Child physical abuse - High school students' mental health and parental relations depending on who perpetrated the abuse.

The aim of this study was to contribute to the research of child physical abuse (CPA) by examining if there were any differences in high school students' mental health (in this study symptoms of depression and anxiety, self-esteem and sense of coherence) and/or, in how they perceive their parents, depending on whether or not they had been subjected to CPA during childhood. In addition, if high school students reported different mental health and/or, relationships with their parents, depending on if their mother, father or both parents were the perpetrators of CPA. A representative national sample of high school students (N=3288, data collected 2009) participated in the study. Participants completed the following: questions about CPA and alleged perpetrators, the Hopkins Symptom Checklist, Rosenberg Self-Esteem Scale, the Sense of Coherence Scale and Parental Bonding Instrument. The results showed students who reported experiences of CPA were more likely to report symptoms of mental illness and negative perceptions of their parents' parenting. However, there were no mental health differences depending on whether their mother, father or both parents were the perpetrators of CPA. Still, there were differences in perceived parenting indicating that mothers' parenting was perceived as more negative when mothers only or both parents were perpetrators of the abuse than when only fathers were perpetrators.

Identification of new TRIP12 variants and detailed clinical evaluation of individuals with non-syndromic intellectual disability with or without autism.

The ubiquitin pathway is an enzymatic cascade including activating E1, conjugating E2, and ligating E3 enzymes, which governs protein degradation and sorting. It is crucial for many physiological processes. Compromised function of members of the ubiquitin pathway leads to a wide range of human diseases, such as cancer, neurodegenerative diseases, and neurodevelopmental disorders. Mutations in the thyroid hormone receptor interactor 12 (TRIP12) gene (OMIM 604506), which encodes an E3 ligase in the ubiquitin pathway, have been associated with autism spectrum disorder (ASD). In addition to autistic features, TRIP12 mutation carriers showed intellectual disability (ID). More recently, TRIP12 was postulated as a novel candidate gene for intellectual disability in a meta-analysis of published ID cohorts. However, detailed clinical information characterizing the phenotype of these individuals was not provided. In this study, we present seven novel individuals with private TRIP12 mutations including two splice site mutations, one nonsense mutation, three missense mutations, and one translocation case with a breakpoint in intron 1 of the TRIP12 gene and clinically review four previously published cases. The TRIP12 mutation-positive individuals presented with mild to moderate ID (10/11) or learning disability [intelligence quotient (IQ) 76 in one individual], ASD (8/11) and some of them with unspecific craniofacial dysmorphism and other anomalies. In this study, we provide detailed clinical information of 11 TRIP12 mutation-positive individuals and thereby expand the clinical spectrum of the TRIP12 gene in non-syndromic intellectual disability with or without ASD.

Mutations in FLVCR2 associated with Fowler syndrome and survival beyond infancy.

Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH, OMIM 225790), also known as Fowler syndrome, is a rare autosomal recessive disorder, caused by mutations in FLVCR2. Hallmarks of the syndrome are glomerular vasculopathy in the central nervous system, severe hydrocephaly, hypokinesia and arthrogryphosis. The disorder is considered prenatally lethal. We report the first patients, a brother and a sister, with Fowler syndrome and survival beyond infancy. The patients present a phenotype of severe intellectual and neurologic disability with seizures, absence of functional movements, and no means of communication. Imaging of the brain showed calcifications, profound ventriculomegaly with only a thin edging of the cerebral cortex and hypoplastic cerebellum. Investigation with whole-exome sequencing (WES) revealed, in both patients, a homozygous pathogenic mutation in FLVCR2, c.1289C>T, compatible with a diagnosis of Fowler syndrome. The results highlight the power of combining WES with a thorough clinical examination in order to identify disease-causing mutations in patients whose clinical presentation differs from previously described cases. Specifically, the findings demonstrate that Fowler syndrome is a diagnosis to consider, not only prenatally but also in severely affected children with gross ventriculomegaly on brain imaging.

Replication of genomewide associations with allergic sensitization and allergic rhinitis.

