Life at school in Australia and Japan: the impact of stress and support on bullying and adaptation to school

In this international, comparative study, path analysis was used to examine eight different aspects of Japanese and Australian students' experiences of school life in relation to their effect on adaptation to school. Adaptation was constructed to include information on enjoyment of school, feelings of belonging to school, and relationships with other students. Two separate path models were tested to compare questionnaire data from over 3000 Australian and 6000 Japanese students across Years 5-10. The questionnaire was developed collaboratively by the authors to examine issues of common concern in both countries. Issues that related to the impact on adaptation to school of stress and support: family teachers, peers and school work, as well as bullying were of particular interest. Lack of support and the influential effect of stress were found to exert direct negative effects on adaptation to school, especially for high school students in Japan and Australia. The path results also confirmed the stressful effects of bullying in both countries. The finding of a strong relationship between bullying others and being victimised is discussed in the paper. Finally, the differences and similarities between Japanese and Australian students' perceptions of school life are extrapolated

Germline TP53 alterations in Finnish breast cancer families are rare and occur at conserved mutation-prone sites

We have screened for germline TP53 mutations in Finnish BRCA1 and BRCA2 mutation-negative families. This study represents the largest survey of the entire protein-encoding portion of TP53, and indicates that mutations are only found at conserved domains in breast cancer families also meeting the criteria for Li-Fraumeni/Li-Fraumeni-like syndrome, explaining only a very small additional fraction of the hereditary breast cancer cases. © 2001 Cancer Research Campaign http://www.bjcancer.co

Absence of autoantibodies connected to autoimmune polyendocrine syndrome type I and II and Addison's disease in girls and women with Turner syndrome

<p>Abstract</p> <p>Background</p> <p>A disturbance in the immune system has been described in Turner syndrome (45,X), with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45,X), thyroiditis being the most common. Other autoimmune diseases seen are inflammatory bowel disease, insulin dependent diabetes mellitus, Addison's disease, rheumatoid arthritis, myasthenia gravis, vitiligo, alopecia, pernicious anaemia and hypoparathyroidism, but the association to Turner syndrome is not definite.</p> <p>Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency) ear problems are common. Otitis media and a progressive sensorineural hearing disorder are commonly seen. In the normal population there are known inner ear disorders related to autoimmune diseases. The aim of this study was to investigate patients with Turner syndrome regarding autoantibodies connected to the autoimmune disorders; autoimmune polyendocrine syndrome type I and II and Addison's disease, to screen for overlapping profile of autoantibodies.</p> <p>Blood samples from 110 Turner patients (7–65 years) were investigated using <it>in vitro </it>transcription, translation and immunoprecipitation techniques regarding autoantibodies connected to autoimmune polyendocrine syndrome type I and II and Addison's disease (21-hydroxylase, 17α-hydroxylase, side-chain cleavage enzyme, aromatic L-amino acid decarboxylase, tyrosine hydroxylase and tryptophan hydroxylase).</p> <p>Results</p> <p>The autoantibodies investigated were not overrepresented among the Turner patients.</p> <p>Conclusion</p> <p>The autoimmune disorders associated with Turner syndrome do not seem to be of the same origin as Addison's disease, the type I or II autoimmune polyendocrine syndrome.</p

Neurocognitive impairment, employment, and social status in radiotherapy-treated adult survivors of childhood brain tumors

Background. Little is known of the cognitive functions, employment, and social status in adult survivors of childhood brain tumor (BT). We aimed to determine the long-term neurocognitive profile of radiotherapy-treated adult survivors of childhood BT and the relationship between cognitive functions and employment and social status. Methods. Neurocognitive profiles of survivors were assessed in a Finnish national cohort of 71 radiotherapy-treated survivors of childhood BT (median follow-up time: 21 years [range: 5-33 years]) using a cross-sectional design. Neurocognitive outcomes were compared to control (n = 45) and normative values. Tumor- and treatment-related data were collected from the patient files. Information on employment and social status was gathered. Results. Survivors' (median age: 27 years [range: 16-43 years]) median verbal and performance intelligence quotient (IQ) was 90 (range: 49-121) and 87 (range: 43-119), respectively. The cognitive domains with the greatest impairment were executive functions (median z score, 3.5 SD [range: -25.0 to 1.3 SD]), and processing speed and attention (median z score, -2.5 SD [range: -24.9 to 0.5 SD]). Executive functions were associated with employment, educational level, living independently, having an intimate relationship, and having a driving license. Processing speed and attention were related to educational level, living independently, having an intimate relationship, and having a driving license. Performance IQ was associated with educational level and employment status. Working memory was associated with educational level and living independently. Conclusions. Radiotherapy-treated adult survivors of childhood BT experience significant neurocognitive impairment, which is associated with difficulties related to employment and social status.Peer reviewe

An intronic deletion in megakaryoblastic leukemia 1 is associated with hyperproliferation of B cells in triplets with Hodgkin lymphoma

Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor and together regulate transcription of actin cytoskeleton genes. MKL1 is associated with hematologic malignancies and immunodeficiency, but its role in B cells is unexplored. Here we examined B cells from monozygotic triplets with an intronic deletion in MKL1, two of whom were previously treated for Hodgkin lymphoma. To investigate MKL1 and B cell responses in HL pathogenesis, we generated Epstein Barr virus-transformed lymphoblastoid cell lines from the triplets and two controls. While cells from the Hodgkin lymphoma treated patients had a phenotype close to healthy controls, cells from the undiagnosed triplet had increased MKL1 mRNA, increased MKL1 protein, and elevated expression of MKL1-dependent genes. This was associated with elevated actin content, increased cell spreading, decreased expression of CD11a integrin molecules, and delayed aggregation. Moreover, cells from the undiagnosed triplet proliferated faster, displayed a higher proportion of cells with hyperploidy, and formed large tumors in vivo. This phenotype was reversible by inhibiting MKL1 activity. Interestingly, cells from the triplet treated for Hodgkin lymphoma in 1985 contained two subpopulations: one with high expression of CD11a that behaved like control cells and the other with low expression of CD11a that formed large tumors in vivo similar to cells from the undiagnosed triplet. This implies that pre-malignant cells had re-emerged a long time after treatment. Together, these data suggest that dysregulated MKL1 activity participates in B cell transformation and Hodgkin lymphoma pathogenesis

Use of a T cell interferon gamma release assay in the investigation for suspected active tuberculosis in a low prevalence area

<p>Abstract</p> <p>Background</p> <p>In settings with low background prevalence of tuberculosis (TB) infection, interferon-γ release assays (IGRA) could be useful for diagnosing active TB. This study aims to evaluate the performance of QuantiFERON^®-TB Gold (QFT-G) in the investigation for suspected active TB, with particular attention to patients originating in high-incidence countries. Furthermore, factors associated with QFT-G results in patients with active TB were assessed.</p> <p>Methods</p> <p>From patients investigated for clinically suspected active TB, blood was obtained for QFT-G testing, in addition to routine investigations. Positive (PPV) and negative (NPV) predictive values for QFT-G were calculated, comparing patients with confirmed TB and those with other final diagnoses. QFT-G results in TB patients originating from countries with intermediate or high TB incidence were compared with QFT-G results from a control group of recently arrived asymptomatic immigrants from high-incidence countries. Factors associated with QFT-G outcome in patients with confirmed TB were assessed.</p> <p>Results</p> <p>Among 141 patients, 41/70 (58.6%) with confirmed TB had a positive QFT-G test, compared to 16/71 (22.6%) patients with other final diagnoses, resulting in overall PPV of 71.9% and NPV of 67.6%. For patients with pulmonary disease, PPV and NPV were 61.1% and 67.7%, respectively, and 90.5% and 66.7% for subjects with extrapulmonary manifestations. Comparing patients from high-incidence countries with controls yielded a PPV for active TB of 76.7%, and a NPV of 82.7%. Patients with confirmed TB and positive QFT-G results were characterized by a lower median peripheral white blood cell count (5.9 × 10⁹/L vs. 8.8 × 10⁹/L; <it>P </it>< 0.001) and a higher median body mass index (22.7 vs. 20.7; <it>P </it>= 0.043) as compared to QFT-G-negative TB patients.</p> <p>Conclusion</p> <p>The overall PPV and NPV of QFT-G for identifying active TB were unsatisfactory, especially for pulmonary disease. Thus, the usefulness of QFT-G for this purpose is questionable. However, a high PPV was observed for extrapulmonary TB and QFT-G might be considered in the diagnostic process in this situation. The PPV and NPV for identifying active TB among persons originating from regions with high-and intermediate TB incidence was similar to that observed in subjects originating in the low-incidence region.</p

FANCM mutation c.5791C > T is a risk factor for triple-negative breast cancer in the Finnish population

The FANCM c.5101C > T nonsense mutation was previously found to associate with breast cancer in the Finnish population, especially among triple-negative cases. Here, we studied the prevalence of three other FANCM variants: c.5791C > T, which has been reported to predispose to familial breast cancer, and the c.4025_4026delCT and c.5293dupA variants recently identified in Finnish cancer patients. We genotyped the FANCM c.5791C > T mutation in 4806 invasive breast cancer patients, including BRCA1/2 mutation negative familial cases and unselected cases, and in 2734 healthy population controls from four different geographical areas of Finland. The association of the mutation with breast cancer risk among patient subgroups was statistically evaluated. We further analyzed the combined risk associated with c.5101C > T and c.5791C > T mutations. We also genotyped 526 unselected ovarian cancer patients for the c.5791C > T mutation and 862 familial breast cancer patients for the c.4025_4026delCT and c.5293dupA variants. The frequency of the FANCM c.5791C > T mutation was higher among breast cancer cases than in controls (OR 1.94, 95% CI 0.87-4.32, P = 0.11), with a statistically significant association with triple-negative breast cancer (OR 5.14, 95% CI 1.65-16.0, P = 0.005). The combined analysis for c.5101C > T and c.5791C > T carriers confirmed a strong association with breast cancer (OR 1.86, 95% CI 1.32-2.49, P = 0.0002), especially among the triple-negative patients (OR 3.08, 95% CI 1.77-5.35, P = 0.00007). For the other variants, only one additional c.4025_4026delCT carrier and no c.5293dupA carriers were observed. These results support the role of FANCM as a breast cancer susceptibility gene, particularly for triple-negative breast cancer.Peer reviewe