINTbase is freely accessible at http://cm.jefferson.edu/MINTbase/. Dataset submissions to MINTbase can be initiated at http://cm.jefferson.edu/MINTsubmit/

isidore.rigoutsos@jefferson.edu

Supplementary data are available at Bioinformatics online.

BACKGROUND

Psychometric instruments are used increasingly within research and clinical settings, and therefore standardization has become an important prerequisite, even for investigating very young children. Currently, there are no standardized psychometric instruments available for assessment of preschool children in Denmark.

OBJECTIVE

The aim was to achieve Danish national norm scores for the Child Behavior Checklist for Ages 1(1/2)-5 (CBCL/1(1/2)-5) and the Caregiver Report Form (C-TRF).

METHODS

The study was based on an age- and gender-stratified cohort sample of 1750 children aged 1(1/2)-5 years born at Aarhus University Hospital, Denmark. The CBCL/1(1/2)-5 and C-TRF were mailed to parents, who were asked to pass on the C-TRF to the preschool caregiver. The national standard register data gave access to information on socio-economic status, family type, ethnicity and parental educational level for analysis of participation and representation.

RESULTS

A total number of 850 (49%) families replied, and 624 caregivers replied. The mean Total Problem Score (TPS) with 95% confidence interval was 17.3 (16.3-18.3) for parents' reports. Age-and gender-specific scale score findings for Danish preschoolers and schoolchildren were comparable. No differences were found in the mean TPS within subgroups related to parental socio-demographic features.

CONCLUSIONS

On the basis of a large sample, Danish national norm scores and profiles of the ASEBA Preschool Forms were established; the scores of descendents must, however, be assessed with some caution. With this reservation, the CBCL/1(1/2)-5 and C-TRF forms are now available in Danish and can be recommended for use in clinical and research settings.

UNASSIGNED

The manuscript by Alves et al. entitled "Genome-wide identification and characterization of tRNA-derived RNA fragments in land plants" describes the identification and characterization of tRNAderived sRNA fragments in plants. By combining bioinformatic analysis and genetic and molecular approaches, we show that tRF biogenesis does not rely on canonical microRNA/siRNA processing machinery (i.e., independent of DICER-LIKE proteins). Moreover, we provide evidences that the Arabidopsis S-like Ribonuclease 1 (RNS1) might be involved in the biogenesis of tRFs. Detailed analyses showed that plant tRFs are sorted into different types of ARGONAUTE proteins and that they have potential target candidate genes. Our work advances the understanding of the tRF biology in plants by providing evidences that plant and animal tRFs shared common features and raising the hypothesis that an interplay between tRFs and other sRNAs might be important to fine-tune gene expression and protein biosynthesis in plant cells. Small RNA (sRNA) fragments derived from tRNAs (3'-loop, 5'-loop, anti-codon loop), named tRFs, have been reported in several organisms, including humans and plants. Although they may interfere with gene expression, their biogenesis and biological functions in plants remain poorly understood. Here, we capitalized on small RNA sequencing data from distinct species such as Arabidopsis thaliana, Oryza sativa, and Physcomitrella patens to examine the diversity of plant tRFs and provide insight into their properties. In silico analyzes of 19 to 25-nt tRFs derived from 5' (tRF-5s) and 3'CCA (tRF-3s) tRNA loops in these three evolutionary distant species showed that they are conserved and their abundance did not correlate with the number of genomic copies of the parental tRNAs. Moreover, tRF-5 is the most abundant variant in all three species. In silico and in vivo expression analyses unraveled differential accumulation of tRFs in Arabidopsis tissues/organs, suggesting that they are not byproducts of tRNA degradation. We also verified that the biogenesis of most Arabidopsis 19-25 nt tRF-5s and tRF-3s is not primarily dependent on DICER-LIKE proteins, though they seem to be associated with ARGONAUTE proteins and have few potential targets. Finally, we provide evidence that Arabidopsis ribonuclease RNS1 might be involved in the processing and/or degradation of tRFs. Our data support the notion that an interplay between tRFs and other sRNAs might be important to fine tune gene expression and protein biosynthesis in plant cells.

RNA fragments deriving from tRNAs (tRFs) exist in all branches of life and the repertoire of their biological functions regularly increases. Paradoxically, their biogenesis remains unclear. The human RNase A, Angiogenin, and the yeast RNase T2, Rny1p, generate long tRFs after cleavage in the anticodon region. The production of short tRFs after cleavage in the D or T regions is still enigmatic. Here, we show that the Arabidopsis Dicer-like proteins, DCL1-4, do not play a major role in the production of tRFs. Rather, we demonstrate that the Arabidopsis RNases T2, called RNS, are key players of both long and short tRFs biogenesis. Arabidopsis RNS show specific expression profiles. In particular, RNS1 and RNS3 are mainly found in the outer tissues of senescing seeds where they are the main endoribonucleases responsible of tRNA cleavage activity for tRFs production. In plants grown under phosphate starvation conditions, the induction of RNS1 is correlated with the accumulation of specific tRFs. Beyond plants, we also provide evidence that short tRFs can be produced by the yeast Rny1p and that, in vitro, human RNase T2 is also able to generate long and short tRFs. Our data suggest an evolutionary conserved feature of these enzymes in eukaryotes.