BACKGROUND: Three genomewide metastudies have recently reported associations with self-reported allergic rhinitis and allergic sensitization. The three studies together identified a set of 37 loci but showed low concordance. This study investigates the reproducibility of the detected single nucleotide polymorphism (SNP) associations in an extensively characterized longitudinal cohort, BAMSE. METHODS: Phenotypic evaluation of allergic rhinitis (AR) and allergic sensitization was performed on 2153 children from BAMSE at 8 and 16 years of age. Allele frequencies of 39 SNPs were investigated for association with the exact allergic phenotypes of the metastudies. Odds ratios and false discovery rates were calculated, and the impact of asthma was evaluated. The cases were also evaluated for age at onset effects (≤ or >8 years of age). RESULTS: Association tests of the 39 SNPs identified 12 SNPs with P-values < 0.05 and Q-values < 0.10. Two of the four loci (TLR6-TLR1 and HLA-DQA1-HLA-DQB1) identified in all three original studies were also identified in this study. Three SNPs located in the TLR6-TLR1 locus had the lowest P-values and Q-values < 0.1 when using a well-defined AR phenotype. Two loci showed significant age at onset effects, but the effect of asthma on the associations was very limited. CONCLUSION: The TLR6-TLR1 locus is likely to have a central role in the development of allergic disease. The association between genetic variation in the SSTR1-MIPOL1 and TSLP-SLC25A46 loci and age at onset is the first report of age at onset effects in allergic rhinitis.

Origin of Swedish hemophilia B mutations.

BACKGROUND: More than 1100 mutations that cause hemophilia B (HB) have been identified. At the same time, specific F9 mutations are present at high frequencies in certain populations, which raise questions about the origin of HB mutations. OBJECTIVES: To describe the mutation spectrum of all HB families in Sweden and investigate if mutations appearing in several families are due to independent recurrent mutations (RMs) or to a common mutation event (i.e. are identical by descent (IBD)). PATIENTS/METHODS: The registered Swedish HB population consists of patients from 86 families. Mutations were identified by resequencing and identical haplotypes were defined using 74 markers and a control population of 285 individuals. The ages of IBD mutations were estimated using ESTIAGE. RESULTS: Out of 77 presumably unrelated patients with substitution mutations, 47 patients (61%) had mutations in common with other patients. Haplotyping of the 47 patients showed that 24 patients had IBD mutations (51%) with estimated ages of between two and 23 generations. A majority of these patients had mild disease. Eight of the 15 mutations observed in more than one family were C>T transitions in CpG sites and all eight were RMs. CONCLUSIONS: The association of IBD mutations with a mild phenotype is similar to what has been previously observed in hemophilia A. Noteworthy features of the mutations that are common to more than one family are the equal proportions of patients with RM and IBD mutations and the correlation between the occurrence of RMs and C>T transitions at CpG sites.

Origin of Swedish hemophilia A mutations.

BACKGROUND: Hemophilia A (HA) has a high level of variation within the disease class, with more than 1000 mutations being listed in the HAMSTeRS database. At the same time a number of F8 mutations are present in specific populations at high frequencies. OBJECTIVES: The simultaneous presence of large numbers of rare mutations and a small number of high-frequency mutations raises questions about the origins of HA mutations. The present study was aimed at describing the origins of HA mutations in the complete Swedish population. The primary issue was to determine what proportion of identical mutations are identical by descent (IBD) and what proportion are attributable to recurrent mutation events. The age of IBD mutations was also determined. PATIENTS/METHODS: In Sweden, the care of HA is centralized, and the Swedish HA population consists of ~ 750 patients from > 300 families (35% severe, 15% moderate, and 50% mild). Identical haplotypes were defined by single-nucleotide polymorphism and microsatellite haplotyping, and the ages of the mutations were estimated with estiage. RESULTS: Among 212 presumably unrelated patients with substitution mutations, 97 (46%) had mutations in common with other patients. Haplotyping of the 97 patients showed that 47 had IBD mutations (22%) with estimated ages of between two and 35 generations. The frequency of mild disease increased with an increasing number of patients sharing the mutations. CONCLUSIONS: A majority of the IBD mutations are mild and have age estimates of a few hundred years, but some could date back to the Middle Ages.

Opposite patterns of diurnal activity in the box jellyfish Tripedalia cystophora and Copula sivickisi.

Cubozoan medusae have a stereotypic set of 24 eyes, some of which are structurally similar to vertebrate and cephalopod eyes. Across the approximately 25 described species, this set of eyes varies surprisingly little, suggesting that they are involved in an equally stereotypic set of visual tasks. During the day Tripedalia cystophora is found at the edge of mangrove lagoons where it accumulates close to the surface in sun-lit patches between the prop roots. Copula sivickisi (formerly named Carybdea sivickisi) is associated with coral reefs and has been observed to be active at night. At least superficially, the eyes of the two species are close to identical. We studied the diurnal activity pattern of these two species both in the wild and under controlled conditions in laboratory experiments. Despite the very similar visual systems, we found that they display opposite patterns of diurnal activity. T. cystophora is active exclusively during the day, whereas C. sivickisi is actively swimming at night, when it forages and mates. At night T. cystophora is found on the muddy bottom of the mangrove lagoon. C. sivickisi spends the day attached to structures such as the underside of stones and coral skeletons. This species difference seems to have evolved to optimize foraging, since the patterns of activity follow those of the available prey items in their respective habitats.

Investigation of disease-associated factors in haemophilia A patients without detectable mutations.

To investigate disease causing mechanism in haemophilia A patients without detectable mutation. Screening for F8 mutations in 307 haemophilia A patients using: re-sequencing and inversion PCR, reverse transcription (RT-PCR) of mRNA, MLPA analysis, haplotyping using SNP and microsatellite markers. No F8 mutations were detected in 9 of the 307 patients (2.9%) using re-sequencing and inversion PCR. MLPA analysis detected duplication in exon 6 in one patient and RT-PCR showed no products for different regions of mRNA in four other patients, indicating failed transcription. No obvious associations were observed between the phenotypes of the nine patients, their F8 haplotypes and the putative mutations detected. The mutation-positive patients carrying the same haplotypes as the mutation-negative patients show a multitude of different mutations, emphasizing the lack of associations at the haplotype level. VWF mutation screening and factor V measurements ruled out type 2N VWD and combined factor V and VIII deficiency respectively. To further investigate a possible role for FVIII interacting factors the haplotypes/diplotypes of F2, F9, F10 and VWF were compared. The nine patients had no specific haplotype/diplotype combination in common that can explain disease. Duplications and faulty transcription contribute to the mutational spectrum of haemophilia A patients where conventional mutation screening fail to identify mutations.

Self-reported attachment style, trauma exposure and dissociative symptoms among adolescents.

The aim of this study was to analyze whether self-reported attachment style (measuring avoidance and anxiety) among adolescents was associated with dissociative symptoms, in addition to self-reported potentially traumatic experiences. A group consisting of 462 adolescents completed three self-assessment questionnaires: Linkoping Youth Life Experience Scale (LYLES), Experiences in Close Relationships, modified version (ECR) and Dissociation Questionnaire Sweden (Dis-Q-Sweden). Self-reported attachment style had a stronger association with dissociative symptoms than self reported traumas. It was also found that scores on a dissociation questionnaire correlated strongly with scores on self-reported attachment style in adolescence. Discussion concerns reasons why self-reported attachment style is an important factor that may influence dissociative symptoms during adolescence.

Effects of gradient encoding and number of signal averages on fractional anisotropy and fiber density index in vivo at 1.5 tesla.