The Child Behavior Checklist's (CBCL) applicability to a sample of 105 Russian 9- and 10-year-old children was evaluated by examining the internal consistency of Russian adaptations of parent and teacher report forms. In addition, child behavior scores were correlated with child report of internalizing symptoms and maternal reports of their own internalizing symptoms and general family functioning. Finally, rates of child behavior problems and patterns of interrater agreement were compared with U.S. normative data. The psychometric properties of the adaptations demonstrate the adequacy of these instruments for use in Russia. Internal consistency and interrater agreement were generally comparable to estimates obtained in U.S. normative samples. Further, an exploration of the construct validity of the Russian versions of the CBCL and Teacher Report Form (TRF) lends additional support to the adequacy of these instrument.

Data are collected with the Child Behavior Check List (CBCL) as well as with the Teacher Report Form (TRF) of 40 VCFS children between 4 and 18 years of age. Half of the group shows very high problem scores in the "clinical" range. The average T-score of the VCFS children as a group are over 60 (one standard deviation above the mean) for the "total problem score" and the "internalising score". The highest scores with the subscales are found with "withdrawn" and "social problems". But also "thought problems" and "attention problems" score over 60. The VCFS children show more behavior problems and personality problems than the matched control children with a craniofacial anomaly. The differences are highly statistically significant.

Fc fragments of human IgG stimulate both proliferation and polyclonal antibody formation by B lymphocytes. T lymphocytes, although not proliferating in response to Fc fragments, are triggered to produce a T cell-replacing factor, which substitutes for T cells in the Fc fragment-induced polyclonal response. The factor is produced within 24 hr after Fc stimulation. Neither Fab fragments nor whole IgG have the capacity to stimulate the release of this activity. This material is a product of Lyt 1+23-, Ia-T lymphocytes and requires Ia+ adherent accessory cells for production. The role of the accessory cell is to process the Fc fragments to biologically active 14,000-daltons subfragments, which directly trigger T cells to factor production. This material has been called (Fc)TRF to distinguish it from other T cell factors.

Leukocyte telomere length (LTL) shortens with age and is potentially a biomarker of human aging. We examined the relation of LTL with physical ability and cognitive function in 548 same-sex twins from the Longitudinal Study of Aging Danish Twins. LTL was measured by Southern blots of the terminal restriction fragments (TRF). Physical ability was evaluated using a self reported scale of 11 questions, while cognitive function was scored by MMSE and a cognitive composite score sensitive to age-related decline. A random intercept model revealed a positive, significant association between LTL and physical ability. For every unit increase in physical ability score, LTL increased by 0.066 kb (p = 0.01), equal to approximately three years of age-dependent LTL shortening. A matched case-co-twin design showed that the group consisting of the twins from each pair with the longer LTL also displayed better physical ability (p < 0.01). Moreover, the intra-pair difference in LTL was associated with intra-pair difference in physical ability (p < 0.01), confirming the association. However, we found no association between cognitive function and LTL. The LTL-physical ability association in the elderly provides further support to the premise that LTL is an index of somatic fitness in the narrow context of human physical health.

BACKGROUND

Recent data suggest that children with new-onset seizures may be at increased risk for behaviour problems. Teachers are an excellent source of data about such problems. They do not have the potential bias that a parent worried about a new onset of seizures might have and, furthermore, they are accustomed to comparing performance of children and work in an environment in which the behavioural problems associated with epilepsy may be quite evident. We obtained teachers' reports of behaviour problems in children in the 2 months prior to their first recognized seizure. We also obtained similar data on children with new-onset, moderate severity asthma. In addition to comparing behavioural scores between children with seizures and children with asthma, we compared teachers' assessments of behaviour in children with no prior seizures to those of children with previously unrecognized seizures.

METHODS

We evaluated 192 children with new-onset seizures, including 129 children with no prior episodes and 63 children with recognized prior seizure-like episodes. The comparison group consisted of 78 children with new-onset, moderate severity asthma. Behaviour was assessed by the teacher's report form (TRF) of the child behaviour checklist (CBCL) or the caregiver-teacher report form for ages 2-5 (C-TRF). Mean scores were compared by two-sample t -tests and analysis of variance (ANOVA).

RESULTS

The children with new-onset seizures had more thought problems than children with asthma. In comparison to children with no prior seizures, the children with prior unrecognized seizures had higher scores in total behaviour problems, internalizing problems, somatic complaints, anxious/depressed, thought problems, and attention problems.

CONCLUSIONS

In this sample, children with prior unrecognized seizures were already at increased risk of teacher-rated behaviour problems before starting medication and before any possible stigma effects related to seizures. This sequence suggests underlying neurological problems causing both behavioural problems and seizures.

The association between behaviour problems and dyslexia was assessed in a population sample of 10- to 12-year-old children. Twenty-five dyslexic children and a matched control group were recruited through a screening in primary schools in the city of Bergen, Norway. For the assessment of behaviour problems the Child Behavior Checklist (CBCL), Teacher Self Report (TRF), and Youth Self Report (YSR) were filled out by parents, teachers, and children, respectively. Information on health and developmental factors were obtained from parents on a separate questionnaire designed for the study. The dyslexic group had significantly more behaviour problems than the control group according to both the CBCL and the TRF. On the YSR there was no significant difference between the groups. Dyslexic children had higher CBCL and TRF scores on the Total Behaviour Problem scale, the Internalizing and Externalizing subdomains, and the Attention problem subscale. The groups differed in social background, prenatal risk factors, birth weight, preschool language problems, and IQ, but these variables showed no relationship to the level of behaviour problems in the present sample. We conclude that pre-adolescent dyslexic children show a wide range of behaviour problems that cannot be attributed to social or developmental background variables.