BACKGROUND: Tensor estimation can be improved by increasing the number of gradient directions (NGD) or increasing the number of signal averages (NSA), but at a cost of increased scan time. PURPOSE: To evaluate the effects of NGD and NSA on fractional anisotropy (FA) and fiber density index (FDI) in vivo. MATERIAL AND METHODS: Ten healthy adults were scanned on a 1.5T system using nine different diffusion tensor sequences. Combinations of 7 NGD, 15 NGD, and 25 NGD with 1 NSA, 2 NSA, and 3 NSA were used, with scan times varying from 2 to 18 min. Regions of interest (ROIs) were placed in the internal capsules, middle cerebellar peduncles, and splenium of the corpus callosum, and FA and FDI were calculated. Analysis of variance was used to assess whether there was a difference in FA and FDI of different combinations of NGD and NSA. RESULTS: There was no significant difference in FA of different combinations of NGD and NSA of the ROIs (P>0.005). There was a significant difference in FDI between 7 NGD/1 NSA and 25 NGD/3 NSA in all three ROIs (P<0.005). There were no significant differences in FDI between 15 NGD/3 NSA, 25 NGD/1 NSA, and 25 NGD/2 NSA and 25 NGD/3 NSA in all ROIs (P>0.005). CONCLUSION: We have not found any significant difference in FA with varying NGD and NSA in vivo in areas with relatively high anisotropy. However, lower NGD resulted in reduced FDI in vivo. With larger NGD, NSA has less influence on FDI. The optimal sequence among the nine sequences tested with the shortest scan time was 25 NGD/1 NSA.

White matter abnormalities in children with idiopathic developmental delay.

BACKGROUND: The underlying cause of developmental delay (DD) often remains unclear despite extensive clinical examination and investigations. Interference in normal development of the brain may result in DD. PURPOSE: To identify the prevalence of abnormalities on magnetic resonance (MR) imaging in idiopathic developmental delay. MATERIAL AND METHODS: Of the 124 children referred for MR imaging with DD, 34 were excluded due to known history of progressive neurodevelopmental disorders, birth asphyxia, congenital CNS infections, metabolic disorder, chromosomal anomalies, and severe epileptic syndromes. The following structures were systematically reviewed: ventricles, corpus callosum, gray and white matter, limbic system, basal ganglia, brainstem, and cerebellum. RESULTS: Ten out of 90 (11%) were referred with DD only, whilst 80/90 (89%) were referred with DD and additional clinical findings, such as seizures, neurological deficit, and abnormal head size. Of the 90 patients, 14 (16%) had normal MR and 76 (84%) had abnormal MR findings. Abnormal ventricles were seen in 43/90 (48%); abnormal corpus callosum was identified in 40/90 (44%). Other MR findings included abnormalities in the white matter (23/90, 26%), hippocampi (5/90, 6%), cerebellum (5/90, 6%), and brainstem (4/90, 4%). CONCLUSION: Abnormalities of the ventricles and corpus callosum were identified in a large proportion of patients with idiopathic DD, indicative of changes in the white matter. Further studies using quantitative methods and diffusion tensor imaging are required to evaluate the white matter in these children.

Long-term follow-up of a patient with traumatic brain injury using diffusion tensor imaging.

This case report describes a patient who sustained severe head trauma with diffuse axonal injury (DAI). Examination with magnetic resonance diffusion tensor imaging (MRDTI), 6 days post-injury, showed a severe reduction in fractional anisotropy (FA) in the rostral pons containing the corticospinal tract, which correlated to the patient's severe hemiparesis. By 18 months post-accident, the patient had recovered completely and conventional MRI showed no pathology. However, although her FA values in the rostral pons had increased, they were still not normalized. It seems that a complete normalization of the FA values is not required to achieve clinical recovery, and that MR-DTI seems to be more sensitive to DAI compared to conventional MRI.

Visually guided obstacle avoidance in the box jellyfish Tripedalia cystophora and Chiropsella bronzie.

Box jellyfish, cubomedusae, possess an impressive total of 24 eyes of four morphologically different types. Two of these eye types, called the upper and lower lens eyes, are camera-type eyes with spherical fish-like lenses. Compared with other cnidarians, cubomedusae also have an elaborate behavioral repertoire, which seems to be predominantly visually guided. Still, positive phototaxis is the only behavior described so far that is likely to be correlated with the eyes. We have explored the obstacle avoidance response of the Caribbean species Tripedalia cystophora and the Australian species Chiropsella bronzie in a flow chamber. Our results show that obstacle avoidance is visually guided. Avoidance behavior is triggered when the obstacle takes up a certain angle in the visual field. The results do not allow conclusions on whether color vision is involved but the strength of the response had a tendency to follow the intensity contrast between the obstacle and the surroundings (chamber walls). In the flow chamber Tripedalia cystophora displayed a stronger obstacle avoidance response than Chiropsella bronzie since they had less contact with the obstacles. This seems to follow differences in their habitats.

The lens eyes of the box jellyfish Tripedalia cystophora and Chiropsalmus sp. are slow and color-blind.

Box jellyfish, or cubomedusae, possess an impressive total of 24 eyes of four morphologically different types. Compared to other cnidarians they also have an elaborate behavioral repertoire, which for a large part seems to be visually guided. Two of the four types of cubomedusean eyes, called the upper and the lower lens eye, are camera type eyes with spherical fish-like lenses. Here we explore the electroretinograms of the lens eyes of the Caribbean species, Tripedalia cystophora, and the Australian species, Chiropsalmus sp. using suction electrodes. We show that the photoreceptors of the lens eyes of both species have dynamic ranges of about 3 log units and slow responses. The spectral sensitivity curves for all eyes peak in the blue-green region, but the lower lens eye of T. cystophora has a small additional peak in the near UV range. All spectral sensitivity curves agree well with the theoretical absorbance curve of a single opsin, strongly suggesting color-blind vision in box jellyfish with a single receptor type. A single opsin is supported by selective adaptation experiments.

The ring nerve of the box jellyfish Tripedalia cystophora.

Box jellyfish have the most elaborate sensory system and behavioural repertoire of all cnidarians. Sensory input largely comes from 24 eyes situated on four club-shaped sensory structures, the rhopalia, and behaviour includes obstacle avoidance, light shaft attractance and mating. To process the sensory input and convert it into the appropriate behaviour, the box jellyfish have a central nervous system (CNS) but this is still poorly understood. The CNS has two major components: the rhopalial nervous system and the ring nerve. The rhopalial nervous system is situated within the rhopalia in close connection with the eyes, whereas the ring nerve encircles the bell. We describe the morphology of the ring nerve of the box jellyfish Tripedalia cystophora as ascertained by normal histological techniques, immunohistochemistry and transmission electron microscopy. By light microscopy, we have estimated the number of cells in the ring nerve by counting their nuclei. In cross sections at the ultrastructural level, the ring nerve appears to have three types of neurites: (1) small "normal"-looking neurites, (2) medium-sized neurites almost completely filled by electron-lucent vacuoles and (3) giant neurites. In general, only one giant neurite is seen on each section; this type displays the most synapses. Epithelial cells divide the ring nerve into compartments, each having a tendency to contain neurites of similar morphology. The number and arrangement of the compartments vary along the length of the ring nerve.

Organic materials for printed electronics.

Organic materials can offer a low-cost alternative for printed electronics and flexible displays. However, research in these systems must exploit the differences - via molecular-level control of functionality - compared with inorganic electronics if they are to become commercially viable.

Bilaterally symmetrical rhopalial nervous system of the box jellyfish Tripedalia cystophora.

Cubomedusae, or box jellyfish, have the most elaborate visual system of all cnidarians. They have 24 eyes of four morphological types, distributed on four sensory structures called rhopalia. Box jellyfish also display complex, probably visually guided behaviors such as obstacle avoidance and fast directional swimming. Here we describe the strikingly complex and partially bilaterally symmetrical nervous system found in each rhopalium of the box jellyfish, Tripedalia cystophora, and present the rhopalial neuroanatomy in an atlas-like series of drawings. Discrete populations of neurons and commissures connecting the left and the right side along with two populations of nonneuronal cells were visualized using several different histochemical staining techniques and electron microscopy. The number of rhopalial nerve cells and their overall arrangement indicates that visual processing and integration at least partly happen within the rhopalia. The larger of the two nonneuronal cell populations comprises approximately 2,000 likely undifferentiated cells and may support a rapid cell turnover in the rhopalial nervous system